Summary Review Chapter 8 PDF

Summary Review e13 2. Local manifestations of inflammation include the classic and killing of microorganisms and limited complement signs of redness, heat, swelling, pain, and loss of function. activity. They are the result of vascular changes associated w...

Summary Review e13 2. Local manifestations of inflammation include the classic and killing of microorganisms and limited complement signs of redness, heat, swelling, pain, and loss of function. activity. They are the result of vascular changes associated with the 2. Aging impairs the immune system due to a process called inflammatory process, including vasodilation and increased immunosenescence which causes impairment of cellular capillary permeability. function in both immunity and wound healing. 3. The principal systemic effects of inflammation are fever, leu- 3. Impaired wound healing in the aging population is multi- kocytosis (increased levels of circulating leukocytes), and an factorial and includes changes in innate immunity, cellular increase in plasma proteins, primarily the acute-phase reac- metabolism, and tissue integrity. tants, IL-1, and IL-6. 4. The elderly are also at risk for excessive and disordered 4. Chronic inflammation is the persistence of the inflammatory innate immune responses called inflammaging that contrib- response often contributing to tissue damage. ute to many chronic diseases. 5. Chronic inflammation is characterized by a dense infiltra- tion of lymphocytes and macrophages. It can take two forms, nonspecific proliferative chronic inflammation and granulo- CHAPTER 8 matous chronic inflammation. 6. Nonspecific proliferative chronic inflammation occurs Overview of Adaptive Immunity when the acute inflammatory response fails to eliminate the 1. Adaptive immunity is a state of protection, primarily against invader/injury or there is dysfunctional resolution of the infectious agents, that differs from inflammation by being acute inflammatory response. slower to develop, being more specific, and having memory 7. Granuloma formation is a process wherein the body walls that makes it much longer lived. off and isolates certain infectious microorganisms or foreign 2. The adaptive immune response is most often initiated by bodies that could not be removed by acute inflammation. It cells of the innate system. These cells process and present serves to protect the body from further tissue damage. portions of invading pathogens (i.e., antigens) to lympho- 8. Both forms of chronic inflammation can contribute to tissue cytes in peripheral lymphoid tissue. dysfunction and organ damage and are the major causes of 3. The adaptive immune response is mediated by two types of chronic disease. lymphocytes—B lymphocytes and T lymphocytes. Each has distinct functions. B cells are responsible for humoral immu- Wound Healing nity that is mediated by circulating antibodies, whereas T cells 1. Resolution (regeneration) is the return of tissue to nearly are responsible for cell-mediated immunity, in which they kill normal structure and function. Repair is healing by scar tis- targets directly or stimulate the activity of other leukocytes. sue formation. 4. B and T lymphocytes leaving the primary lymphoid organs 2. Resolution occurs when little tissue has been lost or where are immunocompetent but have not been exposed to anti- the injured tissue is capable of regeneration. This type of gen, thus are naïve. healing is called healing by primary intention. 5. Clonal selection with cellular proliferation and further dif- 3. Tissues that have sustained extensive damage or tissue types ferentiation of T and B cells into active effort cells of the that are incapable of regeneration heal by repair, a process adaptive immune system is initiated when exposure to an which results in the formation of a scar. This process is called antigen occurs. healing by secondary intention. 4. Wound healing occurs in four overlapping phases; hemo- Antigens stasis, inflammation, proliferation with new tissue forma- 1. Antigens are molecules that bind and react with components tion, and remodeling or maturation. Each of these phases of the immune response, such as antibodies and receptors on is characterized by the complex interaction of multiple cells B and T cells. including platelets, neutrophils, macrophages fibroblasts, 2. Common antigens include infectious agents, allergens, chem- endothelial cells, and epithelial cells. ical agents, and abnormal molecules on the surface of cells. 5. Dysfunctional wound healing can be secondary to ischemia, 3. Large molecules, such as proteins, polysaccharides, and excessive bleeding, excessive fibrin deposition, predisposing nucleic acids, are most immunogenic. Thus, molecular size disorders (e.g., diabetes mellitus), wound infection, inad- is a crucial factor for antigen immunogenicity. equate nutrients, use of NSAIDs and steroids, or altered col- 4. Haptens are antigens too small to be immunogens by them- lagen synthesis. selves but become immunogenic after combining with larger 6. Dehiscence is a disruption where the wound pulls apart at the molecules. suture line. 5. The antigenic determinant, or epitope, is the precise chemi- 7. A contracture is a structural deformity caused by the exces- cal structure with which an antibody or B-cell/T-cell recep- sive shortening of collagen in scar tissue. tor (BCR/TCR) reacts. 