T cell mediated immunity

Question 1

Th1 Inducing cytokines, transcription factors, signature cytokines, and role

Answer 1

Inducing cytokines: IL-12
Transcription Factors: STAT4, T-bet
Signature cytokines: IFN-gamma, TNF

Induced by microbes that are ingested by phagocytes.

Promotes phagocyte mediated (macrophages) killing of INTRACELLULAR microbes via IFN-gamma and CD40L

Promotes IgG production and opsonization as well as complement binding

Involved in autoimmune diseases; tissue damage associated with chronic infections

Question 2

Th2 Inducing cytokines, transcription factors, signature cytokines, and role

Answer 2

Inducing cytokines: IL-4
Transcription factors: STAT6, GATA3
Signature cytokines: IL-4, IL-5, IL-13

Induced by parasitic worm infections

Promote IgE-, mast cell, and eosinophil-mediated destruction of parasites

Inhibit macrophage activation as helminths are too large to be consumed by macrophages.

Involved in allergic reactions to environmental Ags.

Question 3

Th17 Inducing cytokines, transcription factors, signature cytokines, and role

Answer 3

Inducing cytokines: TGF-beta, IL-6
Transcription Factors: ROR(gamma)t, STAT3
Signature cytokines: IL-17, IL-22

Induced by EXTRACELLULAR bacterial and fungal infections.

Promote inflammatory reactions that destroy EXTRACELLULAR bacteria and fungi, by recruiting neutrophils and monocytes

Involved in autoimmune inflammatory diseases

Question 4

Treg Inducing cytokines, transcription factors, signature cytokines, and role

Answer 4

Inducing cytokines: TGF-beta, IL-2
Transcription Factors: FoxP3, STAT6
Signature cytokines:TGF-beta, IL-10, IL-35

Question 5

How is NFAT activated in TCR signal transduction?

Answer 5

• TCR engaged with Ag
• LCK kinase (associated with CD4/CD8) activated; phosphorylates zeta chain ITAM in CD3
• ZAP-70 binds to ITAMs and are also phosphorylated by LCK
• ZAP-70 phosphorylates LAT and SLP-76 (scaffolds)
• Activated LAT recruits GADS and GRB2
• GRB2 phosphorylates PLC1
• PLC1 produces IP3 and DAG
• IP3 leads to increase free Ca2+, which causes NFAT production

Question 6

How is NF-(kappa)B activated in TCR signal transduction?

Answer 6

• TCR engaged with Ag
• LCK kinase (associated with CD4/CD8) activated; phosphorylates zeta chain ITAM in CD3
• ZAP-70 binds to ITAMs and are also phosphorylated by LCK
• ZAP-70 phosphorylates LAT and SLP-76 (scaffolds)
• Activated LAT recruits GADS and GRB2
• GRB2 phosphorylates PLC1
• PLC1 produces IP3 and DAG
• DAG activates PKC and Ras/Rac
• PKC activates NF-(kappa)B

Question 7

How is AP-1 activated in TCR signal transduction?

Answer 7

• TCR engaged with Ag
• LCK kinase (associated with CD4/CD8) activated; phosphorylates zeta chain ITAM in CD3
• ZAP-70 binds to ITAMs and are also phosphorylated by LCK
• ZAP-70 phosphorylates LAT and SLP-76 (scaffolds)
• Activated LAT recruits GADS and GRB2
• GRB2 phosphorylates PLC1
• PLC1 produces IP3 and DAG
• DAG activates PKC and Ras/Rac
• Ras/Rac when activated (bound to GTP) activate MAPK
• MAPK activates ERK and JNK
• ERK induces expression of c-Fos and JNK phosphorylates c-Jun
• Together c-Fos and phosphorylated c-Jun combine to form AP-1

Question 8

T Cell Costimulator Receptor CD28

Answer 8

Stimulator

Binds to either B7-1 (CD80) or B7-2 (CD86)

Question 9

T Cell Costimulator Receptor CTLA-4

Answer 9

Inhibitor
CTLA-4 activation matches stimulatory signaling to TCR, which makes CTLA-4 a signal dampener.
Binds to either B7-1 (CD80) or B7-2 (CD86)

Question 10

T Cell Costimulator Receptor ICOS

Answer 10

Inducible T Cell Costimulator

Stimulator

Question 11

T Cell Costimulator Receptor PD-1

Answer 11

Program death - 1
Inhibitor
Negative regulations of T cells