Chapter 16

Disorders of the Immune Response

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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?

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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
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 Mechanism of Type I Hypersensitivity

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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?

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

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Answer
True 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.

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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?

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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?

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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

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Mechanism of Type II Hypersensitivity

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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 pregnantand besides, the doctor told her that her first child was not at much risk for Rh disease.
Question: Why cant she wait to take RhoGAM if she gets pregnant again and really needs it?

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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 or B antigens on the RBC. c. It has no antibodies in the plasma. d. It has A and B antibodies in the plasma.

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Answer
b. It has neither A or B antigens on the RBC. 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 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

Type III Hypersensitivity

Free-floating antigen + antibody circulating immune complex Autoimmune vasculitis

Glomerulonephritis
Serum sickness Arthus reaction

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Mechanism of Type III Hypersensitivity

Immune complexes deposit on walls of blood vessels and activate complement Blood vessels are damaged

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

Copyright 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins

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

Copyright 2011 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
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Mechanisms of Type IV Hypersensitivity

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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 Antitissue antibodies appear in blood (e.g., antithyroid antibodies)
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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
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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 had, the more likely her bone marrow was to cause GVHD.
Discussion: Why might this be the case?

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

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Answer
False In autoimmune diseases, the immune system is hyperactiveit attacks self-antigens and destroys its own body tissues.

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Immunodeficiency
Primary
B-cell deficiencies Ig deficiencies

T-cell deficiencies
Combined immunodeficiencies Acquired AIDS
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Human Immunodeficiency Virus

Transmitted by body fluids Sexual contact Breast milk

Blood-to-blood contact
Contaminated needles Transfusions During pregnancy or birth

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

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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

Protein subunits are assembled into new virus particles

Viral proteins are produced in a long string called a polyprotein

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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 fusion inhibitor?

a. 1
b. 3 c. 6 d. 8

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

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Course of HIV Infection

Primary infection phase
Signs of systemic infection Seroconversion: immune system responds and antibodies against HIV appear (16 months) Latent period Virus is replicating, TH cell count gradually falls May last 1011 years or longer Overt AIDS TH cell count <200 cells/mL or AIDS-defining illness
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AIDS-Associated Illnesses
Opportunistic infections Respiratory

Gastrointestinal
Nervous system AIDS dementia complex Malignancies Wasting syndrome

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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?

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