Intro to Clinical Sciences Flashcards
Pathology:
Acute inflammation vs. Chronic inflammation
Cells involved?
Onset?
Duration?
Resolves?
Acute: Neutrophil inflammation
- Sudden onset
- Short duration
- Usually resolves
Chronic: Leukocyte inflammation
- Slow onset/follows acute
- Long duration
- May never resolve
Pathology:
Inflammatory cells
Mobile inflammatory cells? (3)
Other cells involved in inflammation? (2)
Neutrophils - pus cells (suppuration)
- short lived
- first on scene
- phagocytic, lysosomal granules, release cytokines/chemokines to attract inflammatory cells
Macrophages
- long lived
- phagocytic, antigen presenting cells
Lymphocytes
- long lived
- release cytokines/chemokines to attract inflammatory cells
- IMMUNOLOGICAL MEMORY
Endothelial cells
- become sticky (allow adhesion) in areas of inflammation
- become porous (allow cell migration)
- grow into areas of damage to form new vessels
- capillaries open (normally shut) in inflammation = redness
- oedema = oncotic pressure in tissues due to migration of plasma proteins
Fibroblasts
- Long lived
- Form collagen (scarring) in areas of chronic inflammation
Pathology:
Example of Acute and Chronic inflammation
Acute = Acute appendicitis
- Generalised pain around epigastric region then progresses to…
- Right lower quadrant/McBurney’s point sharp pain = inflammation reaches abdominal wall
Chronic = Tuberculosis
- Granulomas - mycobacteria
- No initial inflammation
- Fibrosis occurs
Pathology:
Treatment for Inflammation
NSAIDs: Ibuprofen, Aspirin (COX inhibitors)
Corticosteroids: Immune modulators
MOABs - targeted immune therapies
Pathology:
Resolution vs. Repair
Resolution:
- Initiating factor removed
- Tissue undamaged
- Regeneration
Repair:
- Initiating factor still present
- Tissue damage
- No regeneration
- Replacement by collagen (fibroblasts)
e. g. - Heart after MI
- Brain after cerebral infarction
- Spinal cord after trauma
Pathology:
Cells that regenerate?
Cells that cannot regenerate?
Cells that regenerate:
- Hepatocytes
- Pneumocytes
- All blood cells
- Gut epithelium
- Skin epithelium
- Osteocytes
Cells that cannot regenerate?
- Myocardial cells
- Neurones (CNS)
Pathology:
Define:
Thrombus
Thrombosis
Embolus
Embolism
Thrombus = blood clot within a vessel
Thrombosis:
Formation of a solid mass from blood constituents in an intact vessel in a living person
Causes laminar flow to be turbulent if larger enough can occlude
(Verkov’s Triangle)
Embolus = anything that causes embolism
Embolism:
Process of a solid mass (e.g. thrombus/air/fat) in the blood being carried in the circulation to a place it becomes stuck and occludes the vessel
e.g. a deep venous thrombosis of the leg veins which breaks off and embolises through the large veins and right side of the heart to the lungs
Pathology:
Define:
Ischemia
Infarction
Reperfusion injury
Ischemia = reduction in blood flow
Infarction = death of cells due to reduction in blood flow
Reperfusion injury = injury by superoxide radicals due to cellular response to elevated O2
Pathology:
Myocardial infarction is an example of…?
Which organs have dual blood/collateral supply?
Areas more susceptible to infarction?
End artery ischemia
Liver, Lungs, Brain - so infarctions are less likely to be fatal due to redundancy
Watershed ares - area boundary of adjacent arterial territories
Pathology:
Define.. Metaplasia Hyperplasia Dysplasia Neoplasia Atrophy Hypertrophy
Example for each?
Metaplasia – Transition from one cell type to another
e.g. metaplasia in bronchi of a smoker
Hyperplasia – increase in the number of cells within a tissue
e.g. Prostate gland – benign prostate hyperplasia
Dysplasia – Abnormal cell population
Neoplasia – Malignant new cells
Atrophy - Decrease in size of a tissue due to loss of number of cells
Hypertrophy - Increase in the size of a tissue caused by increase in size of constituent cells
e.g. Muscle atrophy/hypertrophy
Gastritis Common cause? Cell population? Cell type shift? Cancer risk?
