© 2013 Pearson Education, Inc. Lectures prepared by Christine L. Case Disorders Associated with the Immune System Chapter 19

© 2013 Pearson Education, Inc. Insert Fig CO 19

© 2013 Pearson Education, Inc.  Response to antigens (allergens) leading to damage  Types of reactions  Anaphylactic  Cytotoxic  Immune complex  Delayed cell-mediated Hypersensitivity Reactions

© 2013 Pearson Education, Inc. 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

© 2013 Pearson Education, Inc. 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

© 2013 Pearson Education, Inc. 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 and other mediators Mast cell or basophil Antigen IgE

© 2013 Pearson Education, Inc. 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

© 2013 Pearson Education, Inc. Type I (Anaphylactic) Reactions  Systemic anaphylaxis  May result in circulatory collapse and death  Localized anaphylaxis  Hives, hay fever, and asthma

© 2013 Pearson Education, Inc. Figure 19.2 Localized anaphylaxis. A micrograph of pollen grains A micrograph of a house mite on fabric

© 2013 Pearson Education, Inc. Figure 19.3 A skin test to identify allergens.

© 2013 Pearson Education, Inc. Preventing Anaphylactic Reactions  Desensitizing injections of antigen  Cause production of IgG, so that IgG antibodies will act as blocking antibodies

© 2013 Pearson Education, Inc. Type II (Cytotoxic) Reactions  Involve IgG or IgM antibodies and complement  Complement activation causes cell lysis or damage by macrophages

© 2013 Pearson Education, Inc. Insert Table 19.2 Table 19.2 The ABO Blood Group System

© 2013 Pearson Education, Inc. If the woman becomes pregnant with another Rh + fetus, her anti-Rh antibodies 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-Rh antibodies. Rh – mother carrying her first Rh + fetus. Rh antigens from the developing fetus can enter the mother's blood during delivery. Rh + father. Placenta

© 2013 Pearson Education, Inc. Figure 19.5 Drug-induced thrombocytopenic purpura. Drug binds to platelet, forming hapten–platelet complex. Complex induces formation of antibodies against hapten. Action of antibodies and complement causes platelet destruction. Anti-hapten antibody Hapten–platelet complex Platelet Drug (hapten) Complement

© 2013 Pearson Education, Inc. Type III (Immune Complex) Reactions  IgG antibodies and antigens form immune complexes that lodge in basement membranes

© 2013 Pearson Education, Inc. Figure 19.6 Immune complex–mediated hypersensitivity. Basement membrane of blood vessel Endothelial cell Immune complexes are deposited in wall of blood vessel. Presence of immune complexes activates complement and attracts inflammatory cells such as neutrophils. Enzymes released from neutrophils cause damage to endothelial cells of basement membrane. Neutrophils Ag

© 2013 Pearson Education, Inc. Type IV (Cell-Mediated) Reactions  Delayed-type hypersensitivities due to T cells  Cytokines attract macrophages and T C cells  Initiate tissue damage

© 2013 Pearson Education, Inc. Figure 19.7 The development of an allergy (allergic contact dermatitis) to catechols from the poison ivy plant. Poison ivy Pentadecacatechol molecules Skin protein Pentadecacatechol molecules combined with skin proteins 7–10 days T cells: Sensitization step T memory cells: Immune response 1–2 days Many active T cells: Disease Dermatitis SECONDARY CONTACTPRIMARY CONTACT Dermatitis on arm (No dermatitis)

© 2013 Pearson Education, Inc. Insert Fig 19.8 Figure 19.8 Allergic contact dermatitis.

© 2013 Pearson Education, Inc. What Is the Delayed Rash? Clinical Focus: A Delayed Rash, unnumbered figure, page 537.

© 2013 Pearson Education, Inc. 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?

© 2013 Pearson Education, Inc. Autoimmune Diseases  Clonal deletion during fetal development ensures self-tolerance  Autoimmunity is loss of self-tolerance

© 2013 Pearson Education, Inc. 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

© 2013 Pearson Education, Inc. 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

© 2013 Pearson Education, Inc. Figure 19.9 Tissue typing, a serological method. Lymphocyte being tested HLA Anti-HLA antibodies attach to HLAs on lymphocyte. Complement and trypan blue dye are added. Cell damaged by complement takes up dye.

© 2013 Pearson Education, Inc. Diseases Related to Specific HLAs Disease Increased Risk of Occurrence with Specific HLA Multiple sclerosis5 times Rheumatic fever4–5 times Addison’s disease4–10 times Graves’ disease10–12 times Hodgkin’s disease1.4–1.8 times

© 2013 Pearson Education, Inc. 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

© 2013 Pearson Education, Inc. Figure 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 and forms a hollow ball of cells about the size of the period at the end of a sentence. (1 day) Embryo, usually a fertilized egg discarded from attempt at in vitro fertilization. Outer cell mass Embryoblast (inner cell mass of embryonic cells) Stem cell lines Blood and lymphatic cells Pancreatic islet cells Nerve cells

© 2013 Pearson Education, Inc. 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

© 2013 Pearson Education, Inc. 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

© 2013 Pearson Education, Inc. The Immune System and Cancer  Cancer cells have tumor-associated antigens  Cancer cells are removed by immune surveillance  CTL (activated T C ) cells lyse cancer cells

© 2013 Pearson Education, Inc. Figure The interaction between a cytotoxic T lymphocyte (CTL) and a cancer cell. The small CTL has already made a perforation in the cancer cell. The cancer cell has disintegrated. CTL Cancer cellRemains of cancer cell CTL

© 2013 Pearson Education, Inc. 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

© 2013 Pearson Education, Inc. 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

© 2013 Pearson Education, Inc. Immunodeficiencies  Congenital: due to defective or missing genes  Acquired: develop during an individual’s life  Due to drugs, cancers, and infections

© 2013 Pearson Education, Inc. DiseaseCells Affected AIDST H (CD4 + ) cells Selective IgA immunodeficiencyB, 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 syndromeB, T cells X-linked infantile (Bruton’s) agammaglobulinemia B cells (decreased immunoglobulins) Immunodeficiencies

© 2013 Pearson Education, Inc. Figure A nude (hairless) mouse infected with Mycobacterium leprae in the hind foot. Site of M. leprae bacteria