I & I

Question 1

Innate immunity in health and disease by Dr. Deborah Chong

What are Natural Killer Cells?

*LOB: Describe the main features of natural killer cells

Answer 1

• From a lymphoid lineage
• recognise infected and stressed cells
• kills irus infected cells and malignant transformed cells
• express cytotoxic enzymes
• produce interferon γ

Question 2

Innate immunity in health and disease by Dr. Deborah Chong

What are the features of Natural Killer Cells?

*LOB: Describe the main features of natural killer cells

Answer 2

• complex for activation
• granules in cytosol of
• perforin (perforate)
• cytolitic enzymes (granzymes A and B)

Question 3

Innate immunity in health and disease by Dr. Deborah Chong

What is Mφ ΝΚ cooperation?

*LOB: Explain the mechanisms underlying target cell recognition by natural killer cells

Answer 3

• Mφ produce IL-12
• IL-12 activates NK
• NK produce IFN γ
• IFN γ helps to activate Mφ

Question 4

Innate immunity in health and disease by Dr. Deborah Chong

How do NK recognise cells?

*LOB: Explain the mechanisms underlying target cell recognition by natural killer cells

Answer 4

integration of signals from inhibitory
and activating receptors

Inhibitory receptors recognise ligands on healthy cells

Activating receptors recognise infected/stressed cells

Question 5

Innate immunity in health and disease by Dr. Deborah Chong

What are the inhibitory receptors of NK Cells

*LOB: Explain the mechanisms underlying target cell recognition by natural killer cells

Answer 5

• KIRs (killer inhibitory receptors)
• NKG2A (C type lectin receptors)
• Leucocyte Ig-like receptors (LIRs)

Inhibitory receptors recognise ligands on healthy cells

These are the receptors on the NK cell that recognise MHC class 1 on self cells.
The aim of these receptors is to PREVENT NK cell killing “healthy” cells

Question 6

Innate immunity in health and disease by Dr. Deborah Chong

What are activating receptors of NK Cells

*LOB: Explain the mechanisms underlying target cell recognition by natural killer cells

Answer 6

• NKG2D, KIRs, CD16
• Adaptor proteins: DAP10, DAP12

Activating receptors recognise infected/stressed cells

Question 7

Innate immunity in health and disease by Dr. Deborah Chong

How do NK not affect healthy cells?

*LOB: Explain the mechanisms underlying target cell recognition by natural killer cells

Answer 7

• All healthy autologous cells have MHC class 1
• Inhibitory receptors recognise MHC 1
• This blocks the recognition from activation receptors
• so NK do not attack autologous cells

Question 8

Innate immunity in health and disease by Dr. Deborah Chong

So how do cells lose the protection of MHC class 1?

*LOB: Describe the main molecules and steps involved in target cell killing by natural killer cells

Answer 8

• Virus infected cells: downregulate MHC I
• Malignant (cancer) cells: downregulate MHC I
• inhibitory receptors are not ligated by MHC class I
• Do not down regulate the activation receptors (NKG2D)

Therefore are killed

However, this doesnt mean NO MHC class 1, rather a lot fewer MHC1 than activating receptors. So signals from activating receptors may overwhelm the signals from inhibitory receptors.

Question 9

Innate immunity in health and disease by Dr. Deborah Chong

What is the biochemical mechanism of NK activation?

*LOB: Describe the main molecules and steps involved in target cell killing by natural killer cells

Answer 9

• Both inhibitory and activatory receptors have intracellular and extracellular portions (immunoreceptor tyrosine-based inhibitory/activatory motif)
• Inhibitory (ITIM) phosphatases block signalling
• Activatory (ITAM) engage protein tyrosine kinase-mediated signalling
  events

Question 10

Innate immunity in health and disease by Dr. Deborah Chong

What do the NK use to “kill”

*LOB: Describe the main molecules and steps involved in target cell killing by natural killer cells

Answer 10

At the site of contact between NK and Target

1) Perforin: forms pores
2) allows Granzymes A, B, C in
3) Granzymes activate Caspases

Question 11

Innate immunity in health and disease by Dr. Deborah Chong

What are the roles of Granzymes A B and C?

*LOB: Describe the main molecules and steps involved in target cell killing by natural killer cells

Answer 11

Granzyme B: can trigger
mitochondrial apoptotic
pathway

Question 12

Innate immunity in health and disease by Dr. Deborah Chong

NK Disease and Defects

*LOB: Describe defects in various components of the innate immune response and explain the mechanisms by which they cause disease

Answer 12

• immuno-deficiencies (e.g. Chediak-Higashi)
• complete absence of circulating NK cells
• functional NK cell deficiencies (normal numbers)

Question 13

Innate immunity in health and disease by Dr. Deborah Chong

Innate lymphoid cells (ILCs)

*LOB: Give some examples of lymphocytes with limited antigen recognition capacity

Answer 13

similar functions to lymphocytes
Lymphocyte-like cells
* ready to act → main mechanism: produce cytokines
* do not express TCRs (T cell receptors)
* responses are faster → innate immunity
* different types of ILCs depending on type of cytokines
ILC1 (Th1-like; IFN-γ); NK cells are related to ILC1
ILC2 (Th2-like; IL-5, IL-13)
ILC3 (Th17-like; IL-17)
* no clonal expansion (proliferation) & no differentiation

LCs do not possess rearranged antigen-specific cell receptors (T-cell receptor [TCR] or B-cell receptor [BCR]), but they mirror T helper (Th) cell diversity

Question 14

Innate immunity in health and disease by Dr. Deborah Chong

What are the roles of ILC

*LOB: Give some examples of lymphocytes with limited antigen recognition capacity

Answer 14

ILCs cross talk with the resident tissue by sensing the cytokines present in their microenvironments and subsequently secreting a plethora of cytokines that regulate innate immunity

Question 15

Innate immunity in health and disease by Dr. Deborah Chong

Examples of lymphocytes with limited diversity

*LOB: Give some examples of lymphocytes with limited antigen recognition capacity

Answer 15

γδ (gamma/delta) T cells
NK-T cells
Mucosa-Associated Invariant T (MAIT) cells
B-1 B cells
Marginal zone B cells

Question 16

Innate immunity in health and disease by Dr. Deborah Chong

Chronic granulomatous disease

*LOB: Describe defects in various components of the innate immune response and explain the mechanisms by which they cause disease

Answer 16

mutation in NADPH component and defect in oxidative burst

Question 17

Innate immunity in health and disease by Dr. Deborah Chong

Chediak-Higashi syndrome

*LOB: Describe defects in various components of the innate immune response and explain the mechanisms by which they cause disease

Answer 17

• defective phagosome-lysosome fusion
• Neutropenia and giant granules on film
• genetic, rare LYSosomal Trafficking regulator (LYST) errror

Question 18

Innate immunity in health and disease by Dr. Deborah Chong

Leucocyte adhesion defects

*LOB: Describe defects in various components of the innate immune response and explain the mechanisms by which they cause disease

Answer 18

Defect in 2-chain integrins (LFA-1, Mac-1)
* Defective neutrophil chemotaxis
* Defect in sialyl-Lewis X (selectin ligand)
decreased levels of integrins on phagocytes
* Impaired clearance of pathogens

Question 19

Innate immunity in health and disease by Dr. Deborah Chong

Complement deficiencies

*LOB: Describe defects in various components of the innate immune response and explain the mechanisms by which they cause disease

Answer 19

• C2, C4, C1q deficiency → SLE-like syndrome
• C3 deficiency → frequent serious infections with pyogenic bacteria (e.g. Staphylococcus aureus, etc.)
• C5-C9 (MAC) deficiency → disseminated infections with Neisseria (N. meningitidis, N. gonorrhoeae)
• C1 INH deficiency → hereditary angioedema
• increased cleavage C4, C2
• DAF, CD59 deficiency → paroxysmal nocturnal haemoglobinuria:
• • recurrent intravascular haemolysis (RBC lysis)

Question 20

Development of Immune Cells by Dr José Saldana

Overview of development of Innate Immune Cells

*LOB: Present an overview of the development of innate and adaptive immune cells

Answer 20

Derived from hematopoietic stem cells (HSCs) in the bone marrow.
Common myeloid progenitor (CMP) gives rise to innate immune cells such as:
Neutrophils, monocytes/macrophages, dendritic cells, mast cells, and natural killer (NK) cells.
Granulocyte-macrophage progenitor (GMP) specifically produces neutrophils, monocytes/macrophages, and dendritic cells.

Question 21

Development of Immune Cells by Dr José Saldana

Overview of Development of Adaptive Immune Cells

*LOB: Present an overview of the development of innate and adaptive immune cells

Answer 21

Also originates from HSCs in the bone marrow.
Lymphoid progenitor cells differentiate into:
B lymphocytes (B cells) in the bone marrow, where they undergo gene rearrangement to generate diverse antigen receptors.
T lymphocytes (T cells) that migrate to the thymus for maturation and selection of T cell receptors (TCRs).

Question 22

Development of Immune Cells by Dr José Saldana

T cell maturation checkpoints

*LOB: Describe the main stages of T and B lymphocyte maturation and selection

Answer 22

1) No Antigen produced -> DIE
2) Partial anitgen produced -> CLONE
3) CLONE doesnt produce partial Ag -> DIE
4) Full Antigen Produced
5) Full Antigen WEAK -> LIVE (Full Mature T Cell)
6) Full Antigen STRONG -> targeted to die to prevent autoimmune

Question 23

Development of Immune Cells by Dr José Saldana

What are the stages in T Cell maturation?

*LOB: Describe the main stages of T and B lymphocyte maturation and selection

Answer 23

Question 24

Development of Immune Cells by Dr José Saldana

What are the stages in T Cell selection?

*LOB: Describe the main stages of T and B lymphocyte maturation and selection

Answer 24

Question 25

Development of Immune Cells by Dr José Saldana

Define positive selection

*LOB: Understand the concept of self/immunological tolerance

Answer 25

Only lymphocytes that express Ag receptors that can recognise Ags/MHC molecules mature & are retained in repertoire

Question 26

Development of Immune Cells by Dr José Saldana

What is negative selection?

*LOB: Understand the concept of self/immunological tolerance

Answer 26

Lymphocytes with Ag receptors that recognise self Ags/MHC molecules too strongly are eliminated (die by apoptosis)

PREVENTS AUTOIMMUNE

Question 27

Development of Immune Cells by Dr José Saldana

What is death by neglect?

*LOB: Understand the concept of self/immunological tolerance

Answer 27

Lymphocytes that express Ag receptors that do not recognise Ags/MHC molecules are eliminated (do not receive survival signals through their Ag receptors and die by apoptosis )

Question 28

Development of Immune Cells by Dr José Saldana

B Cell maturation and selection

*LOB: Describe the main stages of T and B lymphocyte maturation and selection

Answer 28

Question 29

Development of Immune Cells by Dr José Saldana

Immunological Tolerance

*LOB: Understand the concept of self/immunological tolerance

Answer 29

The ability to regulate immune cells to prevent autoimmune disease
Recognition of self.

Question 30

Development of Immune Cells by Dr José Saldana

Central Tolerance

*LOB: Describe the main mechanisms that determine the induction of central tolerance of T and B lymphocytes

Answer 30

induction of tolerance to self Ags during lymphocyte development in central lymphoid organs

In the thymus as only self Ags can be encountered

peripheral tissue-restricted self Ags: AIRE (AutoImmune Regulator Protein)
allows expression of tissue restricted peripheral self Ags in thymic medullary
epithelial cells
Self tolerance – mechanisms (T cells)

Question 31

Development of Immune Cells by Dr José Saldana

Define Anergy

*LOB: Describe the main mechanisms that determine the induction of peripheral tolerance of T and B lymphocytes

Answer 31

Functional unresponsiveness between immature immune cell and effector.

Question 32

Development of Immune Cells by Dr José Saldana

Define Suppresion

*LOB: Describe the main mechanisms that determine the induction of peripheral tolerance of T and B lymphocytes

Answer 32

Block in activation of immature cell by TReg

Question 33

Development of Immune Cells by Dr José Saldana

Peripheral Tolerance

*LOB: Describe the main mechanisms that determine the induction of peripheral tolerance of T and B lymphocytes

Answer 33

tolerance to self Ags is induced when mature lymphocytes respond to Ags in peripheral lymphoid organs or peripheral tissues

Question 34

Development of Immune Cells by Dr José Saldana

What are the effector roles of mature lymphocytes?

*LOB: Describe the main mechanisms that determine the induction of peripheral tolerance of T and B lymphocytes

Answer 34

Question 35

Development of Immune Cells by Dr José Saldana

Peripheral Tolerance and Receptor editing in B Cells.

*LOB: Describe the main mechanisms that determine the induction of peripheral tolerance of T and B lymphocytes

Answer 35

Immature B cells that recognise self Ags with high
avidity (strongly) in bone marrow can:
- change the specificity of their Ag receptors so that
they no longer recognise strongly self Ags
B cell central tolerance: receptor editing
- mechanism: rearranging the genes for the light chain

occurs in the
lymph nodes and spleen

Question 36

Development of Immune Cells by Dr José Saldana

Key players in central tolerance?

*LOB: Describe the main mechanisms that determine the induction of central tolerance of T and B lymphocytes

Answer 36

T Cells: TCR CD4 CD8
Non-T Cells: MHC1 MHC2

Question 37

Development of Immune Cells by Dr José Saldana

Peripheral Tolerance

*LOB: Describe the main mechanisms that determine the induction of peripheral tolerance of T and B lymphocytes

Answer 37

tolerance to self Ags is induced when mature lymphocytes respond to Ags in peripheral lymphoid organs or peripheral tissues

Question 38

Inflammation by Dr Omar Janneh

Define prostanoid

*LOB: Define the terms prostanoid, leukotriene and eicosanoid

Answer 38

derived from arachidonic acid (20c chain)

include prostaglandins, prostacyclins, and thromboxanes

These steps are triggered by many agents, e.g. thrombin on platelets and antigen-antibody reactions on mast cells

Question 39

Inflammation by Dr Omar Janneh

Define leukotriene

*LOB: Define the terms prostanoid, leukotriene and eicosanoid

Answer 39

formed from arachidonic acid
synthesized and released by immune cells, such as leukocytes (white blood cells) and mast cells.

Question 40

Inflammation by Dr Omar Janneh

Define eicosanoid

*LOB: Define the terms prostanoid, leukotriene and eicosanoid

Answer 40

deriving from “eicosa,” which means twenty, referring to the 20 carbon chain arachadonic acid

Question 41

Inflammation by Dr Omar Janneh

Timescale of Events in Inflammation

*LOB: Outline the main effects of eicosanoids with special reference to their roles in inflammation, haemostasis and gastric cytoprotection

Answer 41

Inflammatory steps (5Rs)
Recognition of the injurious agent
Recruitment of leukocytes
Removal of the agent
Regulation (control) of response
Resolution (repair) – inflammation initiates repair

Question 42

Inflammation by Dr Omar Janneh

Histamine Receptor G Proteins

*(not stated as required but might be useful to know)

*LOB: Describe the role of histamine in inflammation and outline the clinical utility of H1 and H2 receptor antagonists and their major side effects

Answer 42

H1 - Gq/PLC, PIP2 production, generation of DAG/IP3, PKC: smooth muscle, endothelium, CNS, sensory nerves

**H2 - Gs/AC, **generation of cAMP, stimulation of PKA: parietal cells, heart, uterus, mast cells, neutrophils

H3 - Gi, decrease in cAMP levels: neuronal presynaptic terminals (autoreceptor: ↓ release of histamine)

H4 - Gi, decrease in cAMP levels: basophils, bone marrow, gut

Question 43

Pathogenesis of TB by Prof Phillip Butcher

History of TB

*LOB: Describe the natural history of tuberculosis infection and give pathological features of the disease

Answer 43

Exposure: TB spreads when someone with active TB coughs or sneezes, releasing bacteria into the air that can be inhaled by others.

Infection: Not everyone exposed gets infected. The immune system usually keeps the bacteria in check, leading to latent TB infection (LTBI).
**
Latent TB Infection (LTBI): In LTBI, bacteria are dormant, causing no symptoms, and individuals are not contagious. A chest X-ray is often normal. However, they can develop active TB if their immune system weakens.
**
Active TB Disease: Immune system compromise can lead to reactivation of the bacteria, causing active TB with symptoms like cough, fever, night sweats, weight loss, and fatigue. Active TB is contagious and spreads through the air.

Question 44

Pathogenesis of TB by Prof Phillip Butcher

Pathogenesis of TB

*LOB: Describe the natural history of tuberculosis infection and give pathological features of the disease

Answer 44

1. Inhalation
2. Alveolar macrophages
3. Lymph nodes
4. Haematogenous spread to other parts of lung
   via lymphatics and capillaries
5. A brief acute inflammatory response -
   neutrophils, cytokine storms
   macrophage recruitment and activation
6. recruitment of CD4, CD8 and NK cells - production of IFN-
7. Down regulation of acute inflammation  chronic inflammation
8. Formation of granuloma - immune containment
9. Caseation
10. Liquifaction, cavitation and release
11. Transmission
    Pathogenesis

Question 45

Inflammation by Dr Omar Janneh

Describe the role of histamine

*LOB: Describe the role of histamine in inflammation and outline the clinical utility of H1 and H2 receptor antagonists and their major side effects

Answer 45

All G-protein-coupled receptors which produce physiological effects by activating second messenger systems

Synthesised, stored and released from:
– Mast cells, which express receptors for IgE, C3a and C5a on cell
surface (connective tissues)
– Basophils (blood)
– Neurons in brain
– Histaminergic cells in gut (ECL, enterochromaffin-like cells)

Released by allergic reactions (IgE-mediated), production of
complement agents (C3a and C5a), insect stings, trauma, etc.
through a rise in [Ca2+]i

Question 46

Inflammation by Dr Omar Janneh

Cyclooxygenases are important because….

*LOB: Define the terms prostanoid, leukotriene and eicosanoid

Answer 46

Conversion of Arachadonic Acid to prostanoids requires the enzyme cyclooxygenase (COX)

COX 1: Constitutively active, involved in regulation of peripheral vascular resistance, renal blood flow, platelet aggregation, gastric cytoprotection

COX 2: Needs to be stimulated (e.g. by inflammatory cytokines- IL-1, TNF)
- Responsible for role of PGs/TXs in inflammatory responses (pain and fever)

COX 3 is similar to COX 1 but pain perception of CNS

Question 47

Inflammation by Dr Omar Janneh

What are the Effects of Stimulation of H1 and H2 Receptors

*LOB: Describe the role of histamine in inflammation and outline the clinical utility of H1 and H2 receptor antagonists and their major side effects

Answer 47

Cardiovascular
dilates arterioles, ↓ TPR (H1)
Increased permeability of post-capillary venules, ↓ BV (H1)
Increase in heart rate (H2) - in vivo reflex to try to retain BP to normal
Generally involved in ↓BP (↓ vascular resistance)

Non-vascular smooth muscle (airways, gut etc.)
Contraction (H1), e.g. bronchoconstriction
Algesia
Pain, itching, and sneezing caused by stimulation of sensory nerves (H1)
Associated exocrine secretions
Increased, due to increased blood flow

Gastric acid
Increase secretion (H2 –mediated effects are of interest)

Question 48

Inflammation by Dr Omar Janneh

What is the Triple Response?

*LOB: Describe the role of histamine in inflammation and outline the clinical utility of H1 and H2 receptor antagonists and their major side effects

Answer 48

Characterised by reddening, wheal and flare.
Refers to LOCAL histamine response

Reddening (Rubor):
initial response to histamine release in the skin.
localized vasodilation
Increased blood flow leads to redness and warmth

Wheal:
raised, swollen, and palpable area at the site of histamine release
the increased permeability of capillaries, allows fluid to accumulate

Flare:
spreading of redness beyond the immediate area due to the dilation of larger blood vessels

Question 49

Inflammation by Dr Omar Janneh

How is the Flare response co-ordinated (Triple Response)

*LOB: Describe the role of histamine in inflammation and outline the clinical utility of H1 and H2 receptor antagonists and their major side effects

Answer 49

Sensory nerves and C fibers, are involved in the perception of pain and sensory information during inflammation.

Substance P is released from C fibers
Substance P contributes to vasodilation

The orthodromic (normal direction) and antidromic (opposite direction) responses of sensory nerves can influence the spread of pain signals and inflammation.

This leads to a flare of the original inflammation beyond its micro localised area.

Question 50

Inflammation by Dr Omar Janneh

How can the Flare response occur outside the site of inflammation? (Triple Response)

*LOB: Describe the role of histamine in inflammation and outline the clinical utility of H1 and H2 receptor antagonists and their major side effects

Answer 50

When histamine stimulates afferent fibres, it is known to stimulate an axon reflex: It orthodromically stimulates nerve impulse which travel towards the spinal cord and the dorsal root ganglia, passing antidromically down the other branches of sensory nerves. These antidromic impulses release nerve impulses → vasodilation (flare, reddening) distant from the site of irritation

This is now being explored as reasoning for migraines
dermatographia

Question 51

Inflammation by Dr Omar Janneh

What is the vasodilator that is involved in Histamine response?
How is it synthesised?

*LOB: Describe the role of histamine in inflammation and outline the clinical utility of H1 and H2 receptor antagonists and their major side effects

Answer 51

Bradykinin

Synthesised by activation of:

Hageman factor (HF, factor XII) & production of plasma kallikrein (makes sense when you think of wound healing)

Production of lysylbradykinin by tissue kallikreins;

Action of cellular proteases

Question 52

Inflammation by Dr Omar Janneh

What are the pharmacological affects of Bradykinin?

