chapter 15 alterations in the immune response

Copyright © 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Chapter 15Alterations 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

Mast cell degranulates

Sensitized Mast cell

Allergen attaches to IgE

IgE attaches to mast cell


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

TrueRationale: 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 vasodilationº What will happen when arterioles vasodilate

throughout the body?– Acetylcholine, kinins, leukotrienes, and

prostaglandins all can cause bronchoconstrictionº What will happen when the bronchioles constrict?


ScenarioA 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

Antigens attached to cell

membraneComplement activated

WBCs attracted to eat cell

Cell lysis

Directly causes cell lysis

Immunoglobulins attach to antigens


ScenarioA 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?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.


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.


Type III Hypersensitivity• Free-floating antigen + antibody

circulating immune complex– Autoimmune vasculitis– Glomerulonephritis– Serum sickness– Arthus reaction


Mechanism of Type III

Hypersensitivity

Immunoglobulins

Antigens

Immune complexes

• Immune complexes deposit on walls of blood vessels and activate complement

• Blood vessels are damaged


Question

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

hypersensitivity reaction.


Answer

TrueRationale: 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

Sensitized TH1 cell

Activated Cytotoxic T cell

Antigen

Direct cell-mediated cytotoxicity: Cytotoxic T cells kill tissue cells

Delayed-type hypersensitivity: TH1 cell secretes inflammatory mediators


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

FalseRationale: 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

º Contaminated needlesº Transfusionsº During pregnancy or birth


HIV Infects a CellBinds to CD4

protein receptor

Reverse transcriptase

• Which of your body cells have CD4 proteins and CD4 receptors?

• What does reverse transcriptase do?


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?

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


Answer

a. 1Rationale: 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/L or AIDS-defining illness


AIDS-associated Illnesses• Opportunistic infections

– Respiratory– Gastrointestinal– Nervous system

• AIDS dementia complex• Malignancies• Wasting syndrome


ScenarioA 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?

chapter 15 alterations in the immune response

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