T cell biology

Question 1

What are the key features of T cells?

Answer 1

1. They’re cells of the adaptive immune system (antigen-specific response)
2. They have 2 main functions:
   - Helper T cells: ‘help’ the immune responses
   - Cytotoxic T cells: kill cells infected by intracellular pathogens (and cancerous cells!)
3. TCR recognises antigen bound to MHC. Once activated – clonal expansion
4. Generate memory T cells that live for >20 years

Question 2

What are the stages in T cell development?

Answer 2

1. Immature T cells migrate from BM to thymus.
2. Formation of TCR: a membrane bound protein
   composed of an a chain and b chain.
   -Each contains one variable region (V= antigen binding site) and one constant (C= doesn’t change) region.
   - During T cell development gene rearrangement
   of TCR genes (VDJ recombination) occurs and variable TCRs with unique specificities are generated.
3. Recognition of self MHC:
   -TCR interacts with MHC expressed on epithelial cells and dendritic cells in the thymus
   -Immature T cells bind MHC and get a positive signal to survive. Interaction at MHC1 or MHC2 result in positive CD8/ CD4 T cell.
4. Negative peptides:
   - If the T cell binds tightly to self peptides, it dies.
   - If it binds weakly/ moderately or not at all, it lives (neg selection)

Question 3

How are T cells activated?

Answer 3

1. Naive T cell has never met and antigen and circulate in 2nd lymphoid organs.
2. Once a TCR recognises an antigen bound to MHC on dendrocyte, the cell is activated.
3. This specific T cell clone proliferates (clonal
   expansion)
4. Naïve T cell differentiates into an effector T cell and leaves lymph node to carry out function

Question 4

What are the 3 signals required for naive T cell activation?

Answer 4

1. Antigen recognition:
   - The TCR recognises a peptide presented on MHC II molecule
   - CD4 co-receptor interacts with residues on the side of MHC class II
   - Activation of the TCR complex activates genes to produce cytokines
   - Adhesion molecules on T cells such as integrin also bind to ligands on APC to stabilise the synapse
   - T cell is primed but not fully activated.
2. Co- stimulation:
   -Microbes will stimulate APCs to express co-stimulatory receptors such as B7 (this only occurs in presence of microbes)
   - Binds to the T cell surface receptor CD28
   - This promotes survival, proliferation and differentiation of antigen-specific T cells
3. Instructive cytokines:
   - Activated APC produces instructive cytokines that aid the differentiation of certain CD4+ T cell subsets.
   - IL-12 and IFNγ stimulate Th1 subset, IL-10 stimulates Th2, IL-23 stimulates Th17.

Question 5

List the different types of T cells.

Answer 5

1. T helper cells (CD4+):
   - Th1 subset
   - Th2 subset
   - Th17 subset
   - T regulatory subset
2. Cytotoxic T cell (CD8+):
   -kill infected or altered cell – killer T cell

Question 6

What are the effector functions of the different types of helper T cells?

Answer 6

1. Th1= IFN-y cytokine: targets Macrophages & Cytotoxic T cells (intracellular pathogens)
2. Th2 = IL-4, IL-5, IL-13: Eosinophils (helminth infections) & Mast cells (Allergy) + B cells to
   produce antibodies
3. Th17 = IL-17, IL-22: Neutrophils (extracellular
   bacterial/yeast infections)
4. T reg (regulatory T cells) – the production of IL-10 helps T reg switch off Th1, Th2 & Th17 responses

Question 7

What are the effector functions of the cytotoxic T cells?

Answer 7

1. Virally infected cell will display viral antigens on MHC class I molecule.
2. Activated cytotoxic T cells bind antigen on MHC class I. They are paced with toxic enzymes for killing (perforin & granzymes).
3. They don’t kill pathogens, they kill cells infected by pathogens.

Question 8

How is self tolerance determined in T cells and why is it needed?

Answer 8

1. To prevent autoimmunity.
2. Central Tolerance: tolerance induced early development of T cells in the thymus where they eliminate most of auto-reactive T cells
3. Peripheral Tolerance: tolerance induced when T cells migrate to the lymph nodes where they eliminate
   T cells which recognise self-antigens not expressed in the thymus

Question 9

Describe T cell immunodeficiencies.

Answer 9

1. DiGeorge syndrome:
   -A deletion on chromosome 22 result in small or absent thymus = poor T cell production.
   -^ Likelihood of recurrent infections with intracellular pathogens. Associated with other congenital issues (heart problems, abnormal features etc.)
2. Severe Combined Immunodeficiency (SCID):
   - Umbrella of rare disorders caused by mutations in different genes that impact on T and B cell = low/absent T/B cells
   - Fatal in first 2 years of life, with severe bacterial, viral and fungal infections
   -X-linked severe SCID or Adenosine deaminase deficiency