infection and immunity revision part 1

Question 1

A student is returning home and is approached in the street by someone who is asking for directions to the underground station. As he tries to help he is stabbed by a needle. He is concerned the needle may be contaminated with HIV. QUESTION: which subtypes of immune cells does the HIV virus infect?

• The virus infects T lymphocytes
• The virus infects B lymphocytes
• The virus infects Th cells
• CD8 positive T cells are infected
• Cytotoxic T cells are infected

Answer 1

• The virus infects Th cells

HIV attacks a specific type of immune system cell in the body. It’s known as the CD4 helper cell or T cell. When HIV destroys this cell, it becomes harder for the body to fight off other infections.

T cytotoxic cells have a major role in killing infected cells but Th cells are the main infected lymphocytes.

There are studies that show HIV can affect B cell function – but the question is which cells does the virus infect

Question 2

An HIV infected patient has developed Kaposi’s sarcoma. QUESTION: why are HIV infected individuals prone to developing Kaposi’s sarcoma?

• Reduced levels of antibody against the infectious organism
• Low levels of cytotoxic T lymphocytes
• Phagocytes infected with HIV and unable to present antigens
• CD4+ cells reduced in number affecting Th cell mediated immune function
• Decline in number of eosinophils

Answer 2

CD4+ cells reduced in number affecting Th cell mediated immune function

HIV attacks a specific type of immune system cell in the body. It’s known as the CD4 helper cell or T cell. When HIV destroys this cell, it becomes harder for the body to fight off other infections.

Question 3

A 52 year old female patient has had urinary tract infection and has been taking antibiotics for a period of one week. She comes to see her GP because she is now concerned that she has thrush. The GP explains to her that the thrush may be a result of taking antibiotics. QUESTION: why would taking antibiotics result in thrush?

• Hypersensitivity reaction to antibiotics
• Removal of harmless residual bacteria allowing replication of candida
• Antibiotics down regulate the number of CD4+ T helper cells
• Antibiotic resistance results in T cell apoptosis allowing candida infection to progress.

Answer 3

Removal of harmless residual bacteria allowing replication of candida

Candidiasis is a fungal infection caused by a yeast (a type of fungus) called Candida.

Question 4

A patient with phagocyte disorder is experiencing frequent infections. Phagocytes are essential components of the immune response. Which of the following statements explains the increased risk of infection in patients with phagocyte defects?

• Phagocytic cells generate antibodies that prevent infection- false they don’t generate antibodies
• Phagocytes identify pathogens through MHC presented antigens killing infected cells
• Phagocytes activate cells encouraging antibody production
• Phagocytes process and present antigens initiating T cell activation

Answer 4

Phagocytes process and present antigens initiating T cell activation

but could also be the one before

Question 5

What statement best describes the role of Natural killer cells?

• Each NK cell has specific affinity for an antigen and can engage in killing infected cells- not specific
• NK cells have specific receptors that engage in release of complement – not specific
• Able to identify cells that have altered surface antigens and can engage in killing these cells
• NK cells have a surveillance role for bacterial pathogens

Answer 5

• Able to identify cells that have altered surface antigens and can engage in killing these cells
• Natural killer cells
• Surveillance role
• Any cell that has changed is a target for killing

Question 6

What statement best describes the structure of antibodies?

• Tetrameric protein with two identical heavy chains and two identical light chains
• Each immunoglobulin molecule has a kappa and a lambda chain
• IgG antibodies have a constant region with no variable section
• IgM antibodies have two constant chains and no variable chains.

Answer 6

Tetrameric protein with two identical heavy chains and two identical light chains.

antibody:
-Y-shaped
Tetrameric protein
-    2 identical heavy chains
-    2 identical light chains

Question 7

A patient who has recently developed symptoms of hepatitis is tested for hepatitis A antibodies. What is the best laboratory based diagnostic strategy for hepatitis A infection?

• Measure Hepatitis A virus specific circulating IgG levels.
• Measure Hepatitis A total immunoglobulin levels
• Assess levels of IgE immunoglobulin in peripheral blood
• Test for the presence of IgM antibodies to hepatitis A virus.

