T cells; Activation and Differentiation

Question 1

Initial events of CD4+ activation?

Answer 1

Occurs in secondary lymphoid tissues
Brings together CD4+ t, antigen, and antigen-presenting cells

CD4+ enter lymph nodes through HEVs, expressing CCR7
Attracted to CCL21 on HEVs

Activated DCs with MHCII-antigen and CCR7 enter through afferent vessels, also to CCL21

Question 2

Activation of CD4+?

Answer 2

Requires two signals - antigen on MHCII DCs and stimulatory molecules
e.g. CD28 (T cells) bind CD80/86 on DCs

Question 3

Lack of co-stimulatory molecule?

Answer 3

Anergy from T cells; unresponsive to antigen

Question 4

How are DCs specialised to activate T cells?

Answer 4

MHCII-antigen presentation and CD80/86 upregulated in response to PRR recognition of pathogen

Question 5

T and D cell adhesion?

Answer 5

Adhesion molecules:
ICAM-1 on DC
LFA-1 (integrin) on T
= loose adhesion
On antigen recognition:
CD4 on T
MHCII on DC
= increases affinity of LDA1/ICAM1 for tight binding

Question 6

How and where do T and DC cells come into contact?

Answer 6

At immunological synapse
TC4/MCHII, co-stim molecules and others cluster in supramolecular activation clusters (SMACs)
pSMAC (peripheral) = LFA1/ICAM1
cSMAC (central) = tight binding

Question 7

After activation events?

Answer 7

Intracellular signalling in T, through interaction with CD3 complex
CD28 directly triggers signals

Clonal expansion occurs - start expressing IL2 cytokine and secreting it to drive this
IL-2 interacts with CD25 (alpha unit of IL-2 receptor) which is upregulated

Question 8

Why must T cells differentiate?

Answer 8

Cope with variety of different pathogens which cause wildly different responses
Relies on cytokines from Th cells

Question 9

Th subsets?

Answer 9

Th1 - intracellular pathogens, produce IL-2, IFN-y and LT
= macrophages, CD8 T, opsonising antibodies
Th2 - extracellular pathogens, produce IL-4, 5, 9, 13
=neutralising antibodies, granulocytes (eosinophils and basophils)

Question 10

Differentiation to Th?

Answer 10

Needs a cytokine signal

For Th1 - IL-12, IFNy
Th2 - cytokines from epithelial cells, IL-4

Question 11

Cross-regulation of differentiation?

Answer 11

Th1 downreg Th2 with IFN-y

Vice versa with IL-4

Question 12

Other Ths?

Answer 12

Effectors e.g. Th17, Tfh

Regulatory e.g. Tregs

Question 13

Th17 cells?

Answer 13

Lungs and intestine, think works at epithelial surfaces
Secrete IL-17, 21 and 22
Driven by TGFbeta, IL 6 and 1
Fungal and bacterial role

Question 14

Tfh cells?

Answer 14

Move to B cell follicles in germinal centres to help B cells differentiate

Question 15

Tregs?

Answer 15

Help reduce autoimmunity by suppressing self-harmful T cells
Can be thymic (natural) - express Foxp3, in thymus in normal development
Or can be induced (peripheral) - from naice CD4+ induced by cytokines like IL-2 or TGFbeta

Produce TGFbeta and IL10

Question 16

T cell plasticity?

Answer 16

Subsets can morph into one another