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Immunology 1: Natural defences + Innate immune response (ii) (Innate…
Immunology 1: Natural defences + Innate immune response (ii)
inflamm
common @ surgical scars
localises infection (contained by thombosis)
local coag
increased platelet adhesion
vessel occlusion
local vasodilation + increased vast permeability to facilitate delivery of cells + proteins to injured/infected site
systemic effects: macrophages produce IL6 -> acts on hepatocytes to decrease transport proteins (albumin) + increase acute phase proteins (CRP)
acute phase reactions: fever, sleep, anorexia, haemodynamic shock
CRP levels rise 6hrs after inflamm begins + fall 6 hrs after inflamm is controlled -> best for monitoring (ESR can also be used but takes longer to increase + decrease)
opsonin formation
CRP binds to phosphocholine
lectin binds to mannose
oedema expands ECM
increased production of lymphocytes, phagocytes, plasma proteins, neutrophils
endothelial effects
disrupted laminar flow
plasma now in centre + cells along wall -> increased leukocyte adhesion (attracted to the IL8)
PGI synthesis
coag
IL1,6,8 + PDGF produced
leukocytes secrete CKs
fibroblast (synthesis collage + ECM) effects: prolif
Innate immune system
rapid (hrs), primitive, nonspecific, no memory, limited, constant response (no improvement)
uses pattern recognitions molecules + Rs (e.g. TLRs)
different to adaptive, which is v specific clonal expansion of precursors + Rs following DNA recombination
phagosome forms in phagocytosis
cells involved...
monocytes
macrophage precursor
carb Rs on macrophages
phagocytic + APC
initiate inflamm + complement
produce ROS
activated macrophages secrete IL1beta, TNFalpha, IL6, CXCL8 (chemotactic), IL12 (activates NK cells + CD4 T cell differentiation)
local + systemic effects
NKs
NK Rs recognise absent self MHC
contain lytic granules (contain granzymes + perforins) to lyse viral-infected cells (apoptosis)
activate macrophages
bigger + more granular than lymphocytes
inhibited by inhibitory Rs (e.g. HLA) that recognise self MHC (if absent then no inhibition)
more efficient when exposed to CKs
mast cells
release histamine, LTs + PGs -> inflamm
detoxify venom + fight parasites
neutrophils
most abundant
migrate from blood into tissues via ICAM + selectin
lobular nucleus
produce ROS + antimicrobial bactericidal peptides
phagocytic
dendritic cells
can phagocytose but rarely do so
present to Th cells (activates Tc cells, B cells + macrophages)
produce CKs + costim signals
APCs in all tissues
soluble factors: opsonins, complement, IFNs, CKs
PAMPs
no variation within 1 class
LPS for gram -ve
on microbes (essential for survival, mutants not viable) but not mammalian cells
peptidoglycan + lipoteichoic acid for gram +ve
Complement
classical activation (antigen-Ig complex, in innate + adaptive)
alternative activation (pathogen surface, innate only)
MB-lectin activation (innate only)
common protein = C3
effects
inflamm
opsonisation (attracts phagocytes)
MAC
C567 bind, then C7 binds to pathogen membrane, C9 binds + polymerise, pore forms
C5-9 deficiency: susceptible to recurrent Neisseria infections
can directly kill fragile pathogens by osmotic lysis (rare)
TLR4 recognises LPS on gram -ve bacterial cell surface
IFN alpha + beta
increase MHC 1 + antigen presentation
activate dendritic cells, macrophages, NKs
increase resistance to viral rep