CS 4.1 Disorders of Immune Response 2024 PDF

CS: 4.1 Disorders of Immune Response REFERENCE: PORTH’S PATHOPHYSIOLOGY, 9TH EDITION, PG.NO:341-352  Objectives ► Describe briefly the immune response in the development of type I, II, III & IV hypersensitivity reactions. ► Discuss the pathogenesis of the following common hypersensitiv...

CS: 4.1 Disorders of Immune Response REFERENCE: PORTH’S PATHOPHYSIOLOGY, 9TH EDITION, PG.NO:341-352  Objectives ► Describe briefly the immune response in the development of type I, II, III & IV hypersensitivity reactions. ► Discuss the pathogenesis of the following common hypersensitivity reactions: ❖ Allergic Rhinitis ❖ Food Allergy ❖ Contact Dermatitis ► Identify the importance for matching of Human Leukocyte Antigens (HLA) types in organ transplantation. ► Describe the phases of acute inflammation  Hypersensitivity ► Abnormal & excessive response of the activated immune system that cause injury & damage to host tissue. Four types: ❖ Type I: IgE-mediated disorders. ❖ Type II: antibody-mediated disorders. ❖ Type III: Immune complex mediated disorder. ❖ Type IV: T cell-mediated disorders. ► They differ in terms of: component of immune response, onset of symptoms, & mechanism of injury.  Type I hypersensitivity Immune Response ► Allergic hypersensitivity. ► It dependent upon IgE-mediated activation of mast cells & basophils. ► Allergen mediated response. ► Allergen (dust, animal hair) interact with antibodies of B cell which start to produce plasma cells. ► Plasma cells start to produce IgE. Which start to interact with mast cells surface. ► Mast cells contain chemicals to react such as; histamine, bradykinine, which react in our smooth muscles, blood vessels, mucus membrane or glands and cause anaphylactic response which cause airway constriction for example and vasodilation..  Type I Hypersensitivity 6 Entry of Allergen (Pollen inhalation) Binds to IgE antibodies attached to mast cells or basophils (a type of white blood cell). Triggers / stimulate the mast cells to release chemicals like histamine. Inflammation, bronchospasm, itchiness, and other allergic responses.  Type II Hypersensitivity ► Antibody mediated or cytotoxic hypersensitivity (binding of IgG or IgM to tissue-specific antigen). ► IgG or IgM antibodies interact with antigen. ► Antigen can be intrinsic or extrinsic ► Clinical manifestation determined by tissue that express target antigen. ► Example; autoimmune (Myasthenia Gravis), thrombocytopenia & hemolytic anemia, Graves disease  Type II Hypersensitivity There are 4 general mechanisms by which type II hypersensitivity reaction takes place, however initiated by binding of IgG or IgM antibody to tissue-specific antigen ► Complement activated cell destruction ► Antibody dependent cell cytotoxicity ► Complement and antibody mediated inflammation ► Antibody mediated cellular dysfunction  Type II OR cytotoxic Hypersensitivity 10 Example Entry of Antigen (Incompatible blood) Formation of IgG or IgM antibodies against the foreign Symptoms blood group antigens Fever Chills Back pain Shock Antibodies bind to the transfused RBCs with foreign antigens. Destruction of the transfused RBCs occurs Activation of the through Complement-mediated lysis complement system (bursting of the cells) Phagocytosis by macrophages.  Type III Hypersensitivity ► Immune Complex (antigens attached to antibodies) Mediated Hypersensitivity. ► Formation of Antigen-antibody immune complex in the blood stream. ► Deposit in vascular epithelium or extravascular tissues. ► Activate complement system & induce massive inflammatory response. ► It involves complement system which trigger the activity of either activation of neutrophil or activation of mast cells which release chemical cause hypersensitivity of the tissue. ► Example; rheumatoid arthritis, SLE, & acute glomerulonephritis. Type III Hypersensitivity  Rheumatoid Arthritis: Type III Hypersensitivity 13 Example Immune system mistakenly Antigen Exposure identifies components of the synovial membrane as foreign antigens Formation of Autoantibodies (rheumatoid factor and protein antibodies) Immune Complex Self-Antigen Formation Autoantibody Reaction Symptoms Deposition in Tissue Joint inflammation Joint Pain Damage  Type IV Hypersensitivity ► Known as Cell mediated & Delayed Hypersensitivity; require incubation time to develop. ► Cell-mediated immune response with sensitized T lymphocytes cause cell & tissue injury. ► T cells secrete cytokines which activate macrophages & cytotoxic T cell. ► Examples: contact dermatitis, type 1 DM.  