*LOB: Describe the role of histamine in inflammation and outline the clinical utility of H1 and H2 receptor antagonists and their major side effects

Answer 52

Potent vasoactive peptide with wide-ranging effects:
Increases vascular permeability
Promotes vasodilation (↓BP)
Pain
Contraction of visceral smooth muscle (gut and bronchus)

Stimulation of arachidonic acid metabolism (initiates phospholipase action → release of numerous lipid mediators of inflammation)
Chemotactic to leukocytes, which defend the body against infections

Dry cough (sensitization of airway sensory nerves via rapidly adapting stretch receptors and C-fiber receptors and substance P)

Metabolism of bradykinin: kininases, I and II (ACE, aminopeptidase P, carboxypeptidase)

Question 53

Inflammation by Dr Omar Janneh

What are H1 and H2 receptor antagonists

*LOB: Describe the role of histamine in inflammation and outline the clinical utility of H1 and H2 receptor antagonists and their major side effects

Answer 53

H1 Antagonists – Treat Acute Inflammation
such as mepyramine, promethazine, diphenhydramine, Terfenadine

H2 Antagonists – Gastric Problems
such as cimetidine, famotidine

Question 54

Inflammation by Dr Omar Janneh

What are major side effects of H1 and H2 receptor antagonists

*LOB: Describe the role of histamine in inflammation and outline the clinical utility of H1 and H2 receptor antagonists and their major side effects

Answer 54

H1
Reduce minor inflammatory reactions (e.g. insect bites, hay
fever), BUT NO significant value in asthma
– 1st generation drugs are sedative – drowsiness is a major side
effect, but sometimes used as a therapeutic effect
– Some (e.g. promethazine) are anti-emetic – ‘motion sickness’
– Anti-muscarinic actions (common in 1st generation drugs) e.g.
atropine-like effects of blurred vision, constipation, etc.
H1 Antagonists – Treat Acute Inflammation

H2
Reduce gastric acid secretion in the treatment of duodenal
and gastric ulcers and Zollinger-Ellison syndrome (duodenum
& pancreas tumours increasing gastrin secretion)
– Increase INMT activity so more rapid breakdown of histamine
– Mental confusion, dizziness, tiredness & diarrhoea sometimes
as side effects
– Cimetidine decreases cytochrome P450 activity so potential
for adverse drug interactions; gynecomastia

Question 55

Inflammation by Dr Omar Janneh

Describe the major pathway leading to prostaglandin

*LOB: Describe the major enzymatic pathways leading to the formation of prostaglandins and leukotrienes, with special reference to areas where drug therapy can be applied

Answer 55

Question 56

Inflammation by Dr Omar Janneh

Describe the enzymatic pathways leading to leukotrienes

*LOB: Describe the major enzymatic pathways leading to the formation of prostaglandins and leukotrienes, with special reference to areas where drug therapy can be applied

Answer 56

Question 57

Inflammation by Dr Omar Janneh

Where can drug therapy be applied to prostaglandins and leukotriene enzymatic pathways?

*LOB: Describe the major enzymatic pathways leading to the formation of prostaglandins and leukotrienes, with special reference to areas where drug therapy can be applied

Answer 57

NSAIDs
Glucocorticoids
Lipoxygenase inhibitors
Leukotriene antagonists

Conversion of AA to prostanoids requires the enzyme cyclooxygenase (COX)

**COX-1 **is constitutively expressed at low levels in many cell types.
The expression of COX-2 is highly regulated.

For example Aspirin interacts with thromboxane synthase and Epoprostenol
interacts with prostacyclin synthase*

Question 58

Inflammation by Dr Omar Janneh

Main effects of eicosanoids

*LOB: Outline the main effects of eicosanoids with special reference to their roles in inflammation, haemostasis and gastric cytoprotection

Answer 58

Inflammation:
Example: Prostaglandins and leukotrienes
**Vasoconstriction and Vasodilation:
**Example: Prostacyclin (PGI2) promotes vasodilation, and thromboxane A2 (TXA2) promotes vasoconstriction.
**Pain and Fever:
**Example: Prostaglandins sensitize pain receptors and raise body temperature, leading to fever.
**Platelet Aggregation:
**Example: Thromboxane A2 (TXA2)
Bronchoconstriction:
Example: Leukotrienes, particularly leukotriene D4 (LTD4)
**Regulation of Blood Flow:
**Example: Prostaglandins
**Gastrointestinal Protection:
**Example: Prostaglandins
**Reproductive Function:
**Example: Prostaglandins
Immunomodulation:
Example: Various eicosanoids can influence immune cell function, including prostaglandins and leukotrienes.

Question 59

Inflammation by Dr Omar Janneh

Physiological effects of eicosanoids

*LOB: Outline the main effects of eicosanoids with special reference to their roles in inflammation, haemostasis and gastric cytoprotection

Answer 59

Question 60

Inflammation by Dr Omar Janneh

How does the eicosanoid prostaglandin have a paradoxical component?

*LOB: Outline the main effects of eicosanoids with special reference to their roles in inflammation, haemostasis and gastric cytoprotection

Answer 60

This is important to allow resolution to occur.

Recruit monocytes for clearance

CyPG CYCLIC PROSTAGLANDINS – inhibits macrophage activation→ ↓ uncontrolled tissue damage; ↓NF-B activation (helps to ↓ activation of inflammatory genes)

Question 61

Inflammation by Dr Omar Janneh

Eicosanoids with Haemostasis

*LOB: Outline the main effects of eicosanoids with special reference to their roles in inflammation, haemostasis and gastric cytoprotection

Answer 61

Eicosanoids, such as thromboxane A2 (TXA2), play a crucial role in hemostasis.
Thromboxane A2 is produced by platelets and promotes vasoconstriction and platelet aggregation.

imbalance- clotting disorders

Question 62

Inflammation by Dr Omar Janneh

Eicosanoids with Gastric cytoprotection

*LOB: Outline the main effects of eicosanoids with special reference to their roles in inflammation, haemostasis and gastric cytoprotection

Answer 62

prostaglandins, are significant regulators of the gastrointestinal system.
Prostaglandins help maintain the integrity of the gastrointestinal mucosa by promoting the secretion of mucus and bicarbonate.
This protective action helps prevent damage to the stomach lining and the development of gastric ulcers.

NSAIDs that inhibit this can cause ulcers

Question 63

Inflammation by Dr Omar Janneh

Why do Eicosainoids cause dry cough and bronchospasm as side effects?

*LOB: Outline the main effects of eicosanoids with special reference to their roles in inflammation, haemostasis and gastric cytoprotection

Answer 63

↑ cellular infiltration of eosinophils, neutrophils
↑ mucus secretion
↑ bronchoconstriction (similar to vascular mechanism)
↑ airway oedema

Leuokotriene are more potent.

Smooth muscle cells in the bronchial airways express receptors for leukotrienes.
Gs -> PLC -> IP DAG

Question 64

Inflammation by Dr Omar Janneh

What are the side effects of Leukotriene receptor antagonists

*LOB: Outline the main effects of eicosanoids with special reference to their roles in inflammation, haemostasis and gastric cytoprotection

Answer 64

Receptor blockade is useful in following:
Prevention of mild to moderate asthma
Early to late bronchoconstrictor effects of allergens
Exercise-induced asthma and asthma provoked by NSAIDs

Side effects:
GI upset
Dry mouth, thirst
Rashes, oedema
Irritability

Question 65

Pathogenesis of TB by Prof Phillip Butcher

Difference between Active and Latent TB

*LOB: Describe the natural history of tuberculosis infection and give pathological features of the disease

Answer 65

Question 66

Pathogenesis of TB by Prof Phillip Butcher

Where can TB spread in body

*LOB: Describe the natural history of tuberculosis infection and give pathological features of the disease

Answer 66

Pleural disease
Lymph nodes – scrofula
Pericardial
Skeletal –Potts disease
Genitourinary
Gut
Peritoneal
Miliary
Meningeal

Question 67

Pathogenesis of TB by Prof Phillip Butcher

Pathological features of the disease

*LOB: Describe the natural history of tuberculosis infection and give pathological features of the disease

Answer 67

**Granuloma Formation: **Immune response to M. tuberculosis leads to granulomas, organized collections of immune cells like macrophages and lymphocytes, containing the bacteria and preventing their spread.

**Caseous Necrosis: **Within granulomas, infected tissue undergoes caseous necrosis, a type of tissue death causing a cheese-like appearance. Accumulation of this necrotic material can create lung cavities.
**
Ghon Focus and Ghon Complex: **Initial infection can result in a Ghon focus, a small lung lesion where bacteria enter. If the immune response successfully controls the infection, it forms a Ghon complex, combining the Ghon focus with associated lymph node involvement.

Miliary TB: In severe cases, the infection can disseminate via the bloodstream, leading to miliary TB. It involves widespread distribution of small TB lesions throughout various organs, resembling millet seeds.

Fibrosis and Scarring: The immune system’s efforts to control the infection often lead to fibrosis and scarring, particularly in affected organs like the lungs.

Question 68

Respiratory Tract Infections by Tim Planche

Global burden of resp inf.

*LOB: Demonstrate an appreciation of the global health burden of disease caused by respiratory infections

Answer 68

eading cause of morbidity and mortality worldwide
High prevalence in developing countries
Significant impact on children and the elderly
Increased risk in crowded or unsanitary living conditions
Major contributors to healthcare costs and economic burden

Question 69

Respiratory Tract Infections by Tim Planche

Clinical presentation of bacterial respiratory infections

*LOB: Outline and differentiate between the clinical presentations of common upper and lower respiratory tract bacterial and viral infections

Answer 69

Sudden onset of symptoms
High fever
Productive cough with purulent sputum
Shortness of breath
Chest pain
Systemic symptoms (fatigue, malaise)

Question 70

Respiratory Tract Infections by Tim Planche

Clinical presentation of viral respiratory infections

*LOB: Outline and differentiate between the clinical presentations of common upper and lower respiratory tract bacterial and viral infections

Answer 70

Gradual onset of symptoms
Low to moderate fever
Dry or minimally productive cough
Runny or stuffy nose
Sore throat
Headache and muscle aches

Question 71

Respiratory Tract Infections by Tim Planche

Clinical presentation of upper respiratory infections

*LOB: Outline and differentiate between the clinical presentations of common upper and lower respiratory tract bacterial and viral infections

Answer 71

Nasal congestion
Sneezing
Runny nose
Sore throat
Cough (usually dry)
Mild fever
Generalized malaise

Question 72

Respiratory Tract Infections by Tim Planche

Clinical presentation of lower respiratory infections

*LOB: Outline and differentiate between the clinical presentations of common upper and lower respiratory tract bacterial and viral infections

Answer 72

Persistent cough with or without sputum
Shortness of breath
Chest discomfort or pain
Wheezing or difficulty breathing
Fever and chills
Cyanosis in severe cases

Question 73

Respiratory Tract Infections by Tim Planche

Organisms which cause community acquired pneumonia

*LOB: List organisms that commonly cause: community acquired pneumonia, croup, epiglottis, tonsillitis, pharyngitis (sore throat)

Answer 73

Streptococcus pneumoniae (most common)
Haemophilus influenzae
Mycoplasma pneumoniae
Chlamydia pneumoniae
Staphylococcus aureus
Legionella pneumophila
Influenza virus
Respiratory syncytial virus (RSV)
Klebsiella pneumoniae (especially in older adults and those with underlying conditions)

Question 74

Respiratory Tract Infections by Tim Planche

Organisms which cause croup

*LOB: List organisms that commonly cause: community acquired pneumonia, croup, epiglottis, tonsillitis, pharyngitis (sore throat)

Answer 74

Parainfluenza viruses (especially type 1)
In some cases, other respiratory viruses like influenza, adenovirus, and respiratory syncytial virus (RSV)

Question 75

Respiratory Tract Infections by Tim Planche

Organisms which cause epiglottis

*LOB: List organisms that commonly cause: community acquired pneumonia, croup, epiglottis, tonsillitis, pharyngitis (sore throat)

Answer 75

Haemophilus influenzae type b (Hib) used to be the most common cause in children (before the introduction of the Hib vaccine).
Streptococcus pneumoniae and Streptococcus pyogenes (Group A Streptococcus) can also cause epiglottitis.
In adults, various bacteria, including Staphylococcus aureus and Streptococcus species, can be responsible.

Question 76

Respiratory Tract Infections by Tim Planche

Organisms which cause tonsillitis

*LOB: List organisms that commonly cause: community acquired pneumonia, croup, epiglottis, tonsillitis, pharyngitis (sore throat)

Answer 76

Bacterial Tonsillitis:
Streptococcus pyogenes (Group A Streptococcus) is a common bacterial cause of tonsillitis. It can lead to a condition known as streptococcal pharyngitis or strep throat.
Viral Tonsillitis:
Numerous respiratory viruses can cause viral tonsillitis, including:
Rhinovirus (common cold)
Adenovirus
Epstein-Barr virus (EBV, causing infectious mononucleosis)
Influenza virus
Herpes simplex virus
Cytomegalovirus (CMV)
Other Possible Causes:
Fungal infections, although rare, can lead to tonsillitis. Candida species are typically responsible for fungal tonsillitis.

Question 77

Respiratory Tract Infections by Tim Planche

Organisms which cause pharyngitis

*LOB: List organisms that commonly cause: community acquired pneumonia, croup, epiglottis, tonsillitis, pharyngitis (sore throat)

Answer 77

Viral Pharyngitis:
Rhinovirus (common cold)
Adenovirus
Influenza virus
Epstein-Barr virus (EBV, causing infectious mononucleosis)
Enteroviruses
Coronavirus (including SARS-CoV-2, which causes COVID-19)
Bacterial Pharyngitis (Strep Throat):
Streptococcus pyogenes (Group A Streptococcus) is the most common bacterial cause of pharyngitis in children and adults.
Other Bacterial Causes (Less Common):
Mycoplasma pneumoniae
Chlamydia pneumoniae
Neisseria gonorrhoeae (usually in the context of sexual transmission)
Arcanobacterium haemolyticum
Corynebacterium diphtheriae (causing diphtheria, a rare but serious condition)

Question 78

Respiratory Tract Infections by Tim Planche

laboratory investigation and diagnosis of respiratory tract infections

*LOB: Outline the principles of laboratory investigation and diagnosis of respiratory tract infections

Answer 78

Laboratory Investigations:
Respiratory Viral PCR Testing:
Collect respiratory specimens (nasopharyngeal swabs, sputum) for PCR testing.
Identify common viruses like influenza, respiratory syncytial virus (RSV), and SARS-CoV-2 (COVID-19).
Microbiological Cultures:
Obtain sputum or tracheal aspirates for bacterial culture and sensitivity testing.
Useful for diagnosing bacterial pneumonia and determining appropriate antibiotics.
Blood Tests:
Complete Blood Count (CBC): Evaluate white blood cell count and differential to assess for infection.
C-reactive protein (CRP) and Procalcitonin: Markers of inflammation and infection.
Chest X-ray:
Consider a chest X-ray for patients with severe or atypical symptoms.
Useful for detecting pneumonia and assessing lung involvement.
Additional Investigations (if indicated):
Pulse Oximetry: Measure oxygen saturation, especially in patients with respiratory distress.
Arterial Blood Gas (ABG) Analysis: Assess oxygen and carbon dioxide levels in severe cases.
Bronchoscopy: May be necessary in select cases for obtaining deeper respiratory samples.
Viral Serology:
In some cases, serological tests may be used to detect past infections or antibodies (e.g., for Mycoplasma pneumoniae or other atypical pathogens).
Molecular Testing:
Polymerase chain reaction (PCR) testing for atypical pathogens like Mycoplasma pneumoniae, Chlamydia pneumoniae, or Legionella pneumophila may be considered in specific clinical scenarios.
Urine Antigen Tests:
Utilize urine antigen tests to diagnose Streptococcus pneumoniae or Legionella pneumophila in certain cases.
Consider Comorbidities:
Evaluate underlying conditions (e.g., chronic lung disease, immunosuppression) that may influence diagnosis and management.
Patient Isolation:
Based on clinical and laboratory findings, implement appropriate infection control measures to prevent the spread of contagious RTIs.
Consultation:
Collaborate with microbiologists, radiologists, and infectious disease specialists for challenging cases.
Antibiotic Stewardship:
Prescribe antibiotics judiciously, guided by laboratory results and clinical assessment, to combat antibiotic resistance.

Question 79

Respiratory Tract Infections by Tim Planche

COPD and resp inf.

*LOB: Explain how COPD may be exacerbated by respiratory infections.

Answer 79

Increased Inflammation
Mucus Production
Bronchospasm
Worsening Airway Obstruction
Reduced Lung Function
Exacerbation of Symptoms
Increased Risk of Hospitalization
Prolonged Recovery
Potential for Long-Term Damage

Question 80

Clinical Aspects of TB by \_\_\_\_\_\_\_\_\_

TB symptoms

*LOB: Describe symptoms and signs found in people affected with pulmonary tuberculosis

Answer 80

Persistent Cough: A cough that lasts for more than three weeks is one of the most common symptoms of TB.
Coughing Up Blood or Phlegm: Sometimes, coughing may produce blood-tinged sputum.
Chest Pain: Pain or discomfort in the chest, often localized.
Fever: Low-grade or high-grade fever, especially in the afternoon or evening.
Night Sweats: Profuse sweating, particularly during the night.
Unintentional Weight Loss: Significant weight loss without diet or exercise changes.
Fatigue: Persistent tiredness and weakness.
Loss of Appetite: A reduced desire to eat and a general feeling of malaise.
Shortness of Breath: Difficulty breathing or shortness of breath, especially with physical activity.
Swelling of Lymph Nodes: Enlarged and tender lymph nodes, typically in the neck or under the armpits.

Question 81

Clinical Aspects of TB by \_\_\_\_\_\_\_\_\_

invesitgating TB

*LOB: Outline the investigation of a patient with suspected TB

Answer 81

Tuberculin Skin Test (TST) or Interferon-Gamma Release Assay (IGRA)
Chest X-ray
Sputum Smear Microscopy
Sputum Culture
Nucleic Acid Amplification Tests (NAATs)
Bronchoscopy
Tissue Biopsy
Blood Tests
HIV Testing
Drug Susceptibility Testing (DST)
Chest CT Scan
Tuberculosis Contact Tracing

Question 82

Humoural Immunity by Dr Tasneem Rahman

How do B Cells mature?

*LOB: Understand the basic principles of B cell maturation and antibody generation

Answer 82

Mature naïve B cells express a membrane-bound IgM

Ag recognition by membrane IgM => activation of signalling pathways => B cell activation

Question 83

Humoural Immunity by Dr Tasneem Rahman

What do mature naive B Cells co express and why?

*LOB: Understand the basic principles of B cell maturation and antibody generation

Answer 83

Co express IgD and IgM
IgM is the 1st immunoglobulin to be produced; Ag receptor

Question 84

Humoural Immunity by Dr Tasneem Rahman

How are antibodies generated?

*LOB: Understand the basic principles of B cell maturation and antibody generation

Answer 84

Question 85

Humoural Immunity by Dr Tasneem Rahman

What is isotype switching?

*LOB: Understand the principles of generation of antibody diversity

Answer 85

During an immune response B cells become capable to produce Abs of different classes but without changing specificity (respond to the same Ag)-

IgM switch to => IgG, IgA, IgE
IgG switch to => IgA, IgE

Isotype switching does not alter specificity for Ag !
Isotype switching does not alter the light chain !

Question 86

Humoural Immunity by Dr Tasneem Rahman

What is Clonal Selection?

*LOB: Understand the principles of generation of antibody diversity

Answer 86

Question 87

Humoural Immunity by Dr Tasneem Rahman

How do T Cells help isotype switching

*LOB: Understand the principles of generation of antibody diversity

Answer 87

1. CD40L on T cell interacts with CD40 on activated B cells
2. Cytokines produced by T cell
   IFN-γ => switch to IgG1, IgG3
   IL-4 => switch to IgE
   TGF-β, IL-5 => switch to IgA

Question 88

Humoural Immunity by Dr Tasneem Rahman

How do antibodies know to isotype?

*LOB: Understand the principles of generation of antibody diversity

Answer 88

Abs retain already rearranged variable regions whilst exchanging constant regions for different Ig classes

Question 89

Humoural Immunity by Dr Tasneem Rahman

What role does somatic DNA recombination play in diversity of antigens

*LOB: Understand the principles of generation of antibody diversity

Answer 89

Limited no of genes for diversity of antigen receptors.
Variable regions= gene segments.
- VH encoded in 3 gene segments (V, D, J)
- VL encoded in 2 gene segments (V, J)
- Gene segment recombination => Ab diversity
Gene segment recombination = random arrangement of gene segments in different combinations:
SOMATIC DNA RECOMBINATION
T and B cells

Gene segments rearrangements (VDJ/VJ) take place during B cell development in bone marrow
Immature B cells:
1st: successful VDJ rearrangement => heavy chain produced
2nd: successful VJ rearrangement => light chain produced
Mature naïve B cells express full IgM/antigen receptor

Question 90

Humoural Immunity by Dr Tasneem Rahman

What is the Germinal centre?

*LOB: Understand the basic principles of B cell maturation and antibody generation

Answer 90

Sustained B cell proliferation and differentiation.
Plasma cells or memory B cells.
Grows in size with immune response, disappears when infection cleared.
3-4 weeks
More effective antibodies vs primary focus.
Dark zone vs light zone
Somatic hypermutation and Affinity maturation.
Survival of B cell that has a high affinity for the antigen.

Question 91

Humoural Immunity by Dr Tasneem Rahman

Antibody diversity is….

