lecture 13: T cells and their receptors Flashcards
(32 cards)
1
Q
CD4 functions
A
- wide range of functions
- providing surface receptors and cytokines, can release lots of useful cytokines to fight infections
2
Q
difference between production of antibodies vs T cell receptors
A
antibodies are easily produced, but T cell receptors are more fussy
3
Q
artificial T cells: chimeric antigen receptor (CAR) T cells
A
- T cells engineered with an artificial receptor that recognise tumour antigens
- retroviral or transposons used to transfer genes into patient or donor T cells
- made up of antibody parts which bind to tumour antigen and trigger a killing effect on the cancer cell
- complementary way of treating cancer, can be used along with chemo and radiation
4
Q
response to chimeric antigen receptor (CAR) T cell
A
70%-83% response rates in B cell lymphomas
- effective against relapsed/refractory diseases
5
Q
outline of TCR formation
A
- production of T cell precursors (very immature t cells) –> bone marrow
- migration, circulate in the blood after they have left the bone marrow and they are destined to become T cells, still immature –> blood
- TCR gene rearrangement, rearrange receptors onto the surface, bring genes together to produce a functional transcriptional unit = forming and alpha and beta chain –> thymus
6
Q
TCR rearrangement
A
- only t cells will rearrange them to produce a functional unit
- make up variable sets of genes
- in joining these genes together, it is deliberately messy, some random genes join, a little bit of disjunction in the joint is good as it adds to the diversity
7
Q
clonal selection
A
= selective expansion of lymphocytes that interact with antigen
8
Q
what are developing T cells screened for
A
- their ability to bind to MHC in the thymus
- most peptide derived from self peptide
- T cells are subjected to being screened by MHC self peptide
9
Q
how does thymic selection work
A
- thymic stroma (epithelial cells) expresses MHC class I & II
- developing thymocytes (very immature T cells) are ‘tested’ for their ability to bind to self-MHC
10
Q
what happens if the shape of the TCR is distorted and cant bind MHC
A
- no signal
- useless T cell
- death by neglect
11
Q
what happens when the TCR attaches to the MHC and produces a moderate signal
A
- ‘just right’ T cell
- positive selection
12
Q
what happens if the peptide is lying in the groove of the TCR and produces a strong signal (high binding)
A
- autoreactive T cell
- still immature t cells, strong signal leads to their death
- negative selection
13
Q
escape from central tolerance
A
- auto reactive T cells can escape if self antigen is expressed at low levels in the thymus
- autoimmunity may result if self antigen is expressed at higher levels in the periphery
14
Q
self-MHC restricted
A
only recognise peptides in the context of self MHC
15
Q
transplant rejection and MHC
A
- MHC are the most polymorphic genes that we possess. this means MHC structures differ greatly between people
- unless donor / recipient are perfectly matched, polymorphisms can result in T cells reaction to other people’s MHC within a transplanted organ
16
Q
what are the advantages of polymorphism
A
- polymorphisms are useful mutations in MHC that have been selected
- MHC polymorphisms allow for a greater diversity microbial peptides to be bound and presented to T cells
17
Q
different types of transplants
A
- autologous = self + self
- syngeneic = self + identical eg: twins
- allogeneic = non-identical members of same species
- xenogeneic = different species
18
Q
what does a t cell receptor recognise
A
- peptide in the context of MHC –> this is very specific, tight series of ligands to bind to
19
Q
T cell development
A
- the maturation of progenitor cells to one of two types of t cells: T helper cells and cytotoxic T lymphocytes
- immature T cells initially bear both CD4 and CD8 but are then selected to have one or the other, but never both
- the type of co-receptor (CD4 or CD8) selected is critical to the future development and activity of the T cell
20
Q
thymus
A
site for T cell development
21
Q
positive selection
A
determines what type of co-receptor the mature T cell will have
22
Q
negative selection
A
all T cells are screened so that any T cell that strongly recognizes self antigen undergoes cell death
23
Q
naive t cells
A
- t cells that leave the thymus and migrate to lymph nodes and the spleen are called mature but naive
naive = fully developed but cannot respond to antigen until instructed by antigen presented on a MHC molecule
24
Q
T cell activation
A
- TCRs play an essential role in T-cell activation, TCRs evolved to detect antigen fragments presented by MHC on the surface of the other cells
- when a mature T cell is able to bind to a peptide in a MHC molecule, it is no longer naive because it now has found the specific peptide that fits its particular binding cleft = first step in T-cell activation
25
what is signal 1 in t cell activation
occurs when an antigen fragment presented in an MHC molecule of an APC is recognised and bound by the appropriate T cell receptor
CD4 = MHC II
CD8 = MHC I
26
why is signal 2 required
- naive CD4 and CD8 cells need costimulatory signal 2 to become activated
- t cells that recieve signal 1 without signal 2 become anergic --> they can recognise antigen, but are unable to respond to it
27
what are the different types of T cells
1. effector T cells
- carry out specific functions to protect the host against foreign antigen
2. memory cells
- mature, educated cells that are quickly reactivated when the host is reintroduced to their specific antigen
3. T helper cells
- also known as CD4 T cells = the adaptive immune systems master regulators
- there are several different types of TH cells
- play a regulatory and coordinating role in the immune system
- don't kill pathogens directly, instead they help activate other immune cells: B cells --> produce antibodies
cytotoxic T cells (CD8) --> to kill infected cells
macrophages --> to engulf pathogens
4. cytotoxic T lymphocytes
- CD8 T cells need to destroy unhealthy host cells
- if the non self antigen is recognized by the TCR of a CD8 T cell, it matures into a cytotoxic T lymphocyte that functions to destroy host cells infected with intracellular pathogens
28
what is thymic selection
- thymic stroma (epithelia cells) expresses MHC class I & II
- developing thymocytes (very immature T cells) are ' tested' for their ability to bind to self MHC
- this is how our body trains T cells in the thymus so they can defend the body without attacking
- thymus has specialized epithelial cells
--> specialized to interact with T cells
--> also have DC cells who screen the T cells
- strength of signal is very important = there is an optimal signal a T cell can get
29
what is central tolerance
= first line of defence against autoimmunity
- the process by which immature T and B cells are eliminated or inactivated during development if they recognise self antigen strongly
- lack of ability to be able to distinguish between self and non self antigen leads to autoimmune diseases
30
how does TCR structure contribute to antigen binding
no binding --> death by neglect
- shape is distorted so cant bind and will die
moderate --> positive selection (survives)
- t cell docked in
high --> death
- signal is to strong through MHC
- strong signal kills immature T cells (mature T cells less likely to die)
31
how is the TCR structure restricted to recognising self MHC
- TCRs are not born MHC restricted, they become MHC restricted through a process called positive selection
- even though TCRs are randomly generated, the selection process ensures only those that structurally fit self-MHC survive
32
generation of diversity
B and T cells undergo this to create unique antigen binding sites in variable regions
