Nature of the tissue barrier
Historical experience shows that the transplantation of one's own tissues (autotransplantation) is usually successful. Ancient Indian physicians were able to engraft patients' own skin using special flap-beating techniques and specific compounds. However, the use of donor material from animals or other humans (heterotransplantation) invariably ended in tissue necrosis.
The reason lies in the individual set of antigens that forms the so-called tissue barrier. The conflict during transplantation has the same nature as during incompatible blood transfusions. Specific leukocyte antigens (over 30 of which have been described) play a key role in the formation of the immune response.
To successfully overcome the tissue barrier, three tasks must be accomplished:
- Study the structure and localization of transplantation antigens.
- Select a compatible donor-recipient pair.
- Learn how to manage the body's defense reaction.
Interestingly, antigens on living, intact cells act much more actively than isolated soluble protein preparations. At the same time, obtaining pure histocompatibility antigens remains a difficult task to this day.
Mechanism of graft rejection
If the donor and recipient antigens do not match (homotransplantation), the lymphatic system triggers a powerful immune response. This process occurs in several stages:
- Mobilization. Foreign graft antigens accelerate the activation of the immunocompetent system.
- Cellular attack. Leukocytes are the first to migrate from the blood to the foreign tissue. Soon, lymphocytes and plasma cells join them. The maximum accumulation of defense cells both inside and around the graft is observed on the 5th–6th day.
- Isolation. A dense protective wall forms around the transplanted tissue.
- Antibody production. Plasma cells begin to synthesize antibodies. Their role is not fully understood: in some cases, they can paradoxically stimulate the growth of foreign tissue.
As a result, the graft dies, undergoes phagocytosis, and is gradually replaced by connective tissue. The essence of this reaction is that the immunity works as a universal mechanism, reacting equally aggressively to both microbes and foreign tissues.
Exceptions and immunological tolerance
Identical twins are ideal donors for each other. Their tissues have an absolutely identical antigenic (protein) structure, so there is no immune antagonism. There are cases where kidneys transplanted between twins functioned successfully for more than 10 years.
In other cases, science seeks ways to "fool" the immune system. A major milestone was the discovery of the phenomenon of immunological tolerance (M. Hašek and P. Medawar). Scientists found that the body's ability to distinguish "self" from "non-self" is established in the late embryonic and early postembryonic periods.
During experiments, embryos or newborn animals were injected with cells (blood, bone marrow, spleen tissue) from a future donor. The immune system memorized this foreign protein as "self." When the animal grew up, skin from the same donor was transplanted onto it, and the graft successfully took root. A state of acceptance—tolerance—arose.
Briefly: answers to topical questions
What is the HLA system and what does it stand for?
The HLA system consists of human leukocyte antigens (MHC), which are used to select compatible donors for organ transplantation and to understand the mechanisms of immunological conflict. The abbreviation stands for Human Leucocyte Antigens. These antigens play a key role in self/non-self recognition and the induction of adaptive immune response.
What classes are the major histocompatibility complex antigens divided into?
Major histocompatibility complex (MHC/HLA) antigens are described in sources for classes I and II:
- MHC class I antigens: HLA-A, HLA-B, HLA-C. Present on all nucleated cells of the body; absent on erythrocytes, neurons, and villous trophoblast cells.
- MHC class II antigens: HLA-DR, HLA-DP, HLA-DQ. Main localization: professional antigen-presenting cells: macrophages, dendritic cells, B lymphocytes. May appear on T lymphocytes, endothelium, and epithelium upon activation by γ-interferon.
MHC class III genes are highlighted separately in sources: they are not involved in encoding histocompatibility molecules and do not perform antigen presentation.
What types of graft rejection are distinguished by the time of their development?
According to the timing of development, the following types of graft rejection are distinguished:
- Hyperacute rejection — develops within 1–5 days. Occurs immediately after transplantation if the recipient has preformed antibodies against the donor.
- Acute rejection — develops within 5 to 30 days. The mechanism is due to the activation of cellular immunity.
- Chronic rejection — develops after 6 months or more. Caused primarily by mechanisms of cellular immunity.
To understand immunological tolerance, use the analogy of an "immune passport": if foreign antigens are "entered" into the recognition system at the stage of its formation (in an embryo), then in adulthood the body will consider them "self" and will not attack them.
Class and exam questions
Why did xenotransplantation of tissues from animals to humans in ancient times always end in failure?
Due to the insurmountable tissue barrier. The recipient's organism recognizes foreign graft antigens and triggers an immune response leading to its rejection and destruction.
Where are most transplantation antigens located?
Up to 70% of such antigens are localized on the surface plasma membrane of formed elements of the blood: leukocytes, lymphocytes, and platelets.
Can antigens change during a person's life?
No, the antigenic profile is formed in the embryonic period, inherited from parents, and remains unchanged throughout life.
What does immunogenetics study?
This is an independent scientific field at the intersection of immunology and genetics. It studies the inheritance of antigens and how their presence is associated with a predisposition to certain diseases (e.g., systemic lupus erythematosus or leukemia).
What else to study on this topic
- Historical methods of skin flap preparation in Ancient India
- Erythrocyte isoantigen systems and principles of blood transfusion
- Association of specific antigens (Be, B15, A2, B12) with predisposition to pathologies
- Paradoxical effect of antibodies: why they sometimes enhance graft growth
- Problems of isolating pure histocompatibility antigens
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