Types of Immunological Conflict
The nature of the immunological conflict fundamentally depends on the specific tissue or organ being transplanted. Two primary clinical scenarios exist:
- Transplantation of non-immunocompetent organs. This group includes the heart, kidneys, liver, and other parenchymal organs. In this case, the classic "host-versus-graft" reaction develops. The recipient's immune system recognizes the transplanted organ as foreign and triggers rejection mechanisms.
- Transplantation of immunocompetent tissues. This refers to bone marrow or stem cell pools. The situation changes drastically: a bidirectional immune aggression occurs. In addition to the host's attempts to reject the transplanted cells, a severe "graft-versus-host disease" (GVHD) develops. In this scenario, donor lymphocytes in the new host perceive the recipient's tissues as foreign and actively destroy them.
The primary measure to prevent either conflict is careful donor-recipient matching based on histocompatibility antigens (the HLA system).
Classification of Rejection by Timeline
The timeline of rejection reactions reflects the underlying pathogenetic mechanisms. Clinically, rejection is divided into three temporal intervals:
- Hyperacute rejection. Develops within minutes to hours, typically from days 1 to 5 post-transplant. It is caused by the presence of pre-existing antibodies in the recipient's blood directed against donor antigens. Such sensitization against AB0 or HLA systems usually results from previous blood transfusions or pregnancies.
- Acute rejection. Occurs from 5 days to 30 days post-transplant. The predominant damaging mechanism during this period is the massive deployment and activation of cellular immunity.
- Chronic rejection. Develops slowly, starting 6 months or more after transplantation. Similar to the acute form, cell-mediated immunity plays a major role, progressively leading to tissue fibrosis (sclerosis) and loss of organ function.
Cellular Mechanisms of Destruction
A cascade of immunocompetent cells is involved in the pathogenesis of acute and chronic rejection. Effector structures deliver the primary strike:
- CD8+ cytotoxic T lymphocytes (CTLs). These are the primary soldiers of cellular immunity. They directly recognize foreign antigens on donor organ cells and destroy them.
- NK cells (Natural Killers). Actively participate in direct cytotoxic attacks against the graft, working synergistically with T lymphocytes.
- T helper 2 cells (Th2). Perform a regulatory function by stimulating the humoral response. Under their influence, B lymphocytes are activated, transforming into plasma cells that synthesize destructive antibodies against the transplanted tissue.
Diagnostics and Pharmacological Protection
Prior to surgery, histocompatibility leukocyte antigen (HLA) typing is mandatory. Two approaches are used: serological (microcytotoxicity test using monospecific sera, B lymphocytes, and complement) and molecular-genetic (PCR for precise DNA typing).
Following surgery, the patient is prescribed lifelong immunosuppressive therapy to prevent rejection crises. Several pharmacological classes are available:
- Azathioprine. Acts as a purine antimetabolite, effectively inhibiting the induction and proliferation of cytotoxic T lymphocytes.
- Glucocorticoids (Prednisone). Possess a broad spectrum of activity: they powerfully suppress macrophages and T cells, block inflammatory cytokine synthesis, and halt the complement system.
- Cyclosporine. Selectively blocks interleukin-2 (IL-2) synthesis by T helper cells, depriving the immune system of its primary activation factor.
- Monoclonal antibodies (Daclizumab, Basiliximab). These targeted agents bind specifically to the IL-2 receptor (CD25) on the surface of T lymphocytes, rendering them unresponsive to activating signals.