Defence against Extracellular Pathogens Flashcards
(28 cards)
What does the Fc region of immunoglobulins do while the Fab region is bound to an antigen
Works with other parts of the immune system
Antibody Isotype interaction with defence components
Complement Activation - IgM, IgG
Phagocyte Binding - IgG, IgA
Mast Cell Binding - IgE
NK Cell Binding - IgG
Complement
Collection of proteins found in the circulation and tissue fluids
The pathway occurs as a cascade with amplification
**described by ability to ‘complement’ the effects of antibodies
What are some roles of complement proteins
Activation of Enymes
Direct Immune Responses
Control Proteins
Describe the splitting in complement pathways
Activation steps involve splitting of complement proteins via enzymes (which may be other complement proteins)
e.g. C –> Ca + Cb
Central Event of Compliment Activation
C3 -> C3a + C3b
C3 Convertase Enzyme
Enzyme that splits C3 into C3a + C3b
There are 2 different C3 convertases
C1q
Complement protein that binds to the Fc region of IgG (or IgM); likened to a bunch of tulips with 6 globular tips that can bind to the Fc regions with 6 stems
Only binds to bound IgG
Can bind to up to 6 antibodies
Part of Classical Pathway
C1r, C1s
Activated and bound to C1q after its binding
Act as enzymes that can split C4 and C2; both into Cxa, Cxb
Mannose binding leptase
Binds to Mannose residues on microbial carbohydrates (not antibodies)
It is associated with 4 other proteins (Mannose Binding Leptin Associated Proteases [MASP] 1, 2)
When MBL is activated, it activates MASP enzymes which can split C4, C2, forming the C3 convertase complex (C4b2a)
Part of MB-Lectin Pathway
What happens to C2a and C4b
This forms a C4b2a complex; it is a C3 convertase enzyme
Describe Alternative C3 Convertase Pathway
Trigerred by direct interaction of previously formed C3b (from ticking pathway) to microbial surfaces
When C3b is formed and binds, it binds another complement protein B fragment of factor B
Another stabilising protein P (properdin)
Leads to C3 Convertase:
C3bBbP
How is there enough C3b for alternative pathway
Tiny amoutns of C3 are being constantly degraded by tissue proteases to generate C3a and C3b
Tickover Pathway
What happens to C3b if unstabilised or stabilised
It is very unstable and very rapidly degrades into inactive fragments unless stablised; happens by binding to microbial surfaces which stablises it and allows it to form C3bBbP (so it only happens with infection)
What happens if you bind either C3 convertase enzyme and bind them to another C3b
They become C5 convertase enzymes which split the protein into C5a and C5b
What does C5b do
Forms part of the membrane attack pathway; interacts with C6, C7, C8 and C9 to bring about membrane lysis and form a tube that makes a pore on the pathogen’s surface, destroying the microbe as many hundreds of pores can be formed on one microbe
Opsonins and examples
Molecules that make microbes more “attractive” to phagocytes which have specialised receptors for such opsonins
Mannan-binding lectin
C-reactive protein
Antibodies
Describe opsonisation with antibodies
Microbes are bound to IgG proteins with their Fc regions sticking out
These IgG proteins activate classical complement pathway and lead to C3b being secreted onto surface of microbe
Phagocytes have Fc receptors; also receptors for C3b on surface of microbes
Opsonin and phagocyte interaction stronger than normal PRR and PAMP interaction
Surface membrane engulfs microbe and creates phagosome (vesicle containing microbe); merges with lysosome to form phagolysosome to release the enzymes and put them onto the microbe surface and bring about digestion/destruction
How does digestion of foreign bodies too large to be engulfed by a cell
Eosinophils perform external digestion (done to stuff like worms)
They have C receptors and complement receptors on their surface
If we have a large parasitic helminth with antibodies on it and C3b; eosinophil can bind to parasite via complement and Fc receptors (Fc Gamma and Fc Epsilon)
When bound, eosinophils release digestive enzymes onto parasitic surface
Describe location of mast cells
Tissue resident cells; not circulating but similar function to basophils
What receptors do mast cells have expressed on their surface
High affinity Fc Epsilon receptors (IgE receptors)
Why is IgE concentration high in tissue
IgE binds to mast cells largely so those antibodies diffuse into the tissues where they can bind
How are mast cells activated
Either by the binding of an antigen (in tissue) to bound proteins or the binding of C3a & C5a onto complement receptors
What happens when mast cells are activated
Immediately, they release the contents of vesicles that contain pre-made mediators (e.g. histamine, heparin, tryptase)
After a slightly longer time (5-30 mins), the mediators released later metabolise arachidonic acid into leukotrienes and prostaglandins which can then produce inflammatory cytokines
