T Cells

Question 1

List the six main types of T cells

Answer 1

1. Th1
2. Th2
3. Thfh
4. Th17
5. ThReg
6. CTL

Question 2

Th1 function:

Answer 2

first called delayed hypersensitivity T cells, when circulating and they encounter antigen they secrete lymphokines, most importantly, interferon gamma, a pro-inflammatory and chemotactic for blood monocytes and macrophages. Monocytes and macrophages move into the area and are activated by interferon gamma becoming “classically activated M1”—ANGRY MACROPHAGES. These ingest and kill bacteria/invaders. The macrophages release their own cytokines that increase inflammation including tumor-necrosis factor alpha or IL-1.

Question 3

Th17 function:

Answer 3

makes pro-inflammatory lymphokine IL-17. Resembles Th1 in that its main job is inflammation. Implicated in several autoimmune diseases. Even angrier macrophages

Question 4

Th2 function:

Answer 4

circulate through blood until they encounter antigen. Secrete IL-4 and IL-13 which attract and activate macrophages, but differently than IFNgamma. This is called “alternatively activated M2”. Involved in HEALING (debris removal, scar formation, walling off pathogens). IL-4 is chemotactic for eosinophils what are specialized to kill worms and protozoans. Th2 give rise of Th2 –like follicular cells that go into lymphoid follicles and secrete IL-4 which pushes B cells to swtich from IgM/IgD to make IgE (antibody of parasite resistance and allergy). Th2= 2 roles in parasites, 1: M2 macrophages and 2: stimulate B cells to make IgE.

Question 5

Thfh function:

Answer 5

DC arrives in lymph node, some activated follicular helper T cells migrate into follicles of cortex where B cell are abundant. They help B cells that have recognized antigen become activated and differentiate into antibody secreting plasma cells. Tfh secrete cytokines and direct B cells to switch from IgM to IgG, IgA or IgE. Tfh in the gut switch B cells to IgA, Tfh in the spleen switch B cells to IgG. Without Tfh, it would be hard to make any antibody class, especially those downstream from Ig.

Question 6

ThReg function:

Answer 6

5% of T helper cells, suppresses the activation and function of other T helper cells. Most are CD4+/CD5+. They product TGFbeta and IL-10. Very potent (1 can suppress 1000 Th cells).

Question 7

CTL function:

Answer 7

signals the target cell to commit suicide by activating apoptosis that leads to rapid DNA fragmentation and nuclear collapse. 2 methods: 1. Activate Fas (CD95) “death receptor” on the target (CTLs bear the Fas ligand, CD95L). 2. Secrete contents of lytic granules which contain proteases called granzymes and perforins that allow penetration of granzymes into target cell—apoptosis.

Question 8

Discuss the positive and negative interactions between Th1, Th2, and Treg cells

Answer 8

d. SIBLING RIVALRY: Th1 and Th2. IFNgamma (made by Th1) suppresses Th2 differentiation. IL-4 (made by Th2) suppresses Th1. BALANCE EACH OTHER.
* **Treg?

Question 9

Describe the surface markers that can be used to distinguish between T and B cells in humans

Answer 9

a. T cells have CD3 (virtually ALL T cells), CD4 (Th2, Th1 and Treg cells), CD8 (CTL cells) surface markers (CD= cluster designation). Th1 and Th2 cannot be distinguished via surface (must look at what lymphokines they make)
b. B cells have antibody surface markers. B cells are readily distinguished using antibodies to immunoglobulins or their chains, or to the surface marker CD20.

Question 10

Describe the surface markers that can be used to distinguish between helper and cytotoxic T cells.

Answer 10

CD3 is on the surface of virtually all T cells; CD4 is on T helpers, CD8 is on CTL

Question 11

cytokine

Answer 11

short range mediators made by any cell that affects behavior of the same or another cell. Examples: IL-1, TNFalpha, IL-12.

Question 12

lymphokine

Answer 12

short range mediators made by lymphocyte that affects behavior of the same or another cell. A subset of cytokines. Examples: IL-2, IFNgamma, IL-4, IL-5, IL-10.

Question 13

chemokine

Answer 13

small (6-14 kD) short range mediators made by any cell that causes inflammation. Examples: MIP-1 to -4, RANTES, CCL28, CXCL16

Question 14

Discuss the main lymphokines made by Th1 and their biological functions.

Answer 14

-The most important lymphokine secreted by Th1 is interferon gamma (IFN-gamma) which is pro-inflammatory, being chemotactic for blood monocytes which become tissue macrophages. These cells move in large numbers into the area where the Th1 is recognizing antigen. They are also activated by IFN-gamma, becoming classically-activated M1 or ‘angry’ macrophages which avidly ingest and kill bacteria or other foreign invaders
(The macrophages release their own cytokines that intensify inflammation1 including tumor-necrosis factor alpha (TNFα) and IL-1)
-Th1 also secrete IL-2, which helps CTL (killer T cells) get fully activated after they recognize antigen.

Question 15

Discuss the main lymphokines made by Th2 and their biological functions.

Answer 15

• IL-4 they make has other actions: it attracts and activates macrophages, but differently than IFNγ; such macrophages are called alternatively activated or M2, and are more involved in healing (debris removal, scar formation, walling off pathogens that angry macrophages have failed to kill).
• IL-4 is also chemotactic for eosinophils, cells specialized for killing parasites like protozoans and worms

Question 16

Discuss the main lymphokines made by Th17 and their biological functions.

Answer 16

makes the inflammatory lymphokine IL-17 among others. It resembles the Th1 in that its main job seems to be causing inflammation

Question 17

Discuss the main lymphokines made by Treg cells and their biological functions.

Answer 17

• Most regulatory T cells have the phenotype CD4+/CD25+, and make the transcription factor FoxP3. Surface CD4 puts them in the helper family.
• They produce TGFβ and IL-10. They are very potent; one can suppress 1000 Th cells.