SAQs Flashcards
1
Q
Why are post mortem examinations performed? (9)
A
- 1). Confirm or refute a clinical diagnosis:
- Was the diagnosis correct?
- Can you refine the differential diagnoses?
- Was there another concurrent disease?
- 2). Failure of treatment:
- Why did the treatment of a clinical diagnosis fail?
- Clinical audit - e.g. morbidity + mortality rounds (MM rounds).
- 3). Sudden death - to provide a diagnosis when there is no clinical diagnosis.
- 4). Herd, group or population health:
- Rapid diagnosis of disease.
- Additional opportunity to implement treatment, nutrition or management changes to prevent further losses of individuals or production.
- 5). Surveillance:
- Monitor endemic disease.
- Detect exotic/notifiable disease.
- Monitoring effects of husbandry/management changes.
- Public health.
- 6). Forensic - crime involving animals:
- Cause of death, disease/health status, degree of suffering, obtaining trace evidence.
- Insurance.
- Malpractice inquests.
- 7). Zoological collections - routine samples.
- 8). Obtaining samples - for further samples e.g. histopathology, microbiology, bacteriology, virology, mycology, parasitology, trace element analysis and toxicology.
- 9). Research:
- Toxicology pathology.
- Tissues for further study - pathology, clinical, basic science and retrospective studies.
2
Q
Descriptors used to describe lesions. (11)
A
- 1). Organ/tissue
- 2). Position - topography
- 3). Number
- 4). Weight
- 5). Distribution: random, symmetrical, focal, multifocal, multifocal to coalescing, miliary, segmental, diffuse.
- 6). Contour: raised, depressed, flat.
- 7). Size: measure in 3D, uniform size or non-uniform size.
- Size of organs - smaller/larger than normal, compare paired organs, dynamic organs (being remodelled) - rapidly, moderately, slowly.
- 8). Colour
- 9). Shape e.g. circular, spherical.
- 10). Consistency
- 11). Smell
3
Q
Compare and contrast cytology and histopathology (14)
A
4
Q
Differences between innate and adaptive immunity (7)
A
Innate - first line of defence.
- Humoral and cell-mediated.
- Fast, non-specific.
Adaptive - T-cells and B-cells, highly controlled + more specific.
- Humoral - B-cells produced antibodies.
- Cell-mediated - T-helper cells produced cytokines.
- Slower to develop (5-6+ days).
- Based on clonal selection of antigen-specific cells.
- Primarily mediated by memory, not naive lymphocytes.
5
Q
How do cells get where they are required? (4)
A
- 1). Cytokines (TNF / IL-1) produced by macrophages cause dilation of local small blood vessels.
- 2). Leucocytes move to periphery of blood vessel as a result of increased expression of adhesion molecules (selections, ligands for integrins and chemokines) by endothelium
- Chemokines displayed on endothelial surface and bind to receptors on the rolling leucocytes, resulting in activation of leucocyte integrins to a high-affinity binding state.
- Activated integrins bind to their Ig super family ligands on endothelial cells, mediating firm adhesion of leucocytes.
- Leucocytes crawl to junctions between endothelial cells and migrate through venular wall.
- 3). Leucocytes extravasate out the blood at the site of infection (flow out) at site of infection.
- 4). Blood clotting occurs in microvessels.
6
Q
Phagocytosis (5)
A
- Recognition (using opsonins) and attachment of particle by leucocyte.
- 1). Bacterium becomes attached to the membrane evaginations (pseudopodia).
- 2). Bacterium is ingested, forming phagosome.
- Prior to activation, anti-microbial peptides and enzymes are stored in granules as lysosomes.
- 3). Phagosomes fuses with lysosome —> phagolysosome.
- Phagosomes fuse with primary and secondary granules. Rac2 (G protein) induces assembly of a functional NADPH oxidase in the phagolysosomes membrane, leading to generation of O2^- (destroy bacteria using free radicals).
- Acidification as a result of ion influx released granule proteases from granule matrix.
- 4). Bacterium is killed and then digested by lysosomal enzymes.
- 5). Digestion products are released from cell.
7
Q
Antimicrobial mechanisms of phagocytes (6)
A
8
Q
The complement system activation pathways (3)
A
- 1). Classical - antigen-antibody immune complexes - IgM or IgG binds to multivalent antigen.
- Allows binding of C1q, beginning process of complement deposition.
- 2). Lectin - PAMP recognition by lectins.
- Lectins bound to microbial surfaces serve as docking sites for MBL-associated serine proteases (MASPs).
- MASPs cleave C4 and C2 to form the C3 convertase.
- 3). Alternative - spontaneous hydrolysis or pathogenic surfaces. Initiated in three ways:
- Alternative tickover pathway - when C3 accumulates - usually continuously produced.
- Alternative properdin-activated pathway - properdin should stabilise and activate alternative pathway, binds to microbes and makes properdin (pathogen recognition receptor for Neisseria bacteria (colonies mucosal surfaces).
- Alternative protease-activated pathway.
- Alternative complement activation can occur as a consequence of blood clotting - thrombin and plasmin can cleave C3 + C5 which released toxins C2A and C5A.
