T cells Flashcards
What are lymphoid progenitor cells?
Gives rise to lymphocytes
20-30% peripheral white blood cells
6-10 microns in diameter with large nucleus, small halo of cytoplasm
Upon stimulation by antigen become effector cells or memory cells
2 main types: T cells and B cells
Early developmental stage in the bone then cells pass to thymus- become T cells or stay in bone marrow- become B cells
What of thymus in T cell development?
T cells mature in the thymus
Immature T cells develop in the bond marrow then migrate to the 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
The thymus enlarges during childhood and then atrophies at puberty
What are the different T cell subsets?
ab T cells
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)
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 wither suppressing them or activating them through direct cell contact or by secretion of soluble factors (cytokines)
2 main types: natural or inducible
g/b T cells
TCR formed of g/b chain recognise lipid antigens
What is the T cell receptor?
Dimeric molecule on the surface of a T cell; ab or gb 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- ALL T cells express CD3
Compare ab vs gb
ab
Makes up ~90% of peripheral blood mononuclear lymphocytes
Express CD4 or CD8
Restricted through MHC I or MHC II (major histocompatibility complex)
a chain consists of germline Variable, Joining and Constant regions
b chain consists of germline Variable, Diversity, Joining and Constant regions
Total repertoire of ~1017 possible ab TCRs
gb
Makes up ~10% peripheral blood MNC but up to 70% of mucosal T cells
Some express CD8 and few CD4, most express neither
Some gb T cells are restricted through CD1c ( a member of the MHC family)
Some use the NK receptor family
Some recognise cells stress indicators (HSP, butyrophilin)
gb T cells can recognise a number of bacterial antigens
Can also recognise small aliphatic molecules (isoprenoid pyrophosphates and amines) which may represent a pattern recognition system
Extensive junctional diversity increases the gb TCR repertoire to ~1019 possible receptors
What is the Major Histocompatibility Complex?
Surface expressed molecule which bind peptides derived from antigen and resent 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, stabilised by beta2-microglobulin
MHC Class II (HLA-D): expressed on ‘professional’ Antigen Presenting cells
MHCII on antigen presenting cells presents peptide to CD4+ T cells to qualify the immune response: cytotoxicity or humoral
MHCI on any nucleated cell presents peptide to CD8+ T cells and is a signal for a cytotoxic response (except cross-presentation in APC)
Which T cells present antigens?
Dendritic Cells
Irregularly-shaped cells in most tissues
DC usually myeloid-derived (can be myeloid/lymphoid)
When immature, DCs capture Ag (foreign material) and migrate to lymphoid tissues where they mature and effectively ‘present/show’ antigen to T cells
Subtypes include: Langerhans cells (skin), Interdigitating, Plasmacytoid and follicular DCs (actually fibroblasts)
Only APC that can present to naïve T cells
-Tissue-specific dendritic cells :
Langerhans cells in skin
Interstitial DC in dermis
Blood myeloid DC
Plasmacytoid DC
Blood monocyte-derived DC
-Macrophages
-B-cells
-Endothelial cells under some conditions
What does T cell activation happen?
- APC presents a peptide on its surface in the context of MHC+ (I or II)
- The T cell with then recognise this through its T cell receptor
This is not enough - There are other molecules such as CD28 on the T cell or CD80/86 on the APC which becomes the second signal
- If there is not second signal the T cell will become anergic and will not respond further
- At the same time of these molecules coming together the APC will produce cytokines depending upon the environment that it finds itself in and the cytokines are the 3rd signal to allow the T cell to know what to do
- The T cell with then recognise this through its T cell receptor
What is positive and negative selection?
T-cells in the thymus enter as thymocytes not expressing either CD4 or CD8 (double negative), go through a stage of expressing both (double-positive) followed by a decision be wither CD4+ or CD8+
Are positively selected to bind to molecules called MHC and negatively selected if bind self-peptides (‘education’)
What are CD4 T cells?
Recognise a peptide in the binding groove of MHCII
T-helper cells: produce a cytokine profile which directs the immune response to a particular outcome
T-regulatory cells: responsible for ending an immune response
What are CD4+ Th1 cells?
Express the co-receptor CD4
Help to activate the cellular immune response
Produce g-interferon
Activates Mf and cytotoxic T cells
Th1 response effective against intracellular infections, bacterial, protozoal and viral
What are CD4+ Th2 cells?
Express the co-receptor CD4
Help to activate the humoral immune response
Produce interleukin 4, 5 & 13
Activates B cells to produce antibody
Th2 response effective against extracellular cellular infections, bacterial, protozoal and viral
Effective in production of IgE against helminth infection
What are CD4+ Th17 cells?
Express the co-receptor CD4
Help to protect the gut mucosa
Produce interleukin 17, 22
Recruits neutrophils to sites of infection
Th17 response effective against extracellular bacteria and fungi
Effective in promoting neutrophil-mediated inflammation and helping Th1 cells to induce phagocytosis and subsequent killing of pathogens
What are CD4+ Treg cells?
Express the co-receptor CD4, CD25 and FoxP3
Maintain immune tolerance and suppress immune responses
Produce anti-inflammatory cytokines IL10 and TGFb
Also has contact-dependent immunosuppressive effect
Tregs inhibit the effector functions of CD4+ and CD8+ T cells
Also, inhibit antigen presentation function of B cells and other APC
What are CD4+ cytotoxic T cells and how do they kill?
Express the co-receptor CD8
Eliminate intracellular infections
Produce IL, TNFa and gIFN
Also has a role in anti-tumour immunity and rejection of transplants
Kill infected cells in an antigen-specific and cell-contact dependent manner
CD8+ cytotoxic T cells killing mechanisms:
Contact delivers a lethal hit
CTL can then detach and target another cell
Releases cytolytic molecules from intracellular stores
Triggers apoptosis in target cell