*LOB: Understand the principles of generation of antibody diversity

Answer 91

Over 10^7-10^9 different types of B cells generated randomly
Each of these B cells makes a different antibody
B cells generated in bone marrow where they go through different developmental stages
Naive B cells populate lymph nodes/spleen and ‘wait’ for antigens

In the presence of Infection, Antigens are recognised by lymphocyte clone with the specific antigen receptor for that antigen
=> expansion of antigen-specific clone
=> generation of Abs specific for that Ag only

Question 92

Humoural Immunity by Dr Tasneem Rahman

Structure of Antibodies

*LOB: Describe the structure of antibodies and their role (ie main effector mechanisms) in the immune system

Answer 92

two identical heavy chains + two identical light chains
held together by disulphide bonds

5 types of heavy chains: μ,γ,α,δ,ε (IgM, IgG, IgA, IgD, IgE)
2 types of light chains: κ,λ

Heavy chain (H):
3-4 constant (C) domains + 1 variable (VH) domain
Light chain (L):
1 constant domain and 1 variable (VL) domain
Variable domains: amino acid sequence varies highly between different immunoglobulins
Antigen binding site: VL + VH

Question 93

Humoural Immunity by Dr Tasneem Rahman

What is somatic hypermutation?

*LOB:Understand the process of affinity maturation

Answer 93

Process of introducing mutations in the variable region of Immunoglobulins (rearranged VDJ/VJ)
Initiated by enzyme AID expressed in Germinal centre B cells only.
Mutations with decreased affinity for binding to Ag= NEGATIVE selection (majority)
Mutations with decreased affinity for binding to Ag= POSITIVE selection
higher affinity antibodies => stronger cell signalling; faster proliferation of B cells => advantage over low affinity B cells
Role of T cell in selection

Question 94

Humoural Immunity by Dr Tasneem Rahman

What is affinity maturation?

*LOB:Understand the process of affinity maturation

Answer 94

**Goal: Production of high affinity antibodies = more efficient. **
Abs produced early during primary (1st) immune response have lower affinity (weak binding) for antigen
Later 1st immune response/ 2nd immune responses => production of high affinity antibodies
Achieved through process of Somatic Hypermutation

Question 95

Humoural Immunity by Dr Tasneem Rahman

What are the subtypes of B Lymphocytes?

*LOB:Understand the process of affinity maturation

Answer 95

Follicular B cells
recognise protein antigens => antibodies (anti-protein Ag)
produce mainly high-affinity IgG class/switched antibodies

Marginal zone B cells
recognise polysaccharide; glycolipid; nucleic acid antigens
produce mainly IgM class antibodies

B-1 cells
peritoneal cavity, mucosal tissues
recognise polysaccharide; glycolipid; nucleic acid antigens
produce mainly natural low-affinity IgM class antibodies

Question 96

The Complement System by Dr. Tasneem Rahman

What is the Complement system?

*LOB: Define the complement system

Answer 96

Innate System
Cascade complex
Activation of small soluble heat sensitive protein that can combine and create complexes with proteolytic activity.

RECOGNITION
OPSONISATION
EFFECTOR- inflammation, phagocytosis and membrane attack

Question 97

The Complement System by Dr. Tasneem Rahman

What is the function of Complement?

*LOB: List the main functions of complement in the immune response

Answer 97

RECOGNITION
Innate recognition of non self
Antibodies
Apoptopic cells
OPSONISATION
EFFECTOR- Lysis, Inflammation,
Phagocytosis.
OTHER FUNCTIONS:
Chemotaxis, adhesion of inflammatory cells
Vascular permeability, contraction of smooth muscle cells
Disposal of waste- clearance of immune complexes and apoptotic cells

Question 98

The Complement System by Dr. Tasneem Rahman

What are the main pathways of complement?

*LOB: Describe the main pathways of complement and the terminal complement pathway

Answer 98

3 DISTINCT PATHWAYS
Antibody triggered (Classical)
Presence of pathogen alone (Alternative)
Lectin type protein activation (Lectin)

1 COMMON PATHWAY
-Terminal pathway- lysis

Question 99

The Complement System by Dr. Tasneem Rahman

What is the classical pathway?

*LOB: Describe the main pathways of complement and the terminal complement pathway

Answer 99

When antibodies bind

Formation of C1 Complex

Cascade Activation: C1 activation sets off a series of reactions (a cascade), leading to the activation of other complement proteins, like C4 and C2.

C3 Convertase Formation: The activated C4 and C2 proteins join together to form a new complex called C3 convertase.

C3 Activation: C3 convertase then activates a protein called C3, splitting it into C3a and C3b.

Effector Functions: C3b helps tag the invader for destruction by immune cells and also contributes to the formation of a membrane attack complex (MAC) that punches holes in the invader’s membrane, leading to its destruction.

Question 100

The Complement System by Dr. Tasneem Rahman

What is the alternative pathway?

*LOB: Describe the main pathways of complement and the terminal complement pathway

Answer 100

Spontaneous Activation: “always-on” mode of the complement system, activated by small amounts of complement proteins present in the blood.

C3 Activation: Spontaneous activation causes a protein called C3 to split into C3a and C3b, similar to the classical pathway.

Effector Functions: C3b helps tag invaders for destruction and contributes to the formation of the membrane attack complex (MAC), which can damage and kill invaders.

Question 101

The Complement System by Dr. Tasneem Rahman

What is the lectin pathway?

*LOB: Describe the main pathways of complement and the terminal complement pathway

Answer 101

Lectins recognize sugar molecules on the surface such as bacteria.

Complex Formation

Cascade Activation leading to the activation of complement proteins like C4 and C2.

C3 Activation: The activated C4 and C2 proteins combine to form C3 convertase, which then activates C3, splitting it into C3a and C3b.

Effector Functions: C3b helps label the invader for destruction and contributes to the formation of the membrane attack complex (MAC), which can damage and kill the invader.

Question 102

The Complement System by Dr. Tasneem Rahman

What is the terminal pathway?

*LOB: Describe the main pathways of complement and the terminal complement pathway

Answer 102

Formation of MAC
membrane attack complex
a group of complement proteins that come together and create holes in the membranes of invaders

Question 103

The Complement System by Dr. Tasneem Rahman

Why must complement be regulated?

*LOB: Understand the need for regulation of complement activation, and outline how this is achieved

Answer 103

Protection against Self-Attack
Avoidance of Excessive Inflammation
Prevention of Autoimmunity
Minimization of Infection Risk
Tissue Homeostasis
Prevention of Allergic Reactions
Protection of Host Microbiota
Preservation of Cellular Integrity
Fine-Tuning of Immune Responses
Avoidance of Chronic Inflammation
Minimization of Secondary Tissue Damage

Question 104

The Complement System by Dr. Tasneem Rahman

How is complement regulated?

*LOB: Understand the need for regulation of complement activation, and outline how this is achieved

Answer 104

Question 105

The Complement System by Dr. Tasneem Rahman

Examples of disease in Complement errors.

*LOB: Understand how loss of control of the complement system can lead to disease and relate to clinical examples

Answer 105

Atypical haemolytic uraemic syndrome AHUS
Genetic Defects:
Thrombocytopenia
Microangiopathic haemolytic anaemia
Acute renal failure

Failure to control the alternative pathway

Paroxysmal Nocturnal Haemoglobinuria (PNH)
Lack of glycosylphosphatidylinositol protein in host cells walls reduces anchoring of CD55 and CD59 control factors on erythrocytes
Susceptible to lysis
C3b accumulates on Erythrocyte Surface
Activation of complement Terminal/ Mac pathway
Destruction of Erythrocytes

Question 106

Antigen recognition by T lymphocytes by Dr Deborah Chong

How are antigens recognised by T Cells

*LOB: Discuss the differences between recognition of antigens by T and B cells

Answer 106

T cells recognise antigen processed and presented by APC
APCs process antigens into peptides (for αβ T cells)
peptides bind to MHC molecules
peptide:MHC complexes are presented on the APC surface

CD4+ helper T cells: antigens (peptides) displayed by MHC class II
CD8+ cytotoxic T cells: antigens (peptides) displayed by MHC class I

Question 107

Antigen recognition by T lymphocytes by Dr Deborah Chong

How are antigens recognised by B Cells

*LOB: Discuss the differences between recognition of antigens by T and B cells

Answer 107

B cells recognize antigens directly through their surface immunoglobulins

Question 108

Antigen recognition by T lymphocytes by Dr Deborah Chong

What are the main APC and their roles?

*LOB: Describe the main antigen presenting cells and the signals that they provide to T cells

Answer 108

Dendritic cells → the only APCs capable to present to naïve T cells (occurs in lymph node)

Macrophages → present to previously activated effector T cells (Ag presentation to effector CD4+ T cells (Th1))

B cells → present to previously activated effector T cells (presentation peptides to effector CD4+ T cells (Th2)) (- regulate class switch (e.g. IFN-γ & IgG; IL-4 & IgE))

Question 109

Antigen recognition by T lymphocytes by Dr Deborah Chong

What are the signals for naive T cell activation?

*LOB: Describe the main antigen presenting cells and the signals that they provide to T cells

Answer 109

MHC:peptide // TCR
(B7 family) CD80:CD86 // CD28
Cytokines (IL-12)

Question 110

Antigen recognition by T lymphocytes by Dr Deborah Chong

What is the structure of a T Cell Receptor and MHC?

*LOB: Discuss the main structure of T cell receptors and MHC molecules and their role in antigen recognition by CD4+ and CD8+ T cells

Answer 110

2 chains: α and β (most common TCR type)
(γ and δ (TCR in γδ T cells) )

each chain: 1 variable (V) domain + 1 constant (C) domain
Antigen binding site formed by: Vα + Vβ
V and C domains of TCR and BCR are homologous

Question 111

Antigen recognition by T lymphocytes by Dr Deborah Chong

What is MHC

*LOB: Discuss the main structure of T cell receptors and MHC molecules and their role in antigen recognition by CD4+ and CD8+ T cells

Answer 111

MHC I: presentation of peptides to** CD8**+ T cells
composed of α chain + β2-microglobulin
MHC I: all nucleated cells

MHC II: presentation of peptides to CD4+ T cells
composed of α chain + β chain
MHC II: antigen presenting cells: dendritic cells
macrophages

Question 112

Antigen recognition by T lymphocytes by Dr Deborah Chong

What is exogenous antigen processing?

*LOB: Describe the exogenous antigen processing and presentation pathway (MHC II and CD4+ T cells)

Answer 112

Extracellular antigens are engulfed by APCs.
Antigens are broken down into peptides in endosomes.
Peptides are presented by MHC II to CD4+ T cells.
CD4+ T cells are activated to help B cells and other immune responses.

Question 113

Antigen recognition by T lymphocytes by Dr Deborah Chong

What is endogenous antigen processing?

*LOB: Describe the endogenous (cytosolic) antigen processing and presentation pathway (MHC I and CD8+ T cells)

Answer 113

Intracellular antigens are processed by the proteasome.
Peptides are transported to the endoplasmic reticulum and loaded onto MHC I.
MHC I-peptide complex is presented on the cell surface for CD8+ T cell recognition.
CD8+ T cells are activated to kill infected cells.

Question 114

Antigen recognition by T lymphocytes by Dr Deborah Chong

Why is co-stimulation necessary?

Answer 114

Prevention of Anergy: Co-stimulation helps prevent the induction of anergy (unresponsiveness) in T cells. In the absence of co-stimulatory signals, T cells may become tolerant to the antigen and lose their ability to mount an immune response

Also:
* Discrimination Between Self and Non-Self
* Immune Tolerance
* Immune Memory
* Balancing Immune Responses
* Preventing Hyperactivation

Question 115

Antigen recognition by T lymphocytes by Dr Deborah Chong

If both MHC I and MHC II are produced and assembled in ER how come MHC II can’t load peptides that derive from cytosolic pathogens (viruses) and MHC I can’t load peptides that derive from phagocytosed extracellular pathogens?

Answer 115

Question 116

I&I Blood Group Antigens and Antibodies by James Uprichard.

What is ABO?

Include genetics

*LOB: Describe the genetics of blood group antigens: ABO and Rh systems.

Answer 116

All blood cells have antigens
A and B antigens very common (55% UK)
Anti-A, anti-B or anti-A,B antibodies very common (97% UK)

AA or AO -> A
BB or BO -> B
OO -> O
AB -> AB

Question 117

I&I Blood Group Antigens and Antibodies by James Uprichard.

What is Rh?

Include genetics

*LOB: Describe the genetics of blood group antigens: ABO and Rh systems.

Answer 117

Most important antigen is called D.
People with D antigen are D positive (85% of UK)
People who do not produce any D antigen are D negative (15%)
The other 4 main Rh antigens are known as C, c, E and e

D antigen is very immunogenic and anti-D is easily stimulated

Question 118

I&I Blood Group Antigens and Antibodies by James Uprichard.

What is the mechanism of Haemolytic disease of the newborn?

*LOB: Outline the mechanisms of haemolytic disease of the newborn and current guidelines for prevention of the disease.

Answer 118

Rh antibodies are usually IgG and can cause haemolytic disease of the newborn.
Anti-D is still most common cause of severe HDN

D antigens from the developing fetus can enter the mother’s blood during delivery
The mother will produce anti-D antibodies
In a following pregnancy anti-D antibodies will cross the placenta and damage the fetus

Question 119

I&I Blood Group Antigens and Antibodies by James Uprichard.

How is haemolytic disease of the newborn prevented?

*LOB: Outline the mechanisms of haemolytic disease of the newborn and current guidelines for prevention of the disease.

Answer 119

Through blood tests.
If a mother is Rh-negative and has not been sensitized, she is usually given a drug called Rh immunoglobulin, or RhoGAM.

An injection of anti-D will bind to and remove any fetal D positive red cells in the circulation

In some hospitals 2 smaller (500 iu) doses are given at 28 and 34 weeks instead of the 1 larger dose

Anti-D is also given after any event that may cause a feto-maternal haemorrhage (bleed between mum and fetus) such as:
Abdominal trauma
Intrauterine death
Spontaneous or therapeutic abortion

Question 120

I&I Blood Group Antigens and Antibodies by James Uprichard.

What are the consequences of mis-matched blood transfusions?

*LOB: Explain the possible consequences of mis-matched blood transfusionsDescribe testing for ABO blood group

Answer 120

An acute immune hemolytic reaction

ABO antibodies can activate complement causing INTRAVASCULAR HAEMOLYSIS

Question 121

I&I Blood Group Antigens and Antibodies by James Uprichard.

How are ABO tested?

*LOB: Describe testing for ABO blood group

Answer 121

• Test patient’s red cells with anti-A, anti-B and anti-D
• Agglutination shows that a particular antigen is on the red cells
• No agglutination shows the antigen is absent

Question 122

I&I Blood Group Antigens and Antibodies by James Uprichard.

How is antibody screening carried out?

*LOB: Describe testing for ABO blood group

Answer 122

Patients serum is mixed with 3 selected screening cells, incubated for 15 minutes at 37oc and then centrifuged for 5 minutes.

Any clinically significant antibodies reacting at body temp should be detected and then identified using panel of known phenotyped red cells.

Question 123

I&I Blood Group Antigens and Antibodies by James Uprichard.

What is the indirect antiglobulin test?

*LOB: Describe testing for ABO blood group

Answer 123

Used to detect IgG antibodies
Uses low ionic strength saline

Results in agglutination
Used for:
Screening for antibodies
Identifying antibodies
Cross-matching donor blood with recipient plasma when there are known antibodies or a previous history of antibodies.

NOTE COOL SCIENCE
IgM antibodies can span the gap between RBCs
IgG can not, because too small to overcome ZETA potential (+ve charge)
LISS (low ionic strength saline) is negatively charged, so neutralises positive ZETA potential.
Therefore IgG can now span the gap.

Question 124

I&I Blood Group Antigens and Antibodies by James Uprichard.

Why is low ionic strength saline required for cross matching?

*LOB: Describe testing for ABO blood group

Answer 124

Trying to detect IgG
IgM antibodies can span the gap between RBCs
IgG can not, because too small to overcome ZETA potential (+ve charge)
LISS (low ionic strength saline) is negatively charged, so neutralises positive ZETA potential.
Therefore IgG can now span the gap.

Question 125

I&I Blood Group Antigens and Antibodies by James Uprichard.

What is Cross-matching?

*LOB: Describe testing for ABO blood group

Answer 125

Immediate spin cross-match (ISX)
Antibody screen is negative
Checking donor red cells against patients plasma
ABO check
Incubate for 2 – 5 minutes (room temp), spin and read.

Full Indirect Antiglobulin test (IAT) cross-match
Antibody screen positive or patient has known antibody history.
Select antigen negative donor red cells and incubate with patient serum for 15 minutes at 37oC

Question 126

I&I Blood Group Antigens and Antibodies by James Uprichard

How are antibodies to blood groups produced?

*LOB: Describe the production of naturally occurring antibodies to blood group antigens.

Answer 126

Natural genetic variance causing variance in blood group

Question 127

I&I Investigating Infections by Dr Peter Riley

Define Differential Media

*LOB: Define the terms: differential, selective and enriched media and give examples

Answer 127

Media that allow the differentiation of different bacterial species based on specific growth characteristics or biochemical reactions.

Example: MacConkey’s agar, which differentiates lactose fermenters from non-fermenters based on the ability to produce acid and turn the agar pink.

Question 128

I&I Investigating Infections by Dr Peter Riley

Define selective media

*LOB: Define the terms: differential, selective and enriched media and give examples

Answer 128

Media that **selectively inhibit **the growth of certain types of bacteria while allowing others to thrive.

Example: Mannitol salt agar, which selects for halophilic bacteria like Staphylococcus species while inhibiting the growth of most other bacteria.

Question 129

I&I Investigating Infections by Dr Peter Riley

Define enriched media

*LOB: Define the terms: differential, selective and enriched media and give examples

Answer 129

Media that provide additional nutrients to support the growth of fastidious or nutritionally demanding bacteria.

Example: Blood agar, which contains blood to support the growth of a wide range of bacteria, including those with complex nutritional requirements.

Question 130

I&I Investigating Infections by Dr Peter Riley

Define alpha and beta hemolysis

*LOB: Define the terms: alpha and beta haemolysis; lactose fermenter; anaerobe, and explain how these properties can be shown by culture techniques

Answer 130

Incomplete hemolysis of red blood cells, resulting in a greenish discoloration around bacterial colonies on blood agar.

Complete hemolysis of red blood cells, leading to a clear zone around bacterial colonies on blood agar.

Question 131

I&I Investigating Infections by Dr Peter Riley

Define lactose fermenter

*LOB: Define the terms: alpha and beta haemolysis; lactose fermenter; anaerobe, and explain how these properties can be shown by culture techniques

Answer 131

Bacteria that can metabolize lactose to produce acid and gas.

Question 132

I&I Investigating Infections by Dr Peter Riley

Define anaerobe

*LOB: Define the terms: alpha and beta haemolysis; lactose fermenter; anaerobe, and explain how these properties can be shown by culture techniques

Answer 132

Bacteria that can grow in the absence of oxygen.

Question 133

I&I Investigating Infections by Dr Peter Riley

What is blood agar and why is it important?

*LOB: Explain the value of blood agar and MacConkey’s agar in bacterial identification

Answer 133

: Blood agar is valuable for identifying bacterial species based on their hemolytic activity (alpha or beta hemolysis) and their ability to utilize blood components for growth. It can help differentiate between different Streptococcus species and other pathogens.

Question 134

I&I Investigating Infections by Dr Peter Riley

What is MacConkey’s agar and why is it important?

*LOB: Explain the value of blood agar and MacConkey’s agar in bacterial identification

Answer 134

MacConkey’s agar is useful for identifying lactose fermenters from non-fermenters. It is commonly used in the identification of Enterobacteriaceae, including Escherichia coli, based on their ability to ferment lactose.

Question 135

I&I Investigating Infections by Dr Peter Riley

What is the relationship between bacteria numbers in specimen and UTI?

*LOB: Explain the relationship between bacterial numbers in a urine specimen and urinary tract infections

Answer 135

An increased number of bacteria in a urine specimen, especially in midstream or catheterized samples, is often indicative of a urinary tract infection (UTI). Normally, urine is sterile or contains only a small number of commensal bacteria.

The extent of bacterial growth can be quantified by colony-forming units (CFUs) per milliliter of urine, with a high CFU count indicating a more severe infection.

Question 136

I&I Investigating Infections by Dr Peter Riley

What are the commensal organisms found in the nasopharynx

*LOB: List commensal organisms commonly found in: nasopharynx, skin, gut, vagina (see previous lecture Principles of Infection)

Answer 136

: Commensal bacteria commonly found in the nasopharynx include Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus.

Question 137

I&I Investigating Infections by Dr Peter Riley

What are the commensal organisms found in the skin

*LOB: List commensal organisms commonly found in: nasopharynx, skin, gut, vagina (see previous lecture Principles of Infection)

Answer 137

Commensal organisms on the skin can include Staphylococcus epidermidis, Corynebacterium species, and various yeast species like Candida.

Question 138

I&I Investigating Infections by Dr Peter Riley

What are the commensal organisms found in the gut

*LOB: List commensal organisms commonly found in: nasopharynx, skin, gut, vagina (see previous lecture Principles of Infection)

Answer 138

Bacteroides, Firmicutes, and Escherichia coli.

Question 139

I&I Investigating Infections by Dr Peter Riley

What are the commensal organisms found in the vagina

*LOB: List commensal organisms commonly found in: nasopharynx, skin, gut, vagina (see previous lecture Principles of Infection)

Answer 139

Lactobacillus species, which help maintain the acidic pH and prevent overgrowth of pathogenic bacteria.

Question 140

Non-Steroidal Anti-Inflammatory Drugs by Omar Janeh

What are the uses of NSAIDS?

*LOB: Describe the mechanism of action and uses of non-steroidal anti-inflammatory drugs

Answer 140

Analgesic
Anti-pyretic
Anti-inflammatory

Treat: Low grade pain, Bone pain, Fever, Inflammation

Question 141

Non-Steroidal Anti-Inflammatory Drugs by Omar Janeh

What is the mechanism of action of NSAIDS?

