Term
| What are the properties of cytokines? |
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Definition
1. stimulus is required for production
2. high affinity binding to specific receptors
3. induce gene activation. |
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Term
| What are the General Characteristics of Cytokines? |
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Definition
- low MW proteins
- secreted by a variety of cells
- important role in the induction and regulation of immune reponses. |
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Term
| What are the three primary functions of cytokine-receptor interaction? |
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Definition
1. Autocrine: cytokine releases upon itself
2. Paracrine: release cytokine to a nearby cell (1-3 cells away)
3. endocrine: circulate to a distant cell. |
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Term
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Definition
| Activated Th cells will release IL 4 that will effect multiple cells (b cell, thymocyte, and mast cell) will lead to activation and proliferation |
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Term
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Definition
| Activated Th cell will release IL2, IL4, IL5 onto a B cell and cause proliferation. |
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Term
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Definition
| IL-4 + IL5 will have B cell induce class switch to IgE. |
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Term
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Definition
| IL-4 will be blocked by IFN gamma to block the class switch to IgE. (blocks itself) |
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Term
| Describe the cascade induction. |
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Definition
| Activated Th cell -> IFN gamma -> onto a macrophage -> IL-12 -> release on Activated TH cell -> release IFN gamma, TNF, IL2 and other cytokines. |
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Term
| What are the four structural families of cytokines? |
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Definition
1. hematopoietin family (IL-2 and IL-4)
2. interferon family
3. chemokine family
4. tumor necrosis factor family |
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Term
| What are the primary source of cytokines? |
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Definition
1. Th cells and macrophages
2. Secreted cytokines are multifunctional, short lived, "non specific" activators of a variety of cellular processes. |
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Term
| Why were cytokines hard to identify? |
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Definition
- occurred in small amounts
- hard to characterize |
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Term
| How were cytokines identified? |
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Definition
1. gene cloning technology
2. cytokine-dependent cell lines
3. monoclonal antibodies. |
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Term
| What are the general structure of cytokines? |
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Definition
- are small less than 30 kD
- proteins or glycoproteins
- are assigned to families based on structure four families idenfied. |
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Term
| What are some of the functions of cytokines?1 |
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Definition
1. regulate hematopoeisis
- colony-stuimulating factors
- IL-3 can cause many types of cells to divide
- IL-7 differentiation into pre-b and pre-t cells.
2. innate immune responses
- IL1, IL6, TNFalpha, INFalpha, and INF beta
- produced mostly by macrophages and neutrophils
- fever, acute- phase response, recruit leukocytes to site of damage.
3. Inflammation
- all in part 2 AND
- IFN gamma activate macrophage
- TGF beta terminates inflammatory response
4. specific immune responses
- IL 2 t cell growth factor
- IL 4 t and B cells
- IL 5and IL 6 B cell proliferation and differentiation
5. Chemokines: attract leukocytes
- IL8
- RANTEs |
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Term
| How are cytokine specificity regulated? |
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Definition
| Largely, by the expression patterns of cytokine receptors that can belong in one of the five families a. Ig superfamily b. class I cytokine receptors (hematopoietin) c. class II cytokine receptors (interferon) d. tumor necrosis receptor e. chemokine receptors. |
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Term
| What are the ligands in class I cytokine receptors? Describe the receptor. |
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Definition
IL-2 through IL-7, IL 9, IL-11 through IL-13. LIF, growth hormone, prolactin
Consevered cysteines. Conserved Tryptophan, X serine, X tryptophan-serine. |
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Term
| What are the ligands in interferons? Do they have conserved cysteines? |
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Definition
| a. IFN alpha/beta/gamma and IL 10. b. they do have conserved cysteines. |
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Term
| What are the ligands of TNF receptors? Describe the receptor. |
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Definition
| a. TNF alpha/beta, CD40, Nerve growth factor, FAS. b. have conserved cysteines in a specific repeating pattern C1,C3, and C2 repeats 4x. |
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Term
| Describe the chemokine receptor. What are the ligands? |
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Definition
| 1. 7 transmembrane receptor coupled to a small G protein 2. IL-8, RANTES, MIP 1, PF4, MCAF, NAP2. |
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Term
| Subfamilies of IL-2 receptors have common signaling subunits, what are they? |
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Definition
1. cytokine specific alpha subunit
2. B and gamma chains are important for signal transduction
3. gamma chain subunit are conserved
4. defecetive gamma chain causes X linked severe combined immunodeficiency. |
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Term
| How many affinities do IL 2 have? |
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Definition
| Three affinities, 1. low 2. high 3. intermeiate |
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Term
| What chain is only expressed in activated t cell antigen (TAC) and activated b cells? |
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Definition
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Term
Describe the cytokine-receptor interaction activated intracellular signaling pathways.
