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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: leukemiaInhibitory 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