Helper T cells make molecules {cytokine}| that attract neutrophils and monocytes, which become macrophages: {colony-stimulating factor} {granulocyte-macrophage colony-stimulating factor} (GMCSF) {interleukin}. Tumor necrosis factor alpha {tumor necrosis factor} increases inflammation. Inside cells, Toll-like receptors make MyD88, Mal, Tram, and/or Trif. These make NF-kappaB, which enters cell nucleus to start cytokine production. Cytokines include interleukin-1, interleukin-6, interleukin-8, interleukin-12, and tumor necrosis factor-alpha. Interleukin-1 increases inflammation. Interleukin-6 activates B cells. Interleukin-8 is signal to neutrophils. Interleukin-12 activates T cells. Cytokines attract monocytes and neutrophils. Monocytes become macrophages.
Cells inflamed by injury, allergens, antigens, or invading microorganisms release 8-kDa to 16-kDa soluble proteins {chemokine}, to attract monocytes and granulocytes. Humans have 50 chemokines.
types
Alpha chemokines have amino acids between first two cysteines and have two other cysteines. Beta chemokines have no separation between first two cysteines and have two other cysteines. Gamma chemokines have two cross-linked cysteines. Lymph nodes, lungs, liver, and bone marrow express factors {stromal-cell-derived factor 1} from genes {SDF-1 gene} {CXCL12 gene}.
receptors
Chemokines bind to chemokine receptors {G protein-linked receptor}. Chemokine receptors (CXCR2) (CXCR4) (CCR7) include chemokine receptor 5 (CCR5), used by HIV-1.
receptors: effects
Binding to receptors causes adhesion-protein {B integrin} rearrangement, to increase adhesion to blood-vessel endothelial cells. Later, leukocytes pass between endothelial cells into tissue. Leukocytes use pseudopods and actin movement to migrate along chemokine concentration gradient. High chemokine concentration makes leukocytes produce cytokines, release granule contents, induce intracellular F-actin polymerization, form pseudopods, increase endothelial and other cells, promote vascularization, remodel tissue, heal wounds, and lyse lymphocytes.
Macrophages and endothelial cells make proteins {S100 protein}, such as S100A8 and S100A9, that signal for more macrophages to come.
Tumor necrosis factor, interleukin-l, and interleukin-6 cytokines {pro-inflammatory cytokine} cause sickness responses [Maier and Watkins, 1998] [Watkins and Maier, 1999] [Watkins and Maier, 2002].
4-Zoology-Organ-Immune System-Protein
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Date Modified: 2022.0225