IIH L07 Barrier immunity and innate antigen recognition Flashcards
What do PRRs recognise? L07
PAMPs on non-mammalian cells
Upon binding to their PAMP, what do Toll-like receptors do? L07
Trigger a cascade of signals within the cell that ultimately activates the genes in the nucleus to upregulate inflammatory cytokines
What are the components of complement? L07
A number of soluble pro-enzymes in blood and tissue fluids which are activated in sequence like a cascade
What are the three ways complement can be activated? L07
Classical pathway
Alternative pathway
Lectin-binding pathway
How is the classical pathway activated? L07
Recognition of an antigen-antibody complex
How is the alternative pathway activated? L07
Endotoxin and bacterial cell walls, - gram
What happens in the alternative pathway? L07
Soluble C3 is spontaneously hydrolysed to insoluble C3b, which then binds to any nearby microbial surface activating the rest of the complement cascade
What happens in the lectin-binding pathway? L07
Following infection local tissue macrophages release cytokines (IL-1β and IL-6) which act on the liver to induce release of acute phase proteins: Mannose Binding Lectin (MBL) and C-Reactive Protein (CRP). They can be thought of as soluble PRRs that recognise bacterial cell walls. They bind and trigger complement activation.
What do all three pathways converge to form? L07
C3 convertase
What is the role of C3 convertase? L07
Enzyme complex that converts soluble C3 to insoluble C3b
What is promoted when the microbe is covered in C3b? L07
Opsonisation
What are the functions of complement activation? L07
- Opsonisation for neutrophils and macrophages
- Cell lysis- the MAC binds to cell membranes causing water uptake, swelling, and ultimate cell death
- Mast cell degranulation caused by C3a
- Neutrophil chemotaxis caused by C5a
Which infection are you susceptible to with a C5-9 deficiency? L07
Neisseria
Which infection are you susceptible to with a C1, C2 or C4 deficiency? L07
Immune complex disease e.g lupus
Which infection are you susceptible to with a MBL deficiency? L07
Bacterial infections, mainly in childhood
What components of complement are measured in complement test? L07
C3, C4, C1 inhibitor
What do patients with a low C4 suffer with? L07
Recurrent infection with encapsulated bacteria, telling us the classical pathway is very important for killing bacteria like pneumococcus
What is a possible cause of C4 deficiency? L07
C1 inhibitor deficiency/ hereditary angioedema, any immune complex disease e.g. lupus, rheumatoid vasculitis, or cryoglobulinaemia
What happens in hereditary angioedema? L07
C1 inhibitor blocks C1 formation at the beginning of the classical pathway. It is also an enzyme that increases bradykinin; resulting in increased intravascular permeability and potentially fatal swelling
Possible cause of low C3? L07
Post-streptococcal glomerulonephritis in paediatrics
Four main ways pathogens can enter the body? L07
Skin breach
GIT
Resp tract
Genito-urinary tract
Surface TLRs? L07
TLR-2, TLR-4, TLR-5
What does TLR-2 recognise? L07
Peptidoglycan and lipoteichoic acid
What does TLR-4 recognise? L07
LPS on gram-negative cell wall, viral envelope proteins, and parasitic phospholipids
