Chapter 15 Alterations in the Immune Response

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?

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

Mechanism of Type I Hypersensitivity Mast cell Mechanism of Type I Hypersensitivity Sensitized Mast cell IgE attaches to mast cell Allergen attaches to IgE Mast cell degranulates

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?

Question Tell whether the following statement is true or false. When mast cells degranulate, histamine is released.

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.

Anaphylaxis Systemic response to the inflammatory mediators released in type I hypersensitivity Histamine, acetylcholine, kinins, leukotrienes, and prostaglandins all cause vasodilation What will happen when arterioles vasodilate throughout the body? Acetylcholine, kinins, leukotrienes, and prostaglandins all can cause bronchoconstriction What will happen when the bronchioles constrict?

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?

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

Mechanism of Type II Hypersensitivity Immunoglobulins Immunoglobulins attach to antigens Antigens attached to cell membrane Complement activated Directly causes cell lysis Cell lysis WBCs attracted to eat cell

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?

Question Why is type O blood considered the universal donor? It has both A and B antigens on the RBC. It has neither A nor B antigens on the RBC. It has no antibodies in the plasma. It has A and B antibodies in the plasma.

Answer 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.

Type III Hypersensitivity Free-floating antigen + antibody  circulating immune complex Autoimmune vasculitis Glomerulonephritis Serum sickness Arthus reaction

Mechanism of Type III Hypersensitivity Immunoglobulins Mechanism of Type III Hypersensitivity Antigens Immune complexes deposit on walls of blood vessels and activate complement Blood vessels are damaged Immune complexes

Question Tell whether the following statement is true or false. Administration of certain antibiotics may result in type III hypersensitivity reaction.

Answer True Rationale: A side effect associated with antibiotic administration (especially penicillin) is serum sickness, which may cause a type III hypersensitivity reaction.

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

Mechanisms of Type IV Hypersensitivity TH1 cell Antigen Sensitized TH1 cell Delayed-type hypersensitivity: TH1 cell secretes inflammatory mediators Activated Cytotoxic T cell Direct cell-mediated cytotoxicity: Cytotoxic T cells kill tissue cells

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., anti- thyroid antibodies)

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

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?

Question Tell whether the following statement is true or false. Patients who suffer from autoimmune disease have hypoactive immune systems.

Answer False Rationale: In autoimmune diseases, the immune system is hyperactive—it attacks self-antigens and destroys its own body tissues.

Immunodeficiency Primary B-cell deficiencies Ig deficiencies T-cell deficiencies Combined immunodeficiencies Acquired AIDS

Human Immunodeficiency Virus Transmitted by body fluids Sexual contact Breast milk Blood-to-blood contact Contaminated needles Transfusions During pregnancy or birth

HIV Infects a Cell Which of your body cells have CD4 proteins and CD4 receptors? What does reverse transcriptase do? Binds to CD4 protein receptor Reverse transcriptase

The Infected Cell Produces New HIV Polyprotein broken into subunits by protease HIV may lie dormant in the genome for many years before it is activated to produce viral proteins Viral proteins are produced in a long string called a polyprotein Protein subunits are assembled into new virus particles

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? 1 3 6 8

Answer 1 Rationale: In the illustration, step #1 marks the point of attachment between HIV and the CD4 receptor site on the T lymphocyte.

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

AIDS-associated Illnesses Opportunistic infections Respiratory Gastrointestinal Nervous system AIDS dementia complex Malignancies Wasting syndrome

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?