*LOB: Describe the mechanism of action and uses of non-steroidal anti-inflammatory drugs

Answer 141

COX converts AA to PGs and TXs

COX-1 (constitutively active, platelets)
COX-2 (inducible enzyme e.g. by IL-1β & TNFα)

Inhibition of COX-2 reduces PGs/TXs inflammatory agents

Aspirin acts irreversibly on COX; others act reversibly and this is significant in its use as a prophylactic in cardiovascular disease

Question 142

Non-Steroidal Anti-Inflammatory Drugs by Omar Janeh

How are NSAIDS antipyrexic?

*LOB: Describe the mechanism of action and uses of non-steroidal anti-inflammatory drugs

Answer 142

Endotoxins from bacteria release IL-1β
IL-1β at hypothalamus releases PGE2
PGE2 depresses temperature sensitive neurons and causes fever by elevating end point of body temp

NSAIDs block PGE2 production
Reduces fever back to normal body temperature.
Doesnt affect core Body Temp

Question 143

Non-Steroidal Anti-Inflammatory Drugs by Omar Janeh

How are NSAIDS analgesic?

*LOB: Describe the mechanism of action and uses of non-steroidal anti-inflammatory drugs

Answer 143

PGs sensitise and stimulate nociceptors

PGs interact with other pain producing substances (e.g. kinins, 5-HT, histamine) to produce hyperalgesia and pain sensitivity

Blockade of PG production leads to pain relief

Question 144

Non-Steroidal Anti-Inflammatory Drugs by Omar Janeh

How are NSAIDS Anti-inflammatory?

*LOB: Describe the mechanism of action and uses of non-steroidal anti-inflammatory drugs

Answer 144

PGE2 and PGI2 have powerful acute inflammatory effects

Aspirin inhibits the activation of NF-B

Inhibition of their formation reduces redness and swelling
NSAIDs provide only ‘symptomatic relief’

Question 145

Non-Steroidal Anti-Inflammatory Drugs by Omar Janeh

Is paracetamol an NSAID?

*LOB: Describe the mechanism of action and uses of non-steroidal anti-inflammatory drugs

Answer 145

Not really
Weakly inhibits COX-3 in CNS
Analgesic
Not anti-inflammatory

Question 146

Non-Steroidal Anti-Inflammatory Drugs by Omar Janeh

What are the side effects of NSAIDS?

*LOB: Outline the major side effects of NSAIDs

Answer 146

↓ mucus secretion:
↓ HCO3-:
↑ acid secretion:
↑ LT production:

↑ blood loss:

Interfere with tissue healing (COX-2 inhibition)

Nausea, dyspepsia, GI contraction (COX-1 inhibition)

Question 147

Non-Steroidal Anti-Inflammatory Drugs by Omar Janeh

What anti inflammatory agent treats UC?

*LOB: Outline and compare the mechanisms of other anti-inflammatory agents used to treat gout, ulcerative colitis and inflammatory diseases of joints

Answer 147

Aminosalicylates (5-ASA) target inflammation in the colon by inhibiting the production of prostaglandins and leukotrienes.

Corticosteroids to reduce inflammation.

Immunomodulators suppress the immune system to reduce inflammation by inhibiting the proliferation of immune cells.

Biologics block cytokines (e.g., TNF-α) involved in the inflammatory process.

Janus Kinase (JAK) Inhibitors
Mechanism: Inhibit the activity of JAK enzymes, which are involved in immune signaling and inflammatory pathways.
Common Examples: Tofacitinib.

Question 148

Non-Steroidal Anti-Inflammatory Drugs by Omar Janeh

What anti inflammatory agent treats gout?

*LOB: Outline and compare the mechanisms of other anti-inflammatory agents used to treat gout, ulcerative colitis and inflammatory diseases of joints

Answer 148

NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)
to inhibit COX

Colchicine disrupts microtubules in inflammatory cells, reducing their ability to migrate and respond to urate crystals.

Question 149

Non-Steroidal Anti-Inflammatory Drugs by Omar Janeh

What anti inflammatory agent treats diseases of joints?

*LOB: Outline and compare the mechanisms of other anti-inflammatory agents used to treat gout, ulcerative colitis and inflammatory diseases of joints

Answer 149

NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) to reduce COX
Corticosteroids to suppress inflammation
Disease-Modifying Antirheumatic Drugs (DMARDs)
Biologics target specific cytokines

Question 150

Mechanisms of Bacterial Pathogenesis I by TIm Planche

Define Normal Flora

*LOB: Define the terms: Normal flora; Opportunistic pathogen; pathogen; pathogenesis; virulence; colonisation and normal flora; asymptomatic carriage; infection.

Answer 150

Good bacteria, local colonies
our microbiota
effect on mood weight cancer etc

Question 151

Mechanisms of Bacterial Pathogenesis I by TIm Planche

Define Opportunistic pathogen

*LOB: Define the terms: Normal flora; Opportunistic pathogen; pathogen; pathogenesis; virulence; colonisation and normal flora; asymptomatic carriage; infection.

Answer 151

asymptomatic until immune system reduced such as MRSA and nasal flora

Question 152

Mechanisms of Bacterial Pathogenesis I by TIm Planche

Define pathogenesis

*LOB: Define the terms: Normal flora; Opportunistic pathogen; pathogen; pathogenesis; virulence; colonisation and normal flora; asymptomatic carriage; infection.

Answer 152

is the process by which a disease develops or the mechanism through which a particular disease or condition is cause

Question 153

Mechanisms of Bacterial Pathogenesis I by TIm Planche

Define Virulence Factors

*LOB: Define the terms: Normal flora; Opportunistic pathogen; pathogen; pathogenesis; virulence; colonisation and normal flora; asymptomatic carriage; infection.

Answer 153

What causes disease:
Promote colonisation and adhesion
Can evade immune defences
Promote tissue damage

SUCH AS:
Adherence factors,
Invasion factors
Capsules
Endotoxins
Exotoxins
Siderophores (iron binding)

Question 154

Mechanisms of Bacterial Pathogenesis I by TIm Planche

Define colonisation

*LOB: Define the terms: Normal flora; Opportunistic pathogen; pathogen; pathogenesis; virulence; colonisation and normal flora; asymptomatic carriage; infection.

Answer 154

Colonization refers to the establishment of microorganisms on or within a host, without necessarily causing disease. In the context of normal flora, colonization involves the presence of non-pathogenic microorganisms in or on the body, which can help protect the host and prevent the growth of harmful pathogens.

Question 155

Mechanisms of Bacterial Pathogenesis I by TIm Planche

Define asymptomatic carriage

*LOB: Define the terms: Normal flora; Opportunistic pathogen; pathogen; pathogenesis; virulence; colonisation and normal flora; asymptomatic carriage; infection.

Answer 155

Asymptomatic carriage refers to the presence of a pathogen in a host without causing any noticeable symptoms or disease. In some cases, individuals may carry pathogens without getting sick themselves but can still potentially transmit the pathogen to others.

Question 156

Mechanisms of Bacterial Pathogenesis I by TIm Planche

Define infection

*LOB: Define the terms: Normal flora; Opportunistic pathogen; pathogen; pathogenesis; virulence; colonisation and normal flora; asymptomatic carriage; infection.

Answer 156

3 types
Local: surface or epithelial such as V Cholera
Invasvie: penetrates barriers such as a wound such as Shigella, Staph A
Systemic: via blood and lymph to multiple sites, S.typhi

Can have effects at different site to colony

Question 157

Mechanisms of Bacterial Pathogenesis I by TIm Planche

Define immunopathology

*LOB: Define the terms: Normal flora; Opportunistic pathogen; pathogen; pathogenesis; virulence; colonisation and normal flora; asymptomatic carriage; infection.

Answer 157

Inflammation
Cross reactive antigens (rheumatic heart disease)
Granuloma (TB)

!Not the bacteria but the body response)

Question 158

Mechanisms of Bacterial Pathogenesis I by TIm Planche

List the natural defence mechanisms of the host that protect against bacterial infection

*LOB: List the natural defence mechanisms of the host that protect against bacterial infection

Answer 158

Natural barriers
Defensive cells
Complement
Immune response
Commensal bacteria

Question 159

Mechanisms of Bacterial Pathogenesis I by TIm Planche

What are adhesins?

*LOB: List examples of bacterial virulence determinants: - e.g. adhesins, capsules, exotoxins

Answer 159

Colonize mucosal sites by using pili (fimbriae) to adhere to cells.

Question 160

Mechanisms of Bacterial Pathogenesis I by TIm Planche

What are capsules?

*LOB: List examples of bacterial virulence determinants: - e.g. adhesins, capsules, exotoxins

Answer 160

Polysaccharides protect from opsonisation and phagocytosis.

Question 161

Mechanisms of Bacterial Pathogenesis I by TIm Planche

What are exotoxins?

*LOB: List examples of bacterial virulence determinants: - e.g. adhesins, capsules, exotoxins

Answer 161

Protein toxins and enzymes produced and/or secreted suchas cytotoxins, neurotoxins, enterotoxins,

Question 162

Mechanisms of Bacterial Pathogenesis I by TIm Planche

Describe the main stages of bacterial infection.

*LOB: Describe the main stages of a bacterial infection from adherence, immune evasion, transmission to clearance

Answer 162

Days to weeks
Acquisition
Colonisation and Adherence
Penetration
Multiplication and spread
Immune evasion
Damage
Transmission and shedding
Resolution

Note: disease not always required for transmission- asymptomatic sheddin

Question 163

Mechanisms of Bacterial Pathogenesis I by TIm Planche

What are the indirect effects of bacterial infection that cause tissue damage

*LOB: Describe the direct and indirect effects of bacterial infection that cause tissue damage

Answer 163

inflammatory response, immune cell activation, cytokine storms, toxin production, immune-mediated damage, vascular damage, secondary infections, tissue ischemia, and host-microbiota disruption

Question 164

Mechanisms of Bacterial Pathogenesis I by TIm Planche

Examples of diseases

*LOB: Describe the direct and indirect effects of bacterial infection that cause tissue damage

Answer 164

T1) S.aureus TSST
T1) Streptococcus pyogenes erythrogenic toxin Scarlet fever

T2) Staphylococcus aureus α-toxin
Τ2) Strep.pyogenes streptolysin
Τ2) Strep.pneumoniae pneumolysin
T2) Clostriduim perfringens- GANGRENE

T3) Classified by enzyme action or molecular target and effect
T3) cholera; diphtheria;pertussis
T3) C.difficile Botulism; tetanus

Question 165

Mechanisms of Bacterial Pathogenesis I by TIm Planche

What are the 3 types of bacterial exotoxins?

*LOB: List the 3 main types of bacterial exotoxins. Explain their mechanism of action and how this results in disease

Answer 165

Type 1 - at cell membrane - not transported in
Type II - on cell membrane - membrane damage
Type III - intracellular effect after translocation
Extracellular - cellular matrix or connective tissue

Question 166

Mechanisms of Bacterial Pathogenesis I by TIm Planche

Give examples of exotoxins

*LOB: List the 3 main types of bacterial exotoxins. Explain their mechanism of action and how this results in disease

Answer 166

Question 167

Mechanisms of Bacterial Pathogenesis I by TIm Planche

How do exotoxins produce disease?

*LOB: List the 3 main types of bacterial exotoxins. Explain their mechanism of action and how this results in disease

Answer 167

Disruption of Cellular Function
Direct Damage
Neurological Effects
Fluid and Electrolyte Imbalance
Inflammation
Systemic Effects
Immune System Modulation
Secondary Complications
Tissue and Organ Damage

Question 168

Mechanisms of Bacterial Pathogenesis I by TIm Planche

What are Koch’s postulates

*LOB:Define Koch’s postulates

Answer 168

A microorganism has to:
Be present in every case of the infection.
Be cultured from cases in vitro.
Reproduce disease in an animal.
Be isolated from the infected animal.

HOWEVER
Not possible for non-culturable organisms
e.g. leprosy, syphilis

Need molecular tests e.g. PCR - e.g. HepC
What about food poisoning – B. cereus and toxins
- no infection with organism, but disease

Question 169

Mechanisms of Bacterial Pathogenesis II by Dr Peter Riley

What are the mechanisms of disease pathogenesis?

*LOB: Describe mechanisms of disease pathogenesis as a consequence of bacterial infections

Answer 169

• Adherence and Colonization
• Invasion
• Toxin Production:
• Inflammation and Immune Response:
• Immune Evasion:
• Tissue Damage:
• Dissemination/ systemic inflammation
• Secondary Infections
• Adaptive Immune Response:
• Antibiotic Resistance:
• Host factors such as age

Question 170

Mechanisms of Bacterial Pathogenesis II by Dr Peter Riley

What are the steps of acute inflammation?

*LOB:Describe the role of acute inflammatory changes in disease pathogenesis as a consequence of bacterial infections

Answer 170

Recognition of Bacterial Pathogens
Recruitment of Immune Cells
Neutrophil Infiltration
Macrophage Activation
Release of Antimicrobial Proteins
Phagocytosis and Killing
Inflammatory Response Amplification
Local Tissue Damage
Systemic Effects
Resolution of Inflammation

Question 171

Mechanisms of Bacterial Pathogenesis II by Dr Peter Riley

What are bacterial enzymes?

*LOB: Identify the role of bacterial enzymes, bacterial exotoxins and endotoxins and other causes of sepsis in disease pathogenesis

Answer 171

Facilitate bacterial invasion of host tissues by breaking down the extracellular matrix.
Collagenase produced by Clostridium species.

Question 172

Mechanisms of Bacterial Pathogenesis II by Dr Peter Riley

What are Bacterial Exotoxins in Sepsis?

*LOB: Identify the role of bacterial enzymes, bacterial exotoxins and endotoxins and other causes of sepsis in disease pathogenesis

Answer 172

Directly damage host cells and interfere with cellular functions.
Contribute to tissue damage, immune response disruption, and sepsis pathogenesis.

Staphylococcus aureus produces exotoxins, such as Toxic Shock Syndrome Toxin-1 (TSST-1).

Question 173

Mechanisms of Bacterial Pathogenesis II by Dr Peter Riley

What are Bacterial Endotoxins in Sepsis?

*LOB: Identify the role of bacterial enzymes, bacterial exotoxins and endotoxins and other causes of sepsis in disease pathogenesis

Answer 173

Stimulate a potent and uncontrolled immune response, leading to systemic inflammation.
Release of proinflammatory cytokines contributes to organ dysfunction in sepsis.

Lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria like Escherichia coli.

Question 174

Mechanisms of Bacterial Pathogenesis II by Dr Peter Riley

What are other causes of sepsis?

*LOB: Identify the role of bacterial enzymes, bacterial exotoxins and endotoxins and other causes of sepsis in disease pathogenesis

Answer 174

Influenza virus, Candida fungi, Plasmodium parasites causing malaria.

Question 175

Mechanisms of Bacterial Pathogenesis II by Dr Peter Riley

What is TSS and its mechanism?

*LOB: Describe the mechanism of disease in Toxic Shock Syndrome

Answer 175

SS is a specific condition associated with the release of bacterial exotoxins, such as the toxic shock syndrome toxin-1 (TSST-1) produced by Staphylococcus aureus.

TSST-1 acts as a superantigen, stimulating a massive immune response.

HOW: Binds to MHC Class II Molecules directly
Cross-linking with T Cell Receptors
Activation of T Cells
Uncontrolled release of proinflammatory cytokines
Systemic Inflammatory Response

Question 176

I&I Investigating Infections II by Dr Peter Riley

What is Immune Complex-Related Diseases?

*LOB:Outline immunopathology as a consequence of infection including immune complex related disease, molecular mimicry, autoimmunity and infection, hypersensitivity of microbial origin

Answer 176

Formation of Immune Complexes
Antibodies binding to antigens, including those from infectious agents.
Tissue Deposition
Immune complexes deposit in various tissues.
Inflammation and Tissue Damage
Immune complexes trigger inflammation and tissue damage in affected organs.
Examples
Immune complex-mediated glomerulonephritis, systemic lupus erythematosus (SLE).

Question 177

I&I Investigating Infections II by Dr Peter Riley

What is Molecular Mimicry?

*LOB:Outline immunopathology as a consequence of infection including immune complex related disease, molecular mimicry, autoimmunity and infection, hypersensitivity of microbial origin

Answer 177

Pathogen Antigens Resembling Host Molecules
Pathogens express antigens that structurally resemble host molecules.
Cross-Reactive Immune Responses
Immune responses (antibodies or T cells) target both pathogen and host antigens.
Autoimmune Diseases
Autoimmune diseases can develop as the immune system mistakenly attacks host tissues.
Examples
Rheumatic fever (Streptococcus pyogenes), Guillain-Barré syndrome (Campylobacter jejuni).

Question 178

I&I Investigating Infections II by Dr Peter Riley

What is Autoimmunity?

*LOB:Outline immunopathology as a consequence of infection including immune complex related disease, molecular mimicry, autoimmunity and infection, hypersensitivity of microbial origin

Answer 178

Induction of Autoimmunity
Infections can initiate or exacerbate autoimmune responses.
Mechanisms
Molecular mimicry, bystander activation, epitope spreading.
Autoimmune Diseases
Immune response targets self-antigens due to cross-reactivity.
Examples
Multiple sclerosis (Epstein-Barr virus), Type 1 diabetes (enteroviruses).

Question 179

I&I Investigating Infections II by Dr Peter Riley

What is Hypersensitivity of Microbial Origin?

*LOB:Outline immunopathology as a consequence of infection including immune complex related disease, molecular mimicry, autoimmunity and infection, hypersensitivity of microbial origin

Answer 179

Hypersensitivity Reactions
Allergic and hypersensitivity reactions can result from microbial antigens.
Sensitization to Microbial Antigens
Exposure to microbial antigens triggers immune responses.
Clinical Manifestations
Allergies, asthma, and other hypersensitivity disorders may develop.
Examples
Allergic rhinitis (pollens), asthma (dust mites, mold), food allergies.

Question 180

I&I Investigating Infections II by Dr Peter Riley

What is disc diffusion test?

Explain the microbiological principles and clinical relevance of the following terms: disc diffusion test; MIC; MBC; serum bactericidal test

Answer 180

The isolate is inoculated on semisolid agar medium with antibiotic impregnated discs and incubated for 18-20 hours. The diameter of the zone of inhibition of growth around the disc is measured and the bacterium is categorised as resistant, intermediate or susceptible depending on the zone size and pre-defined criteria

Question 181

I&I Investigating Infections II by Dr Peter Riley

What is MIC?

Explain the microbiological principles and clinical relevance of the following terms: disc diffusion test; MIC; MBC; serum bactericidal test

Answer 181

Disc diffusion zones correspond to minimum inhibitory concentrations (MIC)

MIC have been pre-determined by testing large numbers of organisms using disc-diffusion and quantitative methods in parallel.

Each antibiotic has a “breakpoint” MIC for a particular bacterial species.

If the concentration needed to inhibit the bacterium is below the breakpoint, the bacterium is susceptible.
If the concentration is** higher than the breakpoint**, the bacterium is resistant.

Question 182

I&I Investigating Infections II by Dr Peter Riley

What is MBC?

Explain the microbiological principles and clinical relevance of the following terms: disc diffusion test; MIC; MBC; serum bactericidal test

Answer 182

Minimum bactericidal concentration - MBC

the lowest concentration of an antibacterial agent required to kill a bacterium over a fixed, somewhat extended period, such as 18 hours or 24 hours, under a specific set of conditions.

Question 183

I&I Investigating Infections II by Dr Peter Riley

Why do antibiotic blood levels need to be measured?

*LOB: Discuss why antibiotic blood levels sometimes need to be measured and how this might be accomplished

Answer 183

As the amount of antibiotics that bind to serum proteins will vary between individuals

determine the precise amount of the drug that is bound to serum proteins
and how much is free in the blood, in order to be able to accurately** calculate the optimum dosage**

** avoid the risks associated with potentially toxic levels**

Question 184

I&I Investigating Infections II by Dr Peter Riley

How can antibiotic blood levels be measured?

*LOB: Discuss why antibiotic blood levels sometimes need to be measured and how this might be accomplished

Answer 184

Nanotechnology, Assays, Breath tests,

Question 185

I&I Investigating Infections II by Dr Peter Riley

Compare and contrast bacteriostatic and bacteriocidal.

*LOB: Distinguish between a bactericidal and a bacteriostatic antibiotic. Explain why both types of antibiotics are useful

Answer 185

Question 186

I&I Investigating Infections II by Dr Peter Riley

How are drug resistant bacteria detected?

*LOB: Explain how to detect drug resistant bacteria

Answer 186

measuring bacterial growth in the presence of the antibiotic being tested
Disc diffusion

Question 187

I&I Antibiotics by Dr Kirwan

Define antibiotic

*LOB: Define the term antibiotic, and discuss their microbiological origins and natural functions

Answer 187

antimicrobial substance active against bacteria

Question 188

I&I Antibiotics by Dr Kirwan

What are the origins of antibiotics?

*LOB: Define the term antibiotic, and discuss their microbiological origins and natural functions

Answer 188

Natural products of fungi and bacteria - soil dwellers
- natural antagonism and selective advantage
- kill or inhibit the growth of other microorganisms

most derived from natural products by fermentation,
then modified chemically :- incr pharmacological properties; incr antimicrobial effect

Some completely synthetic - sulphonamides

Question 189

I&I Antibiotics by Dr Kirwan

What are natural functions of the microbiological origins of antibiotics?

*LOB: Define the term antibiotic, and discuss their microbiological origins and natural functions

Answer 189

• Competition for Resources
• Predation and Defense
• Biofilm Formation
• Nutrient Cycling
• Communication and Signaling
• Virulence Regulation
• Antibiotic Resistance Mechanisms
• Symbiotic Relationships
• Biological Control

Question 190

I&I Antibiotics by Dr Kirwan

What makes a good antibiotic?