Inflammation of the stomach
Helicobacter infection (Urea breath test, stain cells to diagnose)
Chronic or acute infection
Giant cells = lots of macrophages
Chronic gastritis increases risk of lymphoma
Atherosclerosis
Define
Where?
What’s in plaque?
Endothelial damage theory?
Build up of sclerotic plaque within arteries
Never within low pressure Common in high pressure
Early stage (reversible) - fatty streaks
Plaque = fibrous tissue, lipids, lymphocytes
Endothelial damage theory
- Free radicals, nicotine, carbon monoxide all damage (smoking) (vaping = fewer ROS but same nicotine)
- Hypertension = shearing forces on endothelial cells
- Poorly controlled diabetes = superoxide anions damage
- Hyperlipidaemia = direct damage to endothelial cells
- Pathogenesis
Recurrant endothelial cell injury
Pathology:
Define Apoptosis
Apoptotic detector protein?
Define Necrosis
Types of necrosis?
Apoptosis – programmed cell (singular) death due to apoptotic switch
e.g. DNA damage
P53 - gatekeeper of genome
Necrosis - traumatic cell death (multiple cells)
e.g. Frostbite, avascular necrosis
Types
Coagulative necrosis – thick and gooey
Liquefactive necrosis – (cerebral infarction)
Caseous necrosis – (Tuberculosis)
Pathology:
Define and give an example for:
genetic disease
congenital disease
acquired disease
Genetic disease - occurs primarily from a genetic abnormality
e.g. Sickle cell anaemia is caused by a point mutation in the β-globin chain of haemoglobin
Congenital disease - disease present at birth; can be genetic disease but also acquired
e.g. Rhesus haemolytic disease of the newborn
Acquired disease– disease occurs after birth; genetic and nongenetic environmental factors
e.g.
Pathology:
Give examples of pathology of ageing - Diagram!
Progeria = increased aging disease
- Cross-linking or mutations of DNA
- Telomere shortening: Hayflick limit
- Time-dependent activation of ageing/death genes
- Free radical accumulation
- Cross linking of proteins
- Loss of DNA repair mechanism
Pathology:
Common sites of carcinoma metastasis
Define adjuvant therapy
- Lymph nodes (drainage route)
- Bone, brain, liver (through the blood)
Adjuvant therapy = extra treatment given following surgical excision
e.g. radiotherapy to breast after lumpectomy
minimise the risk of micro metastases
Patholgy:
Define:
- Carcinogenesis
- Oncogenesis
- Benign/Malignant tumour
Carcinogenesis - The transformation of normal cells to neoplastic cells (cancer) through permanent genetic alterations or mutations - MULTISTEP
Oncogenesis – Formation of benign and malignant tumours (tumour = cancer in solid tissue)
Benign tumour – a growth that is not cancer and does not invade or destroy nearby tissue
Malignant tumour – a growth which is cancer and can invade and metastasise
Pathology:
Carcinogenesis is…?
Period exposure/cancer?
Classes of carcinogenesis
Multistep process Typically a latent interval between exposure and cancer Classes: - Chemical - Radiation (non and ionising) - Biologic (hormones, parasites, mycotoxins - Viral - Host
Pathology:
Define;
Carcinoma
Sarcoma
Neoplasm
Carcinoma – cancer of the epithelium
Sarcoma – malignancy of connective tissue
Neoplasm – lesion resulting from the autonomous or relatively autonomous abnormal growth of cells which persist after the initiating stimulus has been removed – new growth
Pathology:
Structure of a neoplasm?
Maximum size before it must recruit vasculature to grow?
- Neoplastic cells
o derived from nucleated cells – need DNA
o Synthetic activity is related to the parent cell (Thyroid cell still produces thyroxine)
o Growth pattern related to parent cell
o Monoclonal
Within Stroma
o Connective tissue framework (fibrin, collagen)
o Vasculature
o Neoplasm drives the formation of its stroma to nurture itself
2mm
Pathology:
Neoplasm behavioural classification
Histogenesis classification Papilloma? Adenoma? Carcinoma? Adenocarcinoma?
