T-Cell Mediated Immunity

Question 1

What is the role of TCR in mature T cells?

Answer 1

Antigen recognition

Question 2

What is the role of CD4/CD8 in mature T cells?

Answer 2

Cell surface markers

CD4+ cells activate B cells and macrophages

Question 3

What is the role of CD3 in mature T cells?

Answer 3

Makes the TCR complex with zeta for signal transduction

Question 4

What is the role of CD28 in mature T cells?

Answer 4

Constitutively activated, involved in signal transduction (costimulation)
Activated by CD80 ligand which is found on APCs

Question 5

What is the role of CTLA-4 in mature T cells?

Answer 5

Inhibitory receptor, activated by CD80 on APCS and competitively inhibits CD28

Question 6

What is the role of PD-1 in mature T cells?

Answer 6

Inhibitory receptor, activated by PD-L1 and 2 on APCS, tissue cells, and tumor cells

Question 7

What is the role of L-selectin in mature T cells?

Answer 7

Involved in the initial weak adhesion of naive T cells to HEV in lymph node

Question 8

What is the role of LFA-1 in mature T cells?

Answer 8

Adhesion molecule that binds with ICAM-1 to stablely arrest T cells on HEV. Also involved in signal transduction

Question 9

What is the role of CCR7 in mature T cells?

Answer 9

Chemokine receptor that allows lymphocytes to go in and out of tissue by activating integrins and chemotaxis

Ligand on epithelial cells= CCL19 and CCL21

Upregulated when peripheral DC cells are activated allowing the DCs to get to where the T cells are aka lymphatic endothelium and present the Ag

Question 10

How do mature, naive T lymphocytes migrate in the lymphoid tissue?

Answer 10

Enter lymph nodes across the HEV in the cortex where it is able to sample antigen from peripheral

This is done through L-selectin, LFA-1 (b2-integrin), and CCR7

Question 11

What is the role of L-selectin in the migration of mature naive lymphocytes?

Answer 11

Binds with L-selectin ligand for the intial weak adhesion of naive T cells to the HEV in the lymph node

Question 12

What is the role of LFA-1 in the migration of mature naive lymphocytes?

Answer 12

Binding by ICAM-1 causes stable arrest on the HEV

Question 13

What is the immune synapse between an antigen presenting cell and a T Cell?

Answer 13

How an APC is able to present an antigen to a T cell leading to activation and differentiation.

Question 14

What ligands and costimulators are involved leading to activation of the immune synapse between APC and T cells?

Answer 14

CD4 for signal transduction
TCR which binds to Class II MHC on APC
CD3 for signal transduction and amplification
CD28 and CTLA4 which bind to CD80(B7) for signal transduction
LFA-1 with ICAM-1 for adhesion, goes from low to high affinity

Question 15

How are T cells activated?

Answer 15

1. Initiation of formation of the immunologic synapse
2. Activation of ITAMs: Lck and Src kinases associated with CD4 and CD8, phosphorylate and activate tyrosine kinase ZAP70 which is associated with the zeta chain

Question 16

What is the principal action of IL-2? What is its cellular source?

Answer 16

T cell proliferation and regulatory T cell survival
Autocrine signal of T-cell survival that binds IL-2R
Receptor becomes IL-2Ralpha after binding= CD25, allows for more robust proliferation

Activated T cells

Question 17

What is the principal action of Interferon-gamma? What is its cellular source?

Answer 17

Activation of macrophages

CD4+ and CD8+ T cells, NK cells

Question 18

What is the principal action of IL-4? What is its cellular source?

Answer 18

B cell switching to IgE

CD4+ T cells, mast cells

Question 19

What is the principal action of IL-5? What is its cellular source?

Answer 19

Activation of esonophils

CD4+ T cells, mast cells, innate lymphoid cells

Question 20

What is the principal action of IL-17? What is its cellular source?

Answer 20

Simulation of acute inflammation

CD4+ T cells and other cells

Question 21

What is the principal action of IL-22? What is its cellular source?

Answer 21

Maintenance of epithelial barrier function

CD4+ T cells, NK cells, innate lymphoid cells

Question 22

What is the principal action of TGF-beta and IL-10? What is its cellular source?

Answer 22

inhibition of T cell activation, differentiation of regulatory T cells

CD4+ T cells and many other cells

Question 23

What is the role of S1PR in the egress of T cells from lymph nodes?

Answer 23

CD69 binds to S1PR “trapping” the T cell so that is around long enough to mature and activate

Question 24

What is the functional response of Th1 CD4+ Effector T cells? What are its defining cytokines and TF?

Answer 24

Involved in macrophage activation (classical, phagocyte) against intracellular pathogens via secretion of IL-2 and IFN-gamma
Induce cytotoxic protein synthesis
Cytokine support of activation and proliferation of CTLs, provide support for cross presentation which is often necessary for CD8+ activation via IFN-gamma
IFN-gamma stimulates class II HLA and B7

IFN- gamma and IL-12
TF= t-bet

Question 25

What is the functional response of Th2 CD4+ Effector T cells? What are its defining cytokines and TF?

