Human Genetics: Concepts and Applications (Lewis), 9th Edition

Chapter 17: Genetics of Immunity

Chapter Outline

CHAPTER OVERVIEW

1. The immune system functions to protect the body against infectious disease.
2. Foreign antigens (molecules) elicit an immune response from a host.
3. Genetic variability influences resistance and susceptibility to disease, autoimmune disease, allergies and even cancer.
4. Antibodies and cytokines produced by the immune system attack foreign antigens.

1. Human cells are known to carry many molecules on their surface.
2. Blood types, including the ABO groups, result from self antigen patterns on red blood cells.
3. There are 29 major blood types with many subtypes.
4. Genotyping using a BLOODchip is being tested as a way to properly match donors and recipients for more successful blood transfusions.

1. Genes of the major histocompatibility complex (MHC) control many of our cell surface proteins and are important in immunity.
2. Class I and II genes of the MHC encode human leukocyte antigens (HLA).
3. Class III genes produce plasma proteins involved in the immune response.
4. HLA antigens on leukocytes are involved in processing of foreign antigens.
5. They are an important consideration in organ transplantation.
6. HLA proteins are each encoded by several genes with many alleles, and as a result only 2 in every 20,000 unrelated people match for the six major HLA genes by chance.
7. Individuals with certain HLA combinations have an increased risk of developing certain HLA-linked diseases.

1. At the cellular level, the immune system consists of various types of lymphocytes and macrophages.
2. B-cells and T-cells are the major type of lymphocytes.
3. The immune response consists of an immediate, generalized, innate immunity and a slower, more specific adaptive immunity.

1. Skin, mucous membranes, tears, and saliva are examples of physical and chemical barriers that keep pathogens from entering the body.
2. Pathogens that breach this barrier encounter an innate immune response consisting of inflammation, phagocytosis, complement, collectins, and cytokines.

1. The adaptive immune response has humoral and cellular components.
2. The humoral response involves B cells that secrete antibodies in order to neutralize, clump, and stimulate the destruction of pathogens by recognizing and binding specific foreign antigens.
3. Antibodies are made of Y-shaped polypeptides consisting of constant and variable regions.
4. The astounding diversity of antibody binding activities is due to a shuffling of gene segments in B cell development.
5. In the cellular immune response, helper T cells release cytokines that function to stimulate B cells to manufacture antibodies as well as coordinate various other immune responses.
6. Some T cells bind nonself cells or virus-covered cells and burst them.

1. Inherited immune deficiencies represent defects in the genes that encode proteins involved in immunity.
2. Perhaps the best known is severe combined immune deficiencies (SCID) which has been the focus of gene therapy research.

1. HIV causes acquired immune deficiency syndrome.
2. HIV is a retrovirus that infects host cells via binding coreceptors such as CD4 and CCR5.
3. Reverse transcriptase then copies viral RNA into DNA which is inserted into the host genome.
4. HIV uses host protein synthesis machinery to reproduce itself, then bud copies from the cell.
5. Anti-HIV drugs have been effective in treating HIV.
6. HIV continually mutates, and may become resistant to drugs.
7. Some people have natural resistance to HIV as discussed in previous chapters.

1. In autoimmune disorders, autoantibodies attack healthy tissue.
2. Mutations may cause autoimmune disease.
3. It may also result from a virus that incorporates a self antigen, T cells that never learn to recognize self, or healthy cells bearing antigens that resemble nonself antigens.

1. A hypersensitized immune response causes allergies.
2. In an allergic reaction, allergens bind IgE antibodies on mast cells, which release allergy mediators and cause typical symptoms.
3. Allergens also activate certain T cells which secrete immune mediators that contribute to some allergy symptoms.

1. Vaccines use part or all of a weakened or killed pathogen to elicit an immune response.
2. This protects against infection by the virulent pathogen.
3. Vaccination has a long and successful history.

1. Immunotherapy uses immune system components to fight disease.
2. Hybridomas are artificial cells that consist of a B cell fused with a cancer cell to produce monoclonal antibodies (MAbs) that can target specific antigens.
3. Cytokines boost immune function and have limited medical applications.

1. Autografts transfer tissue from one part of a person's body to another.
2. Isografts are tissue transfers between identical twins.
3. Allografts involve tissue transfers between members of the same species. These transplants can cause tissue rejection reactions.
4. A Xenograft is a cross species transplant. A danger of these transplants is that they can set off a hyperacute rejection.
5. The success rates of transplants are improved by the use of immunosuppressive drugs, by stripping antigens from donor tissue, and by matching donor to the recipient.
6. Graft-versus-host disease involves a rejection of recipient tissues by transplanted bone marrow.

1. Analyzing the genomes of pathogens may reveal the molecular basis of pathogenesis and suggest new treatments.

1. Crowd diseases readily spread through populations and can cause epidemics.
2. Indigenous populations with no immunity can be devastated by introduction of new diseases.

1. A variety of pathogens have been adapted to military use, including smallpox, plague and anthrax.