T cell Immunity Flashcards
1
Q
What is the need for T cell immunity?
A
- viruses are intracellular pathogens
2
Q
How does the immune system see viruses within infected cells?
A
- proteolysis of proteins in the cytoplasm occurs in the proteosome
- degraded into short peptides and loaded onto MHC molecules - shipped out via ER/Golgi - presented to outside world on cell surface
- T cells only recognise peptides when bound to MHC on APCs or infected cells
- virus peptides on surface of infected cell - seen by T cells with TCRs that recognise peptide bound MHC - trigger apoptosis
3
Q
How can T-cells recognise its corresponding antigen?
A
- APCS - capture the antigen, process it into a short peptides and present them to T lymphocytes
4
Q
Role of T-cells
A
- eliminate microbes that survive inside cells
- mainly viruses - but some bacteria (M.tuberculosis)
- recognise cell associated antigens only - not free
5
Q
TCR
A
- polymorphic produced by V,D,J,C gene fusion - in thymus
- 2 chains - 𝛼, β (net + charge)
- Each T cell has unique TCR - can recognise particular antigen
- TCR - non covalently associated with CD3 complex
- epsilon
- delta
- gamma
- zeta
*neg charged residues
6
Q
Role of CD3 complex
A
- signal transduction following antigen recognition
7
Q
Composition of tri-molecular complex
A
- TCR
- MHC
- Antigen
8
Q
Thymic education
A
- differentiation of thymic cells to naive T cells
- process eliminates and T cells that could attack self antigen
- T cells remain in thymus when CD1 is expressed on surface (homing receptor)
Cells involved in this process:
- interdigitating DCs (IDCs)
- cortical epi cells
- macrophages
*these cells present self antigens to thymocytes - if they bite - apoptosis
9
Q
Thymocytes
A
- derived from lymphoid stem cheeks
- mature and +/- selected in cortex/medulla
- 99% - 𝛼βTCR
- remainder - ᵧẟTCR (found in gut)
10
Q
Thymocyte maturation stages
A
- βTCR chain rearranges in cytoplasms - CD3 expressed
- CD1+, CD8+, CD4+ co-expression (double+) - 𝛼 chain rearranges - low density TCR surface expression
- mature thymocytes (CD1-) - either CD4+ (Th) or CD8+ (cytotoxic T cells) - high density ẟβTCR surface expression
11
Q
Positive selection of T cells
A
- functional TCR required
- Must recognise MHC molecule on APC surface
12
Q
Negative selection of T cells
A
- deletion of self-reacting T cells/thymocytes
- if TCR recognises self antigens - killed by APCs (apoptosis)
- apoptotic bodies removed by phagocytes (DCs)
13
Q
MHC inheritance
A
- MHC gene inherited as distinct genetic loci - 1 from father and 1 from mother
- co-dominantly expressed - 2 of each 6 expressed = 12
- genes with MHC chromosomal locus - tightly linked - inherited as a UNIT (Halotype)
- one halotype from each parent
14
Q
MHC genes
A
- 3 MHC class I genes - MHC-A,B,C
- single gene for each
- produce single 𝛼 chain protein
- 3 MHC class II genes - MHC-DP,DQ,DR
- 2 genes for each
- produce 𝛼 and β chain protein
15
Q
Examples of MHC variations
A
- DQ2 - MS
- DR4, DQ4 - RA
- DR3, DR4 - DMI
16
Q
Location of MHC molecules
A
- MHC class I - surface of all cells
- presents self-antigens and virus agents to CTLs
- MHC class II - found on surface of APCs (DCs, Macros, B cells)
- presents foreign antigens to Th cells
17
Q
Binding of antigenic peptides to MHC
A
- single MHC allele can present different peptides to T cells
- However… a single TCR can only recognise one of these
- MHC/peptide complex - long half life (hrs to days) - time for APC/MHC/peptide to find TCR
- binding of peptide to MHC is non-covalent interaction
- mediated by AA residues and cleft of MHC molecule
18
Q
Sources of peptides for MHC I & MHC II
A
- MHCI : proteins degraded in proteosomes- found in cell cytosol
- MHC II: proteins degraded in endo-lysosomes - peptides from pathogens that have been phagocytosed by APCs
19
Q
Proteasome
A
- house-keeping function - degrades damaged and improperly folded proteins
- 20% all newly synthesised proteins are misfolded
- recycling of damaged old proteins