1) Benign - localised/non-invasive, slow growth, close resemblence to normal tissue
2) Borderline - defy binary like ovarian lesions
3) Malignant - invasive, metastasise, rapid growth, irregular border
The cell specific cell origin of a tumour
Neoplasm = …oma
Prefix depend on cell type
Papilloma
Benign neoplasm of squamous epithelium
Adenoma
Benign tumour of glandular or secretory epithelium
Carcinoma = Malignant tumour of epithelial cells
Prefix it with name of epithelial cell e.g. transitional cell carcinoma
Adenocarcinoma = carcinoma of glandular epithelium
Pathology:
In-situ neoplasia
What is invasion dependent on?
Define metastasis
In-situ neoplasia = epithelial neoplasms - no invasive carcinoma = no spread
Invasion = metastatic capaility
Invasion dependent on:
- decreased cellular adhesion
- increased cellular motility
- production of lytic enzymes degrade surrounding tissue
Metastasis is the process by which a malignant tumour spreads from its primary site to produce secondary tumours at distant sites
Pathology:
Routes of metastasis, via:
Blood vessels?
Lymphatics?
Due to surgery?
Blood vessels = Haematogenous
Lymphatics = Trans-coelomic
Surgery implantation = iatrogenic
Pathology:
Metastatic cascade (Diagram test) Haematogenous
Haematogenous metastasis:
1) Intravasation
2) Evasion of host immunity
3) Extravasion
4) Growth at metastatic site
5) Angiogenesis
Pathology:
Routes of metastasis
- Vein invasion
- From colon
Appearance of bone mets on X-ray?
Vein:
Vena cava - right side of the heart - Lung mets
Can reinvade (PV -> LA/LV -> Aorta) and spread all around the body
Colon:
Portal vein to liver = hepatic mets
“moth eaten bone”
Immunology:
Describe:
Innate immunity
Adaptive immunity
II – Instictive, non-specific, present from birth, barrier to antigen, Slow response, No memory
AI – Specific, acquired immunity, lymphocyte/antibody dependent, quick response
Immunology:
Describe separated blood:
Plasma
Buffy coat
Red layer
Plasma = straw coloured (90% water, electrolytes, proteins, lipids and sugars)
Buffy coat is Leukocytes (WBCs)
Haemtocrit: Erythrocytes (RBC) volume
Platelets
Immunology:
3 Polymorphonuclear leukocytes?
3 Mononuclear leukocytes?
Poly: Neutrophils, Eosinophils, Basophils
Mono: Monocytes (mature to macrophage in tissue), B-cells (mature to plasma cell), T-cells (CD4+, CD8+, Th17, T-regs
Immunology:
Humoral factors
Actions of complement (3) ?
Which complement carries out each function?
Direct lysis (MAC – membrane attack complex)
Chemotaxis - Attract leukocytes (C3a + C5a)
Opsonisation (C3b)
Immunology:
Describe:
Innate immunity
Adaptive immunity
II – Instictive, non-specific, present from birth, barrier to antigen, Slow response, No memory
AI – Specific, acquired immunity, lymphocyte/antibody dependent, quick response
Both = cells + humoral (Soluble) factors
Immunology:
Describe separated blood:
Plasma
Buffy coat
Red layer
Plasma = straw coloured (90% water, electrolytes, proteins, lipids and sugars)
Buffy coat is Leukocytes (WBCs)
Haematocrit: Erythrocytes (RBC) volume
Platelets
Immunology:
3 Polymorphonuclear leukocytes?
3 Mononuclear leukocytes?
Poly: Neutrophils, Eosinophils, Basophils
Mono: Monocytes (mature to macrophage in tissue), B-cells (mature to plasma cell), T-cells (CD4+, CD8+, Th17, T-regs
Immunology:
Humoral factors
Actions of complement (3) ?
