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Transcript
Week Chapter Alterations in Immune Function Excessive Immune Responses Immune system Defends body against invasion or infection by antigens Patrols for and destroys infected, abnormal or damaged cells Autoimmune and/or hypersensitivity System is over or hyperfunctioning Primarygenetic Secondaryacquired Disorders are either . Excessive immune response . Deficit immune responses Excessive Immune Responses Cont. Effect of functional increase in immune system activity involves multiple, interacting immune cells Autoimmunity Immune system attacks own tissues Describes causes of abnormal excessive immune responses toward own tissues loss of self tolerance Involves several genetic and environmental factors Describes the mechanism of injury May or may not involve autoimmunity Hypersensitivity Autoimmunity Cont. Genetic Factors Different cytokine cycles can be associated with autoimmunity MHC genes HLA Some associated with certain autoimmune disorders Some MHC phenotypes appear to increase risk of autoimmune disorders Gender an issue females at higher risk of autoimmune disorders Autoimmunity Cont. Environmental triggers Chronic or multiple viral or bacterial infections Environmental and/or occupational stress, esp. in genetically susceptible individuals Pharmacotherapies Individualized immunosuppressive therapy most often used Corticosteroids and cytotoxins Therapeutic plasmapheresis Hypersensitivity Normal immune response that is either Inappropriately triggered Excessive Produces undesirable effects on the body Basic mechanism Hypersensitivity types I, II, and III Hypersensitivity type IV Mediated by T cells Specific antigenantibody reaction or specific antigenlymphocyte interaction Mediated by antibodies produced by B lymphocytes TYPES OF HYPERSENSITIVITY The four types of hypersensitivity are . Type I Hypersensitivity IgE mediated . Type II Hypersensitivity Antibody mediated . Type III Hypersensitivity immune complex . Type IV Hypersensitivity cell mediated The first three are mediated by antibody, the fourth by T cells. TYPES OF HYPERSENSITIVITY Immediate Most immediate within minutes of exposure Anaphylaxis systemic shellfish, antibiotics airway obstruction Shock, death Delayed Memory T Cell mediated response Skin irritant poison ivy or oak adhesive tape sunburn PPD response Graph rejection Allergy Mast cell degranulation Asthma, eczema, uritcaria Vasodilation gt vascular permeability Inflammation clinical manifestation Type I Hypersensitivity Etiology Often is a strong genetic or hereditary linkage regarding IgE response to antigens i.e. atopic Also are nonatopic forms Involves ability to respond to antigen and to produce an IgE antibody response High IgE levels although lower levels do not exclude type I Characterized by increased mast cell degranulation Triggered by environmental allergens Type I Hypersensitivity Cont. Pathogenesis Also known as immediate hypersensitivity Reaction occurs minutes after exposure to antigen First exposure to antigen triggers B cell production of IgE IgE binds to Fc receptors on mast cells Subsequent exposure antigen binds to IgE and causes crosslinking of IgEFc receptors Increased intracellular calcium results in immediate, massive, local mast cell degranulation of proinflammatory mediators Released mediators cause inflammatory response Histamine, superoxide, PGs, leukotrienes, bradykinin, interleukins Follows stimulation by cytokines from TH cell activation by allergen MOLECULE EFFECTS PRIMARY MEDIATORS HISTAMINE VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION SEROTONIN ECFA NCFA PROTEASES EOSINOPHIL CHEMOTAXIS NEUTROPHIL CHEMOTAXIS MUCUS SECRETION, CONNECTIVE TISSUE DEGRADATION SECONDARY MEDIATORS LEUKOTRIENES PROSTAGLANDINS BRADYKININ CYTOKINES VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION AND PLATELET ACTIVATION VASCULAR PERMEABILITY, SMOOTH MUSCLE CONTRACTION NUMEROUS EFFECTS INC. ACTIVATION OF VASCULAR ENDOTHELIUM, EOSINOPHIL RECRUITMENT AND ACTIVATION Pathogenic mechanisms Three classes of mediators derived from mast cells Preformed mediators stored in granules histamine Newly sensitized mediators leukotrienes, prostaglandins, platelets activating factor Cytokines produced by activated mast cells, basophils e.g. TNF, IL, IL, IL IL, chemokines These mediators cause smooth muscle contraction, mucous secretion and bronchial spasm, vasodilatation, vascular permeability and edema Elsevier items and derived items , by Saunders, an imprint of Elsevier Inc. Type I Hypersensitivity Cont. Clinical manifestations Mild Hives Seasonal Eczema allergic rhinitis More problematic symptoms Throat constriction edema amp bronchoconstr Localized edema Wheezing Tachycardia to increase blood flow Anaphylaxis Most