1. Lecture 6 clinical immunology Cytokines
Cut back on chemokine stuff
Dave gives a lot of that in the prior lecture
Focus on signaling pathways
Add more on Th1/Th2
Dr. Dalia Galal

2. What Is A Cytokine?
Cytokines: are soluble and small proteins produced in response to microbes and other antigens. They help in the communications between all leukocytes
Low molecular weight proteins
When released from mononuclear phagocytes, these are called monokines.
When released from T-lymphocytes, they are called lymphokines.
When released, cytokines bind to the receptors of the cells and alter gene expression

3. Cytokines play an important role in:
Hematopoiesis
Adaptive (specific) Immunity (T and B cells)
Innate (non-specific) Immunity
Inflammation
Categories of cytokines
TNF family
Chemokine family
Interferon family
Hematopoietin family

4. Functional features Potent Local Highly interactive
Some function acts in very small amount (at Molar)
Local
Autocrine
Paracrine
(sometimes) Endocrine
Highly interactive
Pleiotropic
Redundant
Synergistic
Antagonistic

5. Functional features
Potent
Some
function at
10-15 Molar

6. Functional features Local
Cytokines can bind on the membrane of the same cell that secreting it (Autocrine)
Cytokines can bind another cell close by (Paracrine)
Few cases, cytokines can bind another cell far away (Endocrine)

7. Functional features Highly interactive Pleiotropic
One cytokine can act on
different cells
Redundant
Multiple cytokines can have
the same functional effects
Synergistic
- Two cytokines may produce additive
or synergetic effects
Antagonistic
- Effect of one cytokine is opposite (or
stop) to the other’s action

8. Effects (actions) of cytokines on the cells:
Proliferation of cells (B cells)
Differentiation of cells (Th2 cells)
Inhibition of cells activation (Macrophages)
Stimulate expression of certain molecules (Major Histocompatability Complex, MHC)

9. Key Cytokines Produced by Innate Immune Responses
IL-1 – produced by macrophages, epithelial cells
IL-6 – produced by macrophages, endothelial cells (also T cells)
IL-12 – produced by macrophages, dendritic cells
Tumor necrosis factor (TNF)-a – produced by macrophages, NK cells (also T cells)
Interferone (IFN-a) – produced by marophages and dendritic cells and acts on virally infected cells
Interferone (IFN-b) – produced by fibroblasts and acts on virally infected cells

10. Functions of cytokines in innate immunity
Macrophages activation
2. Inflammation

11. Dual function of TNF:
The release of TNF-a by macrophages induces local protective effects,
but TNF-a can have damaging effects when released systemically (septic shock).

12. Antiviral effects of Type I Interferons (IFN-a/b)
Induction of enzyme that block viral replication
Increases expression of class I MHC molecules on virus-infected cells, thus help killing by cytotoxic T lymphocytes

13. Key Cytokines Produced by T Cells
IL-2 - produced by CD8+ and CD4+Th1 cells
IFNg - produced by CD8+ T cells and CD4+Th1
TNF-a - produced by CD8+ T cells, CD4+Th1 and some CD4+Th2
IL-4 – produced by CD4+Th2
IL-10 - produced by CD4+ Th2

14. Functions of cytokines in acquired immunity
Antibody secretion by B cells
2. Cytotoxic T lymphocyte differentiation

15. Interferons (IFNs)
* Interferons (IFNs): are proteins secreted in response to
viral infections or other stimuli
* They include:
- INF-α produced by leucocytes
induced by virus infected cells
- INF-β produced by fibroblasts
- INF-γ produced by NK cells,TH1 cells, CD8 T-cells

16. Interferons (IFNs) Action of INF-α and IFN-β :
- Prevent viral replication
- Increase MHC-I expression on viral infected cells
helping their recognition by CD8 T-cells
- Increase cytotoxic action of Nk cells
- Inhibit cell proliferation and tumor growth

17. Interferons (IFNs) Action of IFN-γ : - Activate Macrophages
- Increase expression of MHC-I and II on APCs
- Enhance cytotoxic actions of Nk cells
- Promote production of TH1 and inhibits
proliferation of TH2

18. Therapeutic Uses of Cytokines
1) Interferon in treatment of viral diseases, cancer
2) Several cytokines are used to enhance T-cell activation in immunofideficincy diseases, e.g. IL-2, IFN-,TNF-
3) IL-2 and lymphokine activating killer cells (LAK) in treatment of cancer
4) Granulocyte-macrophage colony-stimulating factor) GM-CSF) induces increase in white cell count, it is used:
a- To restore leukocytic count after cytotoxic chemotherapy induced neutropenia
b- After bone marrow transplantation
C- To correct AIDS-associated leukopenia

19. Therapeutic Uses of Cytokines
5) Anti-cytokines antibodies in management of autoimmune diseases and transplant rejection:
a- Anti-TNF in treatment rheumatoid arthritis
b- Anti-IL2R to reduce graft rejection
6) Anti-TNF antibodies in treating septic shock
7) Anti-IL-2R  in treating adult T-cell leukemia
8) Anti-IL-4 is under trial for treatment of allergies