Genetic Rules of Transplantation
The regularities of tissue engraftment were discovered by G. Snell through experiments on genetically pure mouse strains. Four fundamental laws are distinguished:
- Tissues from genetically identical organisms (syngeneic, e.g., between monozygotic twins) successfully engraft.
- Tissues from genetically different individuals of the same species (allogeneic) are inevitably rejected.
- First-generation hybrids (F1) successfully accept transplants from both of their parental lines.
- Parental lines always reject tissues transplanted from their F1 hybrid offspring, although hybrids themselves exchange tissues with one another without rejection.
These rules are based on the codominant nature of inheritance. Genes from both parents function in the hybrid, which is why parental tissue is perceived by it as "self". However, the parental organism recognizes foreign antigens inherited from the second parent in the hybrid's tissues and triggers an immune response.
Terminology: types of tissues and transplants
In modern transplantology, tissues are classified according to the degree of genetic relationship between the donor and recipient:
- Syngeneic — obtained from a genetically identical donor.
- Allogeneic — obtained from a non-identical donor of the same biological species. They contain alloantigens (MHC antigens, blood groups) reflecting intraspecific polymorphism.
- Xenogeneic — tissues from a representative of a completely different species.
Depending on the origin of the material, three types of transplantation are distinguished: autotransplantation (the recipient acts as the donor), allotransplantation (transplantation between different organisms of the same species), and xenotransplantation (interspecies transplantation).
Role of MHC in the immune response
Tissue compatibility is controlled by dozens of loci. Mismatch at so-called minor loci provokes slow rejection, stretching over months (gradual replacement of donor cells by host cells).
However, the main barrier is the MHC (in humans, this complex is called HLA, in mice — H-2). Differences even in a single MHC gene cause a strong reaction with rejection within two weeks. The strongest stimulus is provided by MHC-II molecules, which trigger the T-cell immune response.
Fun fact: The major histocompatibility complex was named precisely because of its discovery during studies of tissue incompatibility. Its primary biological function—presenting antigens to T lymphocytes—was established later.
Mechanisms and stages of rejection
Allograft rejection has a cellular immunological nature. This is confirmed by the formation of memory (re-transplantation of tissue from the same donor is rejected in an accelerated manner — within 6–7 days) and the possibility of transferring immunity to an naive animal using T cells.
The process of skin graft rejection upon MHC mismatch goes through several stages:
- Vascularization (days 3–4): ingrowth of blood vessels into the transplanted tissue.
- Onset of the reaction (days 5–7): infiltration of the tissue by mononuclear cells, start of immune inflammation.
- Rejection (days 10–12): vascular thrombosis, trophic impairment, necrosis, and shedding of the graft.
The reaction mechanism combines cytotoxicity and inflammation. CD8+ T lymphocytes directly destroy graft cells. CD4+ T helper cells initiate inflammation that disrupts tissue trophism. At the same time, the phenomenon of "passenger leukocytes" is critical for starting the response: donor antigen-presenting cells (e.g., Langerhans cells) must be present in the transplanted tissue. They migrate to the recipient's lymph nodes and trigger T cell activation. If these cells are washed out of the graft, it loses its immunogenicity.
Briefly: answers to topical questions
What is the difference between primary and secondary allograft rejection?
Primary and secondary allograft rejection differ in the rate of development of the immune response and the presence of immunological memory.
| Sign | Primary rejection | Secondary rejection |
|---|---|---|
| Time of development | 10–14 days | 6–7 days |
| Nature of the response | Primary immune response | Accelerated rejection (secondary response) |
Secondary rejection occurs upon re-transplantation of tissue from the same donor strain and is due to the immune system's ability to induce memory.
What clinical types of allograft rejection are distinguished by the time of onset?
Based on the time of onset, three clinical types of allograft rejection are distinguished.
- Hyperacute rejection — develops on days 1–5 due to the presence of preformed antibodies in the recipient.
- Acute rejection — occurs within 5 to 30 days as a result of cellular immunity activation.
- Chronic rejection — develops after 6 months or more, with the mechanism predominantly driven by cellular immunity.
What mechanisms ensure the development of immunological tolerance to a graft?
The development of immunological tolerance to a graft is ensured by several mechanisms that suppress the immune response at the level of individual lymphocyte clones.
- Establishment of chimerism — coexistence of donor and recipient cells, which ensures the elimination of reactive T cells via apoptosis during the negative selection stage.
- Induction of anergy — presentation of antigen by immature or tolerogenic dendritic cells without costimulation, which induces specific unresponsiveness of T helper cells.
- Action of regulatory T cells — blocking of active autospecific clones.
What antigen systems, besides the major histocompatibility complex, play a role in human tissue compatibility?
Besides the major histocompatibility complex, blood group antigens and minor histocompatibility loci play an important role in human tissue compatibility.
- Blood group antigens — belong to alloantigens; the presence of preformed antibodies to donor antigens in the recipient can cause hyperacute rejection.
- Minor histocompatibility loci — differences in these loci cause slow rejection, stretching over months.
The rule "A hybrid accepts everyone, but no one accepts it": the F1 hybrid has genes from both mother and parents (codominance). Therefore, parental tissues are "self" to it (they engraft). However, the parent sees the foreign half of the hybrid tissue—obtained from the other ancestor—and rejects it.
Class and exam questions
Why is a repeated tissue transplant from the same donor rejected faster?
This is related to the ability to induce immunological memory. The secondary immune response develops much faster than the primary one, leading to graft destruction in 6–7 days instead of 10–14.
What is the "passenger leukocyte" phenomenon?
This is the presence of bone marrow-derived cells (antigen-presenting cells) in the donor graft. Their migration to the recipient's lymph node is a prerequisite for the recognition of the allogeneic transplant by the immune system.
How to prove that graft rejection is cell-mediated?
Through an immunity transfer experiment. If T cells are taken from a recipient that has already rejected tissue and transferred to a naive syngeneic animal, upon subsequent transplantation of the donor graft, this animal will reject it in an accelerated manner (as in a secondary response).
What else to study on this topic
- Mechanisms of secondary immune response formation upon re-transplantation
- Role of Langerhans cells in the afferent limb of the allograft response
- Interaction of CD4+ and CD8+ T lymphocytes in the development of immune inflammation
- Features of graft rejection in mismatches at minor histocompatibility loci
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