Lecture # 18 T cell Effector Function

Question 1

How many signals activate naive T cells?

Answer 1

1 TCR: MHC-Peptide interaction; # 2 CD28:B7-1/B7-2 interactions; #3 cytokine signals delivered by APCs

Question 2

Signal 1 without signal 2 induces______

Answer 2

Anergy

Question 3

Why are CD4 cells important in CD8 cell activation?

Answer 3

1) CD4+ by definition are helper T cells 2) CD4 sends signals to the APC that then upregulates 4-1BBL to interact with 4-1BB on CD8 Cells; CD4+ cells also help by producing cytokines that stimulate CTL differentiation (through the APCs)

Question 4

What receptors are lost to keep T lymphocytes out of lymph nodes?

Answer 4

CCR7,CD69 and L-Selectin

Question 5

What receptors do DCs express that are important for T cell activation?

Answer 5

1) MHC bound with its peptide 2) B7-1 and B7-2; One cell must deliver each signal

Question 6

Where does co-stimulation occur?

Answer 6

Stimulation occurs in the draining lymph nodes

Question 7

How many days does it take for activated T cells to differentiate into effector cells?

Answer 7

4-5 days

Question 8

What cytokine does Th1 T cells make? What is its function?

Answer 8

IFN g; activates macrophages; IgG production; fights against intracellular microbes

Question 9

What cytokine does Th2 T cells make? What is its function?

Answer 9

IL-4 (helps B cells make antibodies) ; IL-5; IL-13; Activate mast cells, eosinophilsl IgE production; “alternative” macrophage activation; works against helminthic parasites; plays a role in autoimmune disease; tissue damage associated with chronic infections.

Question 10

What cytokine does Th17 T cells make? What is its function?

Answer 10

IL-17 (acts on neutrophils); neutrophilic, monocytic inflammation; fights against extracellular bacteria and fungi

Question 11

What cytokine does CD4 + Treg make? What is its function?

Answer 11

TGF-B inhibits DC and activated T cells; plays a role in autoimmune inflammatory disease

Question 12

Th1 differentiation

Answer 12

;Th1 cells require IL-12 and IFNg signaling through those cytokine R induce STAT 4 and STAT 1, which upregulates T-bet and switches on T cell expression of IFN-g and IL-12R—this “fixes” development of Th1 lineage; IL-12 (DC) and IFN g (NK) are produced when viruses and bacteria interact with DCs and NK cells.

Question 13

T-bet

Answer 13

master transcription factor that induces the expression of interferon gamma in Th1 cells

Question 14

STAT 4 and STAT 1

Answer 14

transcription factors that work with T-bet to induce expression of IFN g

Question 15

Th2 differentiation

Answer 15

Worms and some other parasites induce IL-4 that push Th2 differentiation; • Th2 cells require IL-4, signaling through this cytokine R induces STAT6, which upregulates GATA-3 and switches on T cell expression of IL-4—this “fixes” development of Th2 lineage

Question 16

Th17 differentiation

Answer 16

Bacteria and fungi induce IL-6 and TGF-b that push Th17 differentiation (Extracellular pathogens); Th17 cells require TGF-b and IL-6, signaling through those cytokine R induce STAT3 which upregulates RORgT. RORgt leads to the production of IL-21; Th17 cells produe IL-17 and IL-22

Question 17

In the absence of infection, how are Tregs induced?

Answer 17

In the absence of infection, Treg cells are induced by DC production of TGF-b and low IL-6; • Treg cells require TGF-b, which upregulates FoxP3 and switches on T cell expression of TGF-b and IL-10—this “fixes” development of Treg lineage

Question 18

How are Tregs produced?

Answer 18

Produced naturally in the thymus during thymocyte development and are inducible during immune response-develop from naïve CD4 cells and downregulate immune responses after antigen is cleared by downregulating IL-2 or inhibiting antigen presentation

Question 19

How do TH1 cells activate macrophages?

Answer 19

Th1 effectors recognize pathogen peptide in class II and send signals to Mf through CD40 and IFN-g signals ; CD4 effectors provide additional activating signals to Mf to help kill intracellular pathogens; Macrophages and NK cells are induced to produce ROS, NO to kill pathogens and also produce inflammatory cytokines.

Question 20

How do Th2 cells handle worm (parasitic infections)?

Answer 20

Th2 responses induces IL-4 and IgE production(that activate mast cells) and IL-5 (which activates eosinophils) ; IL-4 and IL-13 also have effects on macrophages for tissue repair; also contribute to airway allergies and asthma

Question 21

How do TH17 cells combat Bacteria and Fungi?

Answer 21

Th17 responses induce neutrophils – help with anti-bacterial and anti-fungal responses; Important at barrier sites-gut immunity

Question 22

What cytokine does Th1 cell make?

Answer 22

IFNg; which helps to activate macrophages; intracellular microbe defense

Question 23

What cytokine does Th2 cell make?

Answer 23

IL-4; helps B cells make antibodies; helminthic parasites and allergies/IgE

Question 24

What cytokine does Th17 cell make?

Answer 24

IL-17; which acts on neutrophils; extracellular fungi and bacteria

Question 25

What cytokine does Treg cell make?

Answer 25

TGF-B; inhibits DC and activated T cells

Question 26

Signal 3 for Treg

Answer 26

TGF-B, which upregulates FoxP3, causing expression of IL-10 and TGF-B

Question 27

Signal 3 for Th17 cells

Answer 27

TGF-B; IL-6; signaling through STAT3, which upregulates RORgt leading to IL-17/22 expression

Question 28

Signal 3 for Th1 cells

Answer 28

IL-12 (DC); IFNg (NK cells); signaling through STAT1/4, which upregulates T-bet, leading to IFNg and IL-12R

Question 29

Signal 3 for Th2 cells

Answer 29

IL-4; signaling through STAT6, which upregulates Gata-3

Question 30

Tuberculoid Leprosy vs lepromatous leprosy

Answer 30

T. Leprosy- Th1 response mounted, low levels of bacteria; L.leprosy- Th2 responses, ineffective, high levels of bacteria

Question 31

Immunological Synapse formation

Answer 31

1) LFA-1 binds to ICAM on APC 2) CD8+ cell produces Granzymes and perforin that kill infected cells

Question 32

pSMAC

Answer 32

LFA-1:I-CAM1

Question 33

cSMAC

Answer 33

TCR, CD4, CD28, MHC:Peptide