B and T Cells and MHC

Question 1

where are T cells derived from?

Answer 1

derived from bone marrow stem cells

Question 2

what happens to T cell precursor cells?

Answer 2

• arrive in thymus
• spend 7-12 days undergoing differentiation and proliferation
• become mature, but antigen naive, phenotype

Question 3

what are the steps of thymine education (educating T cells)?

Answer 3

1. small double thymocytes (CD4, CD8) initially express low levels of TcRs
2. most TcRs wont recognise MHC so T cells die due to lack of positive selection
3. cells that do see MHC mature and express high levels of TcR, and lose CD4 or CD8 to become single positive cells
4. T cells undergo ‘negative selection’ to eliminate those with high MHC affinity i.e. potentially autoreactive

Question 4

what is the structure of T cells?

Answer 4

• two polypeptide chains, membrane bound
• V (variable) and C (constant) region
• cytoplasmic tail
• antigen binding site

Question 5

what is the main difference between antibodies and TcR?

Answer 5

• antibodies bind the antigen on its own

- TcR only recognise an antigen bound by MHC (TcR recognition of antigen is MHC restricted)

Question 6

what are features of MHC class I?

Answer 6

• two chains: heavy and small β2-microglobulin
• upper surface forms a groove into which small 8-10 AA peptides sit
• expressed on almost every cell in body

Question 7

what are features of MHC class II?

Answer 7

• two chains, α and β, membrane bound
• upper surface forms groove into which longer peptides, 20+ AA, sit
• expression more limited to specialised antigen presenting cells and immune cells e.g. macrophages, dendritic cells, B and T cells

Question 8

which T cells recognise MHC class I?

Answer 8

CD8

Question 9

which T cells recognise MHC class II?

Answer 9

CD4

Question 10

what type of peptides do MHC class I pick up?

Answer 10

• mostly derived from internal contents of cells e.g. cytoplasm, nucleus
• meets peptides in endoplasmic reticulum (ER)

Question 11

what type of peptides do MHC class II pick up?

Answer 11

• derived from external sources i.e. outside cells

- meets peptides in endosomes

Question 12

where are polymorphisms located on MHC molecules??

Answer 12

in the peptide-binding groove - means each different MHC molecule will present different peptides to the immune system

Question 13

MHC molecules are associated with autoimmune diseases, for example:

Answer 13

• ankylosing sponylitis
• MS
• type I IDDM
• rheumatoid arthritis

Question 14

why is immunosuppression still required with a full transplant match?

Answer 14

even if full match obtained, still enough different peptides (minor transplantation antigens) to trigger slow graft rejection

Question 15

in what forms of cancer does B and T cell development play a role?

Answer 15

• acute lymphoblastic leukaemia (ALL)
• thymoma
• adult T cell leukaemia
  Hodgkin’s disease

Question 16

what are superantigens?

Answer 16

proteins produced by some bacteria/viruses that interfere with interaction of TcR and MHC, stimulating large numbers of T cells

Question 17

what is DiGeorge’s syndrome?

Answer 17

failure to develop thymic epithelia, few T cells produced

Question 18

where are the polymorphisms located?

Answer 18

in the peptide-binding groove

Question 19

what are examples of super-antigens?

Answer 19

• staphylococcal enterotixin (SEB)

- toxic shock syndrome (TSST-1)