UNDERLYING DISEASE SCREENING IN DOGS WITH IMMUNE-MEDIATED HEMOLYTIC ANEMIA

摘要

Immune mediated diseases are important causes of morbidity and mortality in dogs. Studies suggest that the pathology associated with self-attack by the immune system may result from inappropriate specific targeting of self-antigen, modification of self-antigen so that it is foreign, or from a less specific, "innocent bystander" effect.Several regulatory mechanisms are in place in order to prevent self-attack by the immune system. Central tolerance mechanisms result in the deletion of auto- reactive B and T cells during development. However, evidence suggests that this process is imperfect. Naive T and B cells that have escaped central tolerance mechanisms and have the ability to target and react to self-antigen are present in normal individuals. Several peripheral tolerance mechanisms exist to prevent these cells from being activatedand/or to down-regulate already activated cells to keep them in check.A central player in maintaining peripheral tolerance is the dendritic cell (DC). The DC is a professional antigen presenting cell that processes and presents antigen in the context of MHC I and II to naive T cells. CD4 + T cells that engage the MHCII /Agcomplex in the presence of a costimulatory signal differentiate into T helper (Th) cell subtypes (ie Th-1, Th-2, Th-17 and others). The type of Th cell subset that develops depends on the signaling/cytokine milieu that is present at the time of antigenpresentation. It is important to emphasize that a costimulatory signal [eg binding of DC CD80/86 (B7.1 and B7.2) with T cell CD28] is required to activate a T cell upon initial receptor engagement. Dendritic cells do not express the requisite costimulatory signal unless they have been activated by certain triggers, such as signaling through pattern recognition receptors (PRRs) by pathogen associated molecular patterns (PAMPs). LPS and RNA sequences from bacteria and viruses, respectively, are examples of PAMPs. Cytokines like TNFa also facilitate DC maturation and expression of costimulatory signals. Without the presence of a costimulatory signal the T cell is rendered anergic or undergoes apoptosis. Thus engagement of the TCR in the absence of a costimulatory signal is an important peripheral tolerance mechanism.