cytokines and T cell subsets

Question 1

What type of activity do cytokines normally exhibit? What are the exceptions to this normal function?

Answer 1

paracrine or autocrine.

IL-1, IL-3 and IL-6 are 3 cytokines that have endocrine activity .

Question 2

What are lymphokines?

Answer 2

cytokines produced by lymphocytes (IL-2, IL-4, etc)

Question 3

What are monokines?

Answer 3

cytokines produced by monocytes/macrophages (APCs) (IL-1, TNFa, IL-6)

Question 4

What are interleukins?

Answer 4

cytokines produced by WBCs and act on WBCs [IL-1 through IL-32 (more?)]

Question 5

What are chemokines?

Answer 5

low molecular weight molecules important in the inflammatory response; chemotaxis (IL-8, RANTES, etc)

Question 6

What does it mean to say cytokines are pleiotrophic?

Answer 6

they have different biological effects on different target cells

Question 7

What are the 3 basic ways that cytokines can interact with each other?

Answer 7

cytokines can be:

1. Redundant – multiple cytokines having a similar activity (ex: IL-2, IL-4, IL-5 can all stimulate B ell proliferation)
2. Synergistic – cytokines that work together (ex: IL-4 and IL-5 work together to stipulate B cells to produce IgE)
3. Antagonistic – cytokines that work against each other (ex:IL-4 stimulates class switching while INF-gamma blocks class switching)

Question 8

What are the two major subsets of Th cells and what type of immune response are they active in?

Answer 8

Th1 is active in CMI (inflammation and cytotoxicity)
ex: IL-2, IFN gamma, TNF beta

Th2 is active in humoral immunity
ex: IL-4, IL-5, IL-10

Question 9

What does IL-12 stimulate? What produces it?

Answer 9

Macrophages produce IL-12 which stimulates Th0 to develop into Th1 cells.

Question 10

What will lead to Th2 production from Th0 cells?

Answer 10

The absence of IL-12 and the presence of IL-4 will lead to Th2 production.

The IL-4 and IL-2 are secreted from another cell (not the APC)

Question 11

What is a negative regulator of Th1 production? What is it produced by?

Answer 11

IL-10 (produced by Th2 cells) negatively regulates Th1 production by inhibiting macrophage production of IL-12–> cross-regulation

Question 12

What inhibits Th2 cell production? How does it do this?

Answer 12

IFN gamma (produced by Th1 cells).

IFN gamma binds to a receptor and causes a signaling cascade which stimulates IFN gamma production, and inhibits IL-4 and IL-5 production, resulting in increased Th1 production

Question 13

1. Which Th subset production is found in M. leprae tuberculoid? 2. Lepromatous? 3. Which response is preferred and why?

Answer 13

1. tuberculoid – CMI and granuloma
   Th1 production
   damage of skin and nervous tissue
   patient usually survives
2. lepromatous – Ab response
   Th2 production
   disseminated disease
   associated with fatal outcome
3. M. leprae is intracellular so a Th1 response which will kill the cell is preferred.

Question 14

What are the common components of a cytokine receptor?

Answer 14

at least 2 chains:

1. cytokine specific unit
2. signal transducing unit –> cascade

Question 15

When are cytokine receptors expressed?

Answer 15

After a B cell recognizes its antigen it will begin to express its cytokine receptors

Question 16

What is the structure of an IL-2 receptor?

Answer 16

3 subunits:
IL2Ralpha=CD25=expressed by activated T cells
IL2Rbeta
IL2R gamma

will get a higher affinity binding with 2 or 3 chains.

Question 17

What can a deficiency in the IL-2R gamma subunit cause?

Answer 17

SCID!
the gamma chain is used in IL-2, IL-15, IL-7, IL-9 and IL-4
Without a proper gamma chain, all of these cytokine receptors will be inhibited, limiting both Th1 and Th2 responses and leading to SCID

Question 18

What causes bacterial septic shock?

Answer 18

LPS grom gram negative bacteria causes high levels of cytokine release (esp from IL-1 and TNF alpha from the macrophages) leading to systemic inflammation .

Question 19

What causes toxic shock disease?

Answer 19

super antigens bring together Vbeta chains and stimulate large amounts of cytokine production, resulting in systemic inflammation.

T cells will eventually die because they were activated without the proper 2 signals, reducing the amount of T cells available to fight the microbe.

Question 20

What can be used to block graft rejection?

Answer 20

antibodies to IL-2 or IL-2R which will hinder Th1 cell activity (which normally causes the rejection)

Question 21

What produces IL-1? What is it function?

Answer 21

APC

inflammation and fever

Question 22

What produces IL-2? What is it function?

Answer 22

T cells and NK cells

Th1 cytokine –> inflammation and CMI

Question 23

What produces IL-4? What is it function?

Answer 23

T cells

Th2 cytokine
major role in T cell and B cell development

Question 24

What produces IL-5? What is it function?

Answer 24

T cells

Th2 cytokine–> effect on B cells

Question 25

What produces IL-6? What is it function?

Answer 25

T cells and some APCs

inflammation

Question 26

what is IL-7’s function?

Answer 26

immune cell development. Produced by bone marrow stromal cells

Question 27

What produces IL-8? What is its function?

Answer 27

neutrophils

chemotaxis and inflammation

Question 28

What produces IL-10? What is its function?

Answer 28

Th2 cells

negative regulator of Th1 production

Question 29

What produces IL-12? What is its function?

Answer 29

APCs

major drive of the Th1 lineage

Question 30

What produces IFN gamma? What is its function?

Answer 30

Th1 cytokine

increases MHC expression

Question 31

What produces TNF alpha? What is its function?

Answer 31

T cells and APCs

major role in inflammation

Question 32

What produces INF alpha and beta? What is its function?

Answer 32

any cell

increases MHC expression