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Cytokines
Dr.Marián Sabol, PhD.
P.J. Šafárik University, Medical Faculty,
Institute of Medical Microbiology
Tr. 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 cytokines
Autocrine,
Paracrine and
Endocrine Action
Cytokine
network
PLEIOTROPY
Pleiotropy,
Redundancy,
Synergy,
Antagonism
of Cytokines
REDUNDANCY
SYNERGY
ANTAGONISM
Cytokine
network
Cascade Induction
of Cytokines
Inflammatory response
Fibroblasts
TNF TGF-
PDGF
Hypotalamus
IL-1
Neutrophil
Resting
B cell
IL-1,6
Mph
TNF-
Antigen
Hematopoiesis
IL1, 6, 11, 12
IL- 1,6,8,
IL-8, TNF-
TNF,
CSFs
IL-10,12,15
Stem
cell
IFN
,
IL-3,4.10,13
TNF-
Mast
IFN-,
cell
TNF-
IL-3,6,7
GM-CSF
Antigen
IL- 3,4,10
Resting T
cell
Eosinophils
IL –10,4
IL- 3,5
IL-2
IL-12 (APC)
IL-15
IL-2
IL-2
IL-4
IL-2
Th
IFN-
IL-2,4,5,13
IL-15
TGF-
IL-2
IFN-
IFN-
IL -2 TGF- IL-2
IL-6
Activated
B cell
Plasma Cell
Endothelial cells
TNF IL- 1
Clonal
expansion
NK
IL-12
(via APC)
LAK
T cell
Th1 / Th2
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, IFN and 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.