lifethreatening reaction occurs in very small number of highly allergic individuals Type I Hypersensitivity Manifestations . Allergic Rhinitis activation of mast cells within the nasal mucosa results in sneezing, watery nasal secretions, and pruritus itching inflammation often spreads to the mucosa of the sinuses and the conjuctiva sinusitis and conjuctivitis i.e. red, itchy, watery eyes Pooled secretions can often result in opportunist infections Histamine receptor blockers i.e. Antihistamines, H antagonists often provide symptomatic relief . Atopic Asthma Sensitized mast cells in the respiratory tract, or from the nasal mucosa that have pooled in the airways can produce extrinsic asthma mucous is secreted into the airways inflammatory chemical mediators cause bronchoconstriction ultimately obstruction, air trapping poor blood oxygenation amp hypoxemia Type I Hypersensitivity Manifestations Contd . Food Allergies food allergens activate mast cells in the GI tract the resulting inflammation nausea, vomiting, and diarrhea food allergies may also cause systemic effects e.g. hives or anaphylaxis allergens milk, eggs, peanuts, tree nuts, shellfish, fish . Atopic Dermatitis Eczema eczema is a rash associated with a type I hypersensitivity often caused by foods, irritating fabrics, or a dry environment often is a family history lesions often dry, scaly and itchy treatment hydration, baking soda or oatmeals soaks, corticosteroids Figure Porth TYPE I HYPERSENSITIVITY ANAPHYLAXIS Anaphylaxis is a systemic type I hypersensitivity Allergens introduced by injection, insect sting or absorption across epithelial surface of the skin or GI tract chemical mediators from mast cells enter general circulation Manifestations Skin erythema red with warm or burning sensation Itching and hives urticaria Apprehension, tachycardia and tachypnea Edema around the eyes, lips, tongue, hands, feet In the lungs, mucus, edema and bronchconstriction obstruct the airways Triggers wheezing, chest tightness, dyspnea Leads to hypoxemia Systemic vasodilation and increased capillary permeability result in a rapid decrease in blood pressure dizziness, LOC When the blood pressure is insufficient to perfuse the tissue, this condition is called anaphylactic shock organs start to fail TYPE I HYPERSENSITIVITY ANAPHYLAXIS CONTD Treatment injected epinephrine increases the HR and myocardial contractility, causes vasoconstriction and bronchodilation histamine receptor blockers Type I Hypersensitivity Cont. Pharmacologic management Antihistamines B etaadrenergics epinephrine Corticosteroids Anticholinergics IgE therapy Epinephrine adrenergic agent given subQ or IV during acute allergic reactions Type II Hypersensitivity Also known as tissuespecific, cytotoxic, or cytolytic hypersensitivity Antibodies attack normal antigens on surface of specific cells or tissues Often immediate reaction, but some occur over time mins Cell lysis may be mediated by Activated complement fragments membrane attack complex Phagocytic cells that are attracted to target cells by attached antibodies Type II Hypersensitivity TYPE II HYPERSENSITIVITY CONT. Transfusion reaction Individual receives blood from someone with a different blood group type Preformed Abs in recipients blood attach to donated RBCs Hemolytic disease of the newborn Occurs during pregnancy Rh negative mother is sensitized to her fetuss Rhpositive red cell group antigens Mothers exposure occurs when fetal and maternal blood are mixed Type II Hypersensitivity Cont. Myasthenia gravis Graves disease Lymphocytic thyroiditis Hashimoto thyroditis Hyperacute graft rejection Transplanted donor tissue has an antigen to which recipient has preformed antibodies Rarely occurs Tissue and blood typing prevent most cases Type III Hypersensitivity Also known as immune complex reaction Immune and phagocytic systems fail to effectively remove antigenantibody immune complexes not tissue specific Deposit of antigenantibody complexes in tissues results in Activation of complement Subsequent tissue inflammation Destruction CAUSE OF TYPE HYPERSENSITIVITY NORMALLY SOLUBLE ANTIGENANTIBODY COMPLEX FORMATION REMOVED BY MACROPHAGES IN SPLEEN AND LIVER CAUSE OF TYPE HYPERSENSITIVITY ABNORMALLY INCREASED SOLUBLE ANTIGENANTIBODY COMPLEX FORMATION NOT ALL REMOVED BY MACROPHAGES IN SPLEEN AND LIVER DEPOSITION OF COMPLEXES VIA BLOOD VESSELS MECHANISM OF ACTION STEP Large quantities of soluble antigenantibody complexes form in the blood and are not completely removed by macrophages. MECHANISM OF ACTION STEP These antigenantibody complexes lodge in the blood vessels between the endothelial cells and the basement membrane. MECHANISM OF ACTION STEP These antigenantibody complexes activate the classical complement pathway leading to vasodilation MECHANISM