Disorders of the Immune Response PDF

Disorders of the Immune Response Dr. Jean Marie Osborne Disorders of the Immune Response When working correctly: A complex multidimensional system designed to protect the host against invasion by foreign substances, microorganisms, and toxins. Protects against the proliferation o...

Disorders of the Immune Response Dr. Jean Marie Osborne Disorders of the Immune Response When working correctly: A complex multidimensional system designed to protect the host against invasion by foreign substances, microorganisms, and toxins. Protects against the proliferation of neoplastic cells Plays a key role in the process of inflammation and wound healing Unfortunately, the immune system can become inefficient or hyperactive, causing the development of debilitating and/or life- threatening diseases. Immunodeficiency disorders Allergic or hypersensitivity reactions Transplant rejection Autoimmune disorders Immune System Made up of two distinct but interrelated systems Innate immune system: body's first line defense against infection Adaptive immune system: exhibits "memory" for invading organisms and toxic substances; develops more slowly but with great specificity. Humoral (B-cell mediated) Cell mediated (T-cell mediated) Immunodeficiency Disorders An abnormality in one or more parts of the immune system that results in an increased susceptibility to disease states normally eliminated by a properly functioning immune response. Primary Secondary Immunodeficiency Disorders Humoral (B-Cell) Immunodeficiencies T-Cell Immunodeficiency Combined T-Cell and B-Cell immunodeficiency Complement System Disorders Phagocytosis disorders Stem Cell Transplantation For most of the primary immunodeficiency disorder, stem cell transplantation from allogeneic human leukocyte antigen (HLA) -compatible sibling donors is the treatment of choice because it results in effective immunologic reconstitution and improved survival in ~90% of people. Hypersensitivity Disorders Activation of the immune system normally results in the mobilization and coordination of T-cell and B-cell activity in order to protect the body from invading microorganisms and toxic substances. Unfortunately, this same system is capable of causing serious damage when it does not function as intended. Hypersensitivity is defined as an abnormal and excessive response of the activated immune system that causes injury and damage to the host tissues. The stages are based on the progression and intensity of the host's symptoms, which reflect the host's response to infection over time. Type I, Immediate Hypersensitivity Disorders IgE-mediated reactions that develop rapidly upon exposure to an antigen. Allergens Two types of cells play a key role in the development of a type I hypersensitivity reaction: Type 2 helper T cells Mast cells or basophils Most Type I hypersensitivity reactions develop in two distinct and well defined phases: Primary or initial phase response characterized by vasodilation, vascular leakage, and smooth muscle contraction Secondary (late phase) response characterized by more intense infiltration of tissues with eosinophils and other acute and chronic inflammatory cells as well as tissue destruction in the form of epithelial cell damage Anaphylactic (Systemic) Reactions A catastrophic, systemic, life-threatening IgE-mediated hypersensitivity reaction associated with the widespread release of histamine into the systemic circulation that produces massive vasodilation, hypotension, arterial hypoxia, and airway edema. Clinical Manifestation: occur along a continuum in severity and can be graded on a scale of I to IV. Preloaded epinephrine syringes and education of their use. Atopic (Local) Reactions Local hypersensitivity reactions usually occur when the offending allergen is confined to a particular site of exposure. Most commonly manifest as urticarial rash (hives), allergic rhinitis, atopic dermatitis, bronchial asthma. People with atopic allergic conditions tend to have high total serum and allergen specific levels of IgE as well as increased numbers of eosinophils, basophils, and mast cells. Allergic Rhinitis Common hypersensitivity disorder of the upper respiratory tract. Symptoms include rhinorrhea, nasal obstruction, sneezing, nasal itching, and watery eyes. Severe attacks may be accompanied by systemic malaise, fatigue, headache, and muscle soreness from sneezing. Fever is absent. Clinical manifestations: Perennial rhinitis Seasonal allergic rhinitis Household allergens Occupational exposure Food Allergies Common in western countries, manifesting with life- threatening consequences. Any food is capable of inducing a hypersensitivity reaction in susceptible people and occurs when specific food allergens comes in contact with IgE antibody present in the intestinal mucosa. Peanuts Tree nuts Shellfish Anaphylactic reactions to food allergens are common. Type II, Antibody Mediated Disorders Hypersensitivity reactions are mediated by Igg or IgM antibodies directed against target antigens on specific host cell surfaces or tissues. The antigen may be either intrinsic (part of the host cell) or extrinsic (incorporated into the cell surface upon exposure to a foreign substance or infectious agent. Type III, Immune Complex-Mediated Disorder Caused by formation of antigen-antibody immune complexes in the bloodstream, which are later deposited in vascular epithelium or extravascular tissues. Clinical manifestations: Type III reactions are responsible for the vasculitis seen in many autoimmune disease including SLE and acute glomerulonephritis. Type IV, Cell Mediated Hypersensitivity Disorders Cell mediated and delayed, rather than antibody- mediated and immediate immune response. Composed of a spectrum of disorders that range from mild to severe in clinical presentation. Allergic Contact Dermatitis A type of IV hypersensitivity reaction associated with the activation of T 1H and T helper lymphocytes. The inflammatory response takes place in two phases: Sensitization Elicitation Usually confined to sites on the skin that have come in direct contact with the hapten. Clinical manifestations: erythematous, papular, and vesicular rash that is associated with intense pruritis and weeping; swelling, warmth with exudate formation and crusting. Transplantation Immunopathology Graft: Allograft: Autograft: Donor: Host (recipient): Autologous: Syngeneic: Allogenic: Transplantation Rejection Involves a complex but coordinated cell-mediated and antibody-mediated immune response. Three classic forms of rejection exist: Cell-mediated Antibody mediated Chronic rejection Graft vs Host Disease A major complication that most frequently occurs after allogeneic stem cell transplantation. There are three fundamental requirements for the development of GVHD: The graft must contain cells that are immunologically competent The recipient's cells must express antigens that are not present on donor cells The recipient must be immunologically compromised and incapable of mounting an effective immune response. GVHD can be acute or chronic and usually develops within the first 100 days of transplantation.