Lecture #6

Question 1

T cell direction of maturation in the thymus

Answer 1

Cortex to medulla

Question 2

What is the first stage of T cell maturation in the thymus

Answer 2

Double negative selection T cell precursor mature to double negative T cell by 4 stages DN1 DN2 DN3 DN4 No coreceptors or TCR, gene rearrangment starts *DN2 T cells can proceed to become DN3 or gamma/delta T cells that leave the thymus

Question 3

What is the second stage of T cell maturation in the thymus

Answer 3

Double positive selection After gene rearrangment had terminated the alpha/beta T cells express both CD4+ and CD8+ In this process it is checked if the TCR can recognize self MHC molecules and bind them

Question 4

What is the third stage of T cell maturation in the thymus

Answer 4

Single positive selection Occurs at the border between the medulla and cortex and mediated by cTEC (cortical thymic epithelial cells)

Question 5

What is the fourth stage of T cell maturation in the thymus

Answer 5

Negative selection

Occurs in the medulla and mediated by mTEC which are capable of presenting almost every self antigen

Promiscus antigen presentation

This is possible dur to AIRE transcription factor

Question 6

DC can also participate in the negative selection, how?

Answer 6

By cross dressing and fusion with exosomes from mTEC they can express MHC molecules with self antigens.

Question 7

Where does T cell activation occurs?

Answer 7

In secondary lymphoid organs

Question 8

What are the 3 signals necessary for T cell activation?

Answer 8

1. Binding of the MHC peptide complex to TCR
2. Costimulation by the partner APC mediated by the binding of B7 and CD28
3. Autocrine signal by the secretion of IL2

Question 9

SCID severe combined immunodeficiency

Answer 9

Can develope due to IL2R defect

(The receptor for IL2, 4, 7, 9, 15, 21)

Question 10

Possible results of an immunological synapse

Answer 10

Lymphocyte activation, cytokinne secretion, proliferation, differentiation, negative feedback

Question 11

Alpha beta memory cells

Answer 11

Some effector T cells will become long lived memory cells upon costimulatory signal from an APC

1. Tcm central memory wait in the borders of secondary lymphoid organs, able of self renewal and become effector T cells upon activation

(CD40) and autocrine signal (IL2)

2. Tem effector memory wait along the entry points of pathogens and capable of differentiating int effector cells within hours

Question 12

Th1 Induction by DC

Answer 12

In the thymus

DC secrete IL12

in turn naive T cell will become Th1 secreting IFN gamma, TNF alpha, IL12, IL2

Inducing cellular immune response

(NKC, macrophages and Tc)

Question 13

Th2 Induction by DC

Answer 13

In the thymus

Activation of neutrophils by DC

Neutrophils secrete IL4

Naive T cell will become Th2 secreting IL4, 5, 10, 13

Inducing B cells and anti inflammatory response

Question 14

Th17 Induction by DC

Answer 14

In the thymus

DC secrete IL23

Naive T cells become Th17 secreting IL17

IL17 activates neutrophils

Question 15

Treg Induction by DC

Answer 15

In the periphery

DC secrete TGFbeta

Naive T cells become Treg secreting IL10 TGF beta

Question 16

T cell homing to the site of injury is induced by ___ which increase the expression of ________

In skin injury they induce…

In intestinal injury they induce…

Answer 16

DC

Chemokine receptors and integrins

CCR10, CCR4, P and E selectin

CCR9

Question 17

Gamma/ delta T cells

Answer 17

Do not undergo selection in the thymus and migrate to mucosal surfaces

Ag recognition is not MHC restricted since they have other receptors like TLR, NKG2D

When activated they can act like Th or Tc

Question 18

iNKT cells

Answer 18

Invariant alpha chain of the TCR enables them to bind to glycolipid Ags presented on CD1 molecules

Cytotoxicity