9
Q
Effect of cytokines (innate immunity) (5)
A
10
Q
Innate lymphocytes - NK cells mechanism (4)
A
11
Q
Inflammatory response (innate immunity) (4)
A
12
Q
Dendritic cell function (summary) (4)
A
13
Q
MHC class II - antigen processing and presentation pathway (5)
A
14
Q
MHC class II - antigen processing and presentation pathway (5)
A
15
Q
Cytokine of IL-1 family - pro-inflammatory response (6)
A
- IL-1α and IL-1β bind to IL-1RI/L-1RAcP - has inhibiting ligand/receptor pair to shut down function.
- IL-18 - e.g. of redundancy, also processed in secreting cells, expressed by macrophages and DCs in early responses, inhibition through binding of cytokine before it binds to signalling receptor.
- IL-33- constitutively expressed in smooth muscle and bronchial epithelial, induces Th2 cytokines that promote T-cell interactions with B cells, mast cells and eosinophils. Receptor is also a heterodimer with IL-1RAcP.
16
Q
Haematopoietin (Class I) family cytokines (4)
A
•Gamma-chain IL-2R = protoype.
Beta-chain bearing subfamily - includes receptors for IL-3, IL-5 and GM-CSF.
- Exhibit redundancy - activate granulocytes (eosinophils/basophils); stimulate blood-cell differentiation; activate monocytes.
- Gp130 receptor subfamily - includes IL-6 and IL-12 receptors, signalling pathways induced are similar to those induced by interferons.
17
Q
Class II (Interferon) cytokine family (3)
A
- 1). Type I interferons -secreted by activated macrophages and dendritic cells.
- Interferons alpha = a family of about 20 related proteins.
- Interferon beta = regarded as a primary modulator + potent antiviral effects limited by more restricted receptor expressions.
- 2). Type II interferon (interferon-gamma) - dimer produced by activated T/NK cells.
- Potent modulator of adaptive immunity.
- 3). Type III interferon family.
18
Q
Interferon (Class II) cytokine family signalling and inhibition pathway (6)
A
20
Q
TNF receptors signalling - Fas receptor (5)
A
21
Q
IL-17 family cytokines (7)
A
22
Q
Chemokines directing leucocyte migration - signalling (8)
A
23
Q
Adaptive immunity - signal transduction in B cells (5)
A
24
Q
Adaptive immunity - T-cell receptors and signalling (5)
A
25
Q
Mechanism of V(D)J recombination (3)
A
- Generating large diversity of antigen-specific receptors.
- Mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell receptors (TCRs) found in B cells and T cells, respectively.
26
Q
Mechanisms that generate antibody diversity in naive B cells (4)
A
- 1). Multiple gene segments.
- 2). Nucleotides inserted between joints.
- 3). Exonuclease trimming at junctions.
- 4). Combinatorial diversity, heavy chain pairs light chains.
27
Q
Early thymocyte development (4)
A
- Thymocytes can either express either alpha-beta TCR or gamma-delta TCR - never both.
- DN thymocytes destined to express conventional alpha-beta TCR undergo beta-selection - beta chain is paired with a pre-T-alpha chain to form a pre-TCR complex (with CD3 proteins).
- If functional pairing —> rearrangement of T cell receptor alpha chain + prevents further beta-chain rearrangement = allelic exclusion —> expanded double-positive (DP) thymocytes (CD4 and CD8), stimulates proliferation.
- Positive selection - selects thymocytes bearing receptors capable of binding self-MHC molecules, resulting in MHC restriction.
- Negative selection - selects against thymocytes bearing high-affinity receptors for self-MHC/peptide complexes, resulting in self-tolerance.
Summary: BM —> thymus (thymocytes) —> DN (double negative, CD4^+ and CD8^+ not expressed) —> beta-selection —> DP = express CD4^+ and CD8^+ —> +ive and -ie selection —> SP (CD4^+ or CD8^+ expressed) —> -ive selection removes autoreactive cells —> non-self committed T-cells released from thymus into bloodstream.
28
Q
Innate immunity - B-cell development (3)
A
29
Q
Innate immunity - compare and contrast B- and T- cell development
A
30
Q
Summary of lymphocyte activation, differentiation, memory and effector responses (5)
A
- 1). Antigen recognition - 2^y lymphoid organs, following presentation of processed peptide antigen by MHC I or MHC II molecules on surface of mature professional APC.
- 2). Activation of antigen on specific cell.
- 3). Clonal expansion - driven by autocrine/paracrine action of IL-2 (major T-cell GF, binds to IL-2 receptor on the surface of activated T-cell).
- 4). Engagement of cytokines drives differentiation of activated T-cells to influence effector functions of cell.
- 5). Effector functions - memory/effector cells - migrate to infected tissues —> activation of macrophages, B-cells and other cells or killing of infected “target cells”; macrophage activation.
- Effector cells die by apoptosis and memory cells remain.
