Cytokines ppt

CYTOKINE RECEPTORS
CYTOKINE ANTAGONIST
CYTOKINE SIGNALING
CYTOKINE THERAPY
CYTOKINE DISEASE

1. CYTOKINES SEETU GULIA MSC. BIOTECHNOLOGY CENTRAL UNIVERSITY OF HARYANA

2. DEFINITION PROPERTIES OF CYTOKINES NOMENCLATURE CLASSIFICATION CYTOKINE RECEPTORS CYTOKINE SIGNALING CYTOKINE ANTAGONIST TH1 AND TH2 CYOKINE RELATED DISEASES CYTOKINE THEARPY CYTOKINE IN HEMATOPOIESIS TOPICS

3. PROPERTIES

4. CYTOKINE FAMILIES HEMATOPOIETIN FAMILY INTERFERON FAMILY CHEMOKINE FAMILY TUMOR NECROSIS FACTOR FAMILY

5. Non specificity of cytokines conflicts with established specificity of immune system How does this work? -Careful expression of the receptors for those cytokines on specific cells -Receptors are often only expressed after exposure to antigen Cytokine act in an antigen-non specific manner

6. IL-2R is the most thoroughly studied cytokine receptor -Expressed by T cells for proliferation -Also called CD25, surface marker in mature T cells -Complete receptor has 3 subunits

7. - Majority of cytokine receptors are in Class I and Class II families -These cytokine receptors lack signaling motifs, this was puzzling to researchers -IFN- γ was studied because of it’s ability to block viral replication like other interferons However, this IFN plays immunoregulatory role which lead to understanding the process of signal transduction through cytokine receptors CYTOKINE SIGNALING

8. - Ligand Binds  Subunit -Ligand Binding Causes Dimerization of Receptor -JAKs Get Activated #Phosphorylation of tyrosine residues on receptor #Phosphorylation of JAKs themselves -STATS Dock Receptor #Phosphorylation of STATs by JAKs -Dimerized STATs Translocate To Nucleus -Gene Expression

9. CYTOKINE ANTAGONIST Number of proteins can inhibit cytokine activity Can bind to receptor OR Can bind to cytokine, disabling it Enzymatic cleavage of receptors and release of these can bind cytokines in the blood Marker of chronic T cell activation (transplant rejection, AIDS) Viruses have developed strategies Cytokine homologs Cytokine binding proteins Homologs of cytokine receptors Interference with intracellular signaling Interference with cytokine secretion

10. CD4+ T H cells exert most of helper functions through secreted cytokines 2 populations based on secreted cytokines: T H 1 Cell-mediated functions – delayed hypersensitivity, activation of T C cells, production of opsonization -promoting IgG antibodies T H 2 Stimulates eosinophil activation, provides help to B cells, promotes production of large amounts of IgM , IgE , and noncomplement activating IgG isotypes Supports allergic reactions Some T H cells do not show T H 1 or T H 2 profiles TH1 AND TH2

11. -Promote growth of subset that produces them -Inhibit development and activity of other subset -Progression of some diseases depends on balance between T H 1 and T H 2 -Cytokines profiles are cross regulated.

12. TRANSCRIPTION FACTORS -T-bet Expression Results In T H 1 -T-bet Suppresses T H 2 -GATA-3 Results In T H 2 -GATA-3 Suppresses T H 1 -IFN-  Regulates Expression of T-bet (Stat 1) -IL-4 Regulates Expression of GATA-3 (Stat 6)

13. CYTOKINE RELATED DISEASES -SCID Genetic defects in cytokines, their receptors -Defective receptor for IFN- γ Susceptible to mycobacterial infections

14. Bacterial Septic Shock Certain Gram- bacteria Symptoms: drop in blood pressure, fever, diarrhoea , blood clotting Endotoxins bind TLRs on dendritic cells and macrophages Over-produce IL-1 and TNF- α Cytokine imbalance causes abnormal temp, abnormal respiration, capillary leakage, tissue injury, organ failure Neutralization by monoclonal antibodies may help

15. -Bacterial Toxic Shock -Superantigens -Bind simultaneously to Class II MHC and T cell receptor, activating T cell despite antigenic specificity -Symptoms similar to sepsis

16. -Abnormalities in production of cytokines or receptors are associated with certain types of cancer -Chaga’s Disease -Caused by Trypanosoma cruzi -Severe immunosuppression -Evidence that soluble factor produced by T. cruzi leads to reduction in T cell IL-2 (CD25) receptor

17. CYTOKINE THERAPY

18. Problems with cytokine therapies: -Effective dose levels -Short half-life -Potent biological response modifiers -Can cause unpredictable side effects

19. -Cytokines play essential role in hematopoiesis

20. Cytokines are low MW proteins that are produced and secreted by a variety of cell types . The biological activities of cytokines exhibit pleiotropy , redundancy , synergy , antagonism and cascade induction. Families of cytokines : hematopoietin , interferons , chemokines and TNF. Cytokine receptors: Ig superfamily , class 1,class 2,TNF and chemokine receptors. Cytokine- induced multimerization of class 1 and class2 receptors activate JAT/STAT signal transduction pathway. SUMMARY

21. Therapies based on cytokines and cytokine receptors have entered clinical practice Cytokines have role in hematopoiesis SUMMARY

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