Variants of the immune conflict
The nature of the development of the immunological conflict fundamentally depends on the specific tissue or organ being transplanted into the patient. There are two main scenarios:
- Transplantation of non-immunocompetent organs. This group includes the heart, kidneys, liver, and other parenchymal organs. In this case, a classic «host-versus-graft» reaction develops. The recipient's immune system recognizes the transplanted organ as a foreign object and triggers mechanisms for its rejection.
- Transplantation of immunocompetent tissues. This refers to bone marrow or a pool of stem cells. The situation changes drastically: a bidirectional immune aggression arises. In addition to the body's attempts to reject the transplanted cells, a severe «graft-versus-host» reaction (GVHD) develops. Meanwhile, donor lymphocytes, finding themselves in a new organism, begin to perceive the recipient's tissues as hostile and actively destroy them.
The main preventive measure for any of these conflicts is careful donor-recipient matching based on histocompatibility antigens (HLA system).
Classification of rejection by timeline
The speed of development of the rejection reaction allows one to judge its leading pathogenetic mechanisms. Clinically, three time intervals are distinguished:
- Hyperacute rejection. Develops fulminantly, within 1 to 5 days after surgery. Its cause is the presence in the recipient's blood of already formed (preformed) antibodies to donor antigens. Such sensitization according to ABO or HLA systems is usually the consequence of previous blood transfusions or pregnancies.
- Acute rejection. Occurs within 5 to 30 days. The leading damage mechanism during this period is the massive deployment and activation of cell-mediated immunity reactions.
- Chronic rejection. Forms slowly, 6 months or more after transplantation. As with the acute form, the cellular link of immunity continues to play the main role here, gradually leading to sclerosis and loss of organ function.
Cellular mechanisms of destruction
A whole cascade of immunocompetent cells is involved in the pathogenesis of acute and chronic rejection. The main blow is dealt by effector structures:
- CD8+ cytotoxic T lymphocytes (CTLs). These are the main «soldiers» of cell-mediated immunity. They directly recognize foreign antigens on the cells of the donor organ and destroy them.
- NK cells (natural killers). Take an active part in the direct cytotoxic attack on the graft, working in synergy with T lymphocytes.
- Type 2 T-helper cells (Th2). Perform a regulatory function: they stimulate the development of the humoral response. Under their influence, B lymphocytes are activated, transforming into plasma cells and beginning to synthesize destructive antibodies against the transplanted tissue.
Diagnostics and pharmacological protection
Before surgery, typing for the major histocompatibility complex (MHC) is mandatory. Two approaches are used for this: serological (microcytotoxicity test using monospecific sera, B lymphocytes, and complement) and molecular genetic (PCR for precise DNA typing).
After surgery, the patient is prescribed lifelong immunosuppressive therapy to prevent rejection crises. There are several groups of drugs in the doctors' arsenal:
- Azathioprine. Acts as a protein synthesis antimetabolite, effectively suppressing the induction and proliferation of cytotoxic T lymphocytes.
- Glucocorticosteroids (Prednisolone). Possess a wide spectrum of action: they powerfully inhibit macrophages and T cells, block the synthesis of inflammatory cytokines, and halt the complement system.
- Cyclosporine A. Selectively blocks the synthesis of interleukin-2 (IL-2) by T-helper cells, depriving the immune system of its main activation factor.
- Monoclonal antibodies (Daclizumab, Basiliximab). These modern drugs bind precisely to IL-2 receptors (CD25) on the surface of T lymphocytes, making them «blind» to activating signals.
Briefly: answers to topical questions
What side effects develop with the use of calcineurin inhibitors after organ transplantation?
Nephrotoxicity is possible with the use of calcineurin inhibitors. For tacrolimus compared to cyclosporine, nephrotoxicity and neurotoxicity are more pronounced; a specific risk is the development of insulin-dependent diabetes mellitus. Tacrolimus does not cause hirsutism and arterial hypertension.
What clinical manifestations are characteristic of the «graft-versus-host» reaction?
Acute graft-versus-host disease is characterized by damage to three main target organs. The experimental triad (enlargement of the spleen, liver, and lymph nodes) is rare in humans.
The main clinical manifestations include:
- Skin — the epidermis is damaged, which manifests as a rash.
- Liver — the epithelium of the bile ducts is damaged (but not hepatocytes), leading to jaundice.
- Gastrointestinal tract — the mucous membrane is damaged, resulting in diarrhea and intestinal bleeding.
A severe complication that can lead to a fatal outcome is massive desquamation of the intestinal mucosal epithelium.
Class and exam questions
Why does a «graft-versus-host» reaction occur during bone marrow transplantation?
Bone marrow contains immunocompetent cells (donor lymphocytes). Entering the recipient's organism, they recognize its tissues as genetically foreign and begin to attack them.
What causes hyperacute rejection?
Hyperacute rejection is caused by the presence in the recipient's blood of preformed antibodies (to HLA or ABO antigens) that formed previously due to blood transfusions or pregnancies.
What is the mechanism of action of Cyclosporine A?
Cyclosporine A selectively blocks the production of interleukin-2 (IL-2) by T-helper cells, which prevents the further activation and proliferation of T lymphocytes attacking the graft.
What else to study on this topic
- Molecular genetic methods of DNA typing of the HLA system
- Methodology for performing the microcytotoxicity test
- Mechanisms of complement system involvement in graft rejection
- The role of Th2 lymphocytes in the activation of the humoral link of immunity
- Features of the use of monoclonal antibodies (anti-CD25) in transplantology
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