Alloreactivity describes an immune system response directed towards tissues or cells originating from a genetically distinct individual of the same species. This response is a key consideration in medical procedures involving the transfer of cells or organs, as it represents the body’s natural defense against perceived foreign elements.
How the Immune System Recognizes Differences
The immune system distinguishes between “self” and “non-self” through specialized proteins called major histocompatibility complex (MHC) molecules, known as human leukocyte antigens (HLA) in humans. HLA molecules are on the surface of most cells, displaying unique molecular fingerprints.
T-cells are equipped with receptors that scan these HLA molecules. If a T-cell encounters an HLA molecule it does not recognize as “self,” it can trigger an immune response. This specific recognition forms the basis of alloreactivity, where donor HLA molecules are perceived as foreign by the recipient’s T-cells.
Alloreactivity in Organ and Tissue Transplants
In solid organ transplantation, alloreactivity manifests as transplant rejection. The recipient’s immune system identifies the donor organ’s HLA molecules as foreign, initiating an attack that can lead to damage and eventual failure.
Transplant rejection can be acute or chronic. Acute rejection occurs within the first few months after transplantation, characterized by a strong, rapid immune response. Chronic rejection develops over months or years, involving a slower attack that gradually impairs organ function. Both are driven by the recipient’s T-cells and antibodies targeting the donor’s foreign HLA.
Alloreactivity in Stem Cell Transplants
Alloreactivity in hematopoietic stem cell transplantation, commonly known as bone marrow transplantation, presents a distinct challenge called graft-versus-host disease (GVHD). Here, the donor’s immune cells recognize the recipient’s tissues as foreign. These donor immune cells then attack various recipient organs and tissues.
GVHD can be acute, appearing within the first 100 days after transplant, or chronic, developing later and persisting. Acute GVHD often presents with skin rashes, liver dysfunction, or diarrhea, while chronic GVHD can affect multiple organ systems, leading to widespread complications. Severity depends on the degree of HLA mismatch and other factors.
Strategies for Managing Alloreactivity
Managing alloreactivity involves minimizing the immune system’s recognition of foreign tissues and dampening its response. Tissue typing, specifically HLA matching, is a key strategy for both solid organ and stem cell transplants. Selecting a donor whose HLA molecules closely resemble the recipient’s reduces the likelihood and severity of alloreactivity.
Immunosuppressive medications are administered before, during, and after transplantation to suppress the recipient’s immune system. These drugs inhibit the activity of T-cells and other immune cells responsible for attacking foreign tissues. While effective, these medications require careful monitoring to balance preventing rejection or GVHD with potential side effects, such as increased susceptibility to infections.