© 2013 Pearson Education, Inc. Lectures prepared by Christine L. Case

Disorders Associated

with the Immune System

Chapter 19

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Insert Fig CO 19

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Response to antigens (allergens) leading to damage

Types of reactions

Anaphylactic

Cytotoxic

Immune complex

Delayed cell-mediated

Hypersensitivity Reactions

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Types of Hypersensitivity

Type of Reaction Time After Exposure for Clinical Symptoms

Type I (anaphylactic) <30 min

Type II (cytotoxic) 5–12 hours

Type III (immune complex) 3–8 hours

Type IV (delayed cell-mediated)

≥1 day

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Type I (Anaphylactic) Reactions

IgE attached to mast cells and basophils Antigen binds to two adjacent IgE Mast cells and basophils undergo degranulation,

which releases mediators: Histamine Leukotrienes Prostaglandins

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Figure 19.1a The mechanism of anaphylaxis.

IgE antibodies, produced in response to an antigen, coat mast cells and basophils. When an antigen bridges the gap between two adjacent antibody molecules of the same specificity, the cell undergoes degranulation and releases histamine and other mediators.

Granule

Histamine andother mediators

Mast cell orbasophil

Antigen

IgE

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Figure 19.1b The mechanism of anaphylaxis.

A degranulated mast cell that has reacted with an antigen and released granules of histamine and other reactive mediators

Mast cells

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Type I (Anaphylactic) Reactions

Systemic anaphylaxis May result in circulatory collapse and death

Localized anaphylaxis Hives, hay fever, and asthma

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Figure 19.2 Localized anaphylaxis.

A micrograph of pollen grains A micrograph of a house mite on fabric

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Figure 19.3 A skin test to identify allergens.

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Preventing Anaphylactic Reactions

Desensitizing injections of antigen Cause production of IgG, so that IgG antibodies will

act as blocking antibodies

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Type II (Cytotoxic) Reactions

Involve IgG or IgM antibodies and complement Complement activation causes cell lysis or

damage by macrophages

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Insert Table 19.2

Table 19.2 The ABO Blood Group System

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If the woman becomes pregnant with another Rh+ fetus, her anti-Rhantibodies will cross the placenta and damage fetal red blood cells.

Figure 19.4 Hemolytic disease of the newborn.

In response to the fetal Rh antigens, the mother will produce anti-Rhantibodies.

Rh– mother carrying her first Rh+ fetus. Rh antigens from the developing fetus can enter the mother's blood during delivery.

Rh+ father.

Placenta

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Figure 19.5 Drug-induced thrombocytopenic purpura.

Drug binds to platelet,forming hapten–plateletcomplex.

Complex induces formationof antibodies against hapten.

Action of antibodiesand complement causes platelet destruction.

Anti-haptenantibody

Hapten–plateletcomplex

Platelet Drug (hapten)

Complement

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Type III (Immune Complex) Reactions

IgG antibodies and antigens form immune complexes that lodge in basement membranes

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Figure 19.6 Immune complex–mediated hypersensitivity.

Basementmembrane ofblood vessel

Endothelialcell

Immune complexesare deposited in wallof blood vessel.

Presence of immunecomplexes activatescomplement andattracts inflammatorycells such asneutrophils.

Enzymes releasedfrom neutrophilscause damage toendothelial cellsof basementmembrane.

NeutrophilsAg

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Type IV (Cell-Mediated) Reactions

Delayed-type hypersensitivities due to T cells

Cytokines attract macrophages and TC cells Initiate tissue damage

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Figure 19.7 The development of an allergy (allergic contact dermatitis) to catechols from the poison ivy plant.

Poison ivy

Pentadecacatecholmolecules

Skinprotein

Pentadecacatecholmolecules combined

with skin proteins

7–10 days

T cells:Sensitization

step

T memorycells: Immune

response

1–2 days

Many activeT cells: Disease

Dermatitis

SECONDARY CONTACTPRIMARY CONTACT

Dermatitis on arm

(No dermatitis)

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Insert Fig 19.8

Figure 19.8 Allergic contact dermatitis.

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What Is the Delayed Rash?Clinical Focus: A Delayed Rash, unnumbered figure, page 537.

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What Is the Delayed Rash?

A patient developed a rash 7 days after taking penicillin.

Was this the patient’s first exposure to penicillin? What is the delayed reaction?

