Immune effector responses Flashcards
Humoral and cell-mediated effector responses
Humoral responses are mediated by antibodies
Cell mediated responses rely on NK cells, macrophages, neutrophils, CTLs, Th cells
Antibody-mediated effector functions
Neutralisation Agglutination Opsonisation Complement activation Antibody dependent cell mediated cytotoxicity Degranulation
Antibody isotypes
Differ in Fc region and hinge
Different effector functions depending on which Fc receptor they bind
IgM produced first during infection
IgG abundant in blood
IgA at mucosal sites
IgE against worm infections and allergies
Fc receptors
Have extracellular immunoglobulin domains that recognise Fc domains of antibodies
FcgammaRI (expressed on macrophages, DCs and granulocytes) binds IgG
FceRI (expressed on eosinophils, mast cells and basophils) binds IgE
Opsonisation
IgG/A bind to FcR on macrophages, inducing phagocytosis
Complement fixation
IgG/M recognised by C1 complement complex, leading to activation of the classical complement pathway.
Induces opsonisation and membrane attack complex
ADCC
Antibody dependent cell mediated cytotoxicity
IgG on the surface of infected cells binds FcyRIIIa on NK cells, inducing degranulation (perforins and granzymes)
Granulocyte activation
IgE bound to parasites/allergens causes degranulation of mast cells, eosinophils and basophils.
Induces histamine and other inflammatory mediator release
Cytotoxic effector cells
Natural Killer cells (innate)
CD8+ cytotoxic T Lymphocytes (adaptive)
Natural killer T cells (innate and adaptive)
Induce cell death by apoptosis
Sequential activation of CTLs
APC licensed via interaction with pathogen (PRR) or with activated Th1 cell (MHCII)
licensed APC interacts (MHCI) with naive CD8+ T cell leading to activation and differentiation into CTL
Simultaneous activation of CTLs
APC simultaneously interacts with active Th1 cell and CD8+ T cell.
APC licensing and CTL activation occur at the same time
IL-2 from Th1 promotes CTL differentiation
Action of CTLs
CTL forms immunological synapse with target cell
Granules trafficked along microtubules
Granules fuse with presynaptic membrane and released
Perforins assemble into a pore on the membranes and granzymes enter, cleaving proteins and causing apoptosis
Non-functional perforins
Associated with protracted viral infections.
Polymorphism in PRF gene encodes perforin dysfunction
NKT cells
Natural Killer T cells
Develop in thymus and undergo TCR gene rearrangement but have invariant alphabeta TCR
Can be CD4+ or CD4- and can act as both Th and CTLs