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Chapter 12 Cytokines

Chapter 12 Cytokines. Cytokines: - Any of numerous secreted, low-m-w proteins (usually < 30 kDa) that regulate the intensity and duration of the immune response by exerting a variety of effects on lymphocytes and other immune cells. Role in cell-to-cell communication

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Chapter 12 Cytokines

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  1. Chapter 12 Cytokines

  2. Cytokines: • - Any of numerous secreted, low-m-w proteins • (usually < 30 kDa) that regulate the intensity • and duration of the immune response by exerting • a variety of effects on lymphocytes and other • immune cells. • Role in cell-to-cell communication • Messengers of the immune system

  3. Overview of the Induction and Function of Cytokines (Kd ~ 10-10 to 10-12)

  4. Most Cytokines Exhibit Autocrine and/or Paracrine Action; Fewer Exhibit Endocrine Action

  5. Pleiotropy, Redundancy, Synergy, Antagonism of Cytokines

  6. Cascade Induction of Cytokines

  7. Cytokines, Hormones, and Growth Factors 1. All three are secreted soluble factors that elicit their biological effects at pM concentrations. 2. Growth factors tend to be produced constitutively, whereas cytokine production is carefully regulated. Cytokines are usually secreted after activation of a particular cell, and secretion is short-lived, generally ranging from a few hours to a few days. 3. Hormones generally act long range in an endocrine fashion, most cytokines act over a short distance in an autocrine or paracrine fashion.

  8. Cytokines, Hormones, and Growth Factors 4. Most hormones are produced by specialized glands and tend to have a unique action on one or a few types of target cell. In contrast, cytokines are often produced by a variety of cells and bind to receptors present on numerous types of cells.

  9. Functions of Cytokines • Development of cellular and humoral immune responses • Induction of the inflammatory response • Regulation of hematopoiesis • Control of cellular proliferation and differentiation • Healing of wounds • * Although the immune response to a specific Ag • includes the production of cytokines, cytokines • act in an Ag-nonspecific manner.

  10. (1)

  11. (2)

  12. (3)

  13. (4)

  14. Most of the functions of cytokines have been • identified from analysis of the effects of • recombinant cytokines, often at nonphysiologic • concentrations, added individually to in vitro • system. • - In vivo, however, cytokines rarely, if ever, act • alone. • - Instead, a target cell is exposed to a milieu (環境) • containing a mixture of cytokines, whose • combined syneristic or antagonistic effects can • have very different consequences. • Cytokines often induce the synthesis of other • cytokines, resulting in cascade of activity.

  15. Cytokine Receptor Families • Ig superfamily receptors • Class I cytokine receptor family (hematopoietin) • 3. Class II cytokine receptor family (interferon) • Tumor necrosis factor (TNF) receptor family • Chemokine receptor family

  16. 3 Subfamilies of Class I Cytokine Receptors

  17. CNTF: ciliary neurotrophic factor LIF: leukemia-inhibitory factor OSM: oncostatin M

  18. Interactions between Cytokine-specific Subunits and a Common Signal-transducing Subunit of Cytokine Receptors

  19. Competition of Ligand-binding Chains of Different Receptors for a Common Subunit Can Produce Antagnistic Effects between Cytokines

  20. 3 Forms of the IL-2 Receptor (CD25)

  21. JAK JAK-STAT Signal Transduction Pathways of Cytokine Receptors JAK: Janus kinases Stat: signal tranducers and activators of transcription

  22. (lymphotoxin, LT)

  23. TH1 Response • The TH1 subset is responsible for many cell-mediated • functions (e.g., delayed-type hypersensitivity and activation • of TC cells) and for the production of opsonization- • promoting IgG Abs (i.e., Abs that binds to the high-affinity • FcRs of phagocytes and interact with the C system, such as • IgG3, IgG1, IgG2). This subset is also associated with the • phenomenon of excessive inflammation and tissue injury. • The production of IL-2, IFNg and TNFb makes the TH1 • subset particularly suited to respond to viral infections and • intracellular pathogens. IFNg also inhibits the expansion of • the TH2 population.

  24. TH2 Response • - The TH2 subset stimulates eosinophil activation and • differentiation; provides help to B cells, and promotes the • production of relatively large amounts of IgM, IgE, and • noncomplement-activating IgG isotypes, such as IgG4 • in humans and IgG1 in mice. The TH2 subset also supports • allergic reactions. The production of Il-4, IL-5 and IL-10 • promotes the function of IgE and eosinophils on the anti- • helminth (round worm) immunity.

  25. The Regulation of TH Subsets by Cytokines

  26. Correlation between Type of Leprosy (痲瘋) and Relative TH1 or TH2 Activity

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