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Immunology 3 - Cellular immune response (i) (Lymphocyte markers (CD3 in T…
Immunology 3 - Cellular immune response (i)
Against viruses/cytoplasmic (intracellular pathogens)
innate
IFNs + NKs
Adaptive
Igs (neutralisation) + Tcs
also IFN alpha+beta, TNFalpha, IL12
Lymphocyte markers
CD3 in T cells
CD4 in Th cells
CD19 in B cells
Cd 16+56 in NK cells
CD8 in Tc cells
T cell development
precursors (progenitors) in BM
migrate to thymus
+ve selection: only T cells that bind to self MHC survive
-ve selection: T cells overactive to self MHC die (prevents autoimmunity)
only 1-2% of T cells get through +ve + -ve selection
Secondary lymphoid organs
specialised peripheral organs that increase the chance of lymphocytes meeting an antigen
lymph nodes, spleen, MALT
mature but still naive T cells migrate here (+ to infection sites if any)
T cell activation
Igs bind to epitopes of pathogen antigens (epitopes a TCR would recognise are often buried)
antigen broken down into peptide fragments
peptides bind to MHC on surface of APC (in peptide binding groove)
TCR binds to MHC-antigen complex (ternary complex)
MHC restriction: MHC1 binds to TCR from Th only, MHC 2 binds to TCR from Tc only
MHC
MHC1 has 2 chains (1 variable alpha, 1 invariable beta2-microglobulin)
MCH2 has alpha + beta chain
coded by HLA gene
co-dominent expression
maternal + paternal allele expressed
polygenic (multiple gene expression)
25% chance you'll be HLA-identical with a sibling (NB transplants)
highly polymorphic (1000s of alleles)
highly unlikely you'll be HLA-identical with someone in general pop
highly unlikely that any single pathogen would make humans extinct
2 alpha helices
thymic shadow
should be absent in adult X-ray of ant mediastinum (if it isn't consider a tumour)
should be present in children (if not consider immunodeficiency)
thymus involutes but has ability to reactivate
Antigen presentation
2 pathways
endogenous
peptides already inside cell (e.g. virus/intracellular bacteria)
via MHC1 in ER
all nucleated cells can do this
activates Tcs
exogenous
only APCs can do this (ingest extracellular pathogens via phagocytosis, then cleavage into peptides via eadosomal proteases)
via MHC2 in vesicles
activates Ths (then B cells and Igs)
TCR structure
alpha + beta chain
variable region (antigen binding site here)
constant region
transmembrane region
cytoplasmic tail
Ig structure
2 Fab regions (antigen-binding site here)
Fc region (has Rs for compliment activation, recognising opsonised particles [FcgammaR] + mast/basophil/eosinophil degranulation [FcepsilonR])
MCH2-ThCR interaction requires costim + adhesion molecules
danger signal
B7 on APC + CD28 on Th
ICAM1 + LFA1 (lymphocyte-function associated)
CD40 on APC + CD40L on Th
lead to T cell activation
prolif
apoptosis
anergy (absence of normal immune response)
cks from APC (IL6+12, TGFbeta)
enables T cell activation, survival, differentiation