Immunity

Clinical Immunity
Dr Monem Alshok
Cyokines
Low molecular weight soluble proteins (polypeptides) produced in response to microbes and other antigens. They act via cell surface receptors to mediate and regulate the amplitude and duration of the immune-inflammatory responses, through activation of macrophages, controlling growth and differentiation of T and B cells
General Properties Of Cytokines
*Cytokine secretion is a self limited event (transient)
* They are potent in minute amounts
* One cytokine can act on different cells (pleiotropic)
* Multiple cytokines may have the same functional effects (reduntant)
* Cytokines often influence synthesis and action of other cytokines
* Two cytokines may antagonize each other’s action
(produce additive or synergetic effects)
* Action of cytokine may be local or systemic
* Cytokine act close to the site of production (autocrine act.)
* Cytokine act on a nearby cell (paracrine action)
* Large amount secretion may enter circulation and act
at a distance from site of production (endocrine action)
* Their action is not antigen specific
- It is initiated by binding to specific cytokine
receptors on the membrane of target cells
* They act as intracellular messengers
* The response to cytokine is:
a- Expression of new functions
b- proliferation of target cells
Functional Categories of Cytokines
Cytokines classified according to their biologic actions into three groups:
1) Mediators and regulators of innate immunity
- Produced by activated microphages and NK cells
in response to microbial infection
- they act mainly on endothelial cells and
leukocytes to stimulate the early inflammatory
response to microbes
2) Mediators and regulators of acquired 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-? (TGF-?) and
lymphotoxin (TNF- ?)
3) Stimulators of haematopoiesis
- Produced by bon marrow, stormal cells, leukocytes
- Stimulate growth and differentiation of leukocytes
- Stem cell factor, IL-3, IL-7, GM-CSF
Interferons (IFNs):
* Interferons (IFNs): are proteins secreted in response to viral infections or other stimuli
* They include: INF-? produced by leucocytes induced by virus infected cells . INF-? produced by fibroblasts . INF-? produced by NK cells,TH1 cells, CD8 T-cells
Action of INF-? and IFN-? :
- 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
Action of IFN-? :
- 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
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-g,TNF-a
3) IL-2 and lymphokine activating killer cells (LAK) in treatment of cancer
4) GM-CSF induces increase in white cell count, it is used:
a- To restore leukocytic count after cytotoxic chemotherapy induced neutropenia
b- After bon marrow transplantation
C- To correct AIDS-associated leukopenia
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 a in treating adult T-cell leukemia
8) Anti-IL-4 is under trial for treatment of allergies