chapter 12 cytokines dr. capers. kuby immunology sixth edition chapter 12 cytokines copyright ©...
TRANSCRIPT
![Page 1: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/1.jpg)
Chapter 12
Cytokines
Dr. Capers
![Page 2: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/2.jpg)
Kuby IMMUNOLOGYSixth Edition
Chapter 12Cytokines
Copyright © 2007 by W. H. Freeman and Company
Kindt • Goldsby • Osborne
![Page 3: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/3.jpg)
Cytokines Low-molecular weight regulatory
proteins or glycoproteins Secreted by WBC and various other
cells Assist in regulating development of
immune effector cellsSome possess direct effector functions of
their own Referred to as Interleukins
○ IL-1 through IL-29 have been described
![Page 4: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/4.jpg)
Cytokines bind to specific receptors
Trigger signal transduction pathways that alter gene expression in target cells
Exhibit pleiotropy, redundancy, synergy, antagonism, cascade induction
![Page 5: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/5.jpg)
![Page 6: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/6.jpg)
![Page 7: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/7.jpg)
Activity was 1st recognized in 1960sSupernatants from in vitro cultures of
lymphocytes were found to contain soluble factors
Could regulate proliferation, differentiation, maturation of immune cells
Purification of these was hampered because of low concentration in culture
Gene-cloning techniques changed this – made it possible to produce pure cytokines
![Page 8: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/8.jpg)
ELISA using monoclonal antibodies
![Page 9: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/9.jpg)
Cytokines belong to 4 families○ Hematopoietin family○ Interferon family○ Chemokine family○ Tumor necrosis family
Based on structural studiesAll have molecular mass less than 30kDaAll have similarities and few rarely act alone
![Page 10: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/10.jpg)
![Page 11: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/11.jpg)
Activities of commonly encountered cytokines, expanded list in Appendix II
![Page 12: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/12.jpg)
Nonspecificity of cytokines conflicts with established specificity of immune systemHow does this work?
○ Careful expression of the receptors for those cytokines on specific cells
○ Receptors are often only expressed after exposure to antigen
![Page 13: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/13.jpg)
Cytokine Receptors
Cytokine receptors fall into 5 familiesImmunoglobulin superfamily receptorsClass I cytokine receptor family
(hematopoietin)Class II cytokine receptor family (interferon)TNF receptor familyChemokine receptor family
![Page 14: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/14.jpg)
![Page 15: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/15.jpg)
![Page 16: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/16.jpg)
![Page 17: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/17.jpg)
![Page 18: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/18.jpg)
![Page 19: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/19.jpg)
IL-2R is the most thoroughly studied cytokine receptorExpressed by T cells for proliferation
○ Also called CD25, surface marker in mature T cells
Complete receptor has 3 subunits
![Page 20: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/20.jpg)
![Page 21: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/21.jpg)
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
- Look on next slide
![Page 22: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/22.jpg)
![Page 23: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/23.jpg)
Cytokine Antagonists 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
![Page 24: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/24.jpg)
![Page 25: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/25.jpg)
CD4+ TH cells exert most of helper functions through secreted cytokines2 populations based on secreted cytokines:
TH1- Cell-mediated functions – delayed hypersensitivity,
activation of TC cells, production of opsonization-promoting IgG antibodies
TH2- 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 TH cells do not show TH1 or TH2 profiles
![Page 26: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/26.jpg)
![Page 27: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/27.jpg)
Cytokines produced by TH1 and TH2 subsetsPromote growth of subset that produces
themInhibit development and activity of other
subsetProgression of some diseases depends on
balance between TH1 and TH2
![Page 28: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/28.jpg)
Cytokine Related Diseases SCID
Genetic defects in cytokines, their receptors
Defective receptor for IFN-γSusceptible to mycobacterial infections
![Page 29: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/29.jpg)
Cytokine Related Diseases Bacterial Septic Shock
Certain Gram- bacteriaSymptoms: drop in blood pressure, fever,
diarrhea, blood clottingEndotoxins 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
![Page 30: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/30.jpg)
Cytokine Related Diseases Bacterial Toxic Shock
Superantigens○ Bind simultaneously to Class II MHC and T
cell receptor, activating T cell despite antigenic specificity
Symptoms similar to sepsis
![Page 31: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/31.jpg)
Cytokine Related Diseases Abnormalities in production of cytokines
or receptors are associated with certain types of cancer
Chaga’s DiseaseCaused by Trypanosoma cruziSevere immunosuppression
○ Evidence that soluble factor produced by T. cruzi leads to reduction in T cell IL-2 (CD25) receptor
![Page 32: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/32.jpg)
Cytokine-based Therapies Problems with
cytokine therapies:Effective dose levelsShort half-lifePotent biological
response modifiers○ Can cause
unpredictable side effects
![Page 33: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/33.jpg)
![Page 34: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/34.jpg)
![Page 35: Chapter 12 Cytokines Dr. Capers. Kuby IMMUNOLOGY Sixth Edition Chapter 12 Cytokines Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne](https://reader033.vdocuments.mx/reader033/viewer/2022061403/56649dd25503460f94ac844e/html5/thumbnails/35.jpg)
Cytokines play essential role in hematopoiesis