Direct lysis (MAC – membrane attack complex)
Chemotaxis - Attract leukocytes (C3a + C5a)
Opsonisation (C3b)
Immunology:
Immunoglobulin characteristics: IgA IgD IgE IgG IgM
IgA – Dimer, Secretory IgA dimer
IgD – Surface of mature B cells
IgE – Hypersensitivity, mast cell surface crosslinking = degranulation + histamine
IgG – Most predominant 75%
IgM – Pentamer, found in blood; also find monomeric IgM on B-cells
Immunology:
Cytokine function
- Interferon
- Interleukins
- Colony stimulating factors
- Tumour necrosis factor
- Interferon
Viral infections - Interleukins
IL-1 = pro-inflammatory
IL-10 = anti-inflammatory - Colony stimulating factors
Division/differentiation e.g. EPO - Tumour necrosis factor
Inflammation and cytotoxicity, TNF-alpha causes increased adhesion (macrophage release)
Immunology:
Examples of chemokines - Chemotaxic
Receptors for chemokines?
CXCL "Chemokine ligand-1 CXC motif" CCL "Chemokine ligand 1" CX3CL XCL Chemokine ligands have specific receptors
Immunology:
Physical and chemical barriers (diagram)
Skin: commensals, fatty acids, barrier
Bronchi: mucus, cilia (sterile*)
Gut: Stomach acid low pH, commensals in intestines
Nose: turbulent air flow (turbinates) traps particles
Tears: lysosymes
Vagina: Low pH
Urinary tract = flushing
Immunology:
Define inflammation
What happens? 2 key things?
“a series of reactions that bring cells and molecules of the immune system to sites of infection or damage”
- Increased blood supply
- Increased vascular permeability = increased ‘extravasation’ – immune cell transendothelial migration
Immunology:
Steps of phagocytosis (5)
- Binding
- Engulfment
- Phagosome formation
- Phagolysosome
- MHC class II dependent antigen presentation
Immunology:
Mechanisms of microbial killing? (in terms of oxygen)
- O2 dependent: ROS; superoxides, Nitric oxide
- O2 independent: Enzymes, proteins, pH denaturing
Immunology:
What is foetal thymus T-cell selection?
Any T-cells that recognise self-antigens are removed
Immunology:
Primary lymphoid?
Secondary lymphoid?
diagram?
Primary = Thymus or Bone marrow
Secondary = Spleen, Lymph nodes, MALT?
Immunology:
Which antigen corresponds to which MHC class, which T-cell and TCR?
Extrinsic or intrinsic antigen?
- IMPORTANT*
- DIAGRAMS*
MHC class I = Tc (CD8+) = Intrinsic antigens CD “hate”/8 = cytotoxic
MHC class II = T helper (CD4+) = Extrinsic antigens
CD “four the people” = helper
Help B-cell maturation Ab production to that antigen
Immunology:
What needs to happen for TCR recognition and activation?
Activation causes?
Co-stimulation:
1. MHC + TCR
2. CD80/86 + CD28
Activation = T-cell division, effector functions, memory
Immunology:
Tc (CD8+) activated functions (3)
- Cell lysis: release of perforin + granulysin
- IFN gamma- macrophage activation
- Chemokines – inflammatory cell recruitment
Immunology:
How many epitopes can a B-cell be specific to?
What happens to B-cells that recognise self-antigens (usually)?
B-cells are specific to one epitope (antigen)
Undergo apoptosis in the bone marrow = B-cell selection
Immunology:
T-helper cell activation (diagram) steps
APC presents extrinsic antigen (MHC class II) to TCR (CD4+) on niave T-cell = Stimulation of IL-12 release from APC = activation to CD4 Th1 cell
Immunology:
T-cytotoxic cell activation (diagram) steps
CD8+ TCR combines with intrinsic antigen presented on MHC Class I on ANY cell = activation of naive CD8 to cT-cell
Immunology:
Which immunoglobulins are expressed on B-cells?
Monomeric IgD
Monomeric IgM
(mIgD or mIgM)
Immunology:
What are the functions of Immunoglobulins (antibodies) (4)
- Neutralisation of toxins
- Opsonisation for phagocytosis
- Link adaptive and innate immunity
- Activate complement via complement cascade
Immunology:
Th1 vs Th2 cells
Th1 = Macrophage activation (APC = IL-12 maturation)
Th2 = B-cell activation (APC = IL-4 maturation)
Immunology:
T-B cell cooperation
What happens?
What are the two resultant effector cells?