31
Q
T-cell activation and signal hypothesis (3)
A
- Signal 1 - antigen-specific TCR engagement with MHC on APC
- Signal 2 - contact with co-stimulatory ligands on APC surface, needed for optimal T-cell activation and proliferation.
- Clonal energy results if a co-stimulatory signal is absent (peripheral mechanism body protects itself against autoreactive T-cells not removed in the thymus)
- Signal 3 - distinct polarising cytokines directing T-cell differentiation into distinct effector cell types from APC/other cellular sources
- All three combine to deliver necessary activation signals driving gene expression —> activation, proliferation + differentiation
32
Q
T-dependent B cell responses
A
33
Q
B cell responses maturation in germinal centres (2)
A
34
Q
Antibody-mediated effector functions (4)
A
- 1). Virus and toxin neutralisation —> prevents pathogen-host binding.
- 2). Opsonisation —> phagocytosis.
- 3). Complement fixation and formation of membrane attack complex —> phagocytosis/lysis.
- 4). Antibody-dependent cell-mediated cytotoxicity (ADCC) —> NK-induced apoptosis.
37
Q
CD8^+ CTLs recognise and kill infected/tumour cells via TCR activation (5)
A
38
Q
How CD8^+ CTLs kill cells meachanism (2)
A
42
Q
Acute inflammation - cell-derived mediators (7)
A
- 1). Vasoactive amines - first mediators at scene, pre-packaged in cells.
- Histamine - in mast cell granules (+ basophils and platelets), binds to H1 (histamine) receptors on microvascular endothelial cells, causes dilation of arterioles and increases permeability of venules.
- Serotonin (also dilates vessels like histamine) - in platelets, certain neuroendocrine cells + mast cells, stimulated when platelets aggregate, link between clotting and inflammation.
- 2). Arachidonic acids are degraded by enzymes to form metabolites (prostaglandins, leukotrienes and lipoxins) with effects such as:
- Vasodilation / inhibition of platelet aggregation / vasoconstriction / platelat aggregation / vasodilation / inhibit neutrophil adhesion / bronchospasm / increased vascular permeability
- 3). Platelet-activating factor (phospholipid-derived mediator) - from inflammatory cells and cause:
- Platelet aggregation, vasoconstriction, bronchoconstriction; extremely low conc = vasodilation, increased venular permeability.
- Inc leucocyte adhesion to endothelium, chemotaxis, degranulation and oxidative burst.
- Inc synthesis of other mediators by leucocytes and other cells.
- 4). Oxygen-derived free radicals (reactive oxygen species (ROS)) - production dependent on activation of NADPH oxidase, stimulate inflammation as they cause more damage.
- Amplify inflammatory response - inc expression of chemokines, cytokines and endothelial leucocyte adhesion molecules.
- ROS in leucocytes destroy phagocytosed microbes so their release can cause host damage: endothelial cell damage, with resultant inc vascular permeability, injury to other cells, inactivation of antiproteases, leads to unopposed protease activity w/ increased destruction of ECM.
- 5). Nitric oxide - produced by endothelial cells and macrophages, relaxes smooth muscle —> dilation.
- 6). Cytokines and chemokines (substances released from damaged/dying cells):
- Cytokines e.g. TNF and IL1 - local effects inflammatory = inc expression of leucocyte adhesion molecules, inc procoagulant activity, activation of leucocytes, production of further cytokines, and repair = proliferation of fibroblasts, inc collagen synthesis; systemic effects = fever, leucocytosis, inc APPs, dec appetite, lethargy.
- Chemokines - chemoattractant for different leucocytes.
- 7). Neuropeptides - secreted by sensory nerves and leucocytes, include substance P and neurokinin A.
- Substance P - transmission of pain signals (lowers pain threshold, feel pain), regulation of blood pressure (ANS), stimulation of section of endocrine cells, inc vascular permeability.
43
Q
Acute inflammation - cell-derived mediators, arachidonic acid (AA) metabolites + pharmacology (3)
A
- Cell membrane phospholipids - phospholipase (inhibited by steroids, no metabolites made) - Ca^2+ can activate, it digests a bit of the membrane to make arachidonic acid (key ‘ingredient’ of pro-inflammatory material).
- 1). Cyclooxygenase (COX-1 and COX-2 inhibited by NSAIDs e,g, aspirin) - degrades arachidonic acid into prostaglandin G2 (PGG2) which then degrades into a number of others, different prostaglandins have different effects, some may be anti-inflammatory:
- In-built anti-inflammatory system - calms down inflammation.
- Prostacyclin (PGl2) - vasodilation, inhibits platelet aggregation.
- Thromboxane A2 (TXA2) - vasoconstriction, promotes platelet aggregation. (Antagonistic)
- 2). Lipoxygenase - acts on arachidonic acid to make:
- Lipoxins inhibit neutrophil adhesion and chemotaxis.
- Leukotrienes (blocked by montelukast drug) - vasoconstriction, bronchospasm, increased vascular permeability (effects of asthma).
- Shoudn’t give asthmatics NSAIDs/COX inhibitors as it removes one of the substrates which could lead to the increase in production of leukotrienes as they become more favoured, results in bronchospasm.
