PRIMING => PRIMARY IMMUNE RESPONSE (see also secondary immune response)

Table of contents :

  • antibody-mediated immunity (AMI)
  • cell-mediated immunity (CMI)

  • Immune response = f [(dangerous stimuli)(DC subset)(antigen-recognition receptor)(cytokine microenvironment)] : any response of the immune system to an antigenic stimulus, including antibody production, cell-mediated immunity, and immunologic tolerance

    lymphocyte activation : stimulation of lymphocytes by specific antigen or nonspecific mitogens resulting in macromolecular synthesis (RNA, protein, and DNA) and production of lymphokines; it is followed by proliferation and differentiation of the progeny into various effector and memory cells. NFAT5 has an important role in enabling lymphocytes to adapt to osmotic stress in lymphoid tissues : the proliferation of Nfat5+/D T cells was inhibited by > 60% under conditions  of hyperosmotic stress. Similar to T-cell responses, Nfat5+/D B-cell proliferation after stimulation with LPS is markedly reduced in hypertonic but not isotonic media. Despite it is generally thought that unlike unicellular organisms, most mammalian cells are not normally subjected to extremes of hypertonic stress in vivo because of the maintenance of body-fluid homeostasis.
    lymphocyte transformation : the morphologic changes accompanying lymphocyte activation, in which small, resting lymphocytes are transformed into large, active lymphocytes (lymphoblasts)
    Lymphoid tissues have increased osmolarity compared with the serum, and brain and lung tissues : this might reflect high cell density or the presence of highly metabolically active cells in the lymphoid tissuesref
    A major challenge is understanding what endows the overall ensemble with both sensitivity and global reliability despite variations in the concentration, initial state, local behavior, or previse number of partecipating components. Emerging evidence suggests that these properties arise from a combination of :

    The primary immune response : the immune response occurring on the first exposure to an antigen. After a lag or latent period of from 3 to 14 days depending on the antigen, specific antibodies appear in the blood. There is a peak of IgM production lasting several days followed immediately by a peak of IgG production. Antibody production ceases after several weeks, but memory cells remain in circulation. Interferon-a promoter stimulator 1 (IPS-1) => ... => TBK1 and IKKi protein kinases => ... => activation of IRF3, IRF7 and NF-kB transcription factors => ... => type I interferon and interferon-inducible genesref
    CARD11 / CARMA1 - a member of the membrane-associated guanylate kinase (MAGUK) family of proteins - is essential for lymphocyte activation.

    (reproduced with permission from Nature Reviews Immunology (Vol 3, No. 11, pp 867-878 (2003)) copyright Macmillan Magazines Ltd)

    S1P1, which is highly expressed by T and B cells, is essential for lymphocyte recirculationref (i.e. T-cell exit from the thymus and B cell leave from peripheral lymphoid organs into the circulation to mediate their effector functions : agonism inhibits transendothelial migration of medullary T cells to lymphatic sinusesref). RAPL is indispensable in the integrin-mediated adhesion and migration of lymphocytes and dendritic cells, essential for immunosurveillanceref. Sphingosine kinase and sphingosine-1-phosphate regulate migration, endocytosis and apoptosis of dendritic cells via S1P1 > S1P2 = S1P3ref

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