Major Histocompatibility Complex

The genes that code for HLA antigens are called histocompatibility genes


They are a group of related proteins.

They are localized to a region on the short arm of chromosome 6, known as the major histocompatibility complex.

The HLA system is important in organ transplantation, where HLA typing and matching of donor and recipient are now widely used to predict tissue compatibility. 

  1.  
    HLA antigens
     
    The two major classes are separated on the basis of structure and tissue distribution.
     
    1.  
      Class I antigens include the HLA-A, HLA-B, and HLA-C antigens, which are found on almost all human cells.
       
      1.  
        Inline ImageClass I antigens are the principal antigens involved in tissue graft rejection. Serologic testing for HLA-A and HLA-B antigens is used to predict the likelihood of long-term graft survival.
      2.  
        Standard serologic techniques are used for identification.
    2.  
      Class II antigens are chiefly found on immunocompetent cells, including macrophages, dendritic cells, Langerhans cells, B cells, and some T cells.
       
      1.  
        The HLA-DP, HLA-DQ, and HLA-DR antigens are identifiable by standard serologic techniques or mixed lymphocyte reactions.
      2.  
        The HLA-D antigens are identifiable only by mixed lymphocyte reactions.
  2.  
    Association of HLA antigens with disease
     
    There is a significant association of certain HLA antigens with a number of specific diseases. Many HLA-associated disorders involve immunologic abnormalities, but the mechanisms for these observed associations await full explanation.
     
    1.  
      Inline ImageHLA-B27 antigen is associated with almost 90% of cases of ankylosing spondylitis.
    2.  
      Specific HLA antigens are also associated with insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis, uveitis, and Reiter syndrome (urethritis, conjunctivitis, and arthritis), as well as with many other entities.
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  4. The genes are localized to a region on the short arm of chromosome 6, known as the major histocompatibility complex. \
  6. The HLA system is important in organ transplantation, where HLA typing and matching of donor and recipient are now widely used to predict tissue compatibility. 
    1.  
      HLA antigens
       
      The two major classes are separated on the basis of structure and tissue distribution.
       
      1.  
        Class I antigens include the HLA-A, HLA-B, and HLA-C antigens, which are found on almost all human cells.
         
        1.  
          Inline ImageClass I antigens are the principal antigens involved in tissue graft rejection. Serologic testing for HLA-A and HLA-B antigens is used to predict the likelihood of long-term graft survival.
        2.  
          Standard serologic techniques are used for identification.
      2.  
        Class II antigens are chiefly found on immunocompetent cells, including macrophages, dendritic cells, Langerhans cells, B cells, and some T cells.
         
        1.  
          The HLA-DP, HLA-DQ, and HLA-DR antigens are identifiable by standard serologic techniques or mixed lymphocyte reactions.
        2.  
          The HLA-D antigens are identifiable only by mixed lymphocyte reactions.
    2.  
      Association of HLA antigens with disease
       
      There is a significant association of certain HLA antigens with a number of specific diseases. Many HLA-associated disorders involve immunologic abnormalities, but the mechanisms for these observed associations await full explanation.
       
      1.  
        Inline ImageHLA-B27 antigen is associated with almost 90% of cases of ankylosing spondylitis.
      2.  
        Specific HLA antigens are also associated with insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis, uveitis, and Reiter syndrome (urethritis, conjunctivitis, and arthritis), as well as with many other entities.
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    4. The Major Histocompatibility Complex (MHC) is a set of genes that codes for proteins found on the surfaces of cells that help the immune system recognize foreign substances. The MHC plays a critical role in the immune response by presenting protein fragments (antigens) to immune cells, which then determine whether the proteins are from the body's own cells or from invaders like viruses or bacteria.
    5. ### Key Aspects of the MHC:
    6. 1. **MHC Classes**:
      - **Class I MHC**: These molecules are found on almost all nucleated cells in the body. They present antigens from inside the cell (such as viral proteins) to cytotoxic T-cells (CD8+ T-cells). This triggers the immune system to destroy cells that are infected with a virus or have become cancerous.
      - **Class II MHC**: These molecules are primarily found on specialized immune cells like B-cells, macrophages, and dendritic cells. They present antigens from outside the cell (such as bacterial proteins) to helper T-cells (CD4+ T-cells). This helps coordinate the immune response, including the activation of other immune cells.
    7. 2. **Function in the Immune System**:
      - **Antigen Presentation**: MHC molecules bind to fragments of proteins (peptides) within the cell and display them on the cell's surface. The displayed peptides are then recognized by T-cells, which determine if they are self or non-self (foreign).
      - **T-cell Activation**: When a T-cell receptor recognizes a peptide-MHC complex, it can activate the T-cell. This activation can lead to a variety of immune responses, including the destruction of infected cells or the activation of other immune cells to fight off the invader.
    8. 3. **Genetic Diversity**:
      - The MHC genes are highly polymorphic, meaning there is a great deal of variation in these genes among individuals. This diversity ensures that the population as a whole can recognize and respond to a wide array of pathogens.
      - In humans, the MHC genes are located on chromosome 6 and are referred to as Human Leukocyte Antigens (HLA).
    9. 4. **Role in Transplantation**:
      - The MHC is crucial in organ and tissue transplantation. The more similar the MHC molecules between a donor and recipient, the less likely the recipient’s immune system will reject the transplanted organ or tissue. Mismatched MHC can lead to graft rejection.
    10. 5. **Disease Association**:
      - Certain MHC types are associated with susceptibility to specific autoimmune diseases. For example, the HLA-B27 allele is strongly associated with ankylosing spondylitis, an inflammatory disease of the spine.
    11. The MHC is essential for the proper functioning of the immune system and plays a vital role in distinguishing between self and non-self, protecting the body from infections, and maintaining overall immune health.

 

 

Organogenesis, Tissue Structure and Function of the Body Systems

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