Chapter 9: Hypersensitivity: Allergy, Autoimmunity, and Alloimmunity PDF

Summary Review e15 degranulation and the release of histamine (the most potent 5. Macrophages are activated by interferon-γ (IFN-γ). From Th1 mediator) and other inflammatory substances. cell...

Summary Review e15 degranulation and the release of histamine (the most potent 5. Macrophages are activated by interferon-γ (IFN-γ). From Th1 mediator) and other inflammatory substances. cells. Activated M1 macrophages secrete proinflammatory 7. Histamine, acting through the H1 receptor, contracts cytokines and kill infected cells within their phagolysosomes. bronchial smooth muscles, causing bronchial constric- tion; increases vascular permeability, causing edema; and Immunologic Memory increases blood flow into the affected area, causing vaso- 1. When T and B cells are activated, they make long-lived cop- dilation. Histamine with H2 receptors results in increased ies of themselves called memory cells. gastric acid secretion and a decrease of histamine released 2. Upon re-exposure, these memory cells will rapidly become from mast cells and basophils. new plasma cells or effector T cells 8. Type II (tissue-specific) hypersensitivity reactions are caused by five possible mechanisms: complement-mediated Pediatric Considerations: Age-Related Factors Affecting lysis, opsonization and phagocytosis, neutrophil-mediated Mechanisms of Self-Defense in the Newborn Child tissue damage, antibody-dependent cell-mediated cytotox­ 1. Neonates often have a transiently depressed inflammatory icity, and modulation of cellular function. function, particularly neutrophil chemotaxis and alternative 9. Type III (immune complex–mediated) hypersensitivity complement pathway activity. reactions are caused by the formation of immune complexes 2. The T cell-independent immune response is adequate in that are deposited in target tissues, where they activate the the fetus and neonate, but the T cell-dependent immune complement cascade, generating chemotactic fragments that response develops slowly during the first 6 months of life. attract neutrophils into the inflammatory site. Neutrophils 3. Maternal IgG antibodies are transported across the placenta release lysosomal enzymes that result in tissue damage. into the fetal blood and protect the neonate for the first 6 10. Immune complex disease can be a systemic reaction, such months, after which they are replaced by the child’s own as serum sickness, or a localized response, such as the antibodies. Arthus reaction. 11. Type IV (cell-mediated) hypersensitivity reactions are Geriatric Considerations: Age-Related Factors Affecting caused by cytotoxic T lymphocytes (Tc cells), lymphokine- Mechanisms of Self-Defense in the Elderly producing Th1 cells and activated macrophages. 1. Elderly persons are at risk for impaired wound healing, usu- 12. Typical allergens include pollen, molds and fungi, certain ally because of chronic illnesses. foods (milk, eggs, fish, peanuts), animals, certain drugs, 2. T-cell function declines, and the relative kind of T cells pro- cigarette smoke, and house dust. duced is altered in elderly persons. 13. Clinical manifestations of allergic reactions usually are con- 3. Elderly individuals also develop impaired humoral immu- fined to the areas of initial intake or contact with the aller- nity and are at risk for increased levels of circulating autoan- gen. Ingested allergens induce gastrointestinal symptoms, tibodies (antibodies against self-antigens). airborne allergens induce respiratory tract or skin manifes- tations, and contact allergens induce allergic responses at the site of contact. CHAPTER 9 14. Autoimmune diseases originate from the coincidence of an initiating event in a genetically predisposed individual Hypersensitivity: Allergy, Autoimmunity, and Alloimmunity leading to an autoimmune mechanism that affects specific 1. Inappropriate immune responses are exaggerated mis- target tissues or cells. Central tolerance develops during the directed responses innocuous environmental antigens embryonic period. Peripheral tolerance is maintained in (allergy), the host’s own tissues (autoimmunity), or benefi- secondary lymphoid organs by regulatory T lymphocytes cial foreign tissues (alloimmunity); or insufficient responses or antigen-presenting dendritic cells. to protect the host (immune deficiency). 15. Heparin-induced thrombocytopenia is a condition in which 2. Allergy, autoimmunity, and alloimmunity are collectively heparin molecules attach to proteins in the surface of plate- known as hypersensitivity reactions. lets resulting in the formation of autoantibodies that destroy 3. Mechanisms of hypersensitivity are classified as type I (IgE- platelets (bleeding) and promote clotting (thrombosis). mediated) reactions, type II (tissue-specific) reactions, type 16. Systemic lupus erythematosus (SLE) is a chronic, multisys- III (immune complex–mediated) reactions, and type IV tem, inflammatory disease and is one of the most serious (cell-mediated) reactions. of the autoimmune disorders. SLE is characterized by the 4. Hypersensitivity reactions can be immediate (develop- production of a large variety of autoantibodies. ing within minutes to a few hours) or delayed (developing 17. Alloimmunity is the immune system’s reaction against anti- within several hours or days). gens on the tissues of other members of the same species. 5. Allergens are antigens that cause allergic responses. 