L8 - K Okkenhaug - T cells Flashcards
what does the T cell receptor bind / response to?
fragmented antigenic peptides bound to MHC molecules.
describe a class 1 CD8 cytotoxic T cell
CD8 cytotoxic
describe a class 2 helper T cell
how are TCRs and antibodys closely related?
what structure do they share in commen?
The TCR is closely related to a single antibody Fab fragment
how is TCR variability generated?
VDJ recombination - much like antibodies
describe TCRs peptide structure?
two polypeptide chains each containing a constant and a variable region.
4 differences between TCR and antibodies
TCR is:
- monovalent
- membrane bound - no secreted counterpart
- no somatic hypermutation
- solely used for antigen recognition
- not linked to effector function
where do T cells mature
thymus
do you understand how VDJ recombination works?
____ is the most variable region in TCR and is focused on the VDJ junctions.
CDR3 is the most variable region in TCR and is focused on the VDJ junctions.
CDR3s role in the TCR is
CDR3 makes the major contact with peptide present in the MHC groove.
Only abou X% of
double-positive (CD4+ /CD8+) thymocytes survive selection.
Only about 1-2% of
double-positive (CD4+ /CD8+) thymocytes survive selection.
in T cell selection, whats the purpose of negative selection?
Negative selection helps prevent autoimmunity by deleting autoreactive cells.
in T cell selection, whats the purpose of Positive selection?
Positive selection ensures that peripheral T cells will be useful since cells that cannot recognise self MHC cannot become activated.
CD8+ T cells are selected for by MHC X molecules. CD4+ T cells are selected for by MHC X molecules
CD8+ T cells are selected for by MHC I molecules. CD4+ T cells are selected for by MHC II molecules
Pictuer to help understanding of T cell selection
is positive selection unique to T cells
yes
T cell undergo positive and negative selection in the ____
T cell undergo positive and negative selection in the thymus
where does positive selection take place?
cortical epithelium in thymus
explain positive selection in the cortical epithelium in the thymus for t cells
Newly rearranged T-cell receptors are tested against self peptide/MHC complexes expressed on cortical epithelial cells.
TCRs with a “moderate affinity” for self MHC/peptide receive a positive signal to continue maturation.
Lack of interaction results in death by neglect.
Expression of CD4 and CD8 co-receptors is altered to match MHC restriction.
Cells that survive will be CD4+ single positive if selected against MHC class II/peptide or CD8+ single positive if selected against MHC class I/peptide.
thymus organisation picture
where does negative selection occur
thymus medulla
where do mature t cells travel to after the thymus
secondary lymph tissue
describe negative selection
- potentially autoreactive thymocytes expressive TCRs with high affinity for MHC/self peptides
are eliminated from the repertoire by programmed cell death (apoptosis).
- Negative selection can not eliminate T cells with receptors recognising MHC/peptide combinations that are not expressed in the thymus. These are dealt with by mechanisms that operate in the periphery.
why are macrophages important in the thymus
Macrophages are important for removing thymocytes that fail to mature.
regarding T cell stimulation - what is teh 2 hit hypothesis
signal 1 is delivered by TCR engagement and co-stimulatory molecules deliver signal 2.
CD40L on the T cell interacts with CD40 which activates the APC.
is the second corstimulation for the activation of a T cell imporntat?
yep - Without CD28 costimulation, the T cells can become unresponsive to further exposure to the same antigen.
describe how APCs present to T cells
Infection in the periphery is initially sensed by mechanisms of innate immunity.
DCs, potent antigen presenting cells that reside in most tissues, take up antigen in the infected tissues and are activated by TLRs and CD40 receptors.
They increase MHC class II synthesis and begin to express co-stimulatory molecules (B7.1 and B7.2) at the cell surface.
Together with their antigen cargo they migrate to draining lymph nodes where they remain and present antigen to circulating T cell.
how do T helper Cells activate B cells?
B cell must bind antigen via its specific surface Ig and internalise it
The endocytosed antigen is then processed and presented on the surface as MHC class II/peptide complexes
The peptide MHC complex expressed by B cell is the same as that originally presented by the DC and can be recognised by the activated helper T cell
The B cell-T cell interaction requires CD28 and CD40L on the T cell to bind B7 and CD40 on the B cell.
Cross-linking of CD40 on the B cell (B cell activation signal 2) promotes B cell proliferation, provides B cell survival signals and promotes immunoglobulin class switching.
Interaction between B cell and T cell co-stimulatory molecules (CD28/B7 and CD40L/CD40) is essential and leads to their mutual activation (B-T cell co- operation).
long card
fate specifying cytoines and cytokines secreted
how do Treg cells modulate T cell differentiation
During inflammation in the presence of IL- 6 Tregs continue to produce TGF-β
maintains homeostasis by inhibiting TH1 and TH2 cell differentiation
IL-6 can drive TH17 commitment
TGF-β prevents TH1 and TH2 cells from producing IL-4 or IFN-gamma that would otherwise inhibit the TH17 response.
Pictrue summary
summary picture of ILCs
another summary picture
