Immune Disorders and AIDS Chapter 23 Immune Disorders and AIDS

23.1 Type I Hypersensitivity Represents a Familiar Allergic Response Type I hypersensitivity is induced by allergens. The sensitizing dose is the first dose of antigen. The immune system responds as it would to a pathogen. The person is sensitized as IgE antibodies attach to mast cells and basophils. Figure 23.02: The various forms of hypersensitivities.

Figure 23.03: Type I IgE-Mediated Hypersensitivity. On subsequent allergen exposure, IgE antibodies are cross-linked. This causes degranulation of mast cells which releases mediator substances: Histamine is released into the blood and causes smooth muscle cell constriction. Leukotrienes are potent smooth muscle constrictors. Prostaglandins can constrict bronchial tubes. Cytokines can stimulate inflammation. Figure 23.03: Type I IgE-Mediated Hypersensitivity.

Figure 23.05: The top 10 causes of allergies. Type I Hypersensitivities can be localized or systemic Atopic disorders are the most common form of a Type I hypersensitivity. Atopic disease is a common (seasonal) allergy caused by the inhalation of pollen. Year-round allergies can result from chronic exposure to allergens. Figure 23.05: The top 10 causes of allergies. Source: Marist Institute for Public Opinion

Food allergies can cause symptoms like: Swollen lips Abdominal cramps Nausea Diarrhea Hives Anaphylaxis Common allergenic foods Fish and shellfish Eggs Wheat Milk Soy Peanuts Figure MF01: Peanuts. Courtesy of USDA-ARS

Systemic anaphylaxis is an immediate whole-body reaction Allergens in the bloodstream can trigger mast cell degranulation that contracts smooth muscle Small veins constrict and capillary pores expand, forcing fluid into the tissues A drop in blood pressure, edema, and hives occur Contractions in the gastrointestinal tract and bronchial muscles cause cramps and shortness of breath The lungs fill with carbon dioxide This can cause death by asphyxiation in 10–15 minutes

Then a recruitment of eosinophils and neutrophils into the lower Allergic reactions are also responsible for triggering many cases of asthma. Asthma is a chronic condition that can be caused by airborne allergens, exercise, or cold temperature. Degranulation of mast cells releases mediators in the lower respiratory tract, causing: bronchoconstriction. vasodilation. mucus buildup. Then a recruitment of eosinophils and neutrophils into the lower respiratory tract can cause: tissue injury. airway blockage. Figure 23.07: Airway narrowing during an asthma attack.

Figure 23.06: Using an Asthma Inhaler. Why do only some people have IgE-mediated hypersensitivities? Atopic people may lack sufficient IgA-secreting lymphocytes to block antigen stimulation in IgE. Atopic people may have defective suppressor T cells, allowing for more IgE production. Allergies may help expel pathogens through: sneezing. gastrointestinal tract contractions. Figure 23.06: Using an Asthma Inhaler. © Michael Donne/Photo Researchers, Inc.

Figure 23.08: An Allergy Skin Test. Therapies can sometimes control Type I hypersensitivities. Identify the allergen through skin test or ELISA blood test Avoid the allergen. Antihistamines block the effect of histamine. Corticosteroids are inhaled through the nose to relieve symptoms. Some also block mediator release Allergen immunotherapy or Desensitization involves a series of injections of allergens which may: Cause gradual reduction of granules in sensitized mast cells. Cause production of IgG antibodies that neutralize allergens Figure 23.08: An Allergy Skin Test. Courtesy of Jeffrey Pommerville

Figure 23.09: Type II cytotoxic hypersensitivity. 23.2 Other Types of Hypersensitivity Represent Immediate or Delayed Reactions Type II cytotoxic hypersensitivity involves antibody-mediated cell destruction. It occurs when IgG reacts with antigens, often activating complement. Figure 23.09: Type II cytotoxic hypersensitivity.

Figure 23.10: Hemolytic disease of the newborn. If incompatible blood types are mixed, agglutination occurs and complement is activated. Hemolytic disease of the newborn or Rh disease can lead to stillbirth or jaundice in an Rh negative mother. The reaction can be prevented for future pregnancies by an injection of RhoGAM (Rh antibodies) Figure 23.10: Hemolytic disease of the newborn.

Figure 23.11: Type III immune complex hypersensitivity. Type III immune complex hypersensitivity is caused by antigen-antibody aggregates. Figure 23.11: Type III immune complex hypersensitivity.

Serum sickness occurs when IgG is produced against residual proteins in a serum. This can cause: kidney damage. symptoms of type I anaphylactic hypersensitivity. In the Arthus phenomenon, very large amounts of IgG complex with antigens. This can lead to thromboses in blood vessels.

