T Cell Function

Question 1

How are T cells contributing to the pathogenesis of periodontitis?

Answer 1

…

Question 2

What are the two types of cell-mediated immunity?

Answer 2

1. CD4 helper T cells produce cytokines that activate and recruit other cells
2. CD8 cytotoxic T cells kill infected cells with microbes in cytoplasm

Question 3

Th1 cells

Answer 3

S subset of CD4 T cells; initiate inflammation and immunity by activating macrophages by secreting interferon gamma

Question 4

Th17 cell

Answer 4

A subset of CD4 T cells that are characterized by production of the cytokine IL-17. They help recruit neutrophils to sites of infection.

Question 5

describe the discovery of cell-mediated immunity

Answer 5

• Experiment showing transferable from immune animals to naive animals by T cells but not serum
• bacteria were killed in vitro by activated macrophages not T cells

Question 6

How do helper T cells develop and mediate their function? (overview)

Answer 6

Different cytokines are involved

Question 7

How is the recognition of antigen by T cell receptor very specific?

Answer 7

T cell clones express TCR that can only recognize one peptide/MHC complex

Question 8

Though TCR are very specific, presentation of antigen to T cells by APCs is very ___

Answer 8

diverse

Question 9

How is the presentation of antigen to T cells by APC very diverse?

Answer 9

• several peptides can be presented by different MHC I and MHC II molecules on the surface of the same dendritic cell
• T cells patrol LN in search of DC with the perfect fit

Question 10

Give the characteristics of CD4 helper T cell subsets

Answer 10

Th1: make IFNgamma and activate macrophages. This targets intracellular pathogens.

Th2: make IL4, IL5, and IL13 and activate eosinophils. This targets parasites (helminths) through IgE

Th17: make IL17 and IL22 and activate neutrophils. This targets extracellular pathogens.

Question 11

describe the development of T helper effector cells

Answer 11

• different cytokines are produced by DC or other innate cells that have recognized different types of microbes
• the cytokines induce different transcription factors
• transcription factors determine the fate of the helper T cells

Question 12

development of Th1 cell

Answer 12

1. intracellular microbe discovered
2. dendritic cell releases IL-12 cytokine, NK cell releases IFN-gamma cytokine
3. T cell now antigen-activated and expresses transcription factors T-bet, STAT4, and STAT1
4. Th1 cell formed

Question 13

development of Th2 cell

Answer 13

1. helminth (parasite) discovered
2. dendritic cell and mast cells and eosinophils involved, release cytokine IL-4
3. T cell now antigen-activated and expresses transcription factors GATA-3 and STAT6
4. Th2 cell formed

Question 14

development of Th17 cell

Answer 14

1. extracellular fungi or bacteria discovered
2. dendritic cell involved, releases cytokines IL-1, IL-6, IL-23, and TGF-beta
3. T cell now antigen activated and expresses transcription factors ROR-gt and STAT3
4. Th17 cell formed

Question 15

Function of Th1 cells

Answer 15

Secrete IGNgamma to induce macrophages to kill ingested microbes in classical macrophage activation (enhanced microbial killing)

Question 16

how are macrophages activated by Th1 cells?

Answer 16

• involves CD40L (on CD4 cell) and CD40 (expressed on APCs - macrophage, dendritic cell, B cells)
• involves IFNgamma secreted by CD4 cell and IFNgamma receptor
• macrophages produce cytokines, up-regulate MHC, costimulatory molecules, and microbicidal activities

Question 17

what is the response of macrophage activated by Th1 cells?

Answer 17

• secretion of cytokines TNF, IL-1, IL-12, chemokines
• increased expression of MHC and costimulators (B7 molecules)
• killing of phagocytosed bacteria

Question 18

Function of Th2 cells

Answer 18

• IL4 induces B cells to produce IgE
• IL5 induces eosinophil activation
• mediates worm elimination, mast cell degranulation, intestinal mucus secretion and peristalsis, and alternative macrophage activation (enhance fibrosis/tissue repair)

Question 19

compare classical and alternative macrophage activation

Answer 19

M1: killing (by ROS, NO, and lysosomal enzymes) and inflammation

M2: tissue repair and inhibit inflammation (happens at end of immune response)

Question 20

what triggers a monocyte to differentiate into an M2?

Answer 20

IL-13 and IL-4

Question 21

what triggers a monocyte to differentiate into an M1?

Answer 21

Microbial TLR-ligans, IFNgamma

Question 22

Functions of TH17 cells

Answer 22

• IL17 mediate recruitment of neutrophil via induction of cytokines/chemokines production from other cells
• IL22 mediates antimicrobial peptides and increased barrier integrity through epithelial cells
• important for extracellular microbes

Question 23

functions of Tfh cells

Answer 23

• found in the B cell zone
• make IL21 which mediates production of Ig (immunoglobulin) by B cells

Question 24

How do cytotoxic T cells mediate their function? (overview)

Answer 24

Recognition of antigens and killing via perforin and granzyme FasL

Question 25

cytotoxic cells of the innate immune response

Answer 25

NK

Question 26

cytotoxic cells of the adaptive immune response

Answer 26

CD8 T cells

Question 27

describe the killing by CD8 CTL

Answer 27

- antigen recognition and binding of CTL to target cells: CTL binds to target cells via ICAM-1 (target cells)--LFA-1 (CD8 cell) interaction - Perforin and granzyme released from granules mediates killing: perforin facilitates entry of granzymes into the cytosol, grandames activate apoptosis

Question 28

Describe FasL-mediated killing by CD8 CTL

Answer 28

- activated CTL express FasL - FasL binds to Fas on target cells and induces cell death - minor role in killing (homeostasis - perforin and granzyme major killers)

Question 29

describe the cooperation between Th1 cells, CD8 cells, and macrophages in killing intracellular bacteria

Answer 29

- Th1 cells activate macrophage using IFNg to lyse intravesicular microbes - CD8 kill infected cells with the help from Th1 cells (for cases when microbe is in the cytoplasm and not the phagolysosome)

Question 30

describe the response of CD8 cells to acute or chronic viral infection

Answer 30

- acute infection induces a protective response; memory T cells form in case re-infected - chronic infection induces expression of inhibitory molecules and leads to exhaustion

Question 31

How do Th17 cells play a role in periodontitis?

Answer 31

- Th17 contribute to the inflammation through IL-17 (inflammation already present with neutrophils) - Th17 induce fibroblasts to produce G-CSF (further neutrophil recruitment and granulopoeisis and mobilization in the bone) - G-CSF recruit more neutrophils