W12 The adaptive immune response - focus on T cells Flashcards
Lymphoid progenitor cell
Gives rise to Lymphocytes
20-30% peripheral blood white cells
6-10 microns in diameter with large nucleus, small halo of cytoplasm
Upon stimulation by Ag become EFFECTOR CELLS or MEMORY CELLS
2 main types of lymphoid progenitor cell: T cells and B cells
(T-lymphocytes and B-lymphocytes)
Early developmental stage, cells pass to Thymus – become T cells or stay in Bone marrow – become B cells
Role of the thymus in T cell development
T cells mature in the thymus
Immature T cells develop in bone marrow → migrate to thymus to encounter self-antigen
During this process many T cells die by apoptosis leaving just those that can generate a useful response to infection
thymus enlarges during childhood and then atrophies at pubert
Helper T cells (express CD4 and CD3)
Helper T cells (express CD4 and CD3)
activated to secrete cytokines to help
immune responses or to become
memory cells
2 main sub-groups: TH1 & TH2 ( also Th17)Cytotoxic T cells (express CD8 and CD3)
Cytotoxic T cells (express CD8 and CD3)
activated to kill infected targets or to become memory cells
usually cytotoxic in nature and kill via the release of the toxic
contents of granules or through induction of apoptosis
Regulatory T-cells
mainly CD4+ (some CD8+) T cells able to affect immune responses by either suppressing them or activating them through direct cell contact or by the secretion of soluble factors (cytokines)
2 main types: natural or inducible
Gamma/delta T cells
TCR formed of g/d chain recognise lipid antigens
The T cell receptor
Dimeric molecule; ab or gd chains covalently linked by S-S
Each chain has a variable and constant Ig like domain
The variable region has hypervariable regions which are the antigen binding sites
Associated with the signalling complex CD3
CD3 is the identifier of the T cell
alpha/beta
Makes up ~90% of peripheral blood MNC
Express CD4 or CD8
Restricted through MHC I or MHC II
a chain consists of germline Variable, Joining and Constant regions
b chain consists of germline Variable, Diversity, Joining and Constant regions
Total repertoire ~1017 possible ab TCRs
gamma/delta
Makes up ~10% peripheral blood MNC but up to 70% of mucosal T cells
Some express CD8 and few CD4, most double negative
Some gd T cells are restricted through CD1c
Some use the NK receptor family
Some recognise cells stress indicators (HSP, butyrophilin)
gd T cells can recognise a number of bacterial antigens
gamma/delta can also recognise…
Can also recognise small aliphatic molecules (isoprenoid pyrophosphates and amines) which may represent a pattern recognition system
Extensive junctional diversity increases the gd TCR repertoire to ~1019 possible receptors
MHC: The Major Histocompatibility Complex
Surface expressed molecule which bind peptides derived from antigen and present to T cells.
MHC encodes for the human leukocyte antigens (HLA)
Two types: MHC Class I (HLA-A, B and C): expressed on all nucleated cells
MHC Class II (HLA-D): expressed on ‘professional’ Antigen Presenting cells
MHCII on APC
presents peptide to CD4+ T cells to qualify the immune response: cytotoxicity or humoral
MHCI on any nucleated cell
cell presents peptide to CD8+ T cells and is a signal for a cytotoxic response (except cross-presentation in APC)
Antigen processing and presentation to CD4 cells
Uptake of extracellular proteins into vesicular compartments of APC
Processing of internalized proteins in endosomal/lysosomal vesicles
Biosynthesis + transport of class II MHC molecules to endosomes
Association of processed peptides w/class II MHC molecules in vesicles
Expression of peptide-MHC complexes on cell surface