6. Self-antigens are antigens on an individual’s own cells. Pediatric and Geriatric Considerations The individual’s immune system does not usually recog- 1. Neonates often have transiently depressed inflammatory nize self-antigens as immunogenic, a condition known as function, particularly decreased phagocyte chemotaxis tolerance. e14 Summary Review Lymphocyte Development only on APCs. Tc cells require that the antigen be presented 1. The generation of clonal diversity results in the production by MHC class I molecules. of B and T lymphocytes with receptors against millions of 3. The T cell binds to the presented antigen through the TCR antigens that possibly will be encountered in an individual’s and accessory molecules: CD4 or CD8. CD4 is found on Th lifetime occurs in the fetus in the primary lymphoid organs: cells and reacts specifically with MHC class II. CD8 is found the thymus for T cells and portions of bone marrow for B on Tc cells and reacts specifically with MHC class I. cells. 4. Further differentiation of these Th0 cells results in the forma- 2. The generation of clonal diversity is the differentiation of tion of Th1 cells, which help Tc cells respond to antigen; Th2 lymphoid stem cells into B and T lymphocytes with specific cells, which help B cells develop into plasma cells; and Th17 BCRs and TCRs, respectively. cells, which help activate macrophages. 3. The enormous repertoire of BCR specificities is made pos- sible by rearranging existing deoxyribonucleic acid (DNA) Humoral Immunity (Antibodies) during B-cell development in the primary lymphoid organs, 1. The humoral immune response consists of molecules (anti- a process called somatic recombination. bodies) produced by B cells. B cells are lymphocytes. B cells 4. Somatic rearrangement of the antibody variable regions will can detect antigen with their BCR molecules and differenti- frequently result in a BCR that recognizes the individual’s ate into APCs that interact closely with Th cells. own antigens, which may result in attack on “self ” antigens 2. Th cell activation by B cells results in the production of expressed on various tissue and organs. Many of these “auto- IL-4, which, along with costimulatory molecules CD40 and reactive” B cells are eliminated in the bone marrow. Most of CD40L, activate the B cell to become an antibody-producing the developing B cells undergo apoptosis. This entire process plasma cell. is referred to as clonal deletion or central tolerance. 3. B cells can also be activated to become antibody-producing 5. Treg cells are a diverse group of T cells that control the plasma cells through a T-cell independent process. immune response, usually suppressing the response and 4. A typical antibody molecule is constructed of two identical maintaining tolerance against self-antigens. Treg cells pro- heavy chains and two identical light chains (either κ or λ) duce very high levels of immunosuppressive cytokines, and has two Fab portions that bind antigen and an Fc portion which induce tolerance. that interacts with complement or receptors on cells. 6. The process of T-cell proliferation and differentiation is 5. Antibodies are plasma glycoproteins that can be classified by similar to that for B cells. The primary lymphoid organ for chemical structure and biologic activity as immunoglobulin T-cell development is the thymus. Lymphoid stem cells travel G (IgG), IgM, IgA, IgE, or IgD. through the thymus, where they gain a TCR, and receptors 6. The protective effects of antibodies may be direct through the become immunocompetent. Self-reactive T cells undergo action of antibody alone or indirect, requiring activation of clonal deletion. other components of the innate immune response. 7. Proteins called CD4 and CD8 are expressed on the devel- 7. IgE is a special class of antibody produced against environ- oping T cells. As the cell matures, it retains either the CD4 mental antigens that are the primary cause of common aller- molecule or the CD8 molecule but not both. Eventually, CD4 gies. It also protects the individual from infection by large cells develop into T-helper cells (Th cells), and CD 8 cells parasitic worms (helminths). become T-cytotoxic cells (Tc cells). Other mature T cells 8. The secretory immune system protects the external surfaces include T-regulatory cells (Treg cells) and memory cells. of the body through the secretion of antibodies in bodily 8. The generation of clonal diversity concludes when immuno- secretions, such as tears, sweat, saliva, mucus, and breast competent T and B cells migrate from the primary lymphoid milk. IgA is the dominant secretory immunoglobulin. organs into the circulation and secondary lymphoid organs to await antigen. Cell-Mediated Immunity 1. The cells of cell-mediated immunity include Tc cells, NK Induction of the Adaptive Immune Response cells, and macrophages. These cells kill damaged, cancerous, 1. The induction of an immune response, or clonal selection, or infected cells, begins when antigen enters the individual’s body and inter- 2. Tc cells bind with antigen presented on the MHC I molecule acts with antigen-presenting cells (APCs) (e.g., dendritic on an APC. This, along with IL-2 from Th cells, activates the cells, macrophages, and B cells). Tc cell. 2. To induce an optimal cellular or humoral immune response, 3. Tc cell attachment to a target cell activates multiple killing APCs must present antigens to Th cells. Antigen is processed mechanisms through which the target cell is induced to in the APCs and presented on the cell surface by molecules undergo apoptosis. of the major histocompatibility complex (MHC). The par- 4. Natural killer (NK) cells are a special group of lymphoid cells ticular MHC molecule (class I or class II) that presents anti- that express various cell surface activation receptors that gen determines which cell will respond to that antigen. Th identify protein changes on the surface of cells infected with cells require that the antigen be presented in a complex with viruses or that have become cancerous. After attachment, the MHC class II molecules. MHC class II molecules are found NK cell kills its target like that of Tc cells.  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