Answer 7

-Test for the presence of IgM antibodies to hepatitis A virus.

Immunoglobulin E(IgE) – usually an immediate response to a foreign substance that has entered the body normally found in small amountsin theblood.

IgGcan take time to form after an infection or immunisation

ImmunoglobulinM (IgM): Found mainly in blood and lymph fluid, thisisthe first antibody the body makes when it fights a new infection.

ImmunoglobulinA (IgA) – plays a rolein theimmune function of mucous membranes.

Question 8

What do B lymphocytes do?

Answer 8

Make antibodies
Immunoglobulins 
There are two types
IgM – made first
IgG – made later

Question 9

How do T cells recognise antigens?

• T cells have T cell receptors which are able to attach to antigens and recognise them.
• T cells have MHC class I receptors which bind to antigenic sites on infected cells
• CD4+ T cells recognise antigens displayed on infected cells by MHC I
• CD8+ T cells have T cell receptors which recognise antigen displayed by MHC I molecules

Answer 9

• CD8+ T cells have T cell receptors which recognise antigen displayed by MHC I molecules

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

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

Question 10

how do natural killer cells use perforin and granzymes work to destroy defective cells? also what is the one other thing that they produce apoptosis

Answer 10

perforin- creates pores in the target cell
granzymes- release cytotoxic enzymes which cause apoptosis. (granzyme B can trigger mitochondrial apoptotic pathway)

• interferon y (gamma)

Question 11

how are natural killer cells inhibited or activated.

Answer 11

Inhibitiory receptors recognise self MHC class 1 and then send a blockadge of signals from the activated recptors.

However virus infected and malignant cells downregulate the expression of MHC 1 so there would be low levles of it on the cell. hence the inhibitory receptors are not ligated my MHC 1 as low levels. so signals from activating receototrs are not blocked. NK cells are activated and attack.

Question 12

what are the receptors involved in NK cells activation and inhibition.

Answer 12

ITIM (for inhibition) and ITAM (for activation) have tyrosine motifs that can become phosphorylated in order to propagate the cell signalling to lead to either inhibition or activation depending on the receptor.

Question 13

CD4+ and CD8+ are types of t cells what are they exactly?

Answer 13

CD4+ are helper t cells (cannot kill but oder other cells to do so) looks for MCH2 from APCs
CD8+ are cytotoxic cells (can kill cancer/virus infected cells) looks for MCH1

Question 14

which is not an a ‘lymphoctye with limited capacity’

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

Answer 14

dendritic cell

Question 15

which immune cells are from myeloid lineage and which are from lymphoid lineage?

Answer 15

myeloid: phagocytes, basophils, eosionphils, mast cells

lymphoid cells:T lymphocytes, B lymphocytes, NK cells, innate lymphoid cells, lymphocytes with limited diversity

Question 16

how do macrophages and nk cells work together to create and immune response.

Answer 16

when macrophages engage in phagocytosis they produce cytokine IL-12 which is good at activating NK cells. The NK cells then become activated and produce interferon y (gamma) which also enhances macrophages ability to kill.

Question 17

innate lymphoid cells (ILCs) and lymphocytes with limited diversity are the innate immune system what are their roles.

Answer 17

ILCs similar to T lymphoctes but do not express T cell receptors hence no colonal expansion (proliferation). main mechanism is to produce cytokines

Lymphocytes with limited diversity combine feautres of T/B cells and innate cells

Question 18

what is the role of histamine and where is it released from?

Answer 18

histamine stimulates inflammation and is released from mast cells

• causes vasodilation (causes redness)
• makes blood vessels more permeable
• pain at site of injury and attracts immune cells.

Question 19

what is the general mechanism of B lymphocytes?

Answer 19

B cells have receptors that bind to a specific antigen when it meets the right one it digests it and projects MHC 2 cells for helper t cells to bind to it.

