adaptive immunity - T cells Flashcards
the role of t cells in antigen-specific response:
—– help the immune response
—- they kill cells infected by intracellular pathogens and cancerous cells
helper T cells
cytotoxic T cells
—- are cell surface receptors specialised in presenting antigens and they present only —
the MHC-peptides have — amino acids and are complexes recognised by —
—recognises presented peptides, binds and becomes activated
MHC class ii is aka —
MHC class i is also known as —
MHC class ii and MCH class I
peptides antigens
5-20 amino acids
T cells
TCR
t helper cells
cytotoxic T cells
( in antigen representation they communicate ab pathogens to the adaptive immune arm )
features of T cells:
- T cells must — w other cells
- tcr recognise – and bound to –
- each T cell has a unique — which is hugely diverse repertoire
- once a T cell is activated —>
- t helper and cytotoxic T cells have different effector functions
- generate memory T cells that live for –
- interact
- antigen
- mch
- tcr
- colonal expansion
- more than 20 years
life cycle of a T cell:
1- T cell development occurs in —- and this occurs prior to antigen exposure :
- — rearrangement
- — proves
- differentiation into —
- known as —
2- T cell activation occurs in — and this occurs initial antigen exposure :
- T cell is —-
- —- of antigen specific clone
- differentiation into —
3- T cell effector function occurs in —– and this happens response to recognise antigen
- helps given to —
- thymus ( primary lymphoid tissue )
- TCR
- selection
- CD8/CD4
- naive T cells
- lymph nodes ( secondary lymphoid tissue )
- activated
- clonal expasnion
- effector cell
- peripheral tissue ( any tissue )
- b cells and macrophages ( direct killing in this process )
immature T cells migrate from — to —
undergoes development in —-
mature cells exit to the circulation as – as either — or —-
bone marrow
thymus
thymus
naive T cells( which means they didnt meet antigen yet )
cd4 or cd8
— are required to ensure the selection of appropriate T cells
-In fact, 98% of all Thymocytes (immature T cells) will —
Thymus majority –
- checkpoints:
1- +ve selection when can you recognise an MHC
2- -ve selection do you recognise self antigen - will not leave
- die
TCR :
* Millions of T cells with a — TCR
* It is a —– composed of an —and —
* Each chain contains one — and one—
region
* —- is the antigen binding site
which is different for every T cell
clone
* — region doesn’t change
- single
- membrane bound protein
- a chain and b chain
- variable and constant region
- v region
- constant
-At any one time we have millions of T cells in our body, each having a
TCR with a different —- for antigen
-During T cell development — of TCR genes (VDJ recombination) occurs and variable TCRs with unique specificities are generated
- —- randomly combine V(D)J genes to form VDJ or VJ segments → — different combinations
-Rearranged at the DNA
level once changed it cant —
- specificity
- gene rearrangement
- VDJ recombination
- 10 power 14
- cant alter
CD4 and CD8 are aka —
co receptors
postive selection:
- The TCR interacts with MHC expressed on — and — in
the —
- immature T cells bind MHC and get a — signal to survive
-Depending on whether the interaction occurred with MHC class I or MHC class II results in a —-
- — selection retains T cells that recognise MHC
- epithelial cells and dendritic cells
- thymus
- positive signals
- single positive cd8 or cd4 T cells
- postive
negative selection:
MHC in the thymus only expresses —-
which occurs in —-
- when tcr bind tightly to self peptide –>
- when tcr bind self peptides weakly/moderatly/not at all ->
- protects against —
- self peptide
- early in development 7-8 weeks gestation
- T cell dies
- T cell lives aka negative selection
- autoimmunity ( central tolerance )
- T cell activation occurs in —
- — never met antigen
- circulates in —-
- diverse arrange of T cell each w a – TCR
- this specific T cell clone — aka —
- naive T cell differentiates into —
- it leave the — to carry out its effector function
lymph nodes
- naive T cells
- 2ndary lymph organs
- single
- proliferates
- clonal expansion
- effector T cell
- lymph nodes
the 3 signals required for naive T cells activation are:
signal 1: antigen specific interactions
signal 2: co stimulatory molecules
signal 3: instructive cytokines
signal one:
* —- is the necessary first signal for activation of T cells
* The TCR recognises a — presented on MHC ii molecule
* — co-receptor interacts with residues on the side of MHC class —
*— molecules on T cells such as— also bind to ligands on
APC to stabilise the —
* T cell is primed but requires signal 2 to become fully activated
signal 2:
* The proliferation and differentiation of naïve T cells require —
* Microbes will stimulate — to express costimulatory receptors such as B7
(this only occurs in presence of microbes)
* Binds to the T cell surface receptor –
* Once — is engaged then T cells are properly activated to promote the
survival, proliferation and differentiation of antigen-specific T cells
signal 3:
* Activated APC produces instructive — that aid the differentiation of certain CD4+ T cell subsets
– IL-12 and IFNγ stimulate — subset
– IL-4 stimulates — (although this is a product of Th2 cells, so who starts it?)
