Cytokines: low-molecular-weight proteins secreted by WBC or other cell types in response to a number of stimuli.

Interleukins (IL): cytokines that are secrected by leukocytes and act upon other leukocytes.

Chemokines: cytokines that stimulate the migration and activation of cells, especially phagocytes and lymphocytes. They have a central role in inflammatory responses.

Most cytokines exhibit autocrine and/or paracrine action

Properties of Cytokines:

• Pleiotrophy

• Redundancy

• Synergy

• Antagonism

• Cascade induction

REDUNDANCY

ELISA assay of cytokines

Cytokines Belong to 4 Structural Families:

• Hematopoietin family

• Interferon family

• Chemokine family

• Tumor necrosis factor family

The two majorcytokine producers;TH cell and macrophage

Cytokine Receptors Belongs to 5 Families:

• Immunoglobulin superfamily receptors

• Hematopoietin receptor family

• Interferon receptor family

• TNF receptor family

• Chemokine receptor family

Subfamilies in Class I Cytokine Receptors

CNTF: ciliary Neurotrophic factor

LIF/OSM: leukemia-Inhibitory factor/oncostatin

Antagonistic Effects between Cykotines

Cytokine Antagonists

IL-1 receptor antagonist (IL-1Ra): binds to the IL-1 receptor but has no activity.

Soluble IL-2 receptor (sIL-2R): a segment of the subunit that can bind to IL-2 and prevent its interaction with membrane-bound IL-2 receptor.

Viral mimics of cytokines and cytokine receptors

Suppress TH1 response

TH1 and TH2 cells can be identified in vitro by the cytokines they secrete:

• TH1 cells promote cell-mediated immunity (e.g.,

activation of TC cells and delayed-type hypersensitivity) and the production of opsonization IgG antibodies. They are also associated with inflammation.

• TH2 cells stimulate eosinophil activation and

differentiation and promote humoral response (secretion of IgM and IgE antibodies). They are related to allergic reactions.

Cytokine-mediated generation and cross regulation of TH subsets

Cross-regulation between IFN- and IL-4

The TH1/TH2 Balance Determines Disease Outcomes

Leprosy: a disease caused by an intracellular pathogen Mycobacterium leprae.

Tuberculoid leprosy: a cell-mediated immune response forms granulomas, resulting in the destruction of most of the mycobacteria.

Lepromatous leprosy: humoral response dominates, sometimes resulting in hypergammaglobulinemia. High numbers of the bacteria in macrophages. The infection will progress and spread into the bone and cartilage with extensive nerve damage.

Cytokine-related Diseases

• Bacterial septic shock: endotoxin in cell wall of gram-negative bacteria stimulate macrophages to over produce IL-1 and TNF-.

• Bacterial toxic shock: caused by superantigens that bind simultaneously to MHC class II and TCR V domain. 5-25% of total T cells may respond to a single superantigen and result in excessive production of cytokines.

Strategies help to prolong the survival of heart transplants

Cytokines in hematopoiesis