It also releases lymphokines which cause the B cells to make plasma cells and the plasma cells make antibodies. Some memory cells are also made.

for the helper t cells that bind they also proliferate and make cytotoxic t cells and memory t cells do the immune response will be faster next time

Question 20

what is the difference between humoral and cell mediated immunity?

Answer 20

humoral immunity (makes antibodies)
- targets exogenous antigens (outside cells)
-macrophages/ APCs englulf exogenous antigens and break them into fragments which are projected into MHC class 2 receptors. this signals the material as being foreign
-

cell mediates immunity
-targets endgroenous antigens (cancer cells or virus infected cells.

Question 21

what is the difference between humoral and cell mediated immunity?

Answer 21

humoral immunity (makes antibodies)

• targets exogenous antigens (outside cells)
• macrophages/ APCs engulf exogenous antigens and break them into fragments which are projected into MHC class 2 receptors. this signals the material as being foreign
• helper t cells bind to this and releases cytokines to activate B cells
• the specific b cell will form antibodies by producing plasma cells.

cell mediates immunity

• targets endgroenous antigens (cancer cells or virus infected cells.
• all nucleated cells present MCH 1s if this is abnormal then this time a different type of t cells (cytotoxic t cells) will respond by killing the cell. can also be done by NK cells.

Question 22

what are some defects that can happen in the innate immune system?

Chediak-hiagashi syndrome
deficiencies in complement proteins
chronic granulomatous disease
leukocyte adhesion disease

Answer 22

Chediak-hiagashi syndrome- decreased number of neutrophils do recurrent infections. As giant granules in cytosol of neutrophil and defects in lysosome fusion. remember lysosomes found in cells and contain digestive enzymes.

deficiencies in complement proteins-
complement proteins aid pathogens destruction by piercing membrane (cellysis) or by making them more attractive to phagocyte cells (osponisation)

chronic granulomatous disease-

• mutation in NADPH component- defects in oxidative burst.
• phagocytosed microbes can’t be killed –> recurrent infections

leukocyte adhesion disease-
impairment of molecules that transport phagocytes out of the blood to the site of infection at the tissue.

Question 23

List the organisms that commonly cause:

community acquired pneumonia, croup, epiglottis, tonsillitis, pharyngitis (sore throat)

Answer 23

CAP- The most common cause of bacterial pneumonia in the is Streptococcus pneumoniae.
Legionella and Staph aureus - significant in very severe CAP

Croup- virsuses e.g Parainfluenza virus.

epigolttitis- • Usually caused by Haemophiluis influenzae (Capsulate type b) = ‘Hib’
• Ages it effects 6-12 years

pharyngitis (sore throat)- bacteria Streptococcus pyogenes)

common cold- rhinovirus

tonsilitis- Usually caused by group A streptococcus bacteria.

Question 24

Explain how COPD may be exacerbated (made worse) by respiratory infections and the treatment for it.

Answer 24

• The current evidence indicates that bacterial infection causes approximately 40–50% of acute exacerbations of COPD.
• Viral Infection – RSV, Flu, Paraflu
• Non-infective causes – Cold, Allergens, etc

COPD patients have:
	Chronic sputum production
	Chronic colonisation with 
bacteria:
    Pneumococcus
   Haemophilus influenzae
   Moraxella catarrhalis
	But: these may also be the causes of exacerbations

COPD Exacerbation – Treatment

•	Maintain oxygenation
•	Treat (possible) underlying cause
•	Amoxicillin 500mg tds/doxycycline
•	Treat airways obstruction
o	bronchodilators
o	corticosteroids
•	Hydration/nutrition

Question 25

what is community acquired pneumonia, croup, epiglottis, tonsillitis, pharyngitis (sore throat), cold and flu
how are they investigates and treated.

