Question

1)Please explain the role of alloimmune antibodies in graft rejection?

2)What is the cause of the tissue injury in DTH reactions?

Answer 1

1.     Role of alloimmune antibodies in graft rejection:-

Pathophysiology of chronic rejection strongly supports that inflammation and subsequent tissue remodeling during the post-transplant period cause exposure of cryptic self-antigens (SAgs) or their determinants within the graft, which, along with a subsequent cytokine response, leads to loss of peripheral tolerance. These events lead to the activation of cell-mediated immunity towards development of de novo immune responses to SAgs. There is also evidence for a role for interplay between allo- and autoimmunity in the development of chronic rejection. Experimental results using murine models of Obliterative Airway Disease (OAD) akin to chronic lung allograft rejection have clearly demonstrated that autoimmune responses to Collagen V (ColV) and K-alpha 1 Tubulin (Kα1T) were induced by administration of antibodies (Abs) against class I major histocompatibility complex antigens. Further, inhibition of interleukin (IL)-17 abrogated the autoimmune response and development of OAD. Recent reports demonstrate that in addition to lung transplant recipients, kidney transplant recipients diagnosed with transplant glomerulopathy can develop de novo Abs to Sags, including Col-IV and fibronectin and heart transplant recipients can develop immune responses to cardiac myosin and vimentin. Abs to SAgs were identified frequently with donor specific anti-human leukocyte antigen antibodies, supporting the concept of crosstalk between auto- and alloimmunity. The increased frequency of SAg specific interferon-gamma and IL-17 cells with reduction in IL-10 demonstrates tolerance breakdown to SAgs which may play a significant role in the pathogenesis of chronic rejection.

2.

Delayed-type hypersensitivity also describes a positive response to the common test for tuberculosis (subcutaneous injection of mycobacterial purified protein derivative, or PPD). In this case, inactivated toxoid from mycobacteria recruits pre-primed T cells and macrophages, which initiate an inflammatory response. A positive test occurs only if a significant number of antigen-specific T cells are already present as a result of prior (or ongoing) exposure to mycobacterial antigens. Paradoxically, patients with disseminated tuberculosis may not respond to PPD because of significant immunosuppression produced by severe infection. The interaction of T cells and macrophages with antigen results in the production of IFN-γ and TNF-α to orchestrate a strong inflammatory reaction that may be granulomatous in character (see below). Some types of natural killer cell inflammatory responses may be described as delayed-type hypersensitivity in that they are mediated exclusively by cellular components of the immune system but are not antigen specific.