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Autoimmune Diseases

Clonal deletion during fetal development ensures self-tolerance

Autoimmunity is loss of self-tolerance

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Autoimmune Diseases

Cytotoxic: antibodies react with cell-surface antigens Graves’ disease

Immune complex: immune complexes of IgM, IgG, and complement deposit in tissues Systemic lupus erythematosus

Cell-mediated: mediated by T cells Psoriasis

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HLA Reactions

Histocompatibility antigens: self antigens on cell surfaces

Major histocompatibility complex (MHC): genes encoding histocompatibility antigens

Human leukocyte antigen (HLA) complex: MHC genes in humans

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Figure 19.9 Tissue typing, a serological method.

Lymphocytebeing tested

HLA

Anti-HLA antibodiesattach to HLAs on lymphocyte.

Complementand trypan blue dye are added.

Cell damagedby complementtakes up dye.

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Diseases Related to Specific HLAs

Disease Increased Risk of Occurrence with Specific HLA

Multiple sclerosis 5 times

Rheumatic fever 4–5 times

Addison’s disease 4–10 times

Graves’ disease 10–12 times

Hodgkin’s disease 1.4–1.8 times

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Reactions to Transplantation

Transplants may be attacked by T cells, macrophages, and complement-fixing antibodies

Transplants to privileged sites do not cause an immune response

Stem cells may allow therapeutic cloning to avoid rejection Embryonic stem cells are pluripotent Adult stem cells have differentiated to form specific cells

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Figure 19.10 Derivation of embryonic stem cells.

Embryonic stem cells from embryoblast are grown on feeder cells in culture medium. Stem cell lines and groups of stem cells form colonies in culture medium. Different conditions, as well as growth factors added to culture medium, direct stem cells to become stem cell lines for various tissues of the body (e.g., blood and lymphatic cells, pancreatic islet cells, nerve cells).

(1–5 days) Blastocyst stage; the embryo divides repeatedly andforms a hollow ball of cells about the size of the period at the endof a sentence.

(1 day) Embryo, usually a fertilized egg discarded from attempt atin vitro fertilization.

Outer cell mass

Embryoblast (inner cellmass of embryonic cells)

Stem cell lines

Blood andlymphatic cells

Pancreaticislet cells

Nerve cells

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Grafts

Autograft: use of one’s own tissue Isograft: use of identical twin’s tissue Allograft: use of tissue from another person Xenotransplantation product: use of nonhuman

tissue Hyperacute rejection: response to nonhuman Ag

Graft-versus-host disease can result from transplanted bone marrow that contains immunocompetent cells

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Immunosuppression

Prevents an immune response to transplanted tissues

Cyclosporine and tacrolimus suppress IL-2 Mycophenolate mofetil inhibits T cell and B cell

reproduction Sirolimus blocks IL-2 Basiliximab and daclizumab block IL-2

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The Immune System and Cancer

Cancer cells have tumor-associated antigens Cancer cells are removed by immune surveillance CTL (activated TC) cells lyse cancer cells

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Figure 19.11 The interaction between a cytotoxic T lymphocyte (CTL) and a cancer cell.

The small CTL hasalready made aperforation in thecancer cell.

The cancer cell has disintegrated.

CTL

Cancer cell Remains of cancer cell

CTL

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Immunotherapy for Cancer

Coley’s toxin (gram-negative bacteria) stimulates TNF

Vaccines used against: Marek’s disease Feline leukemia Human cervical cancer Liver cancer (hepatitis B virus) Cervical cancer (HPV vaccine)

Monoclonal antibodies Herceptin

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Immunotherapy for Cancer

Treatment of cancer using immunologic methods

Tumor necrosis factor, IL-2, and interferons may kill cancer cells

Immunotoxins link poisons with a monoclonal antibody directed at a tumor antigen

Vaccines contain tumor-specific antigens

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Immunodeficiencies

Congenital: due to defective or missing genes Acquired: develop during an individual’s life

Due to drugs, cancers, and infections

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Disease Cells Affected

AIDS TH (CD4+) cells

Selective IgA immunodeficiency B, T cells

Common variable hypogammaglobulinemia

B, T cells (decreased immunoglobulins)

Reticular dysgenesis B, T, and stem cells Severe combined immunodeficiency

B, T, and stem cells

Thymic aplasia (DiGeorge syndrome)

T cells (defective thymus)

Wiskott-Aldrich syndrome B, T cells X-linked infantile (Bruton’s) agammaglobulinemia

B cells (decreased immunoglobulins)

Immunodeficiencies

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Figure 19.12 A nude (hairless) mouse infected with Mycobacterium leprae in the hind foot.

Site ofM. leprae bacteria