*LOB: Describe the considerations for the choice of an antibiotic

Answer 190

Selective toxicity
Good killing activity
Slow emergence of resistance
Narrow spectrum of activity
Non-toxic to host
Long plasma half-life
Oral and parenteral dosing forms
No interaction with other drugs

Question 191

I&I Antibiotics by Dr Kirwan

How are antibiotics chosen for use.

*LOB: Describe the considerations for the choice of an antibiotic

Answer 191

Distribution in body - relative to distribution of bacteria
- some not absorbed from gut
- many do not cross blood-brain barrier
- some do not penetrate abscess
- few accumulate inside cells

Spectrum of activity - cidal or static
Toxicity
Excretion
Patient age (renal capacity)
Route of administration (oral , i/v i/m, topical)
Clinical condition
Type of bacteria
Sensitivity of bacteria - mechanism of action of antibiotic
- resistance mechanisms
Cost

Specialist - Medical Microbiologist - Local Policies

Question 192

I&I Antibiotics by Dr Kirwan

Define therapeutic index

*LOB: Explain the microbiological principles of the following terms: therapeutic index, selective toxicity, spectrum of activity, therapeutic index

Answer 192

Therapeutic index (TI) = a ratio comparing the blood concentration at which a drug becomes toxic and the ratio at which it is effective
active dose (MIC) versus toxic effect

** The larger the TI, the safer the drug
**

Question 193

I&I Antibiotics by Dr Kirwan

Define selective toxicity

*LOB: Explain the microbiological principles of the following terms: therapeutic index, selective toxicity, spectrum of activity, therapeutic index

Answer 193

Mechanism of action exploits differences in structure and metabolic pathways between host and pathogen

Aim: harm microorganisms, not the host

More difficult for viruses (intracellular), fungi and parasites (more similar to host cells)

Question 194

I&I Antibiotics by Dr Kirwan

Define spectrum of activity

*LOB: Explain the microbiological principles of the following terms: therapeutic index, selective toxicity, spectrum of activity, therapeutic index

Answer 194

Broad versus narrow spectrum

Appropriate at different stages of infection
Patient is unwell, cause of sepsis is unknown -> start with broad spectrum

Results of cultures and other Ix come back, patient improving -> rationalise to targeted choice

Question 195

I&I Antibiotics by Dr Kirwan

What are the sites of action for antibiotics?

*LOB: Outline the main sites of action of antibiotics in the bacteria

Answer 195

Cell Wall Synthesis
Protein Synthesis
Nucleic Acid Synthesis
Metabolic Pathways
Cell membrane function

Question 196

I&I Antibiotics by Dr Kirwan

What are the components of the bacteria cell wall?

*LOB: Outline the components of the bacteria cell wall and describe their roles in antibiotic action

Answer 196

Peptidoglycan
Lipopolysaccharide
Teichoic Acids (gram positive)
Lipoteichoic Acids (gram positive)

Question 197

I&I Antibiotics by Dr Kirwan

Match a component of bacteria cell wall to antibiotic action

*LOB: Outline the components of the bacteria cell wall and describe their roles in antibiotic action

Answer 197

Question 198

I&I Antibiotics by Dr Kirwan

Outline the role of penicillin binding proteins (transpeptidases) in the synthesis of peptidoglycan

*LOB: Outline the role of penicillin binding proteins (transpeptidases) in the synthesis of peptidoglycan and the action of penicillin’s and cephalosporins

Answer 198

Cross links: PBPs catalyze the cross-linking of adjacent peptide chains within the peptidoglycan layer.
This provides structural integrity

However, PBPs are a target for antibiotics like penicillins and cephalosporins. These antibiotics contain a β-lactam ring, which binds to and inhibits PBPs.

Question 199

I&I Antibiotics by Dr Kirwan

What is the action of penicillins and cephalosporins

*LOB: Outline the role of penicillin binding proteins (transpeptidases) in the synthesis of peptidoglycan and the action of penicillin’s and cephalosporins

Answer 199

Beta lactams
target PBP, prevent crosslinking

This disruption weakens the cell wall, and as the bacterium grows and divides, it is unable to form a strong, intact cell wall. This eventually leads to cell lysis and death.

Gram positive

Question 200

I&I Antibiotic Resistance by Professor Lindsay

What is antibiotic inactivating enzymes?

*LOB: Give an example of each of the following mechanisms of drug resistance: Antibiotic inactivating enzymes, altered target, by-pass metabolic routes, altered transport of drug

Answer 200

enzymes that chemically modify or degrade antibiotics, rendering them inactive.

Beta-lactamase enzymes break down the β-lactam ring present in antibiotics like penicillins and cephalosporins so they cannot break the cell wall.

Question 201

I&I Antibiotic Resistance by Professor Lindsay

What is an altered target

*LOB: Give an example of each of the following mechanisms of drug resistance: Antibiotic inactivating enzymes, altered target, by-pass metabolic routes, altered transport of drug

Answer 201

Altered target resistance involves changes in the target of an antibiotic within the bacterium

MRSA strains have altered penicillin-binding proteins (PBPs), making them less susceptible to β-lactam antibiotics like penicillin.

** PBPs reduce the binding affinity of the antibiotic**

Question 202

I&I Antibiotic Resistance by Professor Lindsay

What is bypass merabolic routes

*LOB: Give an example of each of the following mechanisms of drug resistance: Antibiotic inactivating enzymes, altered target, by-pass metabolic routes, altered transport of drug

Answer 202

Bacteria can develop alternative metabolic pathways that bypass the steps inhibited by an antibiotic.
By acquiring or amplifying genes encoding an alternative.

such as encoding an alternative enzyme that is not affected by an antibiotic, allowing them to synthesize folate despite the antibiotic’s presence

Question 203

I&I Antibiotic Resistance by Professor Lindsay

What is an altered transport of drug?

*LOB: Give an example of each of the following mechanisms of drug resistance: Antibiotic inactivating enzymes, altered target, by-pass metabolic routes, altered transport of drug

Answer 203

changing the transport systems that allow antibiotics to enter the bacterial cell or expel them, preventing effective drug uptake or increasing drug efflux.

multidrug-resistant Escherichia coli may have increased expression of efflux pumps, preventing the buildup of antibiotics

Question 204

I&I Antibiotic Resistance by Professor Lindsay

What are biofilms?

*LOB: Give an example of each of the following mechanisms of drug resistance: Antibiotic inactivating enzymes, altered target, by-pass metabolic routes, altered transport of drug

Answer 204

Often polymicrobial
Often form at site of foreign bodies e.g. prosthetic joints
Bacteria secrete a protective matrix
Decrease in gradient of nutrients and oxygen -> decrease in metabolic activity -> elevates proportion of persistent bacteria

Question 205

I&I Antibiotic Resistance by Professor Lindsay

List 3 ways Gram negative bacteria may be penicillin resistant

*LOB: Detail 3 ways Gram negative bacteria may be penicillin resistant

Answer 205

1. penicillinase that degrades beta-lactam ring
2. Porin mutates or new porin type
3. PBP - mutates or bacteria acquires a new PBP
4. . Efflux pumps pump out the Penicillin more efficiently

Question 206

I&I Antibiotic Resistance by Professor Lindsay

Transduction

*LOB: Explain the following bacterial genetic processes involved in acquisition of antibiotic resistance: transduction, conjugation, transformation

Answer 206

the process by which a virus transfers genetic material from one bacterium to another. Viruses called bacteriophages

Question 207

I&I Antibiotic Resistance by Professor Lindsay

Conjugation

*LOB: Explain the following bacterial genetic processes involved in acquisition of antibiotic resistance: transduction, conjugation, transformation

Answer 207

a major horizontal gene transfer mechanism through which DNA is transferred from a donor to a recipient bacterium by direct contact.

Question 208

I&I Antibiotic Resistance by Professor Lindsay

Transformation

*LOB: Explain the following bacterial genetic processes involved in acquisition of antibiotic resistance: transduction, conjugation, transformation

Answer 208

transformation is the genetic alteration of a cell resulting from the direct uptake and incorporation of exogenous genetic material from its surroundings through the cell membrane.

Question 209

I&I Antibiotic Resistance by Professor Lindsay

How do bacterial plasmids cause drug resistance?

*LOB: Discuss the role of bacterial plasmids in drug resistance

Answer 209

Plasmid Acquisition
Resistance Gene Presence
Horizontal Gene Transfer
Selective Advantage/ Survival
Plasmid Replication independently to daughter cells and horizontal.

The resistance genes may encode for proteins or enzymes that protect against anitbiotics such as inactivating pores, or strengthening cell wall glycans.

Question 210

I&I Antibiotic Resistance by Professor Lindsay

What is antibiotic misuse?

*LOB: Demonstrate recognition of the role of antibiotic misuse in the emergence of bacterial resistance

Answer 210

Incomplete Treatment Courses leads to selective advantage survival bias.
Overuse and Inappropriate Prescribing
Self-Medication and Non-Prescription Use:
Suboptimal Antibiotic Choice
Antibiotic Use in Agriculture leads to resistance which can cross into human population

Question 211

I&I Antibiotic Resistance by Professor Lindsay

What are the concepts behind antibiotic treatment?

*LOB: Explain the concepts behind antibiotic treatment strategies to prevent bacterial drug resistance

Answer 211

• Antibiotic Stewardship ( NICE and UKHSA provide guidelines and recommendations to make informed decisions)
• Targeted Therapy:
• Dosing and Duration:
• Patient Education:
• Infection Control:
• Surveillance and Monitoring:
• Research and Innovation:

Question 212

I&I Antibiotic Resistance by Professor Lindsay

History of MRSA

*LOB:Describe the history of methicillin resistant Staphylococcus aureus (MRSA)

Answer 212

Question 213

I&I Antibiotic Resistance by Professor Lindsay

Why do Gram positive and Gram negative bacteria have different sensitivities?

*LOB:Explain why Gram positive and Gram negative bacteria have different sensitivities to antibiotics

Answer 213

Gram negative have a cell wall which protects against Beta-lactams.
Gram negative LPS can select for entry, neutralize or modify the action of some antibiotics.
Gram-negative bacteria often possess efflux pumps that are better than gram positive

Gram-negative and Gram-positive bacteria may have different genetic characteristics and enzymes that affect antibiotic sensitivity and resistance. For example, the production of β-lactamases, enzymes that break down β-lactam antibiotics, is more common in Gram-negative bacteria.

Question 214

I&I Glucocorticoids by Omar Janneh

What are the metabolic effects of endogenous and synthetic glucocorticoids

*LOB: Describe the major metabolic, cardiovascular, haematological, neuro- and immunological effects of endogenous and synthetic glucocorticoids

Answer 214

Breakdown of protein and fats (muscle wasting, etc.)
Decreased glucose usage & increased gluconeogenesis
Tendency to hyperglycaemia and increased glycogen storage

Question 215

I&I Glucocorticoids by Omar Janneh

What are the cardiovascular effects of endogenous and synthetic glucocorticoids

*LOB: Describe the major metabolic, cardiovascular, haematological, neuro- and immunological effects of endogenous and synthetic glucocorticoids

Answer 215

Decrease in both microvascular permeability & vasodilatation
Hypertension

Question 216

I&I Glucocorticoids by Omar Janneh

What are the hormonal effects of endogenous and synthetic glucocorticoids

*LOB: Describe the major metabolic, cardiovascular, haematological, neuro- and immunological effects of endogenous and synthetic glucocorticoids

Answer 216

Negative feedback on both hypothalamus & pituitary gland

Question 217

I&I Glucocorticoids by Omar Janneh

What are the immunological effects of endogenous and synthetic glucocorticoids

*LOB: Describe the major metabolic, cardiovascular, haematological, neuro- and immunological effects of endogenous and synthetic glucocorticoids

Answer 217

Decreased microvascular fluid exudation
- Reduces influx of cells to areas of inflammation

Decreased inflammatory mediators and cytokines
- Decrease expression of COX-2
- Reduced levels of eicosanoids
- Decreased levels of cytokines and complement levels

Decreased function of inflammatory effector cells
- Inhibition of cell migration and mediator release
- Reduced clonal expansion of T and B cells (↓ adaptive immunity)
- Reduction in chronic inflammatory events
- NB healing and repair are inhibited

Results in impaired keratinocyte migration

Question 218

I&I Glucocorticoids by Omar Janneh

What are the neuro effects of endogenous and synthetic glucocorticoids

*LOB: Describe the major metabolic, cardiovascular, haematological, neuro- and immunological effects of endogenous and synthetic glucocorticoids

Answer 218

mood changes, linked with changes in memory/stress

Question 219

I&I Glucocorticoids by Omar Janneh

What are the haematological effects of endogenous and synthetic glucocorticoids

*LOB: Describe the major metabolic, cardiovascular, haematological, neuro- and immunological effects of endogenous and synthetic glucocorticoids

Answer 219

increase hemoglobin and red cell content of blood ( demonstrated by the occurrence of polycythemia in Cushing disease and mild normochromic anemia in Addison disease)
A single dose of cortisol results in a 70% decrease in lymphocytes and a 90% decrease in monocytes

Question 220

I&I Glucocorticoids by Omar Janneh

what are the major uses of glucocorticoids

*LOB: Outline the major therapeutic uses of glucocorticoids

Answer 220

Adrenal insufficiency or failure (Addison’s disease)
congenital or drug-induced
treatment requires combined GC and MC
Treatment of inflammation
asthma, rhinitis, skin disorders, sports injuries, reduction of cerebral oedema in patients with brain tumours
Immunosuppression
inhibit graft v host reaction in tissue transplantation
Examples of glucorcoticoids:
Hydrocortisone, prednisolone, dexamethasone, betamethasone, beclomethasone

Question 221

I&I Glucocorticoids by Omar Janneh

Describe the mechanisms of action of glucocorticoids

*LOB: Describe the mechanisms of action of steroids, with reference to changes in gene regulation

Answer 221

1) Interaction of steroid/receptor with promoter regions
- these gene promoters have ‘glucocorticoid response elements’ (GREs) and occupancy of GREs turn on/off certain genes

2) Steroid/receptor complexes PREVENT gene activation by other transcription factors
- e.g. AP-1, NFkB: transcription factors involved in switching on COX-2; PLA2, IL-1, ICAM-1, IL-8, eotaxin, IκB-α etc.

Induction of IκBα (inhibitor of NF-κB) which causes NF-κB repression

Question 222

I&I Glucocorticoids by Omar Janneh

what are the major uses of mineralcorticoids

*LOB: Outline the major therapeutic uses of glucocorticoids

Answer 222

Adrenal insufficiency
e.g. Addison’s disease

Orthostatic hypotension (postural hypotension)
Failure of baroreceptor reflex

Electrolyte disorders
- cerebral salt wasting

Example:
Fludrocortisone

Question 223

I&I Glucocorticoids by Omar Janneh

what are the side effects of mineralcorticoids

*LOB: Outline the major therapeutic uses of glucocorticoids

Answer 223

Think Aldosterone

Sodium & water retention → hypertension
Potassium and H+ loss- disturbance of acid base balance
calcium loss.

Question 224

I&I Glucocorticoids by Omar Janneh

what are the side effects of using glucocorticoids

*LOB: Outline the major therapeutic uses of glucocorticoids

Answer 224

Cushing’s syndrome
Opportunistic infection
Osteoporosis
Gastric ulceration
Growth suppression
Behavioural or reproductive problems
Prolonged HPA suppression after cessation of therapy
Diabetes
Hypertension
Cataracts, etc.

Question 225

I&I Glucocorticoids by Omar Janneh

What are Corticosteroids

*LOB: Describe the mechanisms of action of steroids, with reference to changes in gene regulation

Answer 225

Glucocorticoids (zona fasciculata)
‘Sugar’ hormone, carbohydrate & protein metabolism
Potent anti-inflammatory / immunosuppressant

Mineralocorticoids (zona glomerulosa)
‘Salt’ hormone, controls electrolyte & H2O in the kidney

Question 226

Morphology and Biology of Viruses by Christina Baboonian

How are viruses categoried

Revise criteria used for virus classification

Answer 226

Type and organisation of genome
*DNA/RNA
*Single stranded/double stranded
*Genome relatedness
*Viral replication strategy
*For example does it go through reverse transcription?
*Structure and size of the virion
*Does it have an envelope?
*Viral structure – most are icosahedral
Host range
*Tissue tropism
*Pathogenicity
*Mode of transmission
*Physiochemical properties
*Antigenic properties of the virion

Question 227

Morphology and Biology of Viruses by Christina Baboonian

what is the replication cycle of HIV?

Revise replication cycle of herpes simplex and HIV

Question 228

Morphology and Biology of Viruses by Christina Baboonian

what is the replication cycle of HSV?

Revise replication cycle of herpes simplex and HIV

Question 229

Morphology and Biology of Viruses by Christina Baboonian

Describe the structure of HIV

Describe the structure of; Human Immunodeficiency virus, herpes viruses, hepatitis A, B and C viruses, influenza virus, rota virus, norovirus, measles, mumps and rubella viruses, enteroviruses, rhinovirus and adenovirus

Answer 229

Envelope
Viral gp120 & gp41
2 copies of RNA
Reverse transcriptase
Integrase
Protease

Question 230

Morphology and Biology of Viruses by Christina Baboonian

Describe the structure of HSV

Describe the structure of; Human Immunodeficiency virus, herpes viruses, hepatitis A, B and C viruses, influenza virus, rota virus, norovirus, measles, mumps and rubella viruses, enteroviruses, rhinovirus and adenovirus

Answer 230

Herpesviridae
•Icosahedral nucleocapsid
•dsDNA linear
•Enveloped
•Latency and reactivation

Question 231

Morphology and Biology of Viruses by Christina Baboonian

Describe the structure of Influenzae

Describe the structure of; Human Immunodeficiency virus, herpes viruses, hepatitis A, B and C viruses, influenza virus, rota virus, norovirus, measles, mumps and rubella viruses, enteroviruses, rhinovirus and adenovirus

Answer 231

lipid envelope
●this is derived from the host cell membrane.

proteins including:
●hemagglutinin (HA),
●neuraminidase (NA),
●and an ion channel protein (matrix protein 2, M2)
●These are embedded in the lipid bilayer of the viral envelope.
The ribonucleoprotein complex comprises viral RNA segments associated with the viral proteins.
●The matrix (M1) protein is associated with both ribonucleoprotein and the envelope.

Question 233

Morphology and Biology of Viruses by Christina Baboonian

Describe the structure of Hep A

Describe the structure of; Human Immunodeficiency virus, herpes viruses, hepatitis A, B and C viruses, influenza virus, rota virus, norovirus, measles, mumps and rubella viruses, enteroviruses, rhinovirus and adenovirus

Answer 233

Most common viral hepatitis
•Picornaviridae family
•Naked
•Icosahedral
•Single stranded RNA
•+ve sense

Question 234

Morphology and Biology of Viruses by Christina Baboonian

Describe the structure of Hep B

Describe the structure of; Human Immunodeficiency virus, herpes viruses, hepatitis A, B and C viruses, influenza virus, rota virus, norovirus, measles, mumps and rubella viruses, enteroviruses, rhinovirus and adenovirus

Answer 234

Hepadnaviridae family
•Enveloped
•42nm

Icosahedral nucleocapsid
•Circular DNA partially double stranded
•Complete virus and incomplete particles
•Tubular filaments & spherical particles composed of envelope proteins – hep B surface antigen

Question 235

Morphology and Biology of Viruses by Christina Baboonian

Describe the structure of Hep C

Describe the structure of; Human Immunodeficiency virus, herpes viruses, hepatitis A, B and C viruses, influenza virus, rota virus, norovirus, measles, mumps and rubella viruses, enteroviruses, rhinovirus and adenovirus

Answer 235

Flaviviridae family
•Enveloped
•Icosahedral nucleocapsid
•Single stranded RNA
•NS1 non structural protein 1
•E proteins are major envelope proteins of the virus

Question 236

Morphology and Biology of Viruses by Christina Baboonian

Describe the structure of Rota Virus

Describe the structure of; Human Immunodeficiency virus, herpes viruses, hepatitis A, B and C viruses, influenza virus, rota virus, norovirus, measles, mumps and rubella viruses, enteroviruses, rhinovirus and adenovirus

Answer 236

Reoviridae
Double stranded RNA
RNA segmented 11
Non enveloped
Triple layer capsule
Icosahedral structure

Structural proteins and non structural proteins

Question 237

Morphology and Biology of Viruses by Christina Baboonian

Describe the structure of norovirus

Describe the structure of; Human Immunodeficiency virus, herpes viruses, hepatitis A, B and C viruses, influenza virus, rota virus, norovirus, measles, mumps and rubella viruses, enteroviruses, rhinovirus and adenovirus

Answer 237

Caliciviridae
•27nm
•Icosahedral
•Non-enveloped
•Single stranded RNA
•Old name Norwalk virus

Question 238

Morphology and Biology of Viruses by Christina Baboonian

Describe the structure of mumps

Describe the structure of; Human Immunodeficiency virus, herpes viruses, hepatitis A, B and C viruses, influenza virus, rota virus, norovirus, measles, mumps and rubella viruses, enteroviruses, rhinovirus and adenovirus

Answer 238

Paramyxovirus
•pleomorphic
•enveloped
•helical nucleocapsid
•ss RNA linear genome

Question 239

Morphology and Biology of Viruses by Christina Baboonian

Describe the structure of measels

Describe the structure of; Human Immunodeficiency virus, herpes viruses, hepatitis A, B and C viruses, influenza virus, rota virus, norovirus, measles, mumps and rubella viruses, enteroviruses, rhinovirus and adenovirus

Answer 239

Enveloped
•RNA single stranded
•Negative sense
•Paramyxoviridae
•Pleomorphic
•100-300nm

Question 240

Morphology and Biology of Viruses by Christina Baboonian

Describe the structure of rubella

Describe the structure of; Human Immunodeficiency virus, herpes viruses, hepatitis A, B and C viruses, influenza virus, rota virus, norovirus, measles, mumps and rubella viruses, enteroviruses, rhinovirus and adenovirus

Answer 240

Togavirus family
•enveloped
•ssRNA
•icosahedral

Question 241

Morphology adn Biology of Viruses

Describe the structure of enteroviruses

Describe the structure of; Human Immunodeficiency virus, herpes viruses, hepatitis A, B and C viruses, influenza virus, rota virus, norovirus, measles, mumps and rubella viruses, enteroviruses, rhinovirus and adenovirus

Question 242

Morphology and Biology of Viruses by Christina Baboonian

Describe the structure of adenovirus

Describe the structure of; Human Immunodeficiency virus, herpes viruses, hepatitis A, B and C viruses, influenza virus, rota virus, norovirus, measles, mumps and rubella viruses, enteroviruses, rhinovirus and adenovirus

Answer 242

Different serotypes exist

Adenoviridae
•No envelope
•Icosahedral
•DNA double stranded, linear

Question 243

Morphology and Biology of Viruses by Christina Baboonian

Summarise the features of key viruses.