[image] |
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Definition
| 1. Jak bound to Alpha and Beta chain bind to the to cytokine, and you have the phosphorylation of the receptor 2. The tyrosine phosphorylates the STAT by JAK kinase 3. cause dimerization of Stat that goes into nucleus 4. induces Specific gene transcription |
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Term
| what provides specificity during signal transduction in the cytokine? what recognizes promoters of specific genes? |
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Definition
| 1. the expression of receptors and activation of certain JAK and stat proteins. 2. stats recognize promoter regions of specific genes. |
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Term
| What are cytokine antagonists? Example? |
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Definition
| Inhibitory proteins can bind receptor or the cytokine. examples 1. IL-1 receptor antagonists, IL-1Ra 2. Soluble IL-2 receptor releaed during chronic T cell activation 3. Viral products - anti cytokine strategies - decrease the inflammatory response. |
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Term
| Which cytokines in Th1 inhibit the TH2 response? |
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Definition
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Term
| which cytokines in TH2 inhibit the TH1 response? |
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Definition
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Term
| What cytokines influence T cell differentiation baed on the concentration? |
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Definition
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Term
| Explain how IL 12 interacts with a macrophage or dendritic cell? |
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Definition
| it differentiates into a TH1 cell and produceIFN gamma IL 2 and TNF beta |
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Term
| Explain how IL 4 interacts with a TH2 cell. |
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Definition
| IL 4 interacts with a TH2, after it is differentiated by exposure of a macrophage bound a naive t cell (Cd4) that expressed il-2 on itself then getting the product of IL 4, IL 5, IL 10 and IL 13 |
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Term
What is the role of T- Bet and Gata 3 in differentiation of a t cell (CD4)?
[image] |
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Definition
| During transcription factors for Th1 or Th2 cytokine production, t bet will inactivate Gata 3 to promote TH1 by activating IFN gamma, Gata03 will inactivate T bet to activate IL 4 and IL 5 to promote TH2. |
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Term
| What are the cytokin-related diseases? |
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Definition
1. Bacterial septic shock - endotoxins (cell walls) stimulate production of IL-1 and TNF-a
2. Cancers of lymphoid system- overproduction of cytokines such as IL-6 (B cell) or IL-5 (hodgkin's disease) or IL- 2 (adult t cell leukemia)
3. Chagas' disease (parasitic) - suppression of alpha subunit of IL-2 receptor
4. Toxin-conjugated cytokines: kill Th cells and prevent graft rejection |
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Term
| What are some therapeutic uses of cytokines? |
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Definition
| 1. organ transplantation 2. inflammation 3. cancer therapy 4. infectious disease 5. allergy |
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Term
Start from Self renewing Hematopoietic stem cell and differentiate from common lymphoid progenitor including the interleukins.
[image] |
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Definition
Self reviewing hematopoietic stem cell -(SCF, other)--> common lymphoid progenitor --(IL-7, others)-> T lymphocytes and B lymphocytes Unsure what IL gives natural killer cells
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Term
Describe the differentiation of common myeloid progenitor cell from self renewing hematopoietic stem cells.
[image] |
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Definition
Self-renewing hematopoietic stem cell
--(SCF, other)--> common myeloid progenitor
--(IL-3, GM-CSF, IL6)-->
which differentiates into
a. erythroid progenitor --(erythropoietin--> Erythrocyte.
b. --(thromobpoietin, IL-11)--> megakaryocyte --> platelets
c. Basophil progenitor --> basophil
d. --(IL-5)--> Eosinophil
e. Granolocyte-monocyte progenitor
--(IL-4, GM-CSF)--> 1) G-SCF ->neutrophil
or 2. M-SCF-> monocyte |
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