Autoimmunity Notes

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Disorders Associated with the Immune System

Learning Objectives

Check Your Understanding

19-1    Define hypersensitivity.

Are all immune responses beneficial?

19-2    Describe the mechanism of
anaphylaxis.

In what tissues do we find the mast cells that are
major contributors to allergic reactions such as hay fever?

19-3    Compare and contrast systemic and localized anaphylaxis.

Which is the more dangerous to life: systemic or
localized anaphylaxis?

19-4    Explain how allergy skin tests work.

How can we tell whether a person is sensitive to a particular allergen, such as a tree pollen?

19-5    Define desensitization and
blocking antibody.

Which antibody types need to be blocked to
desensitize a person subject to allergies?

19-6    Describe the mechanism of
cytotoxic reactions and how drugs can induce them.

What, besides an allergen and an antibody, is
required to precipitate a cytotoxic reaction?

19-7    Describe the basis of the ABO and Rh blood group systems.

What are the antigens located on the cell membranes of type O blood?

19-8    Explain the relationships among blood groups, blood, transfusions, and hemolytic disease of the newborn.

If a fetus that is Rh+ can be damaged by anti-Rh
antibodies of the mother, why does such damage never happen during the first such pregnancy?

19-9    Describe the mechanism of
immune complex reactions.

Are the antigens causing immune complex reactions soluble or insoluble?

19-10  Describe the mechanism of
delayed cell-mediated reactions, and name two examples.

What is the primary reason for the delay in a delayed cell-mediated reaction?

19-11  Describe a mechanism for
self-tolerance.

What is the importance of clonal deletion in the
thymus?

19-12  Give an example of immune complex, cytotoxic, and cell-mediated autoimmune diseases.

What organ is affected in Graves’ disease?

19-13  Define HLA complex, and explain its importance in disease susceptibility and tissue transplants.

What is the relationship between the major
histocompatibility complex in humans and the
human leukocyte antigen complex?

19-14  Explain how a transplant is
rejected.

What immune system cells are involved in the
rejection of nonself transplants?

19-15  Define privileged site.

Why is a transplanted cornea usually not rejected as nonself?

19-16  Discuss the role of stem cells in transplantation.

Differentiate an embryonic stem cell from an adult stem cell.

19-17  Define autograft, isograft,
allograft, and xenotransplant.

Which type of transplant is most subject to
hyperacute rejection?

19-18  Explain how graft-versus-host disease occurs.

When red bone marrow is transplanted, many
immunocompetent cells are included. How can this be bad?

19-19  Explain how rejection of a
transplant is prevented.

What cytokine is usually the target of immunosuppressant drugs intended to block transplant rejection?

19-20  Describe how the immune system responds to cancer and how cells evade immune responses.

What is the function of tumor-associated antigens in the development of cancer?

19-21  Give two examples of
immunotherapy.

Give an example of a prophylactic cancer vaccine that is in current use.

19-22  Compare and contrast congenital and acquired immunodeficiencies.

Is AIDS an acquired or a congenital
immunodeficiency?

19-23  Give two examples of how
infectious diseases emerge.

On what continent did the HIV-1 virus arise?

19-24  Explain the attachment of HIV to a host cell.

What is the primary receptor on host cells to which HIV attaches?

19-25  List two ways in which HIV avoids the host’s antibodies.

Would an antibody against the coat of HIV be able to react with a provirus?

19-26  Describe the stages of HIV
infection.

Would a CD4+ T cell count of 300/μl be diagnostic of AIDS?

19-27  Describe the effects of HIV
infection on the immune system.

Which cells of the immune system are the main
targets of an HIV infection?

19-28  Describe how HIV infection is diagnosed.

What form of nucleic acid is detected in a PVL test for HIV?

19-29  List the routes of HIV
transmission.

What is considered to be the most dangerous form of sexual contact for transmission of HIV?

19-30  Identify geographic patterns of HIV transmission.

What is the most common mode, worldwide, by which HIV is transmitted?

19-31  List the current methods of
preventing and treating HIV
infection.

Does circumcision make a man more or less likely to acquire HIV infection?

 

    Key Concepts:

  1. Normal microbiota are important in maintaining a healthy immune system.
  2. The Human Microbiome Project is sequencing the genes for 16s ribosomal RNA to help scientists catalogue normal microbiota that are difficult to culture and identify in the laboratory.
  3. Trichuris suis is a roundworm related to T. trichiura.
  4. Inflammatory diseases are characterized by increased amounts of cytokines produced by T helper cells, including tumor necrosis factor alpha and interleukins.
  • The discussion of HIV/AIDS has been updated with new, informative maps.
  • The chemotherapy of AIDS section has been completely revised, including new figures depicting the action of HIV therapies.

Chapter Summary

Introduction (p. 515)

ASM 5.4: Microorganisms, cellular and viral, can interact with both human and non-human hosts in beneficial, neutral, or detrimental ways.

  1. Hay fever, transplant rejection, and autoimmunity are examples of harmful immune reactions.
  2. Immunosuppression is inhibition of the immune system.
  3. Superantigens activate many T cell receptors that can cause adverse host responses.

Hypersensitivity (pp. 516–526)

  1. Hypersensitivity reactions represent immunological responses to an antigen (allergen) that lead to tissue damage rather than immunity.
  2. Hypersensitivity reactions occur when a person has been sensitized to an antigen.
  3. Hypersensitivity reactions can be divided into four classes: types I, II, and III are immediate reactions based on humoral immunity, and type IV is a delayed reaction based on cell-mediated immunity.

