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  • Hypothesize how genetic polymorphisms within the immune system may lead to variability in responses to infection, transplantation, or immunization
  • Consider the outcome advantages of human leukocyte antigen matching in solid organ transplantation
  • Describe how genetic diversity may influence response to vaccines

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The human body has a great capacity to resist the many organisms and toxins with which it comes in contact. This defensive mechanism is called immunity and involves an intricate system consisting of both innate and acquired immunity. Innate immunity consists of general processes that are present at birth. These processes are considered the first line of defense against an infectious organism and include skin, gastric acid, mucus, neutrophils, and complement. It is different from acquired immunity in that it is nonspecific, has a fast response, and does not have a memory in response to previous infections.

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Active immunity involves humoral and cellular compartments. Although each compartment in the immune system is unique with its own specialized cells, the system works in concert to protect the body from infectious organisms. Active immunity occurs following an initial invasion by a foreign organism or toxin. Each toxin and organism has a unique makeup of proteins or large polysaccharides that differentiates it from other compounds. These proteins and polysaccharides are called antigens.

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The fact that not all those exposed to a particular pathogen will develop infection is an important point in infectious disease. The processes involved in the development of infection are likely the virulence of the pathogen and the host susceptibility. In this section we will focus on the components of the immune system that are known to be polymorphic in humans and may contribute to host susceptibility.

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Antigen Recognition

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B and T cells must have the capacity to recognize and virtually an infinite number of antigens. Both types of lymphocytes have specially adapted receptors for that purpose. The B cell receptor has the same antigen specificity as the antibody it secretes. The T cell receptor is specific and critical for antigen presentation. The genes for these receptors possess unique capacity to undergo deletion, rearrangement, and somatic mutation. The genes for antigen recognition portion of antibodies and T cell receptors are organized in regions. Several copies of the same gene are located within each region. Each copy of the gene is different from the others. These gene cassettes can be rearranged or deleted during the antigen recognition process. In addition, the genes can undergo limited somatic mutation in an effort to create an antibody or T cell receptor that has high affinity for the antigen of interest. These processes allow for the possibility that nearly an infinite number of receptors for antigen recognition can be generated.

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Human Leukocyte Antigen

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Human leukocyte antigen (HLA) displays an unequaled degree of genetic polymorphism among functional human genes.1 Each individual has HLA genes for class I, HLA-A, HLA-B, ...

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