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 major cytokine 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 a 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-g 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-a. Bacterial toxic shock: caused by superantigens that bind simultaneously to MHC class II and TCR Vb 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