Effector Responses Flashcards
What is crosstalk in this context?
Cytokines and antibodies signalling to cells of the immune response after their production by it, to avoid damage to self and save energy
Innate cellular response?
Fast and non-specific
Cells mostly derive from common myeloid progenitor cells
i.e. neutrophils, macrophages etc
What are the phagocytes?
Macrophages
DCs
Neutrophils
Macrophages?
Tissue-resident, formed from monocytes in bone marrow
Also produced during development from embryonic cells
Main phagocytes, using surface receptors and chemotaxis
Neutrophils?
Has dense granules, makes up 90% of our circulating granulocyte pop
Short life span - when dead, cells form pus
Phagocytosis, also use chemotaxis
What are the granulocytes?
Neutrophils
Eosinophils
Basophils
Eosinophils?
2-5% of WBS
Release toxic granules and chemical mediators; eosinophil cationic protein and major basic protein
Basophils?
0.2% of wbs
Release histamine, prostaglandins, heparin, leukotrienes
Mast cells?
Found in tissues, they are like basophils
Cell-surface receptors bind Fc of IgE
Multivalent binding - granule release
Natural killer cells?
Produce cytotoxic molecules
Inhibitory receptors = MHCI, expressed on all cells normally
Excitatory receptors for ligands only work when MHCI is downregulated in abnormal cells
They also inhibit viral replication, producing interferons
Complement innate response?
Antibody independent killing
Uses 30 different soluble proteins (inactive precursors circulate from the liver)
Activation of complement?
Proteolytic cleavage into 2/more parts
Smaller fragment may mediate inflammation
Larger fragment has active enzyme site and binding site for next protein in cascade
Pathways of complement? End point of all?
Classical
Alternative
Lectin
All form C3 convertase, cleaving C3 into C3b (bound to affected cell) and C3a for inflammation
Classical pathway?
IgM (planar form), as a pentamer, binds antigens on bacteria = staple form
C1q binds one IgM
Or C1q binds at least two IgG molecules
C1r activated, cleaving serine proteases C1s.
C1s cleave C4 to a and b, which bind the surface
C4b binds C2, cleaved by C1s to C2 a and b = C4b2a complex
This is an active C3 convertase, able to cleaved up to 1000 molecules of C3
Most C3b binds microbial surface
Alternative pathway?
Complement binds pathogen surface directly
C3 binds water via spontaneous hydrolysis, letting it bind factor B
Factor D cleaves B into Ba and Bd
C3(H20)Bb = C3 convertase
Only active if bound to cell surface
Lectin pathway?
Complement binds mannose binding proteins on pathogens
with mannose binding lectin, present in serum
MBL associated proteases (MASPs) bind MBL = complex, cleaving C4 and C2 to form C4a2b in same way as classical
Effector response of complement?
Induces cell lysis
Opsonisation of pathogen
C3a induces chemotaxis and inflammation
Immune complex clearance (soluble antigen complexes where too few antibodies mean no phagocytosis - complement aggregates these)
Effector function of CD4+ T cells?
Differentiation to Th1 and Th2
Th1 effector?
Intracellular pathogens
Activate macrophages via secretion of IFN-y and CD40 ligand
Macrophages then upregulate MHCII to activate T cells
Also produces:
IL3 and GM-CSF = macrophage differentiation in marrow
IL2 = T cell proliferation
Fas ligand or LTa = killing of infected cells
Can also stimulate antibody production for extracellular action
What is delayed-type hypersensitivity?
Activation of T cells in absence of co-stimulation, through macrophages MHCII binding - much slower, needs attachment to last for some time
Th2 effectors?
Large extracellular pathogens that cannot be phagocytosed
Master TF GATA-3 expressed, to help B cells produce antibody (secreting IL4,5,6 – IgE production from plasma cells)
Activate basophils, eosinophils and mast cells through cytokines directly, or IgE production from B cells
Th17 effectors?
Extracellular bacteria/fungi
Recruits other cells with IL17 (induces cytokine secretion)
IL22 - antimicrobial peptides
CD8+ T cell effector function?
Migrate from lymph to circulation to scan every MHCI in body for infection, without need for second signal as already active
Bind loosely, recognise antigen and reorganise cytoskeleton to localise granules to point of contact
Releases granules to diffuse across synapse = apoptosis
Rapid
Very selective
Also produce IFNy for macrophage activation
TNF-a helps this
LT-a directs killing
CD4+ and CD8+ cross talk?
e.g. in infected macrophages
CD8+ CTLs activate with IFNy or kill
Th1 cells activated with IFNy, increasing macrophage differentiation
Th1 cells produce IL2 to stimulate T cell production, increasing cytotoxic lymphocytes (CTLs)
