Cytokines

Dr.Marián Sabol, PhD.

P.J. Šafárik University, Medical Faculty, Institute of Medical MicrobiologyTr. SNP 1, Košice, Slovakia

Definition

-Low molecular non-antibody proteins

-Secreted by leukocytes and some non-leukocytic cells

- Act as intercellular mediators

- They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialised glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.

Functions of Cytokines

1.Development of cellular and humoral immune responses

2.Induction of the inflammatory response

3.Regulation of hematopoiesis

4.Control of cellular proliferation and differentiation

5. Healing of wounds

* Although the immune response to a specific Ag includes the production ofd of cytokines, cytokines act in an Ag-nonspecific manner.

Properties of cProperties of cytokinesytokines

Autocrine,

Paracrine and

Endocrine Action

Cytokine Cytokine networknetwork

Pleiotropy,

Redundancy,

Synergy,

Antagonism

of Cytokines

PLEIOTROPY

REDUNDANCY

ANTAGONISM

SYNERGY

Cytokine Cytokine networknetwork

Cascade Induction

of Cytokines

Plasma Cell

Inflammatory response

Clonalexpansion

T cell

LAK

NK

ActivatedB cell

Mast cell

Stem cell

Hematopoiesis

Endothelial cellsFibroblasts

Hypotalamus

Neutrophil

Antigen

RestingB cell

Mph

Resting T cell Eosinophils

Th

TNF IL-1

TGF- PDGF

TNF IL- 1

IL- 1, 6, 11, 12TNF, CSFsIL- 1,6,8,

IL-10,12,15IFN , TNF-

Antigen

IL-3,6,7GM-CSFIL- 3,4,10

IL- 3,5

IL-2

IL-2,4,5,13TGF-IFN-

IL-4

IL –10,4

IL -2 TGF-

IL-6

IL-3,4.10,13IFN-, TNF-

IL-8, TNF-

IL-1,6 TNF-

IL-2 IFN- IL-15

IL-2 IL-12 (APC) IL-15 IL-2

IL-2

IL-12(via APC)

IL-2 IFN-

Th1Th1 / / Th2Th2

Regulation of TH Subsets by Cytokines

TH1 Response

-cell-mediated functions (e.g., delayed-type hypersensitivity and activation of TC cells)

-Production of IgG3, IgG1, IgG2 (opsonization and C activation).-Excessive inflammation and tissue injury.- Target: viral infections and intracellular pathogens. ( IL-2, IFNand TNF)

- IFN also inhibits the expansion of the TH2 population.

TH2 Response

-Stimulates eosinophil activation and differentiation

- Provides help to B cells, and promotes the production

of relatively large amounts of IgM, IgE, and IgG4

-Supports allergic reactions.

The production of Il-4, IL-5 and IL-10 promotes the function of IgE and eosinophils on the anti-helminth (round worm) immunity.