Describe the structure of; Human Immunodeficiency virus, herpes viruses, hepatitis A, B and C viruses, influenza virus, rota virus, norovirus, measles, mumps and rubella viruses, enteroviruses, rhinovirus and adenovirus

Answer 243

Question 244

Morphology and Biology of Viruses by Christina Baboonian

what diseases are caused by the key viruses:

Outline clinical features caused by these viruses

Answer 244

Herpes Simplex Virus (HSV):
Cold sores
Genital herpes
Influenza Virus:
Influenza (flu)
Hepatitis A Virus (HepA):
Hepatitis A
Hepatitis B Virus (HepB):
Hepatitis B
Hepatitis C Virus (HepC):
Hepatitis C
Rotavirus:
Gastroenteritis (especially in children)
Norovirus:
Gastroenteritis
Mumps Virus:
Mumps
Measles Virus:
Measles
Rubella Virus:
Rubella (German measles)
Enteroviruses:
Various, including hand, foot, and mouth disease
Adenovirus:
Respiratory and gastrointestinal infections

Question 245

Morphology and Biology of Viruses by Christina Baboonian

What is the repication cycle of respiratory tract infections

Describe the replication cycle of a virus that causes respiratory tract infection, a virus that causes gastrointestinal infection and viruses that are transmitted vertically

Answer 245

Influenza

Subtyped according to its surface antigens - haemagglutinin (HA) and neuraminidase (NA)

Viral attachment- uses haemagglutinin to attach to sialic acid
●Internalised by endocytosis

Inside endosome pH is low
●Virus envelope fuses with the endosome membrane
●Triggers uncoating

Viral nucleocapsid released into cytoplasm
Viral RNA is single stranded – negative sense

mRNA translated in cytoplasm
●Early viral proteins, that is, those required for replication and transcription, are transported back to the nucleus.
●Late in the infection cycle, proteins facilitate the nuclear export of newly synthesized viral RNPs.

RNA segments assembled within nucleocapsid
●The assembly and budding of progeny virions occurs at the plasma membrane.

Question 246

Morphology and Biology of Viruses by Christina Baboonian

Describe the replication cycle of a virus that causes GI infection

Describe the replication cycle of a virus that causes respiratory tract infection, a virus that causes gastrointestinal infection and viruses that are transmitted vertically

Answer 246

Rota virus infects intestinal epithelium
VP7 and VP4 are important for attachment and entry
dsRNA replicates inside virus and leaves via VP6 channel
Virus enters endoplasmic reticulum to acquire outer shell and be released

Question 247

Morphology and Biology of Viruses by Christina Baboonian

What is the replication cycle of a virus that is transmitted vertically.

Describe the replication cycle of a virus that causes respiratory tract infection, a virus that causes gastrointestinal infection and viruses that are transmitted vertically

Answer 247

Initial Infection
Replication in Parent
Transmission to Offspring
- Transovarial Transmission (In Ova)
- Transplacental Transmission
Replication in Offspring
Continuation of the Cycle

Such as Hepatitis B

Question 248

Morphology and Biology of Viruses by Christina Baboonian

What is positive and negative sense?

Answer 248

positive-sense (also positive (+) or simply sense) if its nucleotide sequence corresponds directly to the sequence of an RNA transcript which is translated or translatable into a sequence of amino acids

negative-sense (also negative (−) or antisense), and is reverse complementary to both the positive-sense strand

Question 249

Morphology and Biology of Viruses by Christina Baboonian

Why is Influenza difficult to find a vaccine for?

Describe the replication cycle of a virus that causes respiratory tract infection, a virus that causes gastrointestinal infection and viruses that are transmitted vertically

Answer 249

The surface antigens of Influenza A mutate rapidly because:
●Virus has an enzyme involved in virus replication - RNA polymerase
●This enzyme has low selectivity
●Enzyme has no proof reading mechanism

Question 250

Mechanisms of viral infection and Pathogenesis by Christina Baboonian

What determines host susceptibility to viral infection?

Describe factors that determine host susceptibility to viral infection

Answer 250

Host Immune System: The strength and effectiveness of the host’s immune response.
Host Genetics: Genetic factors that may affect susceptibility to certain viruses.
Age: Infants, the elderly, and individuals with weakened immune systems are often more susceptible.
Health Status: Pre-existing health conditions and nutritional status.
Viral Tropism: The ability of the virus to infect specific cells or tissues.
Exposure and Transmission: The frequency and type of contact with infected individuals or vectors.
Vaccination or Prior Infection: Immunity acquired through vaccination or previous exposure.
Virus Strain: Variability in viral strains and their ability to infect.
Environmental Factors: Environmental conditions that may affect viral stability and transmission.

Question 251

Mechanisms of viral infection and Pathogenesis by Christina Baboonian

Describe Primary and secondary infection

Describe primary and secondary infection, re-infection and reactivation of infection and provide examples for each

Answer 251

The first encounter between a host and a specific virus.
Example: Primary infection with the varicella-zoster virus (VZV) causes chickenpox.

A new infection with the same virus after the primary infection has resolved.
Example: Secondary infection with VZV can occur as shingles (herpes zoster) after chickenpox.

Question 252

Mechanisms of viral infection and Pathogenesis by Christina Baboonian

Describe reinfection

Describe primary and secondary infection, re-infection and reactivation of infection and provide examples for each

Answer 252

Infection with the same virus strain after recovery from a prior infection.
Example: Reinfection with the same strain of the common cold virus.

Question 253

Mechanisms of viral infection and Pathogenesis by Christina Baboonian

Describe reactivation of infection

Describe primary and secondary infection, re-infection and reactivation of infection and provide examples for each

Answer 253

A dormant or latent virus becomes active again.
Example: Reactivation of VZV from latency can cause shingles.

Question 254

Mechanisms of viral infection and Pathogenesis by Christina Baboonian

How do viruses spread within the body?

Using Varicella Zoster virus as an example describe mechanisms that viruses use to spread within the body

Answer 254

Direct Cell-to-Cell Spread: VZV can move directly between cells, often in neurons, to evade immune surveillance.

Bloodstream Dissemination: The virus can enter the bloodstream, facilitating systemic spread.

Neuronal Transport: VZV can use neurons to travel to different areas of the body, leading to latent infections and reactivation.

Respiratory Spread: VZV can be expelled from the respiratory tract during infection, leading to transmission to other hosts.

Question 255

Mechanisms of viral infection and Pathogenesis by Christina Baboonian

What viral mechanisms are used to remain in host?

Describe mechanisms used by viruses to persist within the host and relate to clinical examples

Answer 255

Latency: Some viruses, like VZV and herpes simplex virus, establish latency in neurons, avoiding immune detection.

Immune Evasion: Viruses can adapt to evade host immune responses.

Cell-to-Cell Spread: Viruses can use cell-to-cell transmission, reducing exposure to the immune system.

Antigenic Variation: Some viruses mutate their surface proteins, making them less recognizable to the immune system.

Release decoy particles

Question 256

Mechanisms of viral infection and Pathogenesis by Christina Baboonian

How do viruses cause cancer?

HPV

Describe pathogenesis of viral infections with reference to viruses that cause cancer

Answer 256

• Papillomavirus has to override the cell cycle
• Virus infects basal layers
• Migrates to cell nucleus
• Genome established as independent episome
• Copies of viral DNA made

E2 (Early 2) protein regulates HPV gene expression and replication; binds to the viral DNA and control the expression, including E6 and E7.

E6 and E7 are the key oncoproteins involved in HPV-associated carcinogenesis.

E6 targets the host protein p53 for degradation, preventing it from initiating apoptosis and cell cycle arrest.

E7 interacts with the retinoblastoma (Rb) protein, disrupting its normal function.

leads to the accumulation of genetic mutations in infected cells.

if the viral oncoproteins are not cleared by the immune system, cancer

Question 257

I&I Microbial Immune Evasion Mechanisms by Jose Saldana

Antigenic Variation

*LOB: Define the terms: antigenic variation; phase variation; antigenic drift; antigenic shift

Answer 257

ability of pathogens to alter their surface antigens or markers to escape the host immune system’s recognition

Question 258

I&I Microbial Immune Evasion Mechanisms by Jose Saldana

Phase Variation

*LOB: Define the terms: antigenic variation; phase variation; antigenic drift; antigenic shift

Answer 258

Bacteria alternately switch the expression of specific surface molecules, such as pili or adhesins, to evade the host immune system. This is a reversible change in surface structures

Question 259

I&I Microbial Immune Evasion Mechanisms by Jose Saldana

Antigenic Drift

*LOB: Define the terms: antigenic variation; phase variation; antigenic drift; antigenic shift

Answer 259

gradual genetic change in a pathogen that results in minor variations in surface antigens.

reduced recognition by the immune system

Needs updated vaccines.

Question 260

I&I Microbial Immune Evasion Mechanisms by Jose Saldana

Antigenic Shift

*LOB: Define the terms: antigenic variation; phase variation; antigenic drift; antigenic shift

Answer 260

sudden and major genetic change in a pathogen, often seen in influenza viruses.

reassortment or exchange of genetic material between different strains, leading to the emergence of a completely new subtype.

Question 261

I&I Microbial Immune Evasion Mechanisms by Jose Saldana

What is viral antigenic diversity?

*LOB:Explain the concept of viral antigenic diversity and show how this influences infectivity and disease spread, using influenza as an example

Answer 261

The influenza virus has two major surface proteins: hemagglutinin (HA) and neuraminidase (NA), which are the target of the host immune response.

Antigenic drift leads to gradual changes in HA and NA, making it challenging for the immune system to recognize the virus.

This necessitates the development of updated vaccines each flu season.

Question 262

I&I Microbial Immune Evasion Mechanisms by Jose Saldana

How does viral antigenic diversity influence infectivity and disease spread?

*LOB: Explain the concept of viral antigenic diversity and show how this influences infectivity and disease spread, using influenza as an example

Answer 262

Escape from Immune Recognition
Reduced Cross-Immunity
Viral Drift and Shift
Antigenic Drift
Antigenic Shift
Prolonged Viral Shedding
Enhanced Host Tropism
Transmission Across Geographic Boundaries
Challenges for Vaccination

Question 263

I&I Microbial Immune Evasion Mechanisms by Jose Saldana

How do pathogens avoid the adaptive immune system

*LOB: Outline, with bacterial and viral examples, survival strategies used by pathogens to avoid the adaptive and innate immune systems

Answer 263

AVOID COMPLEMENT

failure to trigger: LPS, capsules

negative binding: coating with non-fixing IgA
Capsule blocks C3b binding
Capsule prevents C3b receptor access

disrupt regulation Factor H sequestration

block/expel MAC C5a proteases , blebbing

Question 264

I&I Microbial Immune Evasion Mechanisms by Jose Saldana

How do pathogens avoid the innate immune system

*LOB: Outline, with bacterial and viral examples, survival strategies used by pathogens to avoid the adaptive and innate immune systems

Answer 264

Staphylococcus: leucocidins kill Mφ and protein A binds Fc of IgG to prevent opsonisation.

Meningococcus and Hib: capsules block contact with immune cells.

Intracellular pathogens:
Promote own uptake (safe) - CR3; mannose lectin receptors
Prepares cell for invasion - Shigella
Inhibit Phagosome-lysosome fusion - M. tuberculosis
Escape Phagosome-lysosome to cytoplasm - Listeria
Resist oxidative killing - produce catalases/peroxidases

Question 265

I&I Microbial Immune Evasion Mechanisms by Jose Saldana

Examples of organisms and how they avoid immune system.

*LOB: Outline, with bacterial and viral examples, survival strategies used by pathogens to avoid the adaptive and innate immune systems

Answer 265

Bacterial Example (Phase Variation): Neisseria gonorrhoeae can alternate expression of pili and opacity-associated proteins (Opa) on its surface, allowing it to evade immune detection and facilitate host colonization.

Viral Example (Antigenic Drift): Influenza viruses accumulate genetic mutations, leading to changes in HA and NA proteins, which allows the virus to evade pre-existing host immunity.

Question 266

I&I Microbial Immune Evasion Mechanisms by Jose Saldana

What are bacterial capsular polysaccharides

*LOB: Describe the role of bacterial capsular polysaccharides in pathogenesis

Answer 266

Bacterial capsular polysaccharides are components of the bacterial capsule that surrounds the cell acts as a physical barrier

It prevents the recognition and binding of bacterial cells by immune cells

Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, use capsular polysaccharides.

Question 267

I&I Microbial Immune Evasion Mechanisms by Jose Saldana

What is antigenic variation in Neisseria gonorrhoeae

*LOB: Outline the general principle of antigenic variation in Neisseria gonorrhoeae

Answer 267

bacterium continuously alters the surface expression of specific proteins known as pili and opacity-associated proteins (Opa proteins).

Pili facilitate adherence to host cells and tissues. Opa proteins, are involved in attachment to host cells and immune evasion.

Variation in these proteins can result in evasion of immune system as the binding mechanisms are new and thus not “recognised”

Question 268

I&I Diagnosis of Viral Infections by Dr Cassie Pope

Which tests are used to diagnose viral infections.

*LOB: Provide an overview of how viral infections are diagnosed with emphasis on laboratory diagnosis

Answer 268

Viral Culture
Polymerase Chain Reaction (PCR)
Serological Tests
Antigen Detection Tests
Next-Generation Sequencing (NGS)
Immunofluorescence Assays (IFA)
Enzyme-Linked Immunosorbent Assay (ELISA)
Loop-Mediated Isothermal Amplification (LAMP)
Direct immunofluorescence
Immunochromatographic methods
Nucleic acid amplification test (NAAT)

Question 269

I&I Diagnosis of Viral Infections by Dr Cassie Pope

Viral Culture

*LOB: Demonstrate an appreciation of the advantages and limitations of the different viral diagnostic tests allowing the most appropriate sample and test to be chosen and the correct diagnosis to be made
*LOB: Understand the science behind the different methods of diagnosing viral infections.

Answer 269

Method: Viral culture involves inoculating clinical samples onto specific cell lines or culture media to promote the growth of the virus. The growth is observed through the development of cytopathic effects (CPE) or other characteristic changes in the cultured cells.

Advantage: Viral culture allows for the isolation and subsequent characterization of the virus, determining its sensitivity to antiviral drugs, and providing valuable information for epidemiological studies.

Disadvantage: It is a time-consuming process, taking several days to weeks for results. It requires specific cell lines and expertise, and it may not be suitable for fast diagnosis or all types of viruses.

Influenza viruses, herpesviruses, noroviruses.

Question 270

I&I Diagnosis of Viral Infections by Dr Cassie Pope

Polymerase Chain Reaction (PCR)

*LOB: Demonstrate an appreciation of the advantages and limitations of the different viral diagnostic tests allowing the most appropriate sample and test to be chosen and the correct diagnosis to be made
*LOB: Understand the science behind the different methods of diagnosing viral infections.

Answer 270

Method: PCR amplifies viral nucleic acids (DNA or RNA) by repeatedly cycling through a series of temperature changes, which leads to the exponential amplification of specific target sequences. It involves denaturation, annealing of primers, and extension by a DNA polymerase.

Advantage: PCR is highly sensitive and specific, capable of detecting low viral loads, and can identify and subtype various viral strains. It is a well-established technique for viral diagnosis.

Disadvantage: PCR requires specialized equipment, trained personnel, and knowledge of the viral sequence to design primers. It is susceptible to contamination and false positives.

SARS-CoV-2 (COVID-19), HIV, Hepatitis B and C viruses.

Question 271

I&I Diagnosis of Viral Infections by Dr Cassie Pope

Serological Tests

*LOB: Demonstrate an appreciation of the advantages and limitations of the different viral diagnostic tests allowing the most appropriate sample and test to be chosen and the correct diagnosis to be made
*LOB: Understand the science behind the different methods of diagnosing viral infections.

Answer 271

Method: Serological tests detect antibodies produced by the host’s immune system in response to viral infection. This is typically done through ELISA, where viral antigens are immobilized, and antibodies from the patient’s serum bind to them.

Advantage: Serological tests are useful for diagnosing past infections, monitoring immune response, and seroprevalence studies. They are relatively simple and cost-effective.

Disadvantage: These tests are not suitable for early infection detection and may give false negatives during the acute phase of the disease. Cross-reactivity with related viruses or previous vaccinations can occur.

HIV, Hepatitis B and C, Syphilis (Treponema pallidum).

Question 272

I&I Diagnosis of Viral Infections by Dr Cassie Pope

Antigen Detection Tests

*LOB: Demonstrate an appreciation of the advantages and limitations of the different viral diagnostic tests allowing the most appropriate sample and test to be chosen and the correct diagnosis to be made
*LOB: Understand the science behind the different methods of diagnosing viral infections.

Answer 272

Method: Antigen detection tests use antibodies that specifically bind to viral proteins or antigens in clinical samples, resulting in a visible signal, such as a colored line.

Advantage: These tests provide rapid results, often within minutes, and are suitable for point-of-care testing. They don’t require expensive equipment or specialized training.

Disadvantage: Sensitivity can vary between different tests and may not detect all viral strains or mutants. False negatives are possible, especially with low viral loads.

SARS-CoV-2 (COVID-19), Influenza A and B viruses, Streptococcus pneumoni

Question 273

I&I Diagnosis of Viral Infections by Dr Cassie Pope

Next-Generation Sequencing (NGS)

*LOB: Demonstrate an appreciation of the advantages and limitations of the different viral diagnostic tests allowing the most appropriate sample and test to be chosen and the correct diagnosis to be made
*LOB: Understand the science behind the different methods of diagnosing viral infections.

Answer 273

Method: NGS is a high-throughput sequencing technique that identifies viral genetic material through massively parallel sequencing, allowing for the analysis of millions of DNA or RNA fragments simultaneously.

Advantage: NGS provides comprehensive genetic information, enabling the identification of novel or mutated viral strains and detailed epidemiological studies.

Disadvantage: It requires expensive equipment, extensive bioinformatics expertise for data analysis, and may not be suitable for routine diagnostics due to time and resource constraints.

Mycobacterium tuberculosis (for drug resistance testing), Zika virus (f

Question 274

I&I Diagnosis of Viral Infections by Dr Cassie Pope

Immunofluorescence Assays (IFA):

*LOB: Demonstrate an appreciation of the advantages and limitations of the different viral diagnostic tests allowing the most appropriate sample and test to be chosen and the correct diagnosis to be made
*LOB: Understand the science behind the different methods of diagnosing viral infections.

Answer 274

Method: IFA uses fluorescently labeled antibodies to detect viral antigens in clinical samples. The sample is exposed to labeled antibodies, and if viral antigens are present, they will bind to the antibodies, producing a fluorescent signal.

Advantage: IFA is useful for identifying viruses in tissue samples and is a valuable tool for direct detection.

Disadvantage: It is less sensitive than PCR and can be labor-intensive. Additionally, it requires trained technicians and specialized equipment for interpretation.

Influenza A and B viruses (IFA for detecting viral antigens), Chlamydia

Question 275

I&I Diagnosis of Viral Infections by Dr Cassie Pope

Enzyme-Linked Immunosorbent Assay (ELISA)

*LOB: Demonstrate an appreciation of the advantages and limitations of the different viral diagnostic tests allowing the most appropriate sample and test to be chosen and the correct diagnosis to be made
*LOB: Understand the science behind the different methods of diagnosing viral infections.

Answer 275

Method: ELISA detects viral antigens or antibodies through enzyme-linked reactions. Viral antigens or antibodies in the sample bind to immobilized molecules on the plate, and an enzyme-conjugated secondary antibody produces a color change.

Advantage: ELISA is versatile and suitable for large-scale testing, as it can be automated. It’s widely used for seroprevalence studies and diagnostic screening.

Disadvantage: Sensitivity and specificity can vary between different ELISA assays, and cross-reactivity may occur.

HIV (ELISA for antibody detection), Rotavirus (ELISA for antigen detect

Question 276

I&I Diagnosis of Viral Infections by Dr Cassie Pope

Direct Immunofluorescence:

*LOB: Demonstrate an appreciation of the advantages and limitations of the different viral diagnostic tests allowing the most appropriate sample and test to be chosen and the correct diagnosis to be made
*LOB: Understand the science behind the different methods of diagnosing viral infections.

Answer 276

Method: Similar to IFA, direct immunofluorescence is used for the rapid detection of viruses in clinical samples. Fluorescently labeled antibodies bind to viral antigens in the sample.

Advantage: It is faster than viral culture and is a valuable tool for rapid diagnosis.

Disadvantage: Like IFA, it requires trained technicians and specialized equipment for interpretation.

Respiratory syncytial virus (RSV), Chlamydia trachomatis

Question 277

I&I Diagnosis of Viral Infections by Dr Cassie Pope

Immunochromatographic Methods:

*LOB: Demonstrate an appreciation of the advantages and limitations of the different viral diagnostic tests allowing the most appropriate sample and test to be chosen and the correct diagnosis to be made
*LOB: Understand the science behind the different methods of diagnosing viral infections.

