1. Basic Immunology University of Tabuk Faculty of Applied Medical Science Department of Medical Laboratory Technology Mr.AYMAN.S.YOUSIF MSc.Medical Microbiology & Immunology Academic Year: 1433-1434 (2012-2013)

2. Mr.AYMAN.S.YOUSIF 17- 18/03/2013 Lecture 6: Innate Immunity Adaptive Immunity Cytokines

3. Objectives At the end of this lecture, you should be able to: 1.Define the cytokines. 2.List the most important cytokines. 3.Know cytokines categories. 4.Understand the action manner of cytokines. 5.Understand the effects of cytokines. 6.Know cytokines receptor families. 7.Classify the cytokines based on the biologic actions. 8.Understand the biological function of the most important cytokines. 1

4. What are cytokines?  A group of low molecular weight polypeptides or proteins or (glycoproteins) which are secreted by activated immunocytes or some matrix cells and possess high activity and various functions.  Their major functions are to mediate and regulate immune response and inflammatory reactions.  Produced in response to microbes and other antigen.  Play an important role in both innate and adaptive immunity. 2

5. Cytokine Names ( Most Important Cytokines )  Interleukins (IL) - produced exclusively by leukocytes.  Lymphokines (LK) - produced by lymphocytes.  Monokines (MK) - produced exclusively by monocytes.  Interferon's (INF) - involved in antiviral responses.  Colony Stimulating Factors (CSF) - support the growth of cells.  Chemokines - promote chemotaxis. 3

6. Cytokine Categories 1. TNF Family. 2. Chemokine Family. 3. Interferon Family. 4. Hematopoietin Family. 4

7. Cytokines Chemical Messengers of the Immune Cells  Interleukins (IL) are cytokines that serve as communicators between leukocytes.  According to the amino acid sequence Interleukins are assigned numbers such as IL 1, etc..  Chemokines cause leukocytes to migrate to an infection area.  Another family of cytokines is the Interferons.  Alpha interferon and IFNβ protect cells against viruses.  Gamma interferon (IFN  ) increases phagocytosis.  Tumor Necrosis Factor (TNF) promotes the inflammatory reaction. 5

8. Cytokines Chemical Messengers of the Immune Cells  Hematopoietic cytokines, function in controlling the pathways by which stem cells develop into different red or white cells.  Overproduction of cytokines leads to cytokines storm, which results in tissue damage. 6

9. How do cytokines tell cells what to do?  Produced by cells as part of normal cellular activity and/or the result of environmental trigger (microbe).  Bind to receptors on (A cytokine acts only on a cell that has a receptor for it). either cell which produced it or another cell.  Receptor binding Trigger signal transduction pathways.  Signal results in altered pattern of gene expression.  Cytokines initiate their actions by binding to specific membrane receptors on target cells.  Signal transduction pathway: The course by which a signal from outside a cell is converted to a functional change within the cell. 7

10. Result of environmental trigger part of normal cellular activity Hematopoietic cytokines 8

11. Cytokines can act in three different manners  Autocrine. Cytokine binds to receptor on cell that secreted it  Paracrine. Cytokine binds to receptors on near by cells.  Endocrine. Cytokine binds cells in distant parts of the body 9

12. The effects of cytokines (Cytokine Actions)  Pleiotropy. Act on more than one cell type (IL 4).  Redundancy. More than one cytokine can do the same thing (IL2, IL4, IL5).  Synergy. Two or more cytokines cooperate to produce an effect that is different or greater than the combined effect of the two cytokines when functioning separately (IL-12 and IL-8) + (IFN  and  TNF   Antagonism. Two or more cytokines work against each other (IL-4 and IL-12) + (IFN  and  IL 10 ). 10

13. Cytokine Actions 11

14. Five cytokine receptor families 1. (Ig) Immunoglobulin superfamily receptors. 2. Class I cytokine receptor family(hematopoietin receptors). Binds most of the cytokines in the immune and hematopoietin systems. 3. Class II cytokine receptor family (interferon receptors). 4. TNF receptor family. 5. Chemokine receptor family. 12

15. Cytokine receptors belong to families of receptor proteins, each with a distinctive structure 13

16. Classification of Cytokines  Cytokines can be classified according to their principal biologic actions to the following 3 groups, however many of them mediate more than 1 of these functions: 1. Mediators and regulators of Innate Immunity :  These are produced by activated MQ and NK cells in response to microbial infections.  They act mainly on endothelia cells and leukocytes to stimulate the early inflammatory reaction to microbes.  They include IL-1,6,10,12,15,18 TNFα, type l interferon (INF-α and INF-β) and chemokines ( IL-8). IL1,6 and chemokines are known as the proinflammatory ctyokines 14

17. Functional categories of Cytokines 2- Mediators and regulators of Acquired immunity: These are produced mainly by T cell in response to specific recognition of foreign Ag.  TH1 produce IL-2, INFγ and TNFβ  TH2 produce IL-4,5,6,8,10,13 3- Stimulators of haematopoiesis:  These are produced by bone marrow, stromal cells, leukocytes, and other cells.  They stimulate the growth and differentiation of immature leukocytes.  These include; stem cell factor, IL-3,7 and GM-CSF 15

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19. http://nfs.unipv.it/nfs/minf/dispense/immunology/lectures/files/immune_network.html 17

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21. Thank You