Past Exam Topics Flashcards
Describe the structure and function of skin in the innate IS.
- Comprised of epithelial cells and acts as an impermeable physical (external) barrier against pathogens
- Largest human organ
- epithelial cells renewed every 10-15 days
What are the important features of the inflammatory response?
- Vasodilation (causes rubor and heat)
- Inc. capillary permeability = influx of fluid, inc. [protein] (swelling, pain)
- Inc. number of phagocytic cells = neutrophils and macrophages (pain, sometimes loss of function)
- Activates C’
- *Draw a pic with before/after**
What is haematopoesis and how does it work?
- The process of blood cell and platelet production
Draw as a flowchart
haematopoetic stem cell –> common erythroid megakaryocyte progenitor –> megakaryocyte (goes to platelets) & erythroblast (then erythrocytes)
What does the spleen do? Why do we care?
- Filters T and B cells and detects faulty RBCs to take out of vascular circulation (blood)
How is C3b generated by each of the three C’ pathways? What is the consequence of generating C3b during the inflammatory response?
Classical pathway: C1(s) cleaves C4 into C4a and b, C2 is also cleaved into a and b subunits. C4b binds to C2a = C4b2a (C3 convertase). C3 convertase cleaves C3 into C3a and C3b.
Lectin pathway: Mannose Binding Lectin cleaves C4 into C4a and b, C4b binds C2a = C3 convertase then cleaves C3 into C3a and C3b.
Alternative pathway: C3 spontaneously degrades into C3a and C3b, C3b binds Factor B and Factor D cleaves Factor B into Ba and Bb sunbits, Bb binds C3b = C3bBb. This is stabilised by PROPERDIN. This forms C3 convertase which cleaves C3 into C3a and C3b.
In each case, C3b acts as an opsonin to tag certain cells for phagocytosis (by neutrophils/macrophages) as well as combining with other C pathway compounds to form C5 convertase and activate the lytic pathway.
What is an idiotype?
The bit that the epitope actually binds to - these are what makes each antibody different from each other (changes in the complementary defining region)
**note: changes in the Fc portion are called allotypes and there is no allotypic variation in an individual but will change between individuals
What part of an antibody contributes to the idiotype?
Variable portion of the Fab fragment (the V bit not the stem)
What (2) types of epitopes can Abs bind to and how do they differ (other than structurally)?
- Linear and conformational epitopes
- Difference: If epitope is denatured, Ab still recognises linear but not the conformational
Describe how T-dependent B cell activation works.
- Ag presented to B cell
- Relatively few Abs in contact with Ag so v weak signalling occurs
- Ag is internalised, processed and presented on MHCII
- Th cell recognises and releases cytokines to activate B cell to differentiate and proliferate into plasma AND memory cells
- Allows isotype switching & affinity maturation to occur
- Occurs in germinal centres of secondary lymphoid tissues
What are monoclonal Abs? How can they be used to kill cancer cells?!
Monoclonal Abs = have 1 idiotype and 1 isotype.
Hybridoma synthesises an Ab which recognises 1 eptiope –> target and destroy cancer cells using diptheria toxin or immunotoxin which are endocytosed, broken up in endosome and targets (inactivates) EF-2 such that protein synthesis is reduced/ceased.
Describe the endogenous pathway of Ag presentation.
- Utilises MHC I
- peptides are presented in the cytosol (from intracellular pathogens eg. virus, mycobacteria)
- cytosolic proteins broken down in proteosome and transported to ER by TAP
- MHC I alpha and beta2 chains assembled in ER
- peptides loaded onto MHC I complexes
- peptide:MHC I structure transported through golgi to exocytic vesicles which fuse with the plasma membrane to stably express the peptide on the cell surface
- recognised by CD8+ T cells (eventually)
Describe the exogenous pathway of Ag presentation.