Th2 cells (primed to antigen) bind B-cells and secrete cytokines IL-4,5,10,13 = CLONAL EXPANSION Plasma cells = antibodies \+ Memory B-cells
Immunology:
What are the functions of Immunoglobulins (antibodies)
- Neutralisation of toxins
- Opsonisation for phagocytosis
- Link adaptive and innate immunity
- Activate complement via complement cascade
Immunology:
B-cell activation steps?
Activation through to long term
Specific antigen binds = activation
Activated B-cell travels to lymph nodes and proliferate and differentiate into plasma cells CLONAL EXPANSION
Plasma cells secrete antibody as IgM which then turn into IgG CLASS SWITCHING
Memory B-cells generated as well as plasma cells – these stick around for years
Re-stimulation of Memory B-cells leads to rapid secondary response
Immunology:
Example of a vaccination?
What is a toxoid?
Tetanus vaccine – Clostridium tetani
Toxoid is an inactivated form of exotoxin
Immunology:
Principal of vaccination
Memory B-cells formed against inactivated version of virus/exotoxin etc to prime the immune system elicit primary antibody response
Subsequent exposure to that specific virus/toxin will be met with a secondary antibody response = aquired immunity
Immunology:
Innate immunity relies on what to recognise fungi/bacteria/viruses?
Pattern recognition receptors – recognise conserved elements of pathogens so that we are able to deal with infections
Immunology:
What do PRRs respond to? (3)
2 classes of PRRs?
Gram +ve/-ve (Bacteria)
dsRNA (Virus)
CpG motifs (DNA)
Secreted/circulating PRRs
Cell associated PRRs
Immunology:
Example of circulating/secreted PRRs?
What do they do?
Defensins, lectins
Antimicrobial peptides which have direct killing effects and immune modulation
Immunology:
Cell associated PRRs?
Toll-like receptor family (TLRs)
Immunology:
Which TLRs are associate with viral patterns?
Where are they found?
TLR3,7,8,9
Often found within endosomes within cells – As viruses are intracellular pathogens
Immunology:
Which TLRs are associated with bacterial patterns?
TLR1,2,4,5,6
TLR4 (also senses viral proteins)
Immunology:
What do Nod-like receptors detect?
What do Rig like helicases detect?
NLRs - Intracellular microbial pathogens e.g. peptidoglycan
RLHs - Intracellular viral dsRNA and DNA
Immunology:
Roles of PRRs? (3)
- Balance of commensal organisms
- Regulation of neutrophils
- Maturation of immune system
Immunology:
Damage recognition –
3 Extracellular damage molecules?
3 Intracellular damage molecules?
Extracellular: - Fibrinogen - Hyaluronic acid - Tenascin C Intracellular: - Heat shock proteins - Uric acid - mRNA
Immunology:
What is passive immunity?
What can it protect against?
Long term memory?
Antisera?
Transfer of preformed antibodies e.g. maternal antibodies across the placenta or via breast milk
Tetanus Diptheria Mumps Rubella Poliovirus
No long term memory
Can’t react to antisera
Immunology:
Why do vaccines not work in children under 2yoa?
Do not have mature enough B-cells which illicit immunological memory
Immunology:
Artificial vs Natural passive immunity????
Natural = breast milk Artificial = injection of antisera (serum of preformed antibodies)
Immunology:
What is Inoculation?
Introduction of viable organism into the subject
Immunology:
Primary goal of immunisation?
Generate a primary antibody response (formation of memory B-cells) from an initial exposure without the risks associated with the actual infection
Immunology:
Characteristics of Initial/primary response
Ig? predominant?
Affinity?
Innate or adaptive?
IgM
Low affinity
Innate immune system
Immunology:
Characteristics of secondary response? Speed? Ig? predominant? Affinity? Innate or adaptive?
High affinity IgG
Rapid and large response
T-cell help
Doesn’t rely on innate immune system - adaptive
Immunology:
Vaccine adjuvant? E.g.?
Something that potentiates the immune response
e.g. TLR4 agonist
Immunology:
BCG vaccine for Tuberculosis is an example of what type of antigen?
Diptheria/tetanus?
Types of antigen for vaccine? (5)
BCG = Whole organism – live attenuated or inactive pathogen
Diptheria/tetanus = Subunit (toxoid – inactivated exotoxin)
Types: Whole organism Subunit Peptide DNA vaccine Engineered virus