OF ACTION STEP The complement proteins and antigenantibody complexes attract leukocytes to the area. MECHANISM OF ACTION STEP The leukocytes discharge their killing agents and promote massive inflammation. This can lead to tissue death and hemorrhage. TYPE III HYPERSENSITIVITY CONT. Immune complex glomerulonephritis Inflammatory renal disorder Typically occurs days to weeks after Streptococcus infection Autoimmune attack own cell Occurs more frequently in women, ages Etiology unknown genetic or hormonerelated Individual develops antibodies against nuclear antigens such as DNA and RNA antinuclear antibodies, ANAs Systemic lupus erythematosus Immune complexes deposit in connective tissue throughout the body Causes inflammation and tissue destruction Vasuculitis in many organs ischemia and tissue destruction TYPE III HYPERSENSITIVITY CONT. Systemic lupus erythematosus Variety of signs and symptoms Diagnosis may be difficult Follow a pattern of exacerbations and remissions Ranges from mild episodes to fatal Rash Alopecia Arthritis Fever, anorexia, malaise, increased ESR chronic inflammation Lungs, heart and GI tract also affected TYPE IV HYPERSENSITIVITY Delayed hypersensitivity Tissue damage resulting from a delayed cellular reaction to an antigen No primary antibody involvement Principal mediators Lymphocytes Lymphocytes Macrophages Principal effector cells Sensitized T cells react with altered or foreign cells and initiate inflammation CAUSE OF TYPE HYPERSENSITIVITY CAUSED BY TCELLS . THELPER CELLS BY SECRETION OF CYTOKINES . MAINLY BY CYTOTOXIC TCELLS BY DIRECT DAMAGE MECHANISM OF ACTION TH CELLS INDUCED STEP ANTIGEN ENTERS THE BODY ENGULFED BY MACROPHAGES PRESENTED TO TH CELLS TH CELLS BECOMES ACTIVATED AND INCREASED IN NUMBER MECHANISM OF ACTION TH CELLS INDUCED STEP SECOND EXPOSURE ENGULFED BY MACROPHAGES PRESENTED TO TH CELLS TH CELLS RELEASE CYTOKINES MECHANISM OF ACTION TH CELLS INDUCED STEP TH or TD CELLS RELEASE CYTOKINES TH CELLS RELEASE IL AND IL ATTRACTION FOR MORE MACROPHAGES AT THE SITE OF ATTACK PROMOTE EXTRACELLULAR KILLING BY EOSINOPHILS MORE INFLAMMATION SKIN LESIONS TISSUE DAMAGE MECHANISM OF ACTION CTOTOXIC T CELLS INDUCED STEP ANTIGEN BINDS TO NORMAL CELL EPITOPE PRESENTED WITH MHC CTL ATTACHED BY TCR/CD ACTIVATION OF TCELL MECHANISM OF ACTION CTOTOXIC T CELLS INDUCED STEP ACTIVATION OF CYTOTOXIC TCELL RELEASE OF . POREFORMING PROTEINS CALLED PERFORINS . PROTEOLYTIC ENZYMES CALLED GRANZYMES . CHEMOKINES MECHANISM OF ACTION CTOTOXIC T CELLS INDUCED STEP PERFORINS FORM PORES GRANZYMES PASS THROUGH PORES ACTIVATE ENZYMES OF CELLS APOPTOSIS MECHANISM OF ACTION CTOTOXIC T CELLS INDUCED Type IV Hypersensitivity Cont. Contact hypersensitivity Most familiar type Epidermal phenomenon Slow reaction hapten very small, incomplete must combine with endogenous carrier protein to become antigenic E.g. latex, cosmetics, dyes, adhesives Tuberculintype hypersensitivity Individual previously infected by tuberculosis is exposed to tuberculin antigen in a tuberculin test Rejection of Transplanted Tissue Recipients immune system damages donated tissue with incompatible MHC HLA profile Rejection can be hyperacute or acute Type II hypersensitivity or chronic Type IV Immunosuppressive drugs delay rejection but leave client susceptible to infection Type IV Hypersensitivity Cont. Mechanisms of Hypersensitivity Elsevier items and derived items , by Saunders, an imprint of Elsevier Inc. Deficient Immune Responses Result from Functional decrease in one or more components of immune system Diseasecausing genotypes Secondary/acquired dysfunction Can affect Lymphocytes Antibodies Phagocytes Complement proteins Primary Immunodeficiency Disorders May be from congenital, genetic, or acquired defects that directly affect immune cell function First clinical indicators signs and symptoms of infection Most cause moderate immune impairment that may not be diagnosed Severe congenital immunodeficiency disorders less common Suspected with severe recurrent, unusual, or unmanageable infections BCELL AND TCELL COMBINED DISORDERS Severe combined immunodeficiency disorders SCID Result from embryonic defects Characterized by severe immune system dysfunction and a variety of clinical features Most severe form reticular dysgenesis Also known as thymic hypoplasia Associated with total or partial loss of thymus gland function Often associated with other congenital problems DiGeorge syndrome Secondary Immunodeficiency Disorders Problems in neuroendocrine and immune system interaction Excessive neuroendocrine response to stress increased corticosteroid production increases susceptibility to infection Immune function impaired as a result of other nonimmune system disorders that secondarily suppress immune function Poor nutrition proteins Stress Drugs