Immunology II cytokines.pptx must view slides

Immunology

1. Immunology II CYTOKINES

2. Learning objectives At the end of the lecture students should be able To know the definition of cytokines To know the different forms and functions of cytokines To know the properties and classification of cytokines To know the regulatory roles of cytokines To know the therapeutic relevance of cytokines

3. Cytokines Cytokines (literally “cell movement”) are a group of small proteins used in cell – signaling . OR Cytokines are a diverse group of proteins released by cells that act as intercellular mediators during immune processes. OR They are low molecular weight soluble proteins produced in response to microbes and other antigens

4. Cytokines They act through cell surface receptors to mediate and regulate immune responses through activation of macrophages, proliferation and differentiation of T and B cells.

5. Naming of Cytokines Monokines: produced by mononuclear phagocytes (monocytes) Lymphokines: produced by activated T cells, primarily helper T cells Interleukins: cytokines made by one leukocytes and acting on other leukocytes Chemokines: cytokines with chemotactic properties

6. Properties of cytokines Produced by cells involved in innate and adaptive immunity. Mediate and regulate immune and inflammatory responses Bind to specific receptors on target cells with high affinity. Secretion is brief and limited. Pleiotropic : different cell types secrete the same cytokine or for a single cytokine to act on several different cell types

7. Redundancy - same function can be carried out by different cytokines

8. Properties of cytokines They often influence the synthesis of other cytokines They can produce cascades, or enhance or suppress production of other cytokines They produce positive and negative regulatory signals for immune and inflammatory responses Often influence the action of other cytokines Antagonisti c- they oppose the effect of other cytokines Synergistic- two or more cytokines acting together to produce an effect

9. Regulatory roles of cytokines Autocrine- act on the same cell that secreted it Paracrine- act on a nearby cell Endocrine- act on a distant cell reached through circulation

10. Classification of Cytokines Classified according to their biological actions into three groups: Mediators and regulators of innate immunity Produced by activated macrophages and NK cells in response to microbial infection They act mainly on endothelial cells and leukocytes to stimulate early inflammatory response

11. Classification of Cytokines Mediators and regulators of adaptive immunity Produced mainly by T lymphocytes in response to specific recognition of foreign antigens They include IL-2, IL-4, IL-5, IL-13, IFN, Transforming growth factor- β and Tumor neurosis factor β Stimulators of hematopoiesis Produced by bone marrow, stromal cells, leukocytes Stimulate proliferation and differentiation of leukocytes, they include stem cell factor, IL-13, IL-17 and GM-CSF

12. Cytokines T cells during the resting stage do not produce any cytokines such as interleukins 2, 4 or 7. Nor do they express large amounts of their receptors Activation of T cells results in the expression of high affinity interleukin-2 receptors and secretion of IL-2 and IL-4 These ILs stimulate proliferation, however their decline results in receptor decay

13. Chemokines Chemokines induce chemotaxis (chemical induced migration) in local cells. Local cells are attracted to these proteins by following their concentration gradient to the source, where the concentration is highest. Mainly produced by macrophages during infection during infection, eg. IL-8 recruits neutrophils to the site during immune response.

14. Chemokine actions Pro-inflammatory – recruits immune cells to the site of infection. They are inducible. Cells produce or upregulate pro-inflammatory chemokines in response to infection or trauma. Their stimulation may be due to other proinflammatory chemokines (TNF α, IFN γ) or microbial products They allow immune cells such as neutrophils and monocytes to exit the bone marrow and hone into affected tissues. Homeostatic- can attract cells required for angiogenesis and allowing for the growth of new blood vessels

15. These chemokines are constitutively produced, i n other words, the body maintains basal levels without the need for a specific stimulus. For example, stromal cells within the bone marrow secrete CXCL12 which binds to its receptor, CXCR4, and this helps to retain neutrophils in the bone marrow until they are mobilized into the circulation during infection. Chemokines are involved in immune surveillance and allow T cells and dendritic cells to migrate and circulate through secondary lymphoid organs in search of potential pathogens. Note: some chemokines have both pro-inflammatory and homeostatic roles.

16. Interferon action (type-1 interferons ) Almost any body cell can produce type-I interferons, including fibroblasts, endothelial cells and macrophages. Type I interferons such as Interferon-α and interferon-β interfere with viral replication and help the immune system fight viral infections Once secreted by the infected cell, they bind to the interferon receptors on the same cell and neighboring cells. They also upregulate NK cell ligands and MHC I on the cell surface. Therefore, NK cells and cytotoxic T cells are more likely to detect and attack virus-infected cells.

17. Type II interferon NK cells, cytotoxic T cells and Th1 cells produce interferon-γ in response to IL-12 and IL-18. Interferon-γ activates macrophages and increases their ability to kill pathogens by enhancing endocytosis and lysosome function. Type-II interferons also upregulate MHC II expression. This promotes antigen presentation and effective phagocytosis.

18. Interleukins Interleukins are another type of cytokine produced by T-lymphocytes, monocytes and macrophages. They promote the production and differentiation of B and T lymphocytes  – Specifically, IL-1α/β, IL-4, IL-7 and IL-21. They activate neutrophils and natural killer cells – for example, IL-2, IL-8 and IL-12.

19. Interleukins Produce detectable signs – interleukin-6 (IL-6) increases body temperature ( fever ) which inhibits microbial growth. IL-6, additionally, raises acute phase proteins such as C-reactive protein (CRP) which is associated with inflammation. Promote vascular permeability which causes swelling and allows faster recruitment of cells involved in immunity

20. Tumor Necrosis Factor Tumor necrosis factor (TNF) is a cytokine mainly produced by macrophages when they encounter an endotoxin. it can also be produced by other cells of the immune system including, mast cells, B cells and T cells. TNF α and β. TNF α and β have similar functions, include Local induction of apoptosis. Increasing local vascular permeability. Neutrophil chemotaxis. etc

21. Tumor Necrosis Factor High concentrations of TNF can induce shock through the increase in vascular permeability and resulting drop in blood pressure. On the other hand, chronic exposure to low levels leads to the syndrome of cachexia which is often seen in chronic infection and cancer.

22. Therapeutic uses of cytokines Used to improve the effectiveness of T cell activation in immunodeficiency diseases eg. IL-2, INF- γ and INF-α INF used in the treatment of viral diseases. IL-2 and lymphokine activating killer cells used in the treatment of cancer GM-CSF induces increase in white cell count, it is used to restore leukocyte count after chemotherapy, after bone marrow transplantation Anti-cytokines used in the management of autoimmune diseases, septic shock and T-cell leukemia