11 - Adaptive Lymphoid Cells: T cells

Question 1

Repertoire of T cell receptors

Answer 1

Repertoire of T cell receptors is of equal diversity to the peptides presented by MHC molecules

Question 2

2nd type of receptor

Answer 2

• 2nd type of receptor – γ & δ
• ca. 1–5% of T-cells in blood
• More common in epithelial-rich tissues such as the skin, intestine, lungs (almost 50% of the T-cell population)

Question 3

How many kinds of signals do APC deliver?

Answer 3

Three
1. activation
2. survival
3. differentiation

Question 4

Activation of T cell dependent on co-binding

Answer 4

1. TCR to MHC Class II
2. B7 of APC to receptors, e.g. CD28

Question 5

What happens with only one signal?

Answer 5

• co-stimulatory signal alone - no effect on T cells
• antigen-specific signal alone - inactivation (energy) or deletion of T cell, decreased TCR signalling through induction of GRAIL and activation of Cbl

Question 6

CD8 T cells

Answer 6

CD8 T cells - the killers

1. stimulation of naive cell T cell - RECOGNITION
2. proliferation T cell - PROLIFERATION/DIFFERENTION - cell both secretes/responds to IL-2
3. active effector T cell kill virus infect targets cell - EFFECTOR FUNCTION - differentiated cytotoxic cell: now responds on recognition of specific antigen alone

Question 7

CD4 T cells

Answer 7

CD4 T Cells – the little helpers
- TH1 cells, TH2 cells, TH17 cels, TFH cells, Treg cells

Question 8

CD4+ TFH Cells – the specialized little helpers

Answer 8

• Specialized subset (1st identified in human tonsils)
• TFH found in the B cell zone of 2° lymphoid organs and in circulation
• Major function is close interactions with B cells.

Question 9

Function TFH cells

Answer 9

• TFH essential for germinal centre formation during an ongoing
  immune response.

(1) TFH provide co-stimulation to B cells via
CD40 interaction
(2) IL-21 drives B cell proliferation

• Additional cytokines from TFH determine
  class of Ab produced

Question 10

CD4+ /CD25 – the regulators (natural vs adaptive tregs)

Answer 10

• Natural Tregs: produced by a normal thymus
• Adaptive Tregs: formed by differentiation of naïve T cells outside the thymus, i.e. in peripheral tissues

Question 11

Tregs

Answer 11

• Expression of nuclear transcription factor Forkhead box P3 (FoxP3) defining feature of natural Treg development and function
• Additional markers of natural Tregs are CD152 (CTLA-4) and GITR (glucocorticoid-induced TNF receptor),

Question 12

What is the failure rate of T cells?

Answer 12

• T cells have high ‘failure rate’ – 98% deleted in thymus due to self-reactivity.
• Diversity generated by T cell receptor

Question 13

What are T cells divided into?

Answer 13

• T cells divided into CD8+ (cytotoxic) and CD4+ (helper) cells, as well as T regulatory cells, characterized by FOXP3 transcription factor

Question 14

What is required for T cell activation?

Answer 14

Two signals required for T cell activation: binding via MHC & TCR, as well as B7 (from APC) binding to T cell CD marker

Question 15

What do cytokines direct?

Answer 15

Cytokines direct the development of naïve T cells into their TC TH or Treg subsets

Question 16

What stimulates killing activity of macrophages?

Answer 16

TC kill virus/intracellular pathogen infected cells and cancer cells. TH stimulate killing activity of Mφ, Ab production by B cells, recruit and stimulate other cell types

Question 17

What do Treg cells do?

Answer 17

*TREG cells regulate – inhibit activation of immune cells