22 - T cell recognition Flashcards
what is T cell recognition involved in?
cell mediated specific immunity
T cell antigen recognition
don’t recognise native or ‘free’ extracellular antigens
recognise antigens on body surfaces that have been processes and presented to them
processed antigens presented via the MHC
2 types of T cells
cytotoxic T cells - go and kill other cells
helper T cells - enhance other cell responses: produce cytokines which promote other cells
T cells express a T cell receptor (TCR), where is it found and whats its structure?
anchored on their cell surface • similarity to an antibody • have immunoglobulin domain • alpha and beta chains • variable region at the top • constant region at the bottom • alpha and beta have transmembrane regions - have small cytoplasmic tails • joined by disulphide bond • have carbohydrates attached
what does the variable region of TCR do?
binds to the antigen
what does the constant region of TCR do?
doesn’t activate immune cells
always remains bound to the cell so not accessible
what does the TCR do?
recognises a peptide fragment (epitope) of Ag on surfaces of other cells in a complex with a MHC
what does antigen recognition by T cells work?
1) antigen gets processed and cleaved into shorter fragments
2) fragments presented by MHC
3) TCR will search all cells
4) T cell will bind and produce cytokines and other immune cells
what are the 2 classes of MHC?
class I class II
class I MHC
not in cells without a nucleus - RBCs
peptide binding cleft made of alpha 1 and alpha 2 domains
has only 1 transmembrane domain
class II MHC
expressed by APCs
peptide binding cleft made of alpha 1 and beta 1 domains
has 2 transmembrane domains
T cell recognition of MHC/peptide complex enables T cells to perform what 3 functions:
to act against extracellular antigens
to act against intracellular infections
to regulate activities of other cells
extracellular antigen presentation by MHC class II
1) extracellular antigens engulfed by cells into endoscope
2) in the endoscope they begin to acidify due to influx of H+
3) this cleaves antigens into smaller fragments
4) small peptides bind to MHC class II molecule
5) take to cell surface and presented on outside
6) T cell receptors bind and activate T helper cells
cytotoxic T cells
- CD8+
- recognise and kill infected cells
- recognise viral antigens presented by MHC class I molecules on infected cells
- kill by a mechanism involving perforin and granzymes
- can go wrong - autoimmunity
what does perforin do?
perforating enzyme
punches holes in cell surface
what do granzymes do?
cause apoptosis
cytotoxic T cell action
1) MHC class I presents short bit of viral peptide
2) cytotoxic T cell comes and binds to it
3) bit of protein sticking our is the CDA which is involved in the binding process
4) kills the cell
5) will continue to kill cells presenting this peptide
helper T cells
- CD4+ / T(H) cells
- recognise antigens taken up by APCs and presented on MHC class II
- modulate other cell types
- 5 groups of T(H) cells
- depletion of T(H) cells leads to infections and tumours
what are the different types of T(H) cells?
T(H) cells leave the thymus as naive (not activated) cells = T(H)0 cells
once they recognise the p(peptide)/MHC class II complexes they can become polarised into: • T(H)1 • T(H)2 • T(H)17 • T(H)FH • Treg
each T(H) cell secreted different cytokines and hence has different effector functions
role of T(H)1 in infection
- recognises MHC class II being presented by macrophages
- has CD4 protein that binds with TCR to stimulate cytokines to activate macrophages
- eradicate intracellular pathogens
- enhance killing power of macrophages
- type I response
secrete IFN-lambda
role of T(H)2 in infection
- controls infection from extracellular parasites
- help recruit and promote response by eosinophils and mast cells
- cytokines produces are required for B cell class switching to IgE
- type II response
secrete IL-4
role of T(H)17 in infection
- controls infection by extracellular bacteria and fungi
- help recruit and promote response by neutrophils
- promotes production of antimicrobial peptides by epithelial cells
- in the urinary tract
secrete IL-17
role of T(H)FH in infection
- stimulate naive B cells to differentiate into plasma cells
- stimulate B cells to generate class-switched antibodies
- contributes to killing of all types of pathogens
- invalid in type I and II response
secrete IL-21
role of Treg in infection
- inhibits and regulates T cell activation
- suppresses immune system
- vital to prevent autoimmunity - overreaction of the immune system
secrete IL-10 and TGF-beta