Answer 277

Method: Immunochromatographic tests involve the use of specific antibodies bound to a strip. The sample, when applied, migrates along the strip and interacts with labeled antibodies or antigens, leading to the formation of visible lines.

Advantage: Immunochromatographic tests provide quick results, often within minutes, and do not require specialized equipment or expertise.

Disadvantage: They have limited sensitivity, primarily provide qualitative results (positive/negative), and may be subject to potential cross-reactivity.

SARS-CoV-2 (COVID-19 rapid antigen tests), Influenza A and B viruses, St

Question 278

I&I Diagnosis of Viral Infections by Dr Cassie Pope

Nucleic Acid Amplification Test (NAAT):

*LOB: Demonstrate an appreciation of the advantages and limitations of the different viral diagnostic tests allowing the most appropriate sample and test to be chosen and the correct diagnosis to be made
*LOB: Understand the science behind the different methods of diagnosing viral infections.

Answer 278

Method: NAAT is a broad category that includes various techniques like PCR and LAMP. It amplifies viral nucleic acids for detection, typically through the use of specific primers and probes.

Advantage: NAATs are highly sensitive, specific, and provide rapid results. They are widely used for diagnosing various viral infections
.
Disadvantage: NAATs require specialized equipment and trained personnel, making them less suitable for point-of-care testing. They are also more expensive compared to some other tests.

SARS-CoV-2, Neisseria gonorrhoeae, Chlamydia .Viral load of HIV

Question 279

I&I Diagnosis of Viral Infections by Dr Cassie Pope

Loop-Mediated Isothermal Amplification (LAMP):

*LOB: Demonstrate an appreciation of the advantages and limitations of the different viral diagnostic tests allowing the most appropriate sample and test to be chosen and the correct diagnosis to be made
*LOB: Understand the science behind the different methods of diagnosing viral infections.

Answer 279

Method: LAMP is an isothermal nucleic acid amplification technique that amplifies DNA at a constant temperature. It uses multiple primers and a DNA polymerase with strand-displacement activity.

Advantage: LAMP provides quick results, requires less expensive equipment, and is well-suited for resource-limited settings.

Disadvantage: It is limited to certain viruses, and specificity can be an issue, especially when dealing with closely related strains.

Human African Trypanosomiasis, various parasitic diseases.

Question 280

I&I Clinical Use of Antiviral Drugs by Dr Peter Riley

What are different types of viral agents?

*LOB: List 4 different types of viral agents that
interfere with viral RNA or DNA synthesis

Answer 280

The antiviral drugs target diverse group of viruses such as herpes, hepatitis, and influenza viruses.

Whereas antiretroviral are the drugs that are used to fight retrovirus infections which mainly include HIV

Question 281

I&I Clinical Use of Antiviral Drugs by Dr Peter Riley

What are possible antiviral targets?

*LOB: List 4 different types of viral agents that
interfere with viral RNA or DNA synthesis

Answer 281

Adsorption – virus binds to host cell
Drugs that block or modify host receptor
Penetration/uptake- uncoating and virus genome now in host cell
Inhibit transport of virus, prevent uncoating
Virus genome replication (interfere with viral RNA and DNA strand synthesis)
Several different processes are possible depending on type of virus
Inhibit enzymes and other factors involved in viral RNA and/or DNA synthesis
Production of viral proteins and enzymes
Inhibit expression of gene/translation
Inhibit action of formed enzyme
Maturation - assembly of virion
Inhibit full assembly of the virus
Release of mature virus
If virus cannot leave cell, it cannot infect others

Question 282

I&I Clinical Use of Antiviral Drugs by Dr Peter Riley

What are difficulties in antiviral design?

*LOB: List 4 different types of viral agents that
interfere with viral RNA or DNA synthesis

Answer 282

Obligate intracellular parasites
Antiviral needs to be intracellular
Viruses use host cell receptors to gain entry
Receptor has important host functions
Replicates in cell and may use some host enzymes/proteins
These also have important functions for the host
Genetic integration (HIV, HBV)
? Impossible target
RNA viruses have high mutation rate (quasispecies)
Rapid development of resistance
Latency common (e.g. Herpes viruses)
Metabolically relatively inert, thus difficult to target

Question 283

I&I Clinical Use of Antiviral Drugs by Dr Peter Riley

Nucleoside Analog Reverse Transcriptase Inhibitors (NRTIs):

*LOB: List 4 different types of viral agents that
interfere with viral RNA or DNA synthesis

Answer 283

NRTIs are antiviral drugs that interfere with the reverse transcription process of retroviruses, such as HIV.

They are incorporated into the viral DNA chain, preventing further synthesis.

Examples include zidovudine (AZT) and tenofovir.

Question 284

I&I Clinical Use of Antiviral Drugs by Dr Peter Riley

Nucleoside and Nucleotide Analog Polymerase Inhibitors:

*LOB: List 4 different types of viral agents that
interfere with viral RNA or DNA synthesis

Answer 284

These agents interfere with the replication of DNA viruses like herpesviruses. Examples include acyclovir, valacyclovir, and cidofovir.

Question 285

I&I Clinical Use of Antiviral Drugs by Dr Peter Riley

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

*LOB: List 4 different types of viral agents that
interfere with viral RNA or DNA synthesis

Answer 285

NNRTIs inhibit the reverse transcriptase enzyme in HIV without being incorporated into the viral DNA. Efavirenz and nevirapine are examples of NNRTIs used in HIV treatment.

All have ‘-vir’ in the middle of their name (exception: fusion inhibitor

Question 286

I&I Clinical Use of Antiviral Drugs by Dr Peter Riley

Integrase inhibitors

*LOB: List 4 different types of viral agents that interfere with viral RNA or DNA synthesis

Answer 286

Integrase is an enzyme that is crucial for the replication of retroviruses, such as HIV. Integrase inhibitors target this enzyme, preventing the integration of the viral DNA into the host cell’s genome.

All have ‘- tegr’ in the middle of their name like Raltegravir

Question 287

I&I Clinical Use of Antiviral Drugs by Dr Peter Riley

Fusion inhibitors

*LOB: List other agents used for the treatment of viral infections

Answer 287

block the fusion of the viral envelope with the host cell membrane, thus preventing the virus from entering
interfering with the interaction between the viral envelope protein (gp41 in the case of HIV) and the host cell receptor (CD4 and CCR5 or CXCR4 co-receptors).

Only two drugs:
THINK - The tide (enfuvirtide)
fuses with the rocks (maraviroc)

Question 288

I&I Disorders of Immune System by C Baboonian

What is hypersensitivity?

*LOB: Outline the pathophysiology underlying types I-IV hypersensitivity reactions and relate to common clinical examples

Answer 288

• exaggerated or inappropriate immune response
• Result tissue damage
• Types I-IV

Question 289

I&I Disorders of Immune System by C Baboonian

what are the causes of type 1 hypersensitivity

*LOB: Outline the pathophysiology underlying types I-IV hypersensitivity reactions and relate to common clinical examples

Answer 289

• Pollen
• Animal hair
• House dust mite
• Moulds
• Insect bites
• Food – peanuts
• Latex
• Medicine - penicillin

Question 290

I&I Clinical Use of Antiviral Drugs by Dr Peter Riley

Other viral treatments

*LOB: List other agents used for the treatment of viral infections

Answer 290

Protease Inhibitors: Inhibit HIV protease to prevent virus maturation (e.g., atazanavir, darunavir).
CCR5 Inhibitors: Block host cell CCR5 co-receptor to prevent certain HIV strains from infecting cells (e.g., maraviroc).
Fusion Inhibitors: Interfere with viral envelope-cell membrane fusion to prevent virus entry (e.g., enfuvirtide).
Polymerase Inhibitors: Target viral RNA/DNA polymerase enzymes, used against various viral infections (e.g., sofosbuvir for hepatitis C).
Maturation Inhibitors: Disrupt virion assembly to prevent mature virus release.
Repurposed Drugs: Reuse drugs developed for other purposes to treat viral infections (e.g., remdesivir for COVID-19).
Vaccines: Induce immunity by training the immune system to recognize and combat viruses.

Question 291

I&I Clinical Use of Antiviral Drugs by Dr Peter Riley

Diseases and Antivirals

*LOB: List other agents used for the treatment of viral infections

Answer 291

Question 292

I&I Disorders of Immune System by C Baboonian

What is the mechanism of type 1 hypersensitivity?

*LOB: Outline the pathophysiology underlying types I-IV hypersensitivity reactions and relate to common clinical examples

Answer 292

• Immediate Hypersensitivity
• B lymphocytes recognise the antigen and present to Th2
• Th2 cells secrete IL4
• IL4 induces B cells to switch class and produce IgE
• IgE binds to mast cells by its tail end the Fc
• region
• On second exposure
• Allergen binds to Antibody on Mast Cells
• Mast Cells contain histamine
• Histamine causes all effects.

Question 293

I&I Disorders of Immune System by C Baboonian

What is the mechanism of type 2 hypersensitivity?

*LOB: Outline the pathophysiology underlying types I-IV hypersensitivity reactions and relate to common clinical examples

Answer 293

• Cytotoxic Hypersensitivity
• (IgG or IgM) targeting antigens on the surface of host cells
• Antibody binding to self-antigens leads to cell destruction through complement activation or antibody-dependent cell-mediated cytotoxicity (ADCC)
• Tissue damage occurs, and inflammation occurs.

Question 294

I&I Disorders of Immune System by C Baboonian

Examples of Type 2 Hypersensitivity

*LOB: Outline the pathophysiology underlying types I-IV hypersensitivity reactions and relate to common clinical examples

Answer 294

Hemolytic disease of the newborn (HDN) due to Rh incompatibility.

Autoimmune hemolytic anemia (AIHA), where antibodies attack red blood cells.

Myasthenia gravis, where antibodies target acetylcholine receptors on muscle cells.

Question 295

I&I Disorders of Immune System by C Baboonian

What is the mechanism of Type 3 hypersensitivity

*LOB: Outline the pathophysiology underlying types I-IV hypersensitivity reactions and relate to common clinical examples

Answer 295

Immune Complex-Mediated Hypersensitivity

Antigen can be own tissue or foreign
material

Immune complexes (antigen-antibody complexes) form in the circulation and deposit in various tissues, activating complement and recruiting inflammatory cells.
This results in widespread inflammation, tissue damage, and vasculitis.

Question 296

I&I Disorders of Immune System by C Baboonian

Example of Type 3 Hypersensitivity

*LOB: Outline the pathophysiology underlying types I-IV hypersensitivity reactions and relate to common clinical examples

Answer 296

SLE
RA

Question 297

I&I Disorders of Immune System by C Baboonian

What is the mechanism of Type 4 Hypersensitivity

*LOB: Outline the pathophysiology underlying types I-IV hypersensitivity reactions and relate to common clinical examples

Answer 297

• Delayed-Type Hypersensitivity
• T cell mediated –but dendritic cells, macrophages
• and cytokines contribute to the disease process
• Antigen-presenting cells (APCs) present the antigen to CD4+ or CD8+ T cells.
• CD4+ T cells release cytokines, activating macrophages and promoting inflammation.
• CD8+ T cells directly attack and damage target cells.

Question 298

I&I Disorders of Immune System by C Baboonian

Example of Type 4 Hypersensitivity

*LOB: Outline the pathophysiology underlying types I-IV hypersensitivity reactions and relate to common clinical examples

Answer 298

• Contact dermatitis, like poison ivy rash, triggered by exposure to an allergen.
• Mantoux test/tuberculin skin test is an example
• Ulcerative colitis and Crohn’s disease
• type I diabetes:
• Beta cells in islets of Langerhans
• Act as autoantigen

Question 299

I&I Disorders of Immune System by C Baboonian

What factors predispose to autoimmunity?

*LOB: Describe immunological factors involved in the development of autoimmunity and relate to common autoimmune conditions

Answer 299

• Genetic Predisposition (such as HLA)
• Loss of Immune Tolerance (such as MS)
• Dysregulation of Regulatory T Cells (Tregs) (rheumatoid arthritis)
• Immunologic Memory (SLE)
• Chronic Inflammation and Cytokine Dysregulation:
• Environmental Triggers (Hypothyroidism)
• Specific autoantigens
• Drugs (Patients on treatment for ventricular
  arrhythmia (procainamide) develop SLE)
• Immunodeficiency (C1q inhibitor deficiency)
  *

Question 300

I&I Disorders of Immune System by C Baboonian

Common autoimune DIABETES and factors that predispose.

*LOB: Describe immunological factors involved in the development of autoimmunity and relate to common autoimmune conditions

Answer 300

Common Autoimmune Condition: Type 1 Diabetes (T1D)

Genetic Predisposition: Inherited genetic factors, particularly HLA class II genes such as HLA-DR and HLA-DQ, increase susceptibility to T1D.
Environmental Triggers: Viral infections, dietary factors, and early childhood exposures contribute to the initiation of autoimmune responses against pancreatic beta cells.
Loss of Self-Tolerance: Autoimmune destruction of pancreatic beta cells occurs due to a breakdown in immune tolerance, leading to insulin deficiency.
Role of Autoantibodies: Autoantibodies targeting pancreatic beta cell antigens, such as insulin, glutamic acid decarboxylase (GAD), and islet antigen-2 (IA-2), are detected in individuals with T1D.
Inflammatory Cytokines: Pro-inflammatory cytokines, including interleukin-1 (IL-1), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α), contribute to beta cell destruction and insulin deficiency.

Question 301

I&I Disorders of Immune System by C Baboonian

Common autoimune SLE and factors that predispose.

*LOB: Describe immunological factors involved in the development of autoimmunity and relate to common autoimmune conditions

Answer 301

Systemic Lupus Erythematosus (SLE)

Genetic Predisposition: Multiple genetic variants, including those in genes involved in immune regulation and clearance of apoptotic cells, increase susceptibility to SLE.
Environmental Triggers: Ultraviolet (UV) light exposure, infections, hormonal factors, and medications can trigger or exacerbate SLE flares.
Loss of Self-Tolerance: Immune dysregulation leads to the production of autoantibodies against nuclear antigens, such as double-stranded DNA (dsDNA) and Smith (Sm) antigen.
Immune Complex Formation: Autoantibodies form immune complexes with self-antigens, leading to tissue inflammation and organ damage, particularly in the kidneys, skin, joints, and cardiovascular system.
Complement Activation: Dysregulated complement activation, including the classical pathway, contributes to tissue injury and inflammation in SLE.

Question 302

I&I Disorders of Immune System by C Baboonian

Common autoimune MS and factors that predispose.

*LOB: Describe immunological factors involved in the development of autoimmunity and relate to common autoimmune conditions

Answer 302

Multiple Sclerosis (MS)

Genetic Predisposition: Genetic factors, particularly within the major histocompatibility complex (MHC) region, influence susceptibility to MS.
Environmental Triggers: Viral infections, vitamin D deficiency, smoking, and other environmental factors are implicated in triggering MS in genetically susceptible individuals.
Loss of Self-Tolerance: Autoimmune attack against myelin proteins, such as myelin basic protein (MBP) and proteolipid protein (PLP), leads to demyelination and axonal damage in the central nervous system.
Role of Autoantibodies: Autoantibodies targeting myelin proteins or components of the blood-brain barrier may contribute to the pathogenesis of MS.
Inflammatory Cytokines: Pro-inflammatory cytokines, including interleukin-17 (IL-17), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α), drive inflammation and tissue damage in MS lesions.

Question 303

I&I Disorders of Immune System by C Baboonian

Examples of primary immunodeficiency

*LOB: Recognise clinical examples of primary immunodeficiency

Answer 303

Complement” ** Immunodeficiency (C1q inhibitor deficiency)
Phagocyte: Chediak-Higashi syndrome – failure of phagolysosome
B cell: Severe combined immunodeficiency syndrome; Hyper IgM; B cells being unable to mature into plasma cells so low IgA/IgG
** T- cell: Di George;

Secondary: HIV, Malnutrition, Tumour, therapeis.,

Question 304

I&I Disorders of Immune System by C Baboonian

Examples of secondary immunodeficiency

*LOB: Recognise clinical examples of primary immunodeficiency

Answer 304

Secondary: HIV, Malnutrition, Tumour, therapeis.,

Question 305

I&I Disorders of Immune System by C Baboonian

Compare Immunodeficiency 1’ and 2’

*LOB: Distinguish between primary and secondary immunodeficiency

Answer 305

Primary immunodeficiency is genetic, present from birth, and often requires specific treatments, while secondary immunodeficiency is acquired, can develop at any age, and is typically managed by addressing the underlying cause.

Question 306

I&I Pharmacology Self Directed Learning by Anthony Albert

Recognise the key clinical signs and symptoms of anaphylaxis

*LOB: Recognise the key clinical signs and symptoms of anaphylaxis and anaphylactic shock

Answer 306

Skin Reactions:
Hives (urticaria) or widespread skin redness.
Swelling of the face, lips, or tongue (angioedema).

Respiratory Symptoms:
Difficulty breathing, including wheezing or coughing.
Rapid, shallow breathing.
Chest tightness or pain.

Cardiovascular Symptoms:
Rapid or irregular heartbeat (palpitations).
Low blood pressure (hypotension).
Feeling lightheaded or faint.

Gastrointestinal Symptoms:
Nausea and vomiting.
Abdominal pain or cramps.

Other Symptoms:
Feeling of impending doom or extreme anxiety.
Confusion.
Weakness.
Swelling of the throat, which can lead to difficulty swallowing.

Question 307

I&I Pharmacology Self Directed Learning by Anthony Albert

Recognise the key clinical signs and symptoms of Anaphylactic Shock:

*LOB: Recognise the key clinical signs and symptoms of anaphylaxis and anaphylactic shock

Answer 307

May contain the same as anaphylaxis but is an acute reaction that is life threatening:

Severe Hypotension:
Profoundly low blood pressure, leading to circulatory collapse.

Loss of Consciousness:
Loss of consciousness or confusion due to inadequate blood flow to the brain.

Cyanosis:
Bluish or pale skin, lips, or extremities due to oxygen deprivation.

Question 308

I&I Pharmacology Self Directed Learning by Anthony Albert

What is the mechanism of Anaphylaxis

*LOB: Apply your understanding of hypersensitivity reactions to outline the stepwise mechanisms the lead to anaphylaxis from allergen exposure

Answer 308

Type 1 Hypersensitivity (Immediate)

• Immediate Hypersensitivity
• B lymphocytes recognise the antigen and present to Th2
• Th2 cells secrete IL4
• IL4 induces B cells to switch class and produce IgE
• IgE binds to mast cells by its tail end the Fc
• region
• On second exposure
• Allergen binds to Antibody on Mast Cells
• Mast Cells contain histamine
• Histamine causes all effects.

Question 309

I&I Pharmacology Self Directed Learning by Anthony Albert

What is the role of histamine in anaphylaxis?

*LOB: Apply your understanding of hypersensitivity reactions to outline the stepwise mechanisms the lead to anaphylaxis from allergen exposure

Answer 309

Vasodilation: Histamine causes blood vessels to dilate, resulting in increased blood flow to the affected area.

Increased Permeability: It increases the permeability of blood vessel walls, allowing plasma and immune cells to leak into tissues.

Bronchoconstriction: In the airways, histamine can cause smooth muscle contraction, leading to bronchoconstriction and reduced airflow.

Mucous Production: It stimulates the production of mucus, further narrowing airways and contributing to respiratory distress.

Itch and Swelling: Histamine release leads to itching, hives (urticaria), and swelling (angioedema) of the skin.

Cardiovascular Effects: Systemic histamine release can lead to hypotension and tachycardia due to vasodilation and increased vascular permeability.

H1 receptors are responsible for allergic symptoms such as itching and bronchoconstriction.
H2 receptors are found in the stomach and are involved in gastric acid secretion.
H3 receptors play a role in regulating neurotransmitter release.

Question 310

I&I Pharmacology Self Directed Learning by Anthony Albert

What is the management of anaphylaxis?

*LOB: Outline the immediate management of anaphylaxis and relate this to the underlying pathophysiology

Answer 310

Vasodilation and Hypotension: Adrenaline constricts blood vessels, raising blood pressure.
Bronchoconstriction: It relaxes airway smooth muscles, improving breathing.
Reduced Mucous Secretion: Adrenaline decreases mucous production.

Antihistamines compete with histamine for binding to H1 receptors, preventing or reducing the histamine-induced responses, alleviate skin reactions and itching

Corticosteroids are used in anaphylaxis to mitigate the prolonged and delayed inflammatory response that can follow the initial release of mediators like histamine.
Inhibit the production and release of various inflammatory mediators, such as cytokines and prostaglandins and supress delayed phases of immune system

Question 311

I&I Maternal Health and Infectious Disease by Bernice Langdon

What is maternal mortality?

*LOB: Explain why maternal morbidity and mortality is important

Answer 311

• annual number of female deaths
• from any cause related to or aggravated by pregnancy or its management (excluding accidental or incidental causes)
• during pregnancy and childbirth
• or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy.

NICE: compared with white women (8/100,000), the risk of maternal death during pregnancy and up to 6 weeks after birth is:
4 times higher in black women (34/100,000)
3 times higher in women with mixed ethnic background (25/100,000)
2 times higher in Asian women (15/100,000; does not include Chinese women)

Question 312

I&I Maternal Health and Infectious Disease by Bernice Langdon

What is maternal morbidity?

*LOB: Explain why maternal morbidity and mortality is important

Answer 312

any health condition attributed to and/or aggravated by pregnancy and childbirth that has negative outcomes to the woman’s well-being.

