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Chapter 15 Alterations in the Immune Response Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Hypersensitivity • Excessive or inappropriate activation of the immune response • The body is damaged by the immune response, rather than by the antigen (often called allergen) Discussion: • How many different allergies do the members of this class have? • What are their common signs and symptoms? • Can the general process of inflammation explain these signs and symptoms? Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Type I Hypersensitivity • Commonly called “allergic reactions” • Systemic or anaphylactic reactions • Local or atopic reactions (genetic) – Rhinitis (hay fever) – Food allergies – Bronchial asthma – Hives – Atopic dermatitis Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Mast cell Mechanism of Type I Hypersensitivity Sensitized Mast cell IgE attaches to mast cell Allergen attaches to IgE Mast cell degranulates Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Type I Allergies Are Mediated by IgE • What cells must be involved in this process: – On the first exposure to the allergen? – On repeated exposure? – When the allergen binds to IgE? – What inflammatory mediators are involved? How? Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Tell whether the following statement is true or false. When mast cells degranulate, histamine is released. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer True Rationale: Histamine is one of the first chemical mediators released during the inflammatory response as a result of mast cell degranulation. Mast-cell stabilizers (used to treat asthma) prevent the histamine from being released; antihistamines (used to treat allergies) compete with histamine for receptor sites, lessening the inflammatory response. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Anaphylaxis • Systemic response to the inflammatory mediators released in type I hypersensitivity – Histamine, acetylcholine, kinins, leukotrienes, and prostaglandins all cause vasodilation º What will happen when arterioles vasodilate throughout the body? – Acetylcholine, kinins, leukotrienes, and prostaglandins all can cause bronchoconstriction º What will happen when the bronchioles constrict? Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Scenario A woman had an anaphylactic reaction and you are trying to explain the mechanism to her husband; he says he can see what you mean, but it does not make sense because what his wife experienced was different. • She said her heart was pounding and she was terrified. • Her eyes were dilated. • She was shaking. Question: • How could anaphylaxis cause these signs and symptoms? Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Type II Hypersensitivity • Cytotoxic • IgG or IgM attack antigens on cell surfaces – Usually involves antigens on red or white blood cells – Transfusion reactions – Rh disease – Drug reactions Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Mechanism of Type II Hypersensitivity Immunoglobulins Antigens attached to cell membrane Directly causes cell lysis Immunoglobulins attach to antigens Complement activated Cell WBCs attracted lysis to eat cell Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Scenario A woman is Rh negative and her husband is Rh positive. • She is pregnant with their first child and the doctor has prescribed RhoGAM, but the woman is confused about this. • She says she does not want to take any drugs while she is pregnant—and besides, the doctor told her that her first child was not at much risk for Rh disease. Question: • Why can’t she wait to take RhoGAM until she gets pregnant again and really needs it? Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Why is type O blood considered the universal donor? a. It has both A and B antigens on the RBC. b. It has neither A nor B antigens on the RBC. c. It has no antibodies in the plasma. d. It has A and B antibodies in the plasma. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer b. It has neither A nor B antigens on the RBC. Rationale: Antigens are the components that elicit an immune response (type II hypersensitivity reaction). Type O blood has no antigens on the RBC, so anyone can receive it because there is nothing to stimulate production of antibodies against it. The fact that type O blood has both A and B antibodies has nothing to do with creating the antigen-antibody response. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Type III Hypersensitivity • Free-floating antigen + antibody circulating immune complex – Autoimmune vasculitis – Glomerulonephritis – Serum sickness – Arthus reaction Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Mechanism of Type III Hypersensitivity Immunoglobulins Antigens • Immune complexes deposit on walls of blood vessels and activate complement • Blood vessels are damaged Immune complexes Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Tell whether the following statement is true or false. Administration of certain antibiotics may result in type III hypersensitivity reaction. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer True Rationale: A side effect associated with antibiotic administration (especially penicillin) is serum sickness, which may cause a type III hypersensitivity reaction. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Type IV Hypersensitivity • Cell-mediated: sensitized T cells attack antigen • Direct cell-mediated cytotoxicity – Viral reactions • Delayed-type hypersensitivity – Tuberculin test – Allergic contact dermatitis – Hypersensitivity pneumonitis Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Mechanisms of Type IV Hypersensitivity TH1 cell Antigen Sensitized TH1 cell Activated Cytotoxic T cell Delayed-type hypersensitivity: TH1 cell secretes inflammatory mediators Direct cell-mediated cytotoxicity: Cytotoxic T cells kill tissue cells Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Autoimmune Diseases • Immune system attacks self-antigens • Normally, self-reactive immune cells are killed in the lymphoid organs or suppressed by regulatory T cells • In autoimmunity, this self-tolerance breaks down • Immune system destroys body tissues • Anti-tissue antibodies appear in blood (e.g., antithyroid antibodies) Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Transplant Rejection • Host-versus-graft disease (HVGD) • Hyperacute – Circulating antibodies react with graft • Acute – Exposure to transplant causes activation of immune system, especially T cells • Chronic – Blood vessels in transplant gradually damaged Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Graft-versus-host Disease • Transplanted immune cells attack host • A recent study suggested that men who get bone marrow transplants from women might be more prone to GVHD than men who get bone marrow transplants from other men • It also suggested that the more children a woman has had, the more likely her bone marrow was to cause GVHD Discussion: • Why might this be the case? Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question Tell whether the following statement is true or false. Patients who suffer from autoimmune disease have hypoactive immune systems. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer False Rationale: In autoimmune diseases, the immune system is hyperactive—it attacks self-antigens and destroys its own body tissues. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Immunodeficiency • Primary – B-cell deficiencies – Ig deficiencies – T-cell deficiencies – Combined immunodeficiencies • Acquired – AIDS Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Human Immunodeficiency Virus • Transmitted by body fluids – Sexual contact – Breast milk – Blood-to-blood contact º Contaminated needles º Transfusions º During pregnancy or birth Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins HIV Infects a Cell Binds to CD4 protein receptor • Which of your body cells have CD4 proteins and CD4 receptors? • What does reverse transcriptase do? Reverse transcriptase Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins The Infected Cell Produces New HIV HIV may lie dormant in the genome for many years before it is activated to produce viral proteins Polyprotein broken into subunits by protease Protein subunits are assembled into new virus particles Viral proteins are produced in a long string called a polyprotein Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Question One AIDS drug is a fusion inhibitor (Fuzeon)—the drug prevents fusion of HIV to the CD4 receptor. In the previous slides’ illustrations, which step in the infection process is targeted by a fusion inhibitor? a. 1 b. 3 c. 6 d. 8 Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Answer a. 1 Rationale: In the illustration, step #1 marks the point of attachment between HIV and the CD4 receptor site on the T lymphocyte. Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Course of HIV Infection • Primary infection phase – Signs of systemic infection – Seroconversion: immune system responds and antibodies against HIV appear (1–6 months) • Latent period – Virus is replicating, TH cell count gradually falls – May last 10–11 years or longer • Overt AIDS – TH cell count <200 cells/mL or AIDS-defining illness Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS-associated Illnesses • Opportunistic infections – Respiratory – Gastrointestinal – Nervous system • AIDS dementia complex • Malignancies • Wasting syndrome Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins Scenario A man was diagnosed as HIV-positive. • He says this is nonsense because the test does not measure whether he is sick or not • In fact, it means “his immune system is working” Question: • Is he right? Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins