The INDIVIDUALIST

A Wiki about biochemical individuality

Immunology

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Description

Cytokines are small secreted proteins which mediate and regulate immunity, inflammation, and hematopoiesis. They must be produced de novo in response to an immune stimulus. They generally (although not always) act over short distances and short time spans and at very low concentration. They act by binding to specific membrane receptors, which then signal the cell via second messengers, often tyrosine kinases, to alter its behavior (gene expression). Responses to cytokines include increasing or decreasing expression of membrane proteins (including cytokine receptors), proliferation, and secretion of effector molecules.

Non-nutrient environmental factors affecting cytokine concentration

From Kaput and Rodriguez (1)

  • Overall sleep time and sleep continuity
  • Oxygen tension, which is related to altitude.
  • Over-the-counter drugs (e.g., nonsteroidal anti-inflammatory drugs)
  • Water intake relative to tea and other beverages.
  • Physical activity, including genetic fitness to activity
  • Psychological factors like stress
  • Exposure to allergens and pollutants
  • Circadian rhythm and seasonal changes
  • Balance between energy intake and expenditure

Discussion

Cytokine blocking has had some clinical applications, including the use of Etanercept, a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human p75 TNF-alpha cellular receptor linked to the Fc portion of human immunoglobulin (Ig)G1 for the treament of Alzheimer's dementia. Etanercept specifically binds to TNF-alpha, rendering it biologically ineffective.(2)

Remicade (infliximab), also a TNF-alpha agonist, has been shown to have effectiveness in a variety of inflammatory conditions, including rheumatoid arthritis, ulcerative colitis and psoriasis. (3)

Cytokine activity decreases over time in stored blood. (4)

There is an expanding body of clinical and experimental evidence that cytokines, especially interleukin-1, tumor necrosis factor, interleukin-6, and interleukin-8, are principle mediators of immune responses to erythrocyte incompatibility. Recent studies have further suggested that the monocyte chemotactic and activating factor, monocyte chemoattractant protein-1, and the anti-inflammatory cytokine interleukin-1 receptor antagonist are produced in experimental models of hemolytic transfusion reactions. Differing levels and patterns of expression of these cytokines may be seen in models of intravascular hemolysis due to ABO incompatibility and extravascular hemolysis due to Rh incompatibility, which correlate with the recognized clinical differences between these two types of reactions. (5)

Selected Immune Cytokines and Their Activities
Cytokine ProducingCell TargetCell Function**
GM-CSF Th cells progenitor cellsgrowth and differentiation of monocytes and DC
IL-1 alpha, IL-1 beta monocytes macrophages B cells DC Th cellsco-stimulation
B cellsmaturation and proliferation
NK cells activation
variousinflammation, acute phase response, fever
IL-2 Th1 cells activated T and B cells, NK cellsgrowth, proliferation, activation
IL-3 Th cells NK cells stem cellsgrowth and differentiation
mast cells growth and histamine release
IL-4 Th2 cells activated B cells proliferation and differentiationIgG1 and IgE synthesis
macrophagesMHC Class II
T cellsproliferation
IL-5 Th2 cells activated B cellsproliferation and differentiation, IgA synthesis
IL-6 monocytes macrophages Th2 cells stromal cells activated B cellsdifferentiation into plasma cells
plasma cellsantibody secretion
stem cellsdifferentiation
various acute phase response
IL-7 marrow stroma thymus stroma stem cellsdifferentiation into progenitor B and T cells
IL-8 macrophages endothelial cells neutrophilschemotaxis
IL-10 Th2 cells macrophagescytokine production
B cellsactivation
IL-12 macrophages B cells activated Tc cellsdifferentiation into CTL(with IL-2)
NK cells activation
IFN- alpha leukocytes variousviral replicationMHC I expression
IFN- beta fibroblasts variousviral replication MHC I expression
IFN- gamma Th1 cells, Tc cells, NK cells various Viral replication
macrophagesMHC expression
activated B cellsIg class switch to IgG2a
Th2 cellsproliferation
macrophagespathogen elimination
MIP-1 alpha macrophages monocytes, T cellschemotaxis
MIP-1 beta lymphocytes monocytes, T cellschemotaxis
TGF-beta T cells, monocytes monocytes, macrophageschemotaxis
activated macrophagesIL-1 synthesis
activated B cells IgA synthesis
variousproliferation
TNF alpha macrophages, mast cells, NK cells macrophagesCAM and cytokines expression
tumor cells cell death
TNF- beta Th1 and Tc cells phagocytesphagocytosis, NO production
tumor cells

cell death

Links

References


1. Kaput J. An introduction and overview of nutritional genomics: Application to type 2 diabetes and international nutrigenomics. In: From Kaput J and Rodriguex R. Nutritional Genomics. 2006 Wiley

2. Tobinick E, Gross H, Weinberger A, Cohen H. TNF-alpha modulation for treatment of Alzheimer's disease: a 6-month pilot study. MedGenMed. 2006;8(2).

3. Penn H. Biologic therapies in autoimmune diseases. Clin Med. 2006 Jan-Feb;6(1):105-8.

4. Mynster T, Dybkjoer E, Kronborg G, Nielsen HJ. Immunomodulating effect of blood transfusion: is storage time important? ox Sang. 1998;74(3):176-81.

5. Davenport R. Cytokines and erythrocyte incompatibility.Curr Opin Hematol. 1994 Nov;1(6):452-6.

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