NURS 7053 Advanced Pathophysiology I for DNP Students PDF

NURS 7053 Advanced Pathophysiology I for DNP Students Alterations in Immune Function - Class Notes Hypersensitivity Reactions Altered immunologic reaction that results in a pathol...

NURS 7053 Advanced Pathophysiology I for DNP Students Alterations in Immune Function - Class Notes Hypersensitivity Reactions Altered immunologic reaction that results in a pathologic response Type I Hypersensitivity Reaction IgE-mediated reaction Characteristics Type I reactions are characterized by the production of antigen-specific IgE after exposure to an antigen Most Type I reactions are in response to environmental antigens (i.e, allergens) Common Allergens Pollens, dusts, molds Food Drugs Bee venom Genetic Predisposition and Atopy Over ten candidates for polymorphic genes have been identified (mutations that affect IL-4 receptors, IL-4 levels, IgE receptors, Class II MHC proteins, etc) – called ‘atopy’ ‘Atopic’ individuals tend to produce higher amounts of IgE, more IgE receptors on mast cells, and an increased eosinophil response. Consequently, atopic individuals have hyperactive immune responses. 1  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations in Immune Function - Class Notes Pathophysiology Dendritic cells (antigen-presenting cells in the skin) present allergen to Th2 cells Th2 cell produces cytokines (IL-4, IL-5) which stimulate IgE–producing B cells IgE binds to receptors on the mast cell’s plasma membrane, which activates the mast cell Result is degranulation of histamine from the mast cell and the release of newly formed mediators (i.e., arachidonic acid metabolites) Eosinophils are also recruited by the release of cytokines from the Th2 & eosinophil chemotactic factor from the mast cell 2  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations in Immune Function - Class Notes Two defined phases occur Initial phase (5 to 30 minutes after exposure) – vasodilation, increased capillary permeability, and non-vascular smooth muscle constriction Late phase (occurs 2 to 8 hours without additional exposure to the allergen) – similar responses – see more intense infiltration of tissues with granulocytes (eosinophils, neutrophils) and mucosal damage Clinical Consequences Allergic reactions (local response): Itching and urticaria (hives); rhinitis; conjunctivitis Anaphylaxis (systemic response) Bronchospasm, bronchoconstriction Hypotension Edema GI cramping 3  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations in Immune Function - Class Notes Type II Hypersensitivity Reactions Destruction of a target cell in the body through the action of antibody against an antigen on the cell’s plasma membrane Common Antigens Tissues with HLA and/or tissue-specific antigen (i.e., autoimmune reactions) Drugs or drug metabolites that bind to plasma membrane of cells (often RBCs or platelets), making the cell a target Transplanted tissues or organs (including blood transfusions) Pathophysiology – mechanisms of antigen destruction Complement-mediated lysis IgM or IgG reacts with an antigen present on the surface of the cell causing activation of complement Results in the activation of the complement proteins (C5-9) that cause plasma membrane damage and cell injury Phagocytosis by macrophages Macrophages recognize and bind to Fc portion of antibody on opsonized target cell and phagocytose the target 4  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations in Immune Function - Class Notes Antibody-dependent cell-mediated cytotoxicity (ADCC) Destruction by a subpopulation of cytotoxic cells called natural killer (NK) cells NK cells bind to Fc portion of antibody on opsonized target cell and releases toxic molecules that destroy the target Inducing target cell malfunction Changes in cell function are induced by the antibodies binding to target cell receptors (Example: hyperthyroidism in Graves disease) Antibody occupies and alters receptors that would bind with the various molecules required for normal cellular function Type III Hypersensitivity Reactions Immune complex diseases Common Antigens Viral, bacterial and parasitic antigen Pollens Vaccines Plasma/Serum Nuclear antigen 5  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations in Immune Function - Class Notes Pathophysiology Antigen-antibody (AKA immune) complexes form in the circulation and are later deposited on endothelium of capillaries or in extravascular tissue Complement proteins are activated Neutrophils ingest the deposited antigen-antibody complex and cause tissue damage Common Target Tissues/Disease Examples Kidneys – causes glomerulonephritis Blood vessels – causes vasculitis Arthus reaction: Repeated