cytokines and T cell subsets Flashcards
What type of activity do cytokines normally exhibit? What are the exceptions to this normal function?
paracrine or autocrine.
IL-1, IL-3 and IL-6 are 3 cytokines that have endocrine activity .
What are lymphokines?
cytokines produced by lymphocytes (IL-2, IL-4, etc)
What are monokines?
cytokines produced by monocytes/macrophages (APCs) (IL-1, TNFa, IL-6)
What are interleukins?
cytokines produced by WBCs and act on WBCs [IL-1 through IL-32 (more?)]
What are chemokines?
low molecular weight molecules important in the inflammatory response; chemotaxis (IL-8, RANTES, etc)
What does it mean to say cytokines are pleiotrophic?
they have different biological effects on different target cells
What are the 3 basic ways that cytokines can interact with each other?
cytokines can be:
- Redundant – multiple cytokines having a similar activity (ex: IL-2, IL-4, IL-5 can all stimulate B ell proliferation)
- Synergistic – cytokines that work together (ex: IL-4 and IL-5 work together to stipulate B cells to produce IgE)
- Antagonistic – cytokines that work against each other (ex:IL-4 stimulates class switching while INF-gamma blocks class switching)
What are the two major subsets of Th cells and what type of immune response are they active in?
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
What does IL-12 stimulate? What produces it?
Macrophages produce IL-12 which stimulates Th0 to develop into Th1 cells.
What will lead to Th2 production from Th0 cells?
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)
What is a negative regulator of Th1 production? What is it produced by?
IL-10 (produced by Th2 cells) negatively regulates Th1 production by inhibiting macrophage production of IL-12–> cross-regulation
What inhibits Th2 cell production? How does it do this?
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
- Which Th subset production is found in M. leprae tuberculoid? 2. Lepromatous? 3. Which response is preferred and why?
- tuberculoid – CMI and granuloma
Th1 production
damage of skin and nervous tissue
patient usually survives - lepromatous – Ab response
Th2 production
disseminated disease
associated with fatal outcome - M. leprae is intracellular so a Th1 response which will kill the cell is preferred.
What are the common components of a cytokine receptor?
at least 2 chains:
- cytokine specific unit
- signal transducing unit –> cascade
When are cytokine receptors expressed?
After a B cell recognizes its antigen it will begin to express its cytokine receptors
What is the structure of an IL-2 receptor?
3 subunits:
IL2Ralpha=CD25=expressed by activated T cells
IL2Rbeta
IL2R gamma
will get a higher affinity binding with 2 or 3 chains.
What can a deficiency in the IL-2R gamma subunit cause?
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
What causes bacterial septic shock?
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 .
What causes toxic shock disease?
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.
What can be used to block graft rejection?
antibodies to IL-2 or IL-2R which will hinder Th1 cell activity (which normally causes the rejection)
What produces IL-1? What is it function?
APC
inflammation and fever
What produces IL-2? What is it function?
T cells and NK cells
Th1 cytokine –> inflammation and CMI
What produces IL-4? What is it function?
T cells
Th2 cytokine
major role in T cell and B cell development
What produces IL-5? What is it function?
T cells
Th2 cytokine–> effect on B cells
What produces IL-6? What is it function?
T cells and some APCs
inflammation
what is IL-7’s function?
immune cell development. Produced by bone marrow stromal cells
What produces IL-8? What is its function?
neutrophils
chemotaxis and inflammation
What produces IL-10? What is its function?
Th2 cells
negative regulator of Th1 production
What produces IL-12? What is its function?
APCs
major drive of the Th1 lineage
What produces IFN gamma? What is its function?
Th1 cytokine
increases MHC expression
What produces TNF alpha? What is its function?
T cells and APCs
major role in inflammation
What produces INF alpha and beta? What is its function?
any cell
increases MHC expression