– IL-23 stimulates — subset
antigen
- peptide
- cd4
- class ii
- adhesion
- intergin
- synaps
- APC
-co stimulation
- CD28
- CD28
- cytokines
-TH1 ( intracellular bacterial infection )
- TH2 ( helminth infection )
- TC17 ( extracellular bacterial and yeast infection )
THE LAST 3 IN BRACKETS R SOOO IMPORTANT!!!
colonal expansion:
* Activated T cells will rapidly start to produce — , a T cell growth factor
* Antigen-specific activated T cells are cloned into large populations
(autocrine signalling via — ), i.e. one activated T cell now must clone
itself to make lots of T cells recognising the same antigen
* A fraction of T cells develop into— T cells which circulate for
years ready to respond to the same microbe
- IL2
- IL2
- memory T cells
t helper is also known as — and they help the mount the appropriate immune response and it has:
cytotoxic T cell is aka — and it kills infected or altered cell aka killer T cell
- cd4+ and has:
- Th1 subset
- Th2 subset
- Th17 subset
- T regulatory subset
- cd8 +
( check slide 37)
cytotoxic t lymphocyte ( cd8):
* Virally infected cell will display — on MHC class – molecule
* Activated cytotoxic T cells bind antigen on MHC class –
* Packed full of vesicles with – enzymes for killing
- released once CTL is — as:
– — forms pores in membrane
– — activate apoptosis
* They don’t kill pathogens, they kill cells infected by pathogens!!!
- viral antigens
- class I
- class I
- toxic
- activated
- perforin
- granzyme
heomostais:
* As the antigen is cleared, 90% of effector T cells die by —
* T cells are deprived of activation signals (antigen, CD28 and IL-2 all —)
* —- pathways are activated (eg. CTLA-4 and PD-1 are CD28 family members which inhibit the second signal in T cell activation)
* T regulatory cells (Treg) can dampen CD4 and CD8 T cell responses
apoptosis
decrease
inhibitory
autoimmunity and immune tolerance:
* —- → unresponsiveness of T cells to self antigens (prevents autoimmunity). It is achieved through:
➢— Tolerance → in the thymus (‘central’ or primary lymphoid organ), it eliminates most of auto-reactive T cells (negative selection)
➢—- Tolerance → in peripheral tissues, it eliminates T cells which recognise self-antigens not expressed in the thymus
* When tolerance fails → auto-reactive T cells recognise self-antigens → autoimmunity → autoimmune disorders (such as multiple sclerosis,
rheumatoid arthritis, IBD etc)
self tolerance
central
peripheral
T cells immunodeficiencies :
DiGeorge syndrome – a deletion on chromosome 22
* A small deletion on Chromosome 22 → thymus is small or
absent → poor T cell production
* Individuals susceptible to recurrent infections
* Also associated with problems across multiple organs, e.g.
congenital heart problems, abnormal facial features, learning
difficulties, psychiatric issues, hypocalcaemia…
Severe Combined Immunodeficiency (SCID)
* Umbrella of rare disorders caused by mutations in different
genes that impact on T and B cells → low/absent T/B cells
* Typically fatal in first 2 years of life, with severe bacterial,
viral and fungal infections
* Examples: X-linked severe SCID (most common worldwide) or
Adenosine deaminase deficiency (most common in Ireland
