About cytokines of Immune system

1. Cytokines/chemokines

2. Cytokines
• “Cytokines” are soluble protein secreted by the
cells of innate and adaptive immunity and
mediate many of the functions of these cells
• Are molecules that communicate among widely
dispersed cells and organs of the immune system

3. Chemical structure of cytokines
• Low molecular weight proteins, < 30kD
• High affinity for receptors
• Active in picomole amounts
–Because their affinities are so high, cytokines
can mediate biological effects at picomolar
concentrations.

4. Names of Cytokines
• Source
– Lymphokines – secreted by lymphocytes
– Monokines – secreted by monocytes
• Function
– Chemokines – cytokines that affect chemotaxis and
other aspects of leukocyte behavior
– Interferons – Involved in antiviral response
– Intercellular action – Interleukins – secreted by some
leukocytes and act upon other leukocytes
Chemokines-regulate mainly Immune cell migration. But,
Cytokines have broader function in cell growth, differentiation, & immune regulation!

5. Action of Cytokines
• Autocrine
– Affects the generating cell (self)
• Paracrine
– Affects cells in the immediate vicinity
• Endocrine
– Affects cells remote from the secreting cell

6. Action of Cytokines

7. T lymphocytes often secret cytokines at the site of contact with APCs.
Most cytokines act close to where they are produced

8. Cytokines have 5 attributes
1. Pleiotropy: when a given cytokine has different effects on
different cells.
2. Redundancy: when two or more cytokines mediate the same
function.
3. Synergism: when the combined effect of two or more cytokines
is greater than the effect of the individual cytokines.
4. Antagonism: when the effects of one cytokine inhibits the
effects of another cytokine.
5. Cascade induction: the action of one cytokine on a target cell
induces that cell to produce one or more other cytokines that in
turn induce other target cells.

10. Cytokines have numerous biological functions
• The generation of cellular and humoral immune
responses,
– IFN-γ, IL-4, 5, 12, TNF-α
• The induction of the inflammatory response,
– IL-1,6, TNF-α
• Control of cellular proliferation and differentiation
– IL-10,13
• The regulation of hematopoiesis,
– GM-CSF, G-CSF
• Wound healing
– TGF-β

11. Cytokines Mediate the Activation, Proliferation, and
Differentiation of Target Cells

12. *Mononuclear phagocytes are the principal source of
cytokines of innate immunity
 Tumor necrosis factor (TNF)
 IL-1
 IL-6
 Type I IFNs
 IL-12
 IL-15
 IL-18
 chemokines
Proinflammatory
cytokines
Cytokines that mediate and regulate innate immunity

13. Roles of cytokines in innate immunity and inflammation
0 1 3 6
Hours after LPS injection

14. Cytokines mediate and regulate adaptive
immunity at different phases

15. Network of cytokine actions produced by leukocytes

16.  Cytokine of adaptive immunity are produced mainly by T
lymphocytes in response to specific recognition of protein Ags.
The function of T helper cells is mediated by cytokines

17. Cytokines Belong to 6 Structural Families:
• Different amino acid sequences, similar structures
Interleukin I family (proinflammatory cytokines)
Hematopoietin family (Class I cytokines)
Interferon family (Class II cytokines)
Interleukin 17 family (inflammatory cytokines)
Tumor necrosis factor (TNF) family
Chemokine family

19. Cytokine receptors
There are five families of cytokine receptors:
1. IL-1 family (Immunoglobulin superfamily)
receptors
2. Class I cytokine receptor family (or
Hematopoietin receptor family).
3. Class II cytokine receptor family (or interferon
receptor family).
4. TNF receptor family
5. Chemokine receptor family
(JAK-STAT)
(IRAK)
G- protien

20. (Chemokine
receptor
family)
(IFN)

22. Chemokines
• A subfamily of cytokines primarily functions in
directing migration of cells, these are called
“chemotactic cytokines” or “chemokines”
• Chemoattractant Cytokines
• Small (8-10kd)
• Promote recruitment and activation of leukocytes

23. Chemokine Subclasses
• Most chemokines have 4 cysteine residues which form
disulphide bonds
–C class – Only has 2 cysteines not 4 (example:
Lymphotactin)
–CC class – The first two cysteines are adjacent
(example: MCP-1/CCL1, RANTES/CCL5)
–CXC class- The first two cysteines are not adjacent
(example: IL-8)
–CX3C class – Has 3 amino acids between the first
two cysteines and a different N-terminal
Monocyte chemoattr Protien-1
Fractalkine.
Attract eosinophils, basophils & T-cells.

24. Chemokine Subclasses

25. Chemokine Function

26. Chemokine Function
• Chemokines promote chemotaxis in the
direction of highest concentration

27. Chemokine Effects

28. Chemokine Receptors
• Specific receptors bind specific chemokine
• There are also shared receptors
• Promiscuous receptors bind any class
• Viral encoded receptors

29. Chemokine Receptors

30. Chemokine Receptors

31. • Chemokine receptors are differentially
expressed on effector T-cells

32. CC-receptors and HIV infection

33. The chemokine/chemokine-receptor family