Allergies and the Microbiome (p. 516)

  1. Childhood exposure to microbes may decrease development of allergies.

Type I (Anaphylactic) Reactions (pp. 516–522)

  1. Anaphylactic reactions involve the production of IgE antibodies that bind to mast cells and basophils to sensitize the host.
  2. The binding of two adjacent IgE antibodies to an antigen causes the target cell to release chemical mediators, such as histamine, leukotrienes, and prostaglandins, which cause the observed allergic reactions.
  3. Systemic anaphylaxis may develop in minutes after injection or ingestion of the antigen; this may result in circulatory collapse and death.
  4. Localized anaphylaxis is exemplified by hives, hay fever, and asthma.
  5. Skin testing is useful in determining sensitivity to an antigen.
  6. Desensitization to an antigen can be achieved by repeated injections of the antigen, which leads to the formation of blocking (IgG) antibodies.

Type II (Cytotoxic) Reactions (pp. 522–524)

  1. Type II reactions are mediated by IgG or IgM antibodies and complement.
  2. The antibodies are directed toward foreign cells or host cells. Complement fixation may result in cell lysis. Macrophages and other cells may also damage the antibody-coated cells.
  3. Human blood may be grouped into four principal types, designated A, B, AB, and O.
  4. The presence or absence of two carbohydrate antigens designated A and B on the surface of the red blood cell determines a person’s blood type.
  5. Naturally occurring antibodies are present in serum against the opposite AB antigen.
  6. Incompatible blood transfusions lead to the complement-mediated lysis of the donor red blood cells.
  7. The absence of the Rh antigen in certain individuals (Rh− ) can lead to sensitization upon exposure to it.
  8. An Rh+ person can receive Rh+ or Rh− blood transfusions.
  9. When an Rh− person receives Rh+ blood, that person will produce anti-Rh antibodies. Subsequent exposure to Rh+ cells will result in a rapid, serious hemolytic reaction.
  10. An Rh− mother carrying an Rh+ fetus will produce anti-Rh antibodies. Subsequent pregnancies involving Rh incompatibility may result in hemolytic disease of the newborn.
  11. HDNB may be prevented by passive immunization of the mother with anti-Rh antibodies.
  12. In the disease thrombocytopenic purpura, platelets are destroyed by antibodies and complement.
  13. Agranulocytosis and hemolytic anemia result from antibodies against one’s own blood cells coated with drug molecules.

Type III (Immune Complex) Reactions (pp. 524–525)

  1. Immune complex diseases occur when IgG antibodies and soluble antigen form small complexes that lodge in the basement membranes of cells.
  2. Subsequent complement fixation results in inflammation.
  3. Glomerulonephritis is an immune complex disease.

Type IV (Delayed Cell-Mediated) Reactions (pp. 525–526)

  1. Delayed cell-mediated hypersensitivity reactions are due primarily to T cell proliferation.
  2. Sensitized T cells secrete cytokines in response to the appropriate antigen.
  3. Cytokines attract and activate macrophages and initiate tissue damage.
  4. The tuberculin skin test and allergic contact dermatitis are examples of delayed hypersensitivities.

Autoimmune Diseases (pp. 526–528)

  1. Autoimmunity results from a loss of self-tolerance.
  2. Self-tolerance occurs during fetal development; T cells that will target host cells are eliminated (clonal deletion) or inactivated.
  3. Autoimmunity may be due to antibodies against infectious agents.
  4. Graves’ disease and myasthenia gravis are cytotoxic autoimmune reactions in which antibodies react to cell-surface antigens.
  5. Systemic lupus erythematosus and rheumatoid arthritis are immune complex autoimmune reactions in which the deposition of immune complexes results in tissue damage.
  6. Multiple sclerosis, insulin-dependent diabetes mellitus, and psoriasis are cell-mediated autoimmune reactions mediated by T cells.

Reactions Related to the Human Leukocyte Antigen (HLA) Complex (pp. 528–532)

  1. MHC self molecules located on cell surfaces express genetic differences among individuals; these antigens are called HLAs in humans.
  2. To prevent the rejection of transplants, HLA and ABO blood group antigens of the donor and recipient are matched as closely as possible.
  3. Transplants recognized as foreign antigens may be lysed by T cells and attacked by macrophages and complement-fixing antibodies.
  4. Transplantation to a privileged site (such as the cornea) or of a privileged tissue (such as pig heart valves) does not cause an immune response.
  5. Pluripotent stem cells differentiate into a variety of tissues that may provide tissues for transplant.
  6. Four types of transplants have been defined on the basis of genetic relationships between the donor and the recipient: autografts, isografts, allografts, and xenotransplants.
  7. Bone marrow transplants (with immunocompetent cells) can cause graft-versus-host disease.
  8. Successful transplant surgery often requires immunosuppressant drugs to prevent an immune response to the transplanted tissue.

The Immune System and Cancer (pp. 532–533)

  1. Cancer cells are normal cells that have undergone transformation, divide uncontrollably, and possess tumor-associated antigens.
  2. The response of the immune system to cancer is called immunological surveillance.
  3. TC cells recognize and lyse cancerous cells.
  4. Cancer cells can escape detection and destruction by the immune system.
  5. Cancer cells may grow faster than the immune system can respond.

Immunotherapy for Cancer (pp. 532–533)

  1. Vaccines against liver and cervical cancer are available; a therapeutic vaccine against prostate cancer also has been approved.
  2. Herceptin consists of monoclonal antibodies against a breast cancer growth factor.
  3. Immunotoxins are chemical poisons linked to a monoclonal antibody; the antibody selectively locates the cancer cell for release of the poison.

Immunodeficiencies (pp. 533–534)

  1. Immunodeficiencies can be congenital or acquired.
  2. Congenital immunodeficiencies are due to defective or absent genes.
  3. A variety of drugs, cancers, and infectious diseases can cause acquired immunodeficiencies.