18. Alloimmune disorders include transient neonatal disease, 6. Type I (IgE-mediated) hypersensitivity reactions are in which the maternal immune system becomes sensitized mediated through the binding of IgE to Fc receptors on against antigens expressed by the fetus; transplant rejection; mast cells and cross-linking of IgE by antigens that bind and transfusion reactions, in which the immune system of to the Fab portions of IgE. Cross-linking causes mast cell e16 Summary Review the recipient of an organ transplant or blood transfusion in control of inflammasome activation or in defects in reacts against foreign antigens on the donor’s cells. cellular receptors of cytokines designed to decrease inflam­ 19. Red blood cell antigens may be the targets of autoimmune mation. These disorders are frequently related to diminished or alloimmune reactions. The most important of these, control of infections of epithelial surfaces. because they provoke the strongest humoral immune 11. Almost any portion of the complement cascade may be response, are the ABO and Rh systems. defective. The most severe defect is C3 deficiency, which 20. Antigens on fetal red blood cells (Rh) can cause maternal results in recurrent life-threatening bacterial infections. antibodies to cross the placenta and cause severe anemia in Defects in proteins of the membrane attack complex usu- the fetus. ally result in unusual, disseminated infections with bacteria 21. Hyperacute graft rejection (preexisting antibody) is imme- of the Neisseria spp. diate and rare, acute rejection is both antibody and cell 12. Bone marrow failure and somatic mutations in immune mediated and occurs days to months after transplantation, genes may also result in severe primary immunodeficiency and chronic rejection is caused by inflammatory damage to states. endothelial cells as a result of a weak cell-mediated reaction. 13. Primary immune deficiencies may sometimes be treated by replacement therapy. Deficient antibody production is Deficiencies in Immunity treated by replacement of missing immunoglobulins with 1. Disorders resulting from immune deficiency are the clinical commercial gamma-globulin preparations. Lymphocyte sequelae of impaired function of components of the immune deficiencies are treated with the replacement of host lym- or inflammatory response, phagocytes, or complement. phocytes with bone marrow and stem cell transplants and 2. Immune deficiency is the failure of mechanisms of self- gene therapies when available. defense to function in their normal capacity. 14. Acquired immunodeficiencies are caused by superimposed 3. Immune deficiencies are either congenital (primary) or conditions, such as aging, malnutrition, infections, malig- acquired (secondary). Primary immune deficiencies are nancies, physical or psychological trauma, environmental caused by genetic defects that disrupt lymphocyte develop- factors, some medical treatments, or other diseases chronic ment, whereas secondary immune deficiencies are second- disease, or infections. ary to disease or other physiologic alterations. 4. The clinical hallmark of immune deficiency is a propensity to unusual or recurrent severe infections. The type of infec- C H A P T E R 10 tion usually reflects the immune system defect. 5. The most common infections in individuals with defects Microorganisms and Humans: A Dynamic Relationship of the cell-mediated immune response are fungal and 1. Infectious disease is a significant cause of morbidity and viral, whereas infections in individuals with defects of the mortality in the United States and worldwide. humoral immune response or complement function are 2. Pathogens have unique characteristics that influence their abil- primarily bacterial. ity to overcome body defense mechanisms and cause disease. 6. Severe combined immunodeficiency is a total lack of T-cell 3. The process of infection includes encounter and transmis- function and a severe (either partial or total) lack of B-cell sion, colonization, invasion, dissemination, and cellular or function. Other combined defects may result from deficien- tissue damage by the pathogenic microorganisms. cies in antigen-presenting molecules (bare lymphocyte syn- 4. There are four distinct stages of infection: incubation period, pro- drome) or cytoskeletal proteins (WAS). dromal stage, invasion or acute illness stage, and convalescence. 7. Chromosome 22q11.2 deletion syndrome (DiGeorge syn- drome) is characterized by complete or partial lack of Infectious Disease the thymus (resulting in depressed T-cell immunity) and 1. Bacteria have virulence factors that promote their ability to the parathyroid glands (resulting in hypocalcemia) and the cause infection and cell injury, including pili, flagella, cap- presence of cardiac anomalies. sules, enzymes, competition for iron, and toxins. 8. Defects in B-cell function are diverse, ranging from a com- 2. Bacteria produce exotoxins or endotoxins. Exotoxins are plete lack of the human bursal equivalent function, the lym- enzymes that can damage the plasma membranes of host phoid organs required for B-cell maturation (as in Bruton cells or can inactivate enzymes critical to protein synthe- agammaglobulinemia), to deficiencies in a single class of sis, and endotoxins activate the inflammatory response and immunoglobulins (e.g., selective IgA deficiency). produce fever. 9. Defects in phagocyte function, which include insufficient 3. Septicemia results from the proliferation of bacteria in numbers of phagocytes or defects of chemotaxis, phago­ blood. Toxins released by bloodborne bacteria cause the cytosis, or killing, can result in recurrent life-threatening release of vasoactive enzymes that increase the permeability infections such as septicemia and disseminated pyogenic of blood vessels. Leakage from vessels causes hypotension lesions. that can result in septic shock. 10. Immune dysregulation disorders are characterized by abnor- 4. Viruses are intracellular parasites. They enter host cells and mally high levels of inflammation secondary to muta­tions use their metabolic processes to proliferate and cause disease.