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Santral toleransDüzenle

Santral tolerans; işlevsel bağışıklık sistemi hücrelerine dönüşmeden önce "self-protein" cevabı veren lenfositlerin öldürülmesi işlemidir. Bu işlem lenfosit gelişimi sırasında timüs bezinde ve kemik iliğinde T ve B lenfositler için yapılır.[1][2]In these tissues, maturing lymphocytes are exposed to self-antigens presented by medullary thymic epithelial cells and thymic dendritic cells, or bone marrow cells. Self-antigens are present due to endogenous expression, importation of antigen from peripheral sites via circulating blood, and in the case of thymic stromal cells, expression of proteins of other non-thymic tissues by the action of the transcription factor AIRE.

Those lymphocytes that have receptors that bind strongly to self-antigens are removed by induction of apoptosis of the autoreactive cells, or by induction of anergy, a state of non-activity.[3] Weakly autoreactive B cells may also remain in a state of immunological ignorance where they simply do not respond to stimulation of their B cell receptor. Some weakly self-recognizing T cells are alternatively differentiated into natural regulatory T cells (nTreg cells), which act as sentinels in the periphery to calm down potential instances of T cell autoreactivity (see peripheral tolerance below).[4]

The deletion threshold is much more stringent for T cells than for B cells since T cells alone can cause direct tissue damage. Furthermore, it is more advantageous for the organism to let its B cells recognize a wider variety of antigen so it can produce antibodies against a greater diversity of pathogens. Since the B cells can only be fully activated after confirmation by more self-restricted T cells that recognize the same antigen, autoreactivity is held in check.[3]

This process of negative selection ensures that T and B cells that could initiate a potent immune response to the host's own tissues are eliminated while preserving the ability to recognize foreign antigens. It is the step in lymphocyte education that is key for preventing autoimmunity (entire process detailed here). Lymphocyte development and education is most active in fetal development, but continues throughout life as immature lymphocytes are generated, slowing as the thymus degenerates and the bone marrow shrinks in adult life.

  1. ^ Sprent, J; Kishimoto H (2001). "The thymus and central tolerance". Philos Trans R Soc Lond B Biol Sci. 356 (1409): 609–616. doi:10.1098/rstb.2001.0846. PMC 1088448 $2. PMID 11375064. 
  2. ^ Hogquist, K; Baldwin T; Jameson S (2005). "Central tolerance: learning self-control in the thymus". Nat Rev Immunol. 5 (10): 772–782. doi:10.1038/nri1707. PMID 16200080. 
  3. ^ a b Murphy, Kenneth. Janeway's Immunobiology: 8th ed. Chapter 8: Garland Sciences. ss. 275–334. 
  4. ^ Kaynak hatası: Geçersiz <ref> etiketi; Janeways ch15 isimli refler için metin sağlanmadı (Bkz: Kaynak gösterme)