7. T cells and cell-mediated immune response

Question 1

Primary lymphoid organs

Answer 1

Thymus and bone marrow

Question 2

Direction of maturation in thymus

Answer 2

Cortex -> medulla

Question 3

Two classes of TCR

Answer 3

1) αβ T cell

2) γδ T cell

Question 4

Double negative lymphocytes

Answer 4

• DN1-DN4
• In cortex
• No TCR, CD4 or CD8
• Determine αβ or γδ cell line
• Gene rearrangement of receptor chain

Question 5

γδ T cell development

Answer 5

• Cells with γδ TCR arise first in embryonic development
• γδ leave thymus without any selection
• Migrate to mucosal and cutaneous tissues: first line defence
• Recognition of antigen not MHC-restricted!!

Question 6

αβ T cell development

Answer 6

• Generation of double positive (DP) T-lymphocytes (CD4+ CD8+)
• Selected in thymus
• > Recognition of self MHC molecules (useless if not)
• > NOT recognition of self antigens (dangerous if it does)

Question 7

Positive selection

Answer 7

Aim: recognize self MHC+peptide

• Test by cortical thymic epithelial cell
• Weak/no binding -> apoptosis

Question 8

Negative selection (central tolerance)

Answer 8

Aim: differentiate self and foreign antigens.
Eliminate self-reactive T cells (bind tight to MHC+self peptide
- Test by dendritic cells
- Tight binding -> apoptosis
*Cannot eliminate T cells w/receptors specific for self peptides not expressed in thymus! These cells enter circulation.

Question 9

Promiscous gene expression

Answer 9

1% of thymic medullary epithelial cells possess this

• Express many different genes
• T cells are selected for self antigens specific for different tissues - while in thymus!

Question 10

AIRE

Answer 10

“Autoimmune regulator”: controls expression of self peptides by mTEC

Question 11

Development of single positive T cell

Answer 11

Bind to MHC I (CD8+) or MHC II (CD4+) on thymic epithelial cell

Question 12

Percentage of αβ T cells that survive selection to leave thymus as naive cells

Answer 12

Positive selection: 45 % survives

NEgative selection: 5 % survives

Question 13

Where T cell and foreign antigen meet

Answer 13

Lymph node

Question 14

How foreign antigen gets to lymph node

Answer 14

By immature dendritic cell via afferent lymphatics

Question 15

T cell activation signals

Answer 15

Signal 1:
- Binding of peptide-MHC complex by TCR+co-receptor (CD4 or CD8)
Signal 2:
- Costimulation (APC: B7-CD28)

Question 16

Activation of T cell by APC

Answer 16

1) MHC II-peptide binds TCR+CD4
2) Costimulation B7 binds CD28
3) Phosphorylation of CD3 ITAM motif
4) Signalling pathways->activate transcription factors
5) IL-2 mRNA transcribed
6) Autocrine activation by IL-2 -> T cell proliferation

Question 17

IL-2 (T cell)

Answer 17

Autocrine growth T-cell-growth-factor

Question 18

Immunological synapse leads to

Answer 18

• Lymphocyte activation
• Cytokine production
• Proliferation
• Differentiation

Question 19

Negative costimulation APC-T cell

Answer 19

B7 binds to CTLA 4

Question 20

Types of T-cells (by receptor)

Answer 20

• Conventional αβ T cells
• γδ T cell
• Non-conventional αβ NK T cell

Question 21

Types of T-cells (by role)

Answer 21

• T effector cells (cytotoxic, helper, regulatory)

- Memory T cells

Question 22

αβ T cells

Answer 22

• Naive CD8+

- Naive CD4+ (->Treg or Th)

Question 23

T helper cell examples

Answer 23

• Th1: IFNγ, TNFα, IL-2
• Th2: IL-4, -5, -13
• Th9: IL-9, -10
• Th17: IL-17, -26, -22
• Th22: IL-22
• TFh: IL-21

Question 24

Treg cytokines

Answer 24

TGFβ and IL-10

Question 25

Cytotoxic T cell (CD8+)

Answer 25

- TCR+CD8 - Fas ligand (bind Fas of infected cell) - Granules with: perforin and granzymes (released into infected cell)

Question 26

CD4+ regulator cells

Answer 26

- Treg (TGFβ and IL-10) - Tr1 (IL-10) - Th3 (TGFβ)

Question 27

CD4+ effector cells

Answer 27

- Th1 (IFNγ -> NK cells and macrophages) - Th17 (IL-17 -> Inflammatory PMNs) - Th2 (IL-4 -> Eosinophils, basophils, B-cells)

Question 28

Th1 cells

Answer 28

- IFNγ, TNFα, IL-2 - Activates Tc cells, NK cells and macrophages - Th1 and Th2 cells can inhibit eachother

Question 29

Th2 cells

Answer 29

- IL-4, -5, -13 | - Activated B-cells and eosinophils, basophils

Question 30

If CD4+ cells have intermediate avidity in thymus

Answer 30

We get Treg cells

Question 31

If CD4+ cells have moderate self/MHC avidity in thymus

Answer 31

We get effector Th cells

Question 32

γδ T cells

Answer 32

- Interact with non-protein antigens that are not processed or associated with MHC molecules - γδ TCR: pattern recognition -> activate γδ T cell -> can be either cytotoxic or helper - Immunosuppressive - Pleiotropic regulatory function

Question 33

NKT cell

Answer 33

- Direct and indirect killing of virally infected and tumor cells - Indirect: Secrete IFNγ -> activate NK or CD8+ T cell - Direct: Has TRAIL and FasL on surface -> bind their receptors on tumor cell -> NKT cell release perforin and granzymes - Has receptors for IL-12 and CD1d (on DCs)