Lecture Slides Alterations of Immune Function PDF

Alterations of Immune Function NURS 7053 Diane Chapman, DNP, APRN, FNP-C, CNE Learning Outcomes Analyze the relationship between normal immune responses and altered immunity. Differentiate between Type I, II, III, and IV hypersensitivity reactions, explaining their key characteristics and m...

Alterations of Immune Function NURS 7053 Diane Chapman, DNP, APRN, FNP-C, CNE Learning Outcomes Analyze the relationship between normal immune responses and altered immunity. Differentiate between Type I, II, III, and IV hypersensitivity reactions, explaining their key characteristics and mechanisms. Explain the underlying processes involved in the development of autoimmunity. Evaluate the pathophysiology of systemic lupus erythematosus as an example of autoimmune disease. Alterations of Immune Function Review Hypersensitivity Reactions Overview Hypersensitivity Reactions Type I Hypersensitivity Reactions Characteristics Type I reactions are characterized by the production of antigen-specific IgE after exposure to an antigen Most Type I reactions in response to environmental antigens (i.e, allergens) Hypersensitivity Reactions Type I Hypersensitivity Reactions Common Allergens Hypersensitivity Reactions Type I Hypersensitivity Reactions Genetic Predisposition and Atopy Over ten candidates for polymorphic genes have been identified – 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. Hypersensitvity Reactions Type I Hypersensitivity Reactions Pathophysiology Dendritic cells present allergen to Th2 cells Hypersensitivity Reactions Type I Hypersensitivity Reactions Pathophysiology Th2 cell produces cytokines (IL-4, IL- 5) which stimulate IgE–producing B cells Hypersensitivity Reactions Type I Hypersensitivity Reactions Pathophysiology IgE binds to receptors on the mast cell’s plasma membrane which activates the mast cell Hypersensitivity Reactions Type I Hypersensitivity Reactions Pathophysiology Result is degranulation of histamine from the mast cell and the release newly formed mediators Hypersensitivity Reactions Type I Hypersensitivity Reactions Pathophysiology Eosinophils are also recruited by the release of cytokines from the Th2 & eosinophil chemotactic factor from the mast cell Hypersensitivity Reactions Type I Hypersensitivity Reactions Phases Early vs. Late Hypersensitivity Reactions Type I Hypersensitivity Reactions Clinical Consequences Allergic reactions (local response): Itching and urticaria (hives); rhinitis; conjunctivitis Hypersensitivity Reactions Type I Hypersensitivity Reactions Clinical Consequences Anaphylaxis (systemic response) Hypersensitivity Reactions One Minute Paper Take a minute to write down everything you can related type I hypersensitivity reactions Type II Hypersensitivity Reactions Overview Destruction of a target cell in the body through the action of antibody against an antigen on the cell’s plasma membrane Hypersensitivity Reactions Type II Hypersensitivity Reactions 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) Hypersensitivity Reactions Type II Hypersensitivity Reactions Pathophysiology Complement-mediated lysis Hypersensitivity Reactions Type II Hypersensitivity Reactions Pathophysiology Phagocytosis by macrophages Hypersensitivity Reactions Type II Hypersensitivity Reactions Pathophysiology Antibody-dependent cell-mediated cytotoxicity (ADCC) Hypersensitivity Reactions Type II Hypersensitivity Reactions Pathophysiology Inducing target cell malfunction From: Kumar et al., Pathologic Basis of Disease 8 th ed. (2010). Fig. 6-16, p. 202. Hypersensitivity Reactions One Minute Paper Take a minute to write down everything you can related type II hypersensitivity reactions Type III Hypersensitivity Reactions Overview Immune complex diseases Hypersensitivity Reactions Type III Hypersensitivity Reactions Common Antigens Viral, bacterial and parasitic antigen Pollens Vaccines Plasma/Serum Nuclear antigen Hypersensitivity Reactions Type III Hypersensitivity Reactions Pathophysiology Antigen-antibody complexes form in the circulation and are later deposited on endothelium of capillaries or in extravascular tissue Hypersensitivity Reactions Type III Hypersensitivity Reactions Pathophysiology Complement proteins are activated Hypersensitivity Reactions Type III Hypersensitivity Reactions Pathophysiology Neutrophils ingest the deposited antigen-antibody complex and cause tissue damage Hypersensitivity Reactions Type III Hypersensitivity Reactions Pathophysiology Summary From: Kumar et al., Pathologic Basis of Disease 8 th ed. (2010). Fig. 6-17, p. 204. Hypersensitivity Reactions Type III Hypersensitivity Reactions Common Target Tissues/Disease Examples Kidneys - Glomerulonephritis Streptococcal proteinase exotoxin B Immune complex deposition Strep pharyngitis infection Hypersensitivity Reactions Type III Hypersensitivity Reactions Common Target Tissues/Disease Examples Blood vessels – causes vasculitis Hypersensitivity Reactions Type III Hypersensitivity Reactions Common Target Tissues/Disease Examples 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. Hypersensitivity Reactions Type III Hypersensitivity Reactions Common Target Tissues/Disease Examples Raynaud disease: Temperature-dependent immune complexes (cryoglobulins) precipitate at below-normal body temperatures http://webrheum.bham.ac.uk/professional/slides/lec3c_part1/default/images/full/3c4.jpg Hypersensitivity Reactions Type III Hypersensitivity Reactions Common Target Tissues/Disease Examples Systemic lupus erythematosus: Immune reaction to nuclear antigen Hypersensitivity Reactions One Minute Paper Take a minute to write down everything