Immune system Flashcards
C3(H20)Bb
Fluid phase C3 convertase
C3bBb
Alternative pathway C3 convertase
C3b2Bb
Alternative pathway C5 convertase
Mannose binding lectin
Soluble PRR that binds mannose and fucose residues on microbes
- Associated with MASP1/2 (serine proteases) that cleave C4 and C2
C4bC2A
Classical C4 convertase
C reactive protein
Soluble PRR that recognises phosphocholine on bacterial surfaces
Binds C1 and activates so C1s (serine protease part) can cleave C4 and C2
Antibody inducing complement
Antibody binds C1q at Fc region causing conformational change to activate C1s/r
C1s can then cleave C4 and C2 to make classical C3 convertase
C4bC2aC3b
Classical C5 convertase
Factor P (properdin)
Stabilises C3 and C5 convertase (alternative) to assist MAC formation
Factor I
Degrades C3b and C4b
Constitutively expressed
Membrane cofactor protein (MCP)
Activates factor I (cofactor)
Dissociates classical and alternative C3 convertase via decay accelerating capacity
Factor H
Cofactor for factor I but binds host sialic acid so specific
Decay accelerating factor
Makes C3 convertases dissociate
On host
Protectin
Prevents C9 recruitment so stops MAC
FcgammaRIIIa
On NK cells to cause granule release for ADCC
And on mast cells for granule release
FcgammaRIIb
-ve signal to turn off antibody response
FcgammaRI
On macrophages for phagocytosis
FcepsilonRI
On eosinophils to cause granules release to defend against helminths
On mast cells, often pretending IgE; cross linking causes degranulation in allergy
IL-12
Activates NK cells
Causes naive T cells to become Th1
Neutrophil recruitment sequence
s-Lex binds P selectin for weak tethering
LFA-1 binds ICAM-1; becomes tight when CXCL8 binds its receptor
LFA-1 interacts with CD31 for passage across tight junction
Follows CXCL8 gradient
Granulation tissue
Macrophages are key
Fibroblasts recruited by FGF
Endothelial cells recruited by VEGF
Metalloproteinases from macrophages break down ECM for remodelling
Repair and inflammation at same time
Master transcription factor for Th1, Th2, Th17, Treg
Th1 = T-bet Th2 = GATA-3 Th17 = RORgammaT Treg = FOXP3
High vs low antigen dose
High dose -> Th1 response, high TCR affinity
Low dose -> Th2 response, low TCR affinity
Anti-inflammatory cytokines
IL-10, TGF-beta
Direct antibody autoimmunity
Graves disease: agonist at TSH receptor so hyperthyroidism
Hashimoto’s disease: anti-TSH so hypothyroidism
Myasthenia Gravis: anti-nAChR so get paralysis and weakness
Immune complex mediated autoimmunity
Systemic Lupus Erythematosus
Autoantibodies against nuclear and cytoplasmic componenets
Not cleared so deposit in kidneys, endothelium
T cell mediated autoimmunity
Rheumatoid arthritis
Multiple sclerosis
Type 1 diabetes
Type 1 hypersensitivity
Allergy
IgE mediated
Dendritic cell presents allergen to naive T cell in presence of IL-4 so get Th2
This release IL-4 and IL-13 to make B cell that produces IgE
This gets rebound to receptors on mast cells which degranulate upon cross linking
Type 2 hypersensitivity
IgM or IgE binding to cells and triggering clearance by macrophages/complement
e.g in blood transfusion/rhesus antigen related
To avoid rhesus antibody production
Add lots of anti-Rh antibodies to mask the presence of Rh antigens
Type 3 hypersensitivity
IgG; immune complex deposition e.g serum sickness
Arthus reaction
Type 4 hypersensitivity
T cell mediated
Haptens modify proteins causing their presentation and Th1 response
Cytokines pro Th1
IL-1, IL-2, IL-12, TNF, IFNgamma
Cytokines pro Th2
IL-4, IL-10, TGFbeta (anti-inflammatory)
NOD like receptor mutation disease
Crohn’s
TLR4
LPS
TLR5
Flagellin
TLR 7 and 8
ssRNA
TLR3
dsRNA
RIG like receptors
Detect viral RNA in cytoplasm
Macrophage produces
IL-1beta
TNFalpha
IL-6: lymphocyte activation, C reactive protein production
CXCL8: chemokine to recruit neutrophils
IL-12: activates NK cells and induces CD4 cells to become Th1
Mast cell releases
Histamine, TNFalpha, leukotrienes, prostaglandins
Vascular endothelium activation
Short term: by histamine; get P selection release from Weber Palade bodies
Longer term: from IL-1 and TNFalpha get E selectin
Monocyte recruitment adhesin molecule
VCAM-1
Anti-inflammatory leukotriene
Lipoxin
Anti-inflammatory cytokines
IL-10, TGFbeta
Staphylococcus interaction with complement
Inhibits C3 convertases and degrades C3b
Two signals to activate T cells
1) Via interaction of MHC with TCR
2) Interaction of B7 (CD80/86 on B cell) with CD28
Defective AIRE expression
Leads to APECED
Lack of FoxP3
IPEX
X linked