Question 313

I&I Maternal Health and Infectious Disease by Bernice Langdon

What is TORCH

*LOB: List key microbes that can cause maternal, congenital, and neonatal infection

Answer 313

a group of diseases that cause congenital (present at birth) conditions if a fetus is exposed to them in the uterus.

Toxoplasmosis
Other
Rubella
Cytomegalovirus (CMV)
Herpes simplex virus (HSV)

Question 314

I&I Maternal Health and Infectious Disease by Bernice Langdon

What is STORCHH

Think Virals

*LOB: List key microbes that can cause maternal, congenital, and neonatal infection

Answer 314

Syphilis
Toxoplasmosis
Other
Rubella
Cytomegalovirus (CMV)
Herpes simplex virus (HSV)
HIV

Question 315

I&I Maternal Health and Infectious Disease by Bernice Langdon

What are the antenatal tests in the UK?

*LOB: Outline antenatal tests for women in the UK and why they are done

Answer 315

HIV
Hepatitis B
Syphilis

Not Rubella

Question 316

I&I Maternal Health and Infectious Disease by Bernice Langdon

Which Vaccinations are given in pregnancy and why?

*LOB: Identify the vaccinations relevant to pregnant women in the UK schedule and explain why they are given

Answer 316

There is a difference in Immune Susceptibility when Pregnant

’The Government has accepted JCVI advice that the seasonal COVID-19 vaccine should be offered this autumn to all pregnant women – because they are at higher risk of severe COVID-19 infection.

’Wherever possible, vaccinations for flu, COVID-19 and pertussis should be offered at the same time

Question 317

I&I Maternal Health and Infectious Disease by Bernice Langdon

Chicken Pox (VZV) in Children

*LOB: Recognise key maternal infections such as chicken pox, parvovirus and genital herpes, the clinical presentation, investigations, and the effect of these infections on the baby

Answer 317

Characteristic scarring skin lesions known as cicatrix occur
Limb abnormalities
Typical ocular defects include chorioretinitis, cataracts
Central nervous system abnormalities include microcephaly

Birthing parent with vesicular rash in pregnancy
Approach; VZV IgM(recent infection) and IgG(longstanding infection) tests on patient promptly and on booking blood
Speak to on call microbiology
May need treatment with VZV Immunoglobulin im

Question 318

I&I Maternal Health and Infectious Disease by Bernice Langdon

Parvovirus in Children

*LOB: Recognise key maternal infections such as chicken pox, parvovirus and genital herpes, the clinical presentation, investigations, and the effect of these infections on the baby

Answer 318

Slapped Cheek
Also known as erythema infectiosum
It is caused by human parvovirus B19
This is a tiny virus, 18 nanometers
It can only replicate in rapidly dividing cells such as erythroid progenitor cells, bone marrow cells and fetal cells

What is the presentation of parvovirus? Usually a non-specific viral illness for 5-7 days. Once the rash appears they are usually on the mend and not infectious.

Birthing parent may have had contact with vesicular rash: Prompt blood tests for IgM (recent infection) and IgG (previous infection) of the relevant virus

Question 319

I&I Maternal Health and Infectious Disease by Bernice Langdon

Genital Herpes and Maternal transmission

*LOB: Recognise key maternal infections such as chicken pox, parvovirus and genital herpes, the clinical presentation, investigations, and the effect of these infections on the baby

Answer 319

The incidence of neonatal HSV infection is estimated to range between 1 in 3000 to 1 in 20,000 live births

Symptoms of congenital herpes usually appear within the first month of the infant’s life. Signs that your baby may have herpes are:
irritability
seizures
trouble breathing, including grunting, blue appearance (cyanosis), rapid breathing and short periods of no breathing
jaundice (yellow skin color)
bleeding easily
shock

RISK
Localized skin infection
Encephalitis
Disseminated herpes infection–the most dangerous type of herpes infection. The herpes virus is spread throughout the body and can affect multiple organs, including the liver, brain, lungs and kidney.

Question 320

I&I Maternal Health and Infectious Disease by Bernice Langdon

Compare immune susceptibility in pregnancy and non-pregnancy

*LOB: Understand the difference in immune susceptibility in pregnancy compared to when people are not pregnant

Answer 320

Decreased total IgG levels during pregnancy, especially in late pregnancy.
Higher IgG1 levels in the three trimesters when compared to non-pregnant women.

Since the 1918 influenza pandemic, it has been apparent that pregnant women suffer more severe complications from influenza infections than non-pregnant women

Researchers have speculated that a shift to Th2 immunity is responsible for the altered responses in the periphery to respiratory viral infections [31] or autoantigens

Question 321

I&I Maternal Health and Infectious Disease by Bernice Langdon

What is Sepsis and how to manage

*LOB: Demonstrate an understanding of the key importance of sepsis during pregnancy and childbirth and outline typical microbial causes such as Group A Strep and Group B strep

Answer 321

Sepsis is a life-threatening reaction to an infection. It happens when your immune system overreacts to an infection and starts to damage your body’s own tissues and organs.

.
1.Oxygen to keep oxygen saturations above 95%
2.Blood cultures, also FBC, U&E, LFT, coagulations, glucose, other cultures
3. Lactate measurement
4 .IV fluids bolus20ml/Kg normal saline stat. If no response repeat unless there are signs of pulmonary oedema
5. IV antibioticsprescribe and commence within 60 minutes from triage/time of diagnosis. Do not wait for results of investigations.
6. Monitoring; respiratory rate, oxygen saturations, BP, heart rate, temperature, consciousness, fluid balance, urinary output.

Question 322

I&I Maternal Health and Infectious Disease by Bernice Langdon

Sepsis in pregnancy and childbirth

*LOB: Demonstrate an understanding of the key importance of sepsis during pregnancy and childbirth and outline typical microbial causes such as Group A Strep and Group B strep

Answer 322

Maternal sepsis is sepsis – a life-threatening condition – that develops during pregnancy, childbirth, or in the months following childbirth. It can also complicate abortions and miscarriages

Pregnant women face a slightly higher risk of sepsis due to naturally occurring immunological changes, the need for procedures or surgery, and risks due to complications, such as premature rupture of membranes or gestational diabetes. 

The most common cause is a severe bacterial infection of the uterus during pregnancy or immediately after childbirth. Maternal sepsis could also be caused by a urinary infection, or pneumonia. 

Due to the physiological changes in pregnancy, the National Early Warning Score (NEWS) is not designed for use in pregnant patients. Use of a **Modified Obstetric Early Warning Score (MEOWS) **alongside the Maternal Sepsis screening tool is recommended to facilitate the early recognition and escalation of deteriorating maternal patients.  

Question 323

I&I Maternal Health and Infectious Disease by Bernice Langdon

Causes of sepsis

*LOB: Demonstrate an understanding of the key importance of sepsis during pregnancy and childbirth and outline typical microbial causes such as Group A Strep and Group B strep

Answer 323

Group A Streptococcal infection

Streptococcus pyogenes
Can cause post puerperal infection, tonsillitis, scarlet fever, erysipelas, rheumatic fever, endocarditis

Colonies cause as beta-haemolysis on blood agar

Question 324

I&I Bacterial and Viral Vaccines by Prof Paul Heath

Define Vaccine

*LOB: Explain the term ‘vaccine’ and the concept of ‘protective immunity’

Answer 324

A vaccine is a biological preparation that stimulates the immune system to recognize and fight specific pathogens, such as viruses or bacteria, without causing the disease itself.

Question 325

I&I Bacterial and Viral Vaccines by Prof Paul Heath

Define protective immunity

*LOB: Explain the term ‘vaccine’ and the concept of ‘protective immunity’

Answer 325

Protective immunity can be achieved through natural infection or vaccination.

It involves the production of antibodies and memory cells, which recognize and fight the pathogen upon exposure, preventing the disease from taking hold or reducing its severity.

Question 326

I&I Bacterial and Viral Vaccines by Prof Paul Heath

Describe types of vaccine

*LOB: Describe types of vaccine, and relate to common clinical examples

Answer 326

Inactivated Vaccines: These vaccines use pathogens that have been killed or inactivated, so they cannot cause the disease.

Live Attenuated Vaccines: These vaccines use weakened forms of the live virus or bacteria. They provide strong and long-lasting immunity.

Subunit, Recombinant, or Conjugate Vaccines: These vaccines contain only specific antigens or protein subunits from the pathogen, not the whole pathogen.

Viral Vector Vaccines: These vaccines use a harmless virus to carry genetic material from the target pathogen.

Nucleic Acid (mRNA or DNA) Vaccines: These vaccines use genetic material to instruct cells to produce a harmless piece of the pathogen, triggering an immune response.

Toxoid Vaccines: These vaccines target toxins produced by bacteria rather than the bacteria itself.

Vector-borne Vaccines: These vaccines target diseases transmitted by vectors like mosquitoes.

Multivalent or Combination Vaccines: These vaccines protect against multiple diseases in a single shot.

Question 327

I&I Bacterial and Viral Vaccines by Prof Paul Heath

List different types of vaccines and examples

*LOB: Describe types of vaccine, and relate to common clinical examples

Answer 327

Inactivated Vaccines: polio vaccine (IPV) and hepatitis A vaccine.

Live Attenuated Vaccines: (MMR) vaccine and the oral polio vaccine (OPV).

Subunit, Recombinant, or Conjugate Vaccines: T hepatitis B vaccine and the Haemophilus influenzae type b (Hib) vaccine.

Viral Vector Vaccines: J&J COVID-19 vaccine, which uses an adenovirus vector.

Nucleic Acid (mRNA or DNA) Vaccines: Pfizer and Moderna COVID-19 vaccines, which are mRNA vaccines.

Toxoid Vaccines: tetanus and diphtheria vaccines.

Vector-borne Vaccines: yellow fever and Japanese encephalitis vaccines.

Multivalent or Combination Vaccines: diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae type b.

Live attenuated
Tuberculosis (BCG), Oral polio vaccine (OPV), Measles, Rotavirus, Yellow fever, Varicella-Zoster virus, Influenzae (intranasal)
Inactivated whole-cell (killed antigen)
Whole cell pertussis, Inactivated polio virus, Hepatitis A, Influenza (injectable)
Toxoid (inactivated toxins)
Tetanus toxoid, Diphtheria toxoid
Subunit (purified antigen)
Acellular pertussis (aP), Haemophilus influenzae type b (Hib), Pneumococcal, Hepatitis B (HepB), Human papillomavirus (HPV)
Viral vectored
SARS-CoV-2 (adenoV), Ebola virus
Nucleic acid vaccines
SARS-CoV-2 (mRNA)

Question 328

I&I Bacterial and Viral Vaccines by Prof Paul Heath

What is considered for when, how and who a vaccine is given to

*LOB: Discuss the considerations for when, how and who a vaccine is given to in relation to common bacterial and viral vaccines used in the immunisation schedule in the UK

Answer 328

Age:
Health Status:
Risk Factors:
Location:
Travel

Question 329

I&I Bacterial and Viral Vaccines by Prof Paul Heath

Why give booster vaccines?

*LOB: Outline the reasons for vaccine booster doses

Answer 329

Reinforce Immunity

Respond to New Threats

Complete Initial Series

Question 330

I&I A Patient Presents with Suspected COVID...

How does COVID present

*LOB: Recognise how COVID-19 might present

Answer 330

Fever
Cough
Fatigue
Myalgia
Arthralgia
Dyspnea
Altered sense of taste/smell
Sore throat
Headache
Rhinorrhea
Nasal congestion
Sneezing
Expectoration.
Less common or uncommon symptoms include:

Chest tightness/pain
Malaise
Dizziness
Confusion
Delirium
Gastrointestinal symptoms
Cutaneous symptoms
Ocular symptoms
Hemoptysis
Audio-vestibular symptoms
Oral mucosal lesions.

Question 331

I&I A Patient Presents with Suspected COVID...

COVID investigations

*LOB: Outline the relevant investigations that should be undertaken for a patient with suspected COVID-19

Answer 331

Blood tests - including Full Blood Count, Urea & Electrolytes, Liver Function Tests, CRP and Blood

Cultures
SARS-CoV-2 PCR swab
Respiratory viral panel PCR swab - testing for alternative respiratory viruses including rhinovirus, influenza amongst others

**Chest X-ray
**
ECG (to screen for features of heart failure, pericarditis etc.)

Urine dipstick (to exclude a urinary infection as the cause of his fevers/lethargy)

CRP is raised (which is a non-specific marker of inflammation but is usually elevated in moderate-severe COVID), and the normal procalcitonin level makes a bacterial infection less likely.

Question 332

I&I A Patient Presents with Suspected COVID...

Managing COVID patients

*LOB: Be familiar with the principles of managing patients with COVID-19

Answer 332

Dexamethasone is a corticosteroid which is now standard-of-care (Recovery trial)

many of the adverse outcomes from COVID-19 are related to a hyper-inflammatory response to the virus (particularly in the lungs).

Low molecular weight heparin (LMWH) is a subcutaneous anticoagulant COVID-19 is a prothrombotic condition and all patients admitted to hospital with COVID-19 should be considered for treatment with LMWH

Remdesivir is an anti-viral medication which has been shown in the Recovery trial to quicken recovery time .

Tocilizumab is an interleukin-6 inhibitor, . It has been shown as part of the Recovery and REMAP-CAP trials to shorten the duration of hospital stay and ICU admission in patients with severe COVID-19, as well as reducing mortality.

Nirmatrelvir/ritonavir (brandname Paxlovid) is the first-line option of a number of antiviral medications which are used to reduce the risk of severe COVID-19 in patients who are extremely vulnerable. This may include those who are immunosuppressed (solid-organ transplant, haematological malignancy) or with severe underlying respiratory disease. It should only be initiated in accordance with local guidance or on specialist advice. Paxlovid is a proetase inhibitor - it aims to suppress viral replication - and is therefore most useful early on in the disease course.

Question 333

I&I A Patient Presents with Suspected COVID...

List COVID complications

*LOB: Recognise some potential complications of COVID-19

Answer 333

Patients with COVID-19 are at increased risk of VTE, particularly PE
Hypoxia
bilateral pulmonary emboli (PEs)

post-intensive care syndrome

thrombosis

cardiovascular complications

acute kidney injury

post-COVID-19 syndrome (long COVID)

post COVID-19 vaccination: myocarditis/pericarditis

acute liver injury

neurologic complications

cardiac arrest

Question 334

I&I Disorders of the Lymphatic System by Dr Kristiana Gordon

What are consequences of lymphatic dysfunction?

*LOB: Understand how lymphatic dysfunction impacts on human disease

Answer 334

• Lymphoedema
• Elephantiasis skin changes
• Infection
• Increased risk of local malignant changes
• Lymphoedema fluid promotes fat deposition in affected limb

Question 335

I&I Disorders of the Lymphatic System by Dr Kristiana Gordon

Functions of lymphatics

*LOB: Describe the functions of the lymphatic system

Answer 335

• drainage system of interstitial fluid
• Protein and fluid homeostasis
• Cellular drainage from tissues
• Immune surveillance
• Regulation of inflammation
• Fat homeostasis

Question 336

I&I Disorders of the Lymphatic System by Dr Kristiana Gordon

How does lymphodema occur?

*LOB: Describe the pathophysiological mechanisms of common lymphatic conditions

Answer 336

drainage because of:
1) increased filtration
e.g. venous hypertension.

2) impaired flow of lymph
e.g. abnormal development of lymphatic vessels (primary lymphoedema);
or interruption of lymphatic pathways (secondary lymphoedema).

Question 337

I&I Disorders of the Lymphatic System by Dr Kristiana Gordon

Staging lymphodema

*LOB: Describe the pathophysiological mechanisms of common lymphatic conditions

Answer 337

Question 338

I&I Disorders of the Lymphatic System by Dr Kristiana Gordon

Signs of Lymphodema

*LOB: Describe the pathophysiological mechanisms of common lymphatic conditions

Answer 338

• Lymphoedema is pitting (initially)
• Lymphoedema causes skin thickening and hyperkeratosis
• Lymphoedema may improve overnight (initially)
• Diuretics have no longterm impact on lymphoedema
• More than one attack of cellulitis has occurred

Question 339

I&I Disorders of the Lymphatic System by Dr Kristiana Gordon

Causes of Secondary Lymphodema

*LOB: Describe the pathophysiological mechanisms of common lymphatic conditions

Answer 339

Secondary Lymphoedema
* Malignancy (disease / treatment)
* Infection (incl. Filariasis)
* Inflammation (RA / psoriasis / eczema / acne / cutaneous Crohn’s)
* Medications (e.g. calcium channel blockers)
* Trauma
* Venous disease
* Immobility / Dependency
* Obesity

Question 340

I&I Disorders of the Lymphatic System by Dr Kristiana Gordon

Causes of Primary Lymphodema

*LOB: Describe the pathophysiological mechanisms of common lymphatic conditions

Answer 340

developmental abnormality of the lymphatic system,

• It is not just one disease. Phenotypes vary in age
  of onset, site, inheritance patterns, associated
  features.
• Multiple causal genes identified

Classified * Associated with other genetic syndromes.
* Associated with systemic lymphatic problems.
* Congenital (swelling present at birth).
* Late-onset (onset after 1 year of age).
* Lymphatic malformations +/- overgrowth disorders.

Question 341

I&I Disorders of the Lymphatic System by Dr Kristiana Gordon

Milroy Disease / VEGFR3 mutation

*LOB: Describe the pathophysiological mechanisms of common lymphatic conditions

Answer 341

• Congenital lymphoedema of lower
  legs
• Autosomal dominant inheritance
• Large calibre veins with venous
  reflux confirmed on ultrasound
  examination

Question 342

I&I Disorders of the Lymphatic System by Dr Kristiana Gordon

Lymphoedema Distichiasis / FOXC2 mutation

*LOB: Describe the pathophysiological mechanisms of common lymphatic conditions

Answer 342

Pubertal onset of lower limb
lymphoedema
* Distichiasis
* Ptosis, cleft palate, congenital
heart disease, scoliosis
* Autosomal dominant inheritance

Question 343

I&I Disorders of the Lymphatic System by Dr Kristiana Gordon

Emberger Syndrome / GATA2 mutation

*LOB: Describe the pathophysiological mechanisms of common lymphatic conditions

Answer 343

Late onset lymphoedema of lower limbs
* +/- Genital lymphoedema
* Mutations in GATA2 are causative
* Autosomal dominant inheritance
* Sensorineural hearing loss
* Cutaneous warts
* Predisposition to AML leukaemia

Question 344

I&I Disorders of the Lymphatic System by Dr Kristiana Gordon

Generalised Lymphatic Dysplasia (Hennekam
Syndrome) / CCBE1 mutation

*LOB: Describe the pathophysiological mechanisms of common lymphatic conditions

Answer 344

Extensive congenital
lymphoedema with visceral
involvement
* Mutations in CCBE1 are causative
* Autosomal recessive inheritance
* Learning difficulties, unusual facial
features

Question 345

I&I Disorders of the Lymphatic System by Dr Kristiana Gordon

Klippel-Trenaunay Syndrome

*LOB: Describe the pathophysiological mechanisms of common lymphatic conditions

Answer 345

Question 346

I&I Disorders of the Lymphatic System by Dr Kristiana Gordon

Managing Lymphodema

*LOB: * Outline the management of chronic lymphoedema

Answer 346

Question 347

I&I Principles of Selective Toxicity by Dr Omar Janneh

Why are some drugs more toxic to tumour and not somatic cells?

*LOB: Explain why some drugs are more toxic to tumour cells and infective organisms than to human cells

Answer 347

Differences between metabolic pathways between normal and tumouric cells
High degree of discrimination (ratio of therapeutic to toxic effect)

Question 348

I&I Principles of Selective Toxicity by Dr Omar Janneh

Mehcnism of penicillin

*LOB: Explain how antibiotics inhibit cell wall synthesis in bacteria

Answer 348

Side chain from the βlactam ring determins the properties of different penicillin but:
penicillin binds to PBP (penicillin binding proteins) which inhibits peptide cross links in the microbial cell wall.

Essentially inhibits transpeptidation- which prevents peptide bridge forming. (NAG and NAM)

Question 349

I&I Principles of Selective Toxicity by Dr Omar Janneh

Mechanism of Aminoglycosides (streptomycin and gentamicin)

*LOB: Explain how antibiotics inhibit protein synthesis in bacteria

Answer 349

Binds to essential portions at the transcription process.
Streptomycin changes 30S: mRNA incorrectly read
Tetracyclin changes how tRNA and mRNA bind

Question 350

I&I Principles of Selective Toxicity by Dr Omar Janneh

What are the site of action for antifungal agents?

*LOB: Explain why some drugs selectively inhibit fungal growth

Answer 350

Question 351

I&I Principles of Selective Toxicity by Dr Omar Janneh

Mechanism of action fro Amphotericin B

*LOB: Explain why some drugs selectively inhibit fungal growth

Answer 351

Interacts hydrophobically with ergosterol in fungal cell membrane and forms pores within it – binds avidly to ergosterol
* Creates transmembrane channel and cell contents (electrolytes) leak out
* Selectively toxic – humans have cholesterol instead of ergosterol

Question 352

I&I Principles of Selective Toxicity by Dr Omar Janneh

What is therapeutic index?

*LOB: Explain why some drugs are more toxic to tumour cells and infective organisms than to human cells

Answer 352

Therapeutic index = 1
it means that the concentration that causes toxicity is = conc. that causes cancer cell death

Therapeutic index should be wide not narrow
Many anticancer agents affect all dividing cells which causes side effects.

Question 353

I&I Principles of Selective Toxicity by Dr Omar Janneh

Mechanism of action of zidovudine

*LOB: Explain how drugs exert an anti-viral action

Answer 353

ZDV synthesised in 964, inhibits HIV 1984
Thymine analogue
Prodrug which must be phosphorylated to activate
Causes comeptition as used instead of thymine in the same reverse transcription enzyme

Causes selective inhibition
Inhibits infection of new cells