- Utilises MHC II for recognition by CD4+ T cells (professional APCs only)
- Ag can be extracellular or phagocytosed
- alpha and beta chains assemble in ER
- peptide minding groove occupied by CLIP so nothing from the cytosol sneaks in there
- Transported through golgi to exocytic vesicles which fuse to lysosomal vesicles
- CLIP bind to DM (not 100% sure what that is) which exposes peptide binding groove to peptides in lysosome
- exocytic vesicles then fuse with plasma membrane to present peptide on cell surface
A resting B cell, once activated into a plasma cell, can produce antibodies with any isotype. What determines the isotype formed?
- Cytokines! (upon activation to a plasma cell)
- IgG = IFNγ
- IgA = TGFβ
- IgE = IL-4
- IgM = ??
Describe the characteristics of Th1 cells and their major function in the immune response.
- differentiation to Th1 stimulated by IL-12
- secretes IFNγ –> helps with Ag presentation and cellular immunity
- primarily for virus and parasitic infections
Describe the characteristics of Th2 cells and their major function in the immune response.
- differentiation stimulated by IL-4
- secretes IL-4, 5, 13 –> helps with allergic reactions and humoral immunity
Describe the characteristics of Th17 cells and their major function in the immune response.
- differentiation stimulated by IL-6, TGFβ
- differentiation inhibited by IL-4 and IFNγ
- secretes IL-17, 21, 22
- useful for tissue inflammation
Discuss the central role of IFNγ and IL-1 in the immune response.
IFNγ: important for macrophage activation, secreted by Th1 cells
IL-1: pro-inflammatory cytokine
What do Tfh cells do?
- promote high affinity Ab production in B lymphotcytes
- secrete IL-21
- located in germinal centres of secondary lymphoid organs
- assist in affinity maturation and isotype switching
What are Treg cells and how are they different from other Th cells?
- Tregs inhibit function of other lymphocytes to prevent autoimmune diseases
- After positive selection in the thymus by cortical thymic epithelial cells (CTECs), migrate to medulla where MTECs express self Ags
- T cells with intermediate affinity will become regulatory T cells (high affinity die and and low affinity become other Th cells)
- decrease risk of auto-immunity
Different classes of MHC molecules responds to different T cell types. Who matches with who?
MHC I = CD8+ T cells = cytotoxic T cells
MHC II = CD4+ T cells = helper T cells
Name 4 mechanisms of T cell tolerance.
- Clonal deletion (central and peripheral)
- Clonal ignorance (peripheral)
- Suppression (peripheral - immunoregulation)
- Clonal anergy
Explain how clonal selection works in context of Ag-specific T lymphocytes.
This is 100% a trick question.. they actually want you to talk about +ve and -ve selection in the thymus…
- Immature T cells enter via corticomedullary junction
- Proliferate in cortex
- CTECs start enabling cells to present CD4, CD8 & TCR and then undergo positive selection (if has all 3 and interacts with INTERMEDIATE affinity with either MHC I or MHC II then migrate to medulla - this is also where either CD4 or CD8 is lost)
- MTECs express self antigens so negative selection commences (if no/low affinity then they can enter circulation as naive T cells, intermediate affinity encourages Treg differentiation, high affinity undergo apoptosis via clonal deletion)
How does the body establish central tolerance?
- Ag independent
- Self reactive B/T cells undergo apoptosis in the bone marrow/thymus through negative selection
- *Remember that selection is based on BCR/TCR response to an Ag
Describe the mechanism that leads to mast cell degranulation in type I hypersensitivity and give examples of common symptoms and management.
- Allergins such as pollen and dust induce a Th2 response
- Ag picked up by Langerhans cell (DC), processed and presented on MHC II
- Migrates to LN and interacts with lymphotcytes to elicit a humoral IR
- Th2 secretes IL-4 which encourages isotype switching to IgE
- IgE binds to mast cells triggering degranulation of molecules such as histamine, causing vasodilation
- Clinical symptoms include low bp, allergic rhinitis (hayfever), anaphylaxis, asthma, bronchospasm
- Management strategies include taking antihistamines, glucocorticoids, avoiding allergins, epinephrine, undergo desensitisation or monoclonal anti-IgE Ab treatment