Answer 25

CAP- . In community-acquired pneumonia (CAP), you get infected in a community setting. It doesn’t happen in a hospital, nursing home, or other healthcare centre.
for test labs you can send:
– Sputum (not if taking antibiotics + saliva.mucoid useless has to be sputum)
– Blood Cultures
– Serum
– Urine (Antigen Kit) (not affected by antibitoics.
– Throat swab (viral testing)

Croup- Inflammation & oedema of larynx & trachea (infection of upper airway). 3 months- 3 years. • Subglottic region – least distensible part of airway- prone to obstruction
-antibiotics no role

epiglottitis- epiglotis becomes thick thumbprint sign.
dont poke around and intubate ASAP.

cold- no treatment but can give symptom relief

influenza- can cause pnemonia which has 3 types A,B,C. A most common and most serious.

Question 26

one of the main cells in the immune system are Granulocytes what do they do?

Answer 26

(wbc’s that has small granules- granules contain proteins)

Question 27

what do immune cells derive from?

Answer 27

They from specific types of stem cells, called multipotent hematopoietic stem cells, in the bone marrow. And then they either come from myeloid lineage or lymphoid lineage.

Question 28

where are B and T lymphocytes made and where do they mature

Answer 28

they both originate in the bone marrow B lymphocytes also mature here but T lymphocytes in the thymus. the rest of the immune cells are made ready to work.

Question 29

how are t and b lymphocytes matured in central tolerance mechanisms

Answer 29

T
this is for immature t cells in the thymus

weak recognition of class 2 MHC + peptide - positive selection CD4+

weak recognition of class 1 MHC + peptide- positive selection CD8+

No recognition of MHC + peptide - death by neglect, failure of positive selection

Strong recognition of MHC + peptide - negative selection (to prevent auto-immune responses)

B

Likewise, in B cells central mechanisms work on immature B lymphocytes and peripheral mechanisms work on mature B lymphocytes.

In B cells central tolerance happens in the bone marrow where there can be deletion by apoptosis due to negative selection, change specific (Ag receptor editing) and anergy. to precent auto-immune responses.

Receptor editing: change the specificity of their Ag receptors so that they no longer recognise strongly self Ags

Question 30

Some self-reactive t and b cells escape central tolerance. So, you have peripheral tolerance which eliminate cells recognising self-antigens.
explain this mechanism for b and t cells and highlight the differences and similarities

Answer 30

Where does this happen for t cells:
•	Peripheral lymphoid organs 
•	Lymph nodes 
•	Spleen 
•	Done on mature T lymphocytes this time 

Where the central tolerance would eliminate ineffective t cells due to negative selection, in peripheral tolerance there can be 1. Apoptosis (deletion) 2. Suppression 3. Anergy

Lymphocytes are said to be anergic when they fail to respond to their specific antigen. Anergy is one of three processes that induce tolerance, modifying the immune system to prevent self-destruction. Basically functional inactivation.

B cells
• Peripheral lymphoid organs
• Lymph nodes
• Spleen

Done by => deletion (die by apoptosis), anergy, blockade of activation by inhibitory receptors, suppression by regulatory T (Treg) cells

Question 31

what is anergy

Answer 31

Lymphocytes are said to be anergic when they fail to respond to their specific antigen. Anergy is one of three processes that induce tolerance, modifying the immune system to prevent self-destruction. Basically functional inactivation.

Question 32

Define myeloma and its typical symptoms and clinical presentation

Answer 32

Multiple myeloma, also known as myeloma, is a type of bone marrow cancer.
It’s called multiple myeloma as the cancer often affects several areas of the body, such as the spine, skull, pelvis and ribs.• Multiple myeloma (MM) is a B-cell malignancy derived from antibody-producing plasma cells in the bone marrow
• Myeloma cells crowd out and interfere with the development and function of normal cells in the bone marrow• The abnormal accumulation of myeloma cells in the bone marrow and production of M-protein have direct and indirect effects on the blood, skeleton, and kidneys. Rise of M protein causes symptoms (paraprotein)

Question 33

Describe the common laboratory abnormalities detected in myeloma and clinical significance of these abnormalities

Answer 33

Multiple myeloma cells produce a single monoclonal antibody
Most common IgG and then IgA
- A paraprotein is an abnormal protein that is produced by plasma cells in the bone marrow.
- A paraprotein (m protein) is an abnormal protein secreted by a clone of plasma cells or lymphocytes. It is usually an intact, complete IgG, IgM or IgA immunoglobulin.

