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Cytokines:

basic concept, and their


implications in health and
therapy
marshnes@yahoo.com

What are they?

Cytokines
Small proteins (ca. 25 kDa)
Released by various cells in response to
external stimuli
Induce subsequent response through
specific receptor, and affecting in
different manner

autocrin, paracrin, endocrin

Various names

Monokines
Lymphokines
Interleukines
Others:
Chemokines (chemotactic cytokines),
interferons, growth factors (CSF, TGF),
tumor necrosis factor (TNF)

General features

Pleiotropic, redundant
Secretion: brief, transient, specific
occasion
Induce or inhibit the synthesis or
action of others; synergy and
antagonize functions; proinflammatory and anti-inflammatory
properties

Characteristics of cytokines in action

Implications in health and as


immunomodulator/therapy

Activated macrophages & DC secrete


cytokines/chemokines

Figure 2-39

Cytokines and chemokines secreted by


activated macrophages

Figure 1-4 part 1 of 3

Figure 2-41 part 1 of 2

Notice the interaction of HIV and chemokine receptor

Figure 2-41 part 2 of 2

Notice the interaction of HIV and chemokine receptor


(contnd)

Basic concept of Th1 and Th2


responses, with cytokine production
profile, expl. in:
Infections
Hypersensitivity reactions
Autoimmunity
Reproductive immunology

Cytokine and infections

The differentiation of CD4+ T cells


into Th1 or Th2 cells

determines whether
humoral or cellmediated immunity
will predominate
The type of cytokines
are different and have
typical pattern
TH1:
IFN-, IL-2, TNF-

TH2:
IL-4, IL-10, IL-5, IL-13

Figure 2-46

Biological activities of cytokines in various organs due to


their responses against infection

Figure 2-44
The pseudopod of
neutrophil inserts
in between
endothelial cells
(blue arrow)

Chemokines affect the leukocyte migration during


inflammatory reaction/infection after an interaction with
endothelium

Figure 2-45

Local vs systemic infections leading to TNFsecretion and their effects on the circulation

Cytokine and Allergy

Hypersensitivity Reactions, esp. type I H (allergy)


Allergy has
many faces
Antibody/B cellmediated allergy

IL-4 cytokine as IgE switch factor

Interaction of IgE antibodies to mast cell membrane

Cytokine and Reproductive


immunology

TH1 vs TH2 cytokine pattern in pregnancy

GM-CSF
IFN-

Cytokine and Autoimmunity

T cell-mediated diseases
Th1 cytokines: IFN-, TNF-
IDDM
Multiple sclerosis

Th2/Th1 cytokines: IL-4, IL-5, IL-10, IL13/IFN-,TNF-

SLE

Cytokine and T reg

Regulatory T cells (T reg)


CD4+CD25+ (autoimmunity)

IL-4, IL-10, TGF-

CD4+CD25- Th3 (mucosal immunity)

IL-4, IL-10, TGF-

CD4+CD25- TR1 (mucosal immunity)

IL-10, TGF-

Cytokine and Corticosteroid

Figure 14-3

The effect of corticosteroid on pro-inflammatory


cytokines

Concluding remarks

Cytokines: soluble mediators of both


innate and adaptive immunity
Those mediate the innate- and adaptive
immune responses are mainly produced by
macrophages/dendritic cells, and T cells,
respectively

Excessive production systemic access


pathologic consequences
Can be used for modifying biologic
response associated with the immune- and
inflammatory diseases

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