Figure 23.12: A positive tuberculin test. Type IV cellular hypersensitivity is mediated by antigen-specific T cells. Cellular hypersensitivity is an exaggeration of cell mediated immunity. It is a delayed reaction characterized by: thickening and drying of skin tissue (induration). surrounding by erythema. Infection allergy occurs when the immune system responds to certain microbial agents. Sensitized lymphocytes remain in the tissue to provide immunity to subsequent infection. Sensitivity can be determined by injection of a purified microbial sample and observation for induration. Figure 23.12: A positive tuberculin test. © Bart's Medical Library/Phototake/Alamy Images

Figure 23.13AB: The Poison Ivy Rash. Contact dermatitis develops after exposure to a variety of allergens. Repeated exposures cause drying to skin with erythema and scaling. Figure 23.13AB: The Poison Ivy Rash. © Bill Beatty/Visuals Unlimited

23.3 Autoimmune Disorders and Transplantation Are Immune Responses to “Self” An autoimmune disorder is a failure to distinguish self from nonself. There are several theories explaining the development of self-tolerance. The clonal deletion theory says that self-reactive lymphoid cells are destroyed during immune system development. The clonal anergy theory says that self-reactive T or B cells are inactivated and cannot differentiate into effector cells. The Regulatory T cell theory says that regulatory T cells suppress exaggerated immune responses

Figure 23.14 Mechanisms of Tolerance and Failure. Autoimmune disorders can be triggered in several ways: Gene mutations can affect cell division and apoptosis. If the immune system gains access to privileged sites, an immune response will be mounted. An antigen can mimic a body substance, causing the immune system to attack “self” substances. Treatment usually involves suppressing the immune system. Figure 23.14 Mechanisms of Tolerance and Failure.

In type I diabetes, pancreatic beta cells are destroyed. In myasthenia gravis, autoantibodies react with receptors on muscle fiber membranes. This causes a loss of muscle activity, weakness and fatigue In type I diabetes, pancreatic beta cells are destroyed. A lack of insulin production results in cells starved for glucose energy Results in blindness, kidney failure and other complications

Figure 23.15: Skin lesions of systemic Lupus erythematosus. In systemic lupus erythematosus (a.k.a. SLE, lupus), nuclear components of disintegrating white blood cells elicit IgG production. Immune complexes aggregate in the skin and organs, causing rash and lesions. Rheumatoid arthritis (RA) is an inflammatory condition resulting in accumulation of immune complexes in joints. Figure 23.15: Skin lesions of systemic Lupus erythematosus. © Scott Camazine/Alamy Images

Transplantation of tissues or organs is an important medical therapy. An autograft is a graft taken from one part of the body and transplanted to another part of the same body. An isograft is a graft from one identical twin to the other twin. Allografts are grafts between genetically different members of the same species. Xenografts are grafts between members of different species (rarely successful).

Rejection of transplants becomes more vigorous as the difference in genetic makeup of donor and recipient MHC proteins increases. If the recipient body sees the transplanted tissue as “nonself,” the tissue is rejected. Cytotoxic T cells attack and destroy transplanted cells. Phagocytes secrete lysosomal enzymes that digest the tissue. In bone marrow transplants, the transplanted marrow can form immune products against the host’s suppressed immune system. Graft-versus-host-reaction (GVHR) can be fatal to the host.

Figure 23.16: Tissue typing for MHC proteins. Rejection is stimulated by recognition of MHC proteins on the surface of graft cells. The closer the match between donor and recipient MHC proteins  the greater the chance of successful transplantation. Immunosuppressive agents prevent allograft rejection Side effects may be tumors Need to remain on medication long term Need for antibiotics to minimize infection Figure 23.16: Tissue typing for MHC proteins.

23.4 Immunodeficiency Disorders Can Be Inherited or Acquired Immunodeficiencies can involve any aspect of the immune system. Primary immunodeficiency is the result of a genetic abnormality. Secondary immunodeficiency is acquired later in life.

X-linked (Bruton) agammaglobulinemia is a congenital humoral immunodeficiency. B cells fail to develop, so patients lack mature B cells, plasma cells, and antibodies. It is a sex-linked trait, more common in males than females. In DiGeorge syndrome, the thymus fails to mature in the embryo, so T cells do not develop.

Figure 23.17: SCID and Gene Therapy. Severe combined immunodeficiency disease (SCID) involves lymph nodes deficient in B and T cells. One form is caused by an enzyme deficiency that can be corrected using gene therapy. In Chédiak-Higashi syndrome, lysosomes within phagocytes cannot release their contents to kill microbes. In chronic granulomatous disease, phagocytes do not produce substances to kill microbes. Figure 23.17: SCID and Gene Therapy. © Peter Menzel/Photo Researchers, Inc.

Secondary immunodeficiency is acquired later in life. Human Immunodeficiency Virus (HIV) is responsible for the Acquired Immunodeficiency Syndrome (AIDS). HIV is a + strand RNA virus with reverse transcriptase that copies SS RNA into DS DNA. gp120 spikes attach to host cells gp41 spikes promote fusion of viral envelope with host plasma membrane Figure 23.19: The Replication Cycle of the Human Immunodeficiency Virus (HIV).

Figure 23.20: HIV Infection and AIDS. Progression of HIV Stage I: Primary HIV Infection – many are asymptomatic Stage 2: Asymptomatic, level of HIV rises in blood Stage 3: HIV Symptomatic diseases Stage 4 AIDS – immune system compromised, opportunistic infections Figure 23.20: HIV Infection and AIDS.

Figure 23.21: Opportunistic Illnesses in AIDS Patients. Transmission of HIV Sharing of blood contaminated needles Unprotected sexual contact Diagnosis: Rapid test (ELISA like) HIV antibody tests Figure 23.21: Opportunistic Illnesses in AIDS Patients.

Figure 23.24: Viral Load and Drug Resistance. Treatment: AZT interferes with reverse transcriptase HAART combination drug treatment to help prevent growing resistance to drugs At this time vaccines are in development Prevention avoid risky behavior like sharing needles or unprotected sex Figure 23.24: Viral Load and Drug Resistance.