Other test that will performed is free light chains.
In a patient with myeloma they would have an excess of light chains and so the ratio of the lambda and the kappa won’t be 1and this can be investigated. Measure concentration of K and L light chains that are not attached to heavy chains.

Question 34

Understand the tests required to make a diagnosis of myeloma

Answer 34

if you test for paraproteins and the ratio of the two light chains should be easier to diagnose/ indicate towards myeloma.

you would need one from both catergories:
1 clonal Bone marrow plasma cells of less than 10% or Biopsy-proven bony of extra-medullary plasmacytoma (tumour consisting of abnormal plasma cells that grows within the soft tissue or bony skeleton).

2
1 crab feature or 1 slim feautre.

Calcium (raised levels as overactive oseteoclasts)
Renal (disease or impairment)
Anaemia (due to suppression of normal cells in the BM due to the plasma cells crowding out and affecting the normal cells)
Bone (lytic bone disease- causes holes in bones)

Sixty percent plasma cells
Light chain ratio >100
Mri lesions

Question 35

what are blood test indicators of myeloma?

Answer 35

1. Beta-2 microglobulin (B2MG)

• B2MG is part of the class I HLA molecule that is present on all nucleated cells.
• As cells “turnover” or are destroyed B2MG is released into the blood but is reabsorbed by kidney tubules
• Indication of tumour burden (increases)
• Indication of renal impairment (increases)
• Not specific marker as it can also be increased during viral infection e.g. HIV
•
2. Lactate dehydrogenase (LDH)

Enzyme involved in carbohydrate metabolism (pyruvate to lactate)
But also Enzyme released into blood due to tissue damage
a. Cancer e.g. lymphoma, myeloma
Not specifc to cancer tough but may be useful indicator when it is combined with outher tests

3. Albumin

• Plasma protein made by the liver
• Major component of blood
• Important for maintaining blood pressure/fluid balance, transporting molecules such as vitamins, hormones, antibiotics around the body
• Reasons for low levels
– Protein loss through damaged kidneys or gut
– Reduced production in response to IL-6
– Malnourishment

Question 36

Understand the possible causes of renal failure in myeloma

Answer 36

Renal stones form as a result of hypercalcaemia (because too much break down of bone) leading to
hypercalcuria and precipitation of excess calcium in the urine
leading to the development of calcium phosphate stones

Obstruction of urine flow leading to stagnant urine with increased risk of infection
Backpressure on Kidney from obstructed urine (hydronephrosis) causing pressure atrophy of the renal parenchema

Failing kidney causing hypertension via the renin-angiotensin system

cast neuropathy- Renal tubules filled with precipitated light chain
Build up of this protein damages the renal tubules
Inflammatory response (interstitial nephritis)
Progressive damage can lead to scarring and renal failure

Question 37

Understand the pathological link between myeloma and amyloidosis

Answer 37

Amyloidosis is the name for a group of rare, serious conditions caused by a build-up of an abnormal protein called amyloid in organs and tissues throughout the body. The build-up of amyloid proteins (deposits) can make it difficult for the organs and tissues to work properly.

The amyloidosis seen in myeloma is AL amyloid (Light chain associated)
Approximately 15-20% patients
The cause is not clear.

detection of amyloid-
To pick up the presence of amyloid a Congo red stain is used. Amyloid appears salmon pink with this stain but appears apple green when viewed by polarised light

Question 38

what is meningitis and its signs and symptoms

Answer 38

Meningitis is an infection of the protective membranes that surround the brain and spinal cord (meninges).

• Non-polio enteroviruses
• Streptococcus pneumoniae (pneumococcus).

a high temperature.
cold hands and feet.
vomiting.
confusion.
breathing quickly.
muscle and joint pain.
pale, mottled or blotchy skin.
spots or a rash