Own to cause autoimmune thrombocytopenia and Procyanidin B1 dose possibly autoimmune neutropenia. Antibodies directed
Own to cause autoimmune thrombocytopenia and possibly autoimmune neutropenia. Antibodies directed against tissue proteins are factors in the etiopathogenesis of autoimmune thyroiditis, adrenalitis, encephalitis, and, conceivably, peripheral neuropathies. Although neuropathy is not a common sequela, organomegaly, endocrinopathy or POEMS syndrome are PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28242652 potential outcomes (reviewed in [17]). Malignant B-cell infiltration into bone marrow suppresses hemopoiesis, causing anemia, granulocytopenia and possibly thrombocytopenia. While combinations of proliferating and infil-Page 3 of(page number not for citation purposes)Theoretical Biology and Medical Modelling 2006, 3:http://www.tbiomed.com/content/3/1/of genes encoding peripheral antigens. On the basis of these findings it has been suggested that thymicallyimposed “central” (self) tolerance plays a pivotal role in the in genesis of autoimmunity [27].Cellular basis of antigen presentation and crosspresentation: role of MHC and T-cells In particular, the MHC haplotype contributes either by enabling peptide epitopes to be presented in the periphery, increasing T cell activation, or by aborting the presentation of self(host)-antigens in the thymus. As a result, more aggressive T cells or fewer regulatory T (Treg) cells are formed in the host. It is known that Th1-type responses such as interferon- [IFN-] and interleukin 12 [IL-12] are associated with destructive autoimmune responses, while Th2-type responses (IL-4, IL-5, IL-13) counter-regulate cell-mediated autoimmune processes [28].ease. Attenuation of the IL-10 and transforming growth factor- (TGF-) effect has been shown to result in inflammation and the onset of autoimmune diseases. In the context of lymphoid malignancy and autoimmunity, the absence of STAT3 from myeloid cells results in the onset of autoimmune diseases [31]. Therefore, the balance between proinflammatory (IL-2, IFN- and TNF) and regulatory (IL-4, IL-10 and TGF-) cytokines probably determines any predisposition to develop autoimmune disease. IL-2 is known to mediate apoptosis through two different pathways, passive cell death (PCD) [32] and activation-induced cell death (AICD) [33]. PCD occurs mostly because crucial pro-survival signals are absent. Lack of cytokine signaling has been shown to cause an increase in mitochondrial permeability and cytochrome c release; along with apoptotic protease-activating factor 1 (APAF1), cytochrome c activates caspase-9 and downstream effector caspases. AICD, which is essential for the pathogenesis of autoimmunity and autoimmune lymphoproliferative syndrome, occurs mainly because of IL-2 mediated signaling via the deathdomain-containing receptor Fas (CD95). After the Fas-associated death domain (FADD) is activated, caspase-8 becomes active and downstream signaling results in cell death. Fas/Fas ligand (FasL; CD178) are deficient in autoimmune lpr and gld mice, which develop profound lymphadenopathies. The autoimmune lymphoproliferative disease (ALPS) found in humans is also consequent on mutations in Fas [33,34]. Furthermore, IL2 has been shown to upregulate CTLA-4 (cytotoxic T-lymphocyte-associated protein 4; CD152), and CTLA-4-deficienciy leads to a fatal lymphoproliferative disease that is more aggressive than the lymphoproliferative disorders caused by either IL-2 or Fas deficiency [35]. However, abrogation or attenuation of chemokine induction (CXCL10, IP-10, inflammatory cytokines) at an auxiliary location would be likely to impair the.