you can related type III hypersensitivity reactions Type IV Hypersensitivity Reactions Overview Delayed hypersensitivity reaction mediated by sensitized T-lymphocytes (Tc or Th) Hypersensitivity Reactions Type IV Hypersensitivity Reaction Examples Tissue graft rejection Contact dermatitis (poison ivy, metals) Tuberculin reaction Other diseases Hypersensitivity Reactions Type IV Hypersensitivity Reactions Pathophysiology Allergen binds to proteins on membranes of epidermal cells From: Kumar et al., Pathologic Basis of Disease 8 th ed. (2010). Fig. 6-19, p. 206. Hypersensitivity Reactions Type IV Hypersensitivity Reactions Pathophysiology Infiltration of site by T lymphocytes and macrophages From: Kumar et al., Pathologic Basis of Disease 8 th ed. (2010). Fig. 6-19, p. 206. Hypersensitivity Reactions Type IV Hypersensitivity Reactions Pathophysiology T lymphocytes bind to target cells and release enzymes that damage/destroy target cell From: Kumar et al., Pathologic Basis of Disease 8 th ed. (2010). Fig. 6-19, p. 206. Manifestations of hypersensitivity delayed by 24-72 hours Hypersensitivity Reactions Type IV Hypersensitivity Reactions Example – Poison Ivy Hypersensitivity Reactions One Minute Paper Take a minute to write down everything you can related type IV hypersensitivity reactions  Collaborative Mind Mapping https://mm.tt/app/map/3409320473?t=ioLUMBFhHr Autoimmunity Overview Altered immunologic reaction that results in a B and T lymphocyte response against the body’s own cells Autoimmunity Immunological Tolerance Immunocompetent B and T lymphocytes with the capability of recognizing all antigen (including self-antigen) are produced during the process of generating clonal diversity. Autoimmunity Immunological Tolerance Mechanisms exist that prevent the immune system from mounting an immune response to self-antigen (and commensal microbes) – a process known as immunological tolerance. Autoimmunity 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’ Autoimmunity Immunological Tolerance Generation of Central 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) Autoimmunity Immunological Tolerance Generation of Central Tolerance Central B lymphocyte tolerance Immunocompetent (immature) B lymphocytes migrate to 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 Autoimmunity Immunological Tolerance Generation of Central Tolerance From: Abbas, Litchman & Pillai (2016). Basic Immunology: Functions and Disorders of the Immune System, 5th Ed. Autoimmunity Immunological Tolerance Generation of Peripheral Tolerance Generation of central tolerance is imperfect Reduction in CD4 Th cell population reduces the B and T lymphocyte response Autoimmunity Immunological Tolerance Generation of Peripheral Tolerance 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 Autoimmunity Immunological Tolerance Generation of Peripheral Tolerance 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 Autoimmunity Immunological Tolerance Generation of Peripheral Tolerance From: Abbas, Litchman & Pillai (2016). Basic Immunology: Functions and Disorders of the Immune System, 5th Ed. Autoimmunity Immunological Tolerance 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 and enhance the immune response to these microbes Autoimmunity Muddiest Point Autoimmune Disease An immune response against self-antigen affecting 1 in 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 MCH (i.e., HLA) genes Autoimmunity Autoimmune Disease Environmental triggers Infections (infection prodromes): infections stimulate antigen presenting cells (APCs) that activate self-reactive lymphocytes; infectious microbes product antigen that are similar to self-antigen Sunlight (UV radiation) Autoimmunity SLE Autoimmune disease that affects the skin, joints, kidneys, heart, liver and other tissues Autoimmunity Jigsaw Activity Systemic Lupus Erythematosus Assignments Group 1: Epidemiology of Systemic Lupus Erythematosus Explore the epidemiology of SLE, focusing on its incidence and prevalence worldwide. Discuss how the disease distribution varies by gender, the typical age of onset, and any significant ethnic or racial disparities. Include recent trends or changes in these demographics. Group 2: Etiology of Systemic Lupus Erythematosus Delve into the potential causes and etiologies of SLE. Discuss the role of genetic predispositions and the influence of envir onmental triggers. Consider how these factors may interact to initiate the disease process. Group 3: Pathophysiology of Systemic Lupus Erythematosus Describe the underlying pathophysiological mechanisms of SLE. Focus on the specific immune responses involved, particularly t he hypersensitivity reactions that play a central role in the disease’s progression. Highlight any relevant cellular or molecula r processes. Group 4: Clinical Manifestations and Consequences of Systemic Lupus Erythematosus Identify and describe the clinical manifestations of SLE. Discuss the wide range of symptoms and organ systems that can be affected. Explore the potential long-term consequences of the disease on a patient’s health and quality of life. Group 5: Diagnostic Criteria for Systemic Lupus Erythematosus Explain the criteria used to diagnose SLE, emphasizing the most current guidelines. Discuss the challenges associated with diagnosis, including the variability of symptoms and the overlap with other autoimmune diseases. Highlight any key laboratory tests or c linical assessments used in the diagnostic process. Autoimmunity SLE Epidemiology Autoimmunity SLE Etiology Autoimmunity SLE Pathophysiology Autoimmunity SLE Clinical Manifestations Autoimmunity SLE Autoimmunity SLE Diagnosis Autoimmunity