Answer 25

Occurs in response to allergens and helminths

• mast cell activation
• mucus production
• IgE class switching to support alternative macrophage development
• IgA
• Eosinophil activation
• all via secretion of IL-4, IL-5, and IL-13

IL-4
TF= GATA-3

Question 26

What is the functional response of Th17 CD4+ Effector T cells? What are its defining cytokines and TF?

Answer 26

Response to bacteria and fungus
Induction of inflammation and leukocyte recruitment
Secrete IL-17 and IL-22 which are important in barrier function and neutrophil activation

Proliferate in response to IL-1 and IL-16 (acute phase cytokines)
Novel TF= RORyt

Question 27

What is the functional response of Tregs CD4+ Effector T cells?

Answer 27

Constitutively express CTLA-4 and CD25, CTLA-4 binds to B7 and shuts off co-stimulatory ligand signaling (competitively inhibits CD28)

Question 28

What is the mechanism of CTL (CD 8+ cytotoxic) mediated killing via granzymes and perforin?

Answer 28

1. Antigen recognition and binding of CTL to target cells
2. CTL activation and granule exocytosis –> release of granzymes which activate caspases and perforin which is necessary fro delivery of granzymes
3. Apoptosis

Question 29

What is the mechanism of CTL (CD 8+ cytotoxic) mediated killing via Fas/FasL

Answer 29

Activated CTLs express FasL which binds to death receptor Fas leading to activation of caspases and apoptosis of Fas-expressing targets
Acts as a “serial killer”
Works with IFNalpha/beta produced by NKs and DCs to inhibit replication of virus and increase expression of MHC I on other infected cells

Question 30

What cooperation between CD4+ and CD8+ T cells is necessary in eradicating intracellular infections?

Answer 30

Need cooperation between CD4+ and CD8+ T cells because if macrophage can’t kill then you have CD8 to help out after CD4+ recognizes

Question 31

How is PD-1 involved in the contraction of T cell mediated immune response to homeostasis?

Answer 31

Inducible on T, B and myloeid cells leading to shut down of signaling via ITIM

Question 32

How is Anergy and Tolerance involved in the contraction of T cell mediated immune response to homeostasis?

Answer 32

If T-cells recognize antigen without binding of co-stimulatory ligands or cytokine support they will not be activated

Question 33

What is the first signal of T cell activation?

Answer 33

binding of MHC/peptide complex to TCR via CD3 and zeta

Question 34

What are the second signals of T cell activation?

Answer 34

CD40L upregulated on T cells and CD40 constitutively expressed on APC –> CD40-CD40L interaction
CD80 (B7) upregulated on APCS and CD28 constitutively activated on T cells –> cytokine production

Maintains the specificity of the response to the epitope

Question 35

How does mycobacteria evade immune response?

Answer 35

Inhibition of phaolysosome function, just hangs out in the phagosome

Question 36

How does HSV evade the immune response?

Answer 36

Inhibition of antigen presentation by interferring with TAP transporter

Question 37

How does CMV evade the immune response?

Answer 37

Inhibition of antigen presentation: inhibition of proteasomal activity, removal of class I MHC from ER

Question 38

How does EBV evade the immune response?

Answer 38

Inhibition of antigen presentation: inhibtion of proteasomal activity
Production of IL-10 –> inhibition of macrophage and DC activation

Question 39

How does Pox virus evade the immune response?

Answer 39

Inhibition of effector cell activation: production of soluble cytokine receptors

Question 40

How do activated Th cells migrate?

Answer 40

After activation by APCs in medulla they change their chemokine receptors (CCR7 expression down and CXCR25 up) and migrate to the edge of the follicular zone aka where they can meet up with B cells

Question 41

What are gamma delta T cells?

Answer 41

Make up less than 5%
found at epithelial boundaries especially in the gut mucosa
Not restricted by Ag

Question 42

How are antigen specific T cells retained in peripheral tissue?

Answer 42

New selectins and inefrins expressed:
VLA binds to ICAM and fibronectin for stable arrest
P and E selectins= weak adhesion to cytokine activated endothelium
CD44 binds to hyaluronoan allowing T cell to be tethered and interact with classical macrophages via CD80

Question 43

What are the mechanisms of NK cell killing? What enhances and inhibits it?

Answer 43

Kill by granzymes and perforin
Enhanced by IFN alpha and beta and IL-12
Inhibited by MHC class I
Surface markers= CD16 and CD56

Question 44

What are memory T cells?

Answer 44

Activated t cell differentiate into effector and memory, most become short-lived effector
Require reactivation to regain their effector function and IL-7 and IL-15 for survival
Able to respond more rapidly than naive