local exposure to antigen causes formation of immune complexes in the walls of local blood vessels leading to local inflammatory skin lesions. Raynaud disease: Temperature-dependent immune complexes (cryoglobulins) precipitate at below-normal body temperatures Systemic lupus erythematosus – Immune reaction to nuclear antigen 6  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations in Immune Function - Class Notes Type IV Hypersensitivity Reactions Delayed hypersensitivity reaction mediated by sensitized T-lymphocytes (Tc or Th) Examples Tissue graft rejection Contact dermatitis (poison ivy, metals) Tuberculin reaction Other diseases: diabetes type 1, RA, MS, Crohn disease, toxic shock, etc… Pathophysiology of type IV hypersensitivity skin reactions Allergen binds to proteins on membranes of epidermal cells Infiltration of site by T lymphocytes and macrophages T lymphocytes bind to target cells and release enzymes (granzymes) that damage/destroy target cell Manifestations of hypersensitivity delayed by 24-72 hours Note: No dermatitis from the primary contact with the allergen 7  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations in Immune Function - Class Notes Autoimmunity Altered immunologic reaction that results in a B and T lymphocyte response against the body’s own cells Immunological Tolerance How the immune system is prevented from destroying self-antigen Immunocompetent B and T lymphocytes with the capability of recognizing all antigen (including self-antigen) are produced during the process of generating clonal diversity. Mechanisms exist that prevent the immune system from mounting an immune response to self-antigen (and commensal microbes) – a process known as immunological tolerance Generation of Central Tolerance Immunocompetent (immature) B and T lymphocytes migrate to the bone marrow and thymus where they are exposed to self antigen and develop ‘tolerance’ Central T lymphocyte tolerance Immunocompetent (immature) T lymphocytes migrate to the thymus where they are exposed to self antigen Recognition of self antigen induces: 1) apoptosis (negative selection) of CD4 (Th) and CD8 (Tc) lymphocytes 2) development of regulatory T lymphocytes (T reg) 8  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations in Immune Function - Class Notes Central B lymphocyte tolerance Immunocompetent (immature) B lymphocytes migrate to or stay in the bone marrow where they are exposed to self antigen Recognition of self antigen induces: 1) receptor editing – a change in receptor specificity 2) apoptosis – “deletion” 3) Anergy – B lymphocyte specificity survives, by the antigen receptor expression is reduced Generation of Peripheral Tolerance Generation of central tolerance is imperfect Reduction in CD4 Th cell population reduces the B and T lymphocyte response Peripheral T lymphocyte tolerance Mature T lymphocytes recognize self-antigen, which causes anergy or apoptosis. Antigen presenting cells (APCs) secrete fewer signaling molecules Mature T lymphocytes are sensitive to the effects of Treg cells 9  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations in Immune Function - Class Notes Peripheral B lymphocyte tolerance Mature B lymphocytes recognize self-antigen, which causes anergy or apoptosis Mature B lymphocytes recognize self-antigen, which engages inhibitory receptors Generation of Tolerance to Commensal Microbes The human body has ~ 1014 bacteria and viruses If the immune system reacted to theses microbes, the body would kill/eliminate them and launch a harmful immune/ inflammatory response There seems to be an abundance of Treg cells that secrete interleukins that suppress rather than enhance the immune response to these microbes Development of Autoimmune Disease An immune response against self-antigen affecting 1 out of every 5 Americans. Associated with the inheritance of susceptibility genes and environmental triggers. Susceptibility genes: Interfere with pathways responsible for self-tolerance (multiple gene loci, many polymorphisms), most affecting MHC (i.e., HLA) genes Environmental triggers Infections (infection prodromes): infections stimulate antigen presenting cells (APCs) that activate self-reactive lymphocytes; infectious microbes produce antigens that are similar to self-antigen Sunlight (UV radiation) 10  NURS 7053 Advanced Pathophysiology I for DNP Students Alterations in Immune Function - Class Notes Systemic Lupus Erythematosus Autoimmune disease that affects the skin, joints, kidneys, heart, liver and other tissues Epidemiology Etiology – genetic susceptibility with environmental trigger(s) Pathophysiology Clinical Consequences – associated with vessel injury and inflammation Diagnosis 11