Type IV Hypersensitivity...Contact dermatitis 16 Example Antigen Exposure Skin exposure to allergen ( henna dye/ Jewelry) Binds to skin protein & Activation of T-Cells Delayed Immune Sensitized T-cells Response release cytokines Redness Entry of macrophages Itching to the site…. Swelling Inflammation Blistering of the skin Types of Hypersensitivity Disorders Pathogenesis of Allergic Rhinitis  Pathogenesis of Allergic Rhinitis ► Allergic rhinitis is a common hypersensitivity disorder of the upper respiratory tract. ► Type 1 allergic reaction –IgE. ► When aeroallergens are inhaled, they are deposited mainly on the nasal mucosa where they are presented to T cells by APCs (antigen-presenting cells). ► In the presence of cellular cytokines, B-cell class switching occurs, resulting in an increase in IgE production. ► Once the allergen–IgE complex is formed, infiltration of the nasal mucosa by T2H cells, mast cells, basophils, eosinophils, and Langerhans cells takes place, inducing a full cell-mediated immune response ► Symptoms include rhinorrhea (runny nose), nasal obstruction, sneezing, nasal itching, and watery eyes (conjunctivitis).  Allergic Rhinitis ► Severe attacks may be accompanied by systemic malaise, fatigue, headache, and muscle soreness from sneezing. ► No Fever. ► Typical allergens include pollens from ragweed, grasses, trees, and weeds; fungal spores; house dust mites; animal dander; and feathers. ► How to diagnose: 1. Clinical presentation 2. Skin prick test 3. Presence of serum-specific IgE antibodies to aeroallergens.  pathogenesis of food allergies ► Most commonly implicated foods include peanuts, tree nuts, and shellfish, milk in kids. ► People with asthma, adolescents, and those with a personal or family history of food allergy are at risk for severe reaction. ► Cooking process ► Type I allergic reaction. Pathogenesis of the Food Allergy ► The allergic reaction is activated when food antigen comes in contact with IgE in the mucous membrane ► Stimulate local and systematic cytokines and histamine leading to occurrence of food allergy symptoms  Food Allergy: Symptoms ► Primary symptoms are seen in the skin, gastrointestinal tract, and respiratory system. ► Acute reactions (hives and anaphylaxis) and chronic reactions (asthma, atopic dermatitis, and gastrointestinal disorders). ► Adults: cardiovascular collapse. ► Kids: abdominal pain, hives, allergic rhinitis, conjunctivitis, and facial flushing.  How to Diagnose Food Allergies ► Diagnosis of food allergies is multifaceted and relies upon a careful food history and provocative diet testing. ► Allergen-specific serum IgE levels if food test is a risk. ► Treatment: EpiPen Pathogenesis of Contact Dermatitis  Pathogenesis of Contact Dermatitis ► Type IV hypersensitivity reaction associated with the activation of T1H and T helper (17) lymphocytes. ► It is usually confined to sites on the skin that have come in direct contact with a hapten (e.g., cosmetics, hair dyes, metals, topical drugs, plant oils).  Contact Dermatitis Sensitization phase and Elicitation phase: 1. Haptens are captured by dendritic cells, 2. Migrate to regional lymph nodes and stimulate T cell production. 3. Re exposure to the specific hapten results in rapid recruitment and activation of memory specific T cells and release of cytokines and other elements. 4. Examples: poison ivy antigens Pathogenesis of Contact Dermatitis  Symptoms of Contact Dermatitis ► Erythematous, papular, and vesicular rash that is associated with intense pruritus and weeping. ► Swollen and warm, with exudate formation and crusting. ► Symptoms usually appear approximately 12 to 24 hours after exposure. ► Diagnosis: skin assessment; include characteristics & distribution of the rashes. ► Treatment: removal of offending agents follow by application of topical medication. Systematic corticosteroids for severe reaction.  Acute inflammation, p.g 306-313 Acute inflammation is the immediate and early response to an injurious agent. The response, which serves to control and eliminate altered cells, microorganisms, and antigens. The primary function of inflammatory response is to limit the injurious effect of the pathologic agent and remove the injured tissue components, thereby allowing tissue repair to take place.  Causes of Acute inflammation Infections Immune reactions Blunt and penetrating trauma Physical or chemical agents (e.g., burns, frostbite, irradiation, caustic chemicals) Tissue necrosis from any cause. Phases of Acute Inflammation Phases of Acute Inflammation Vascular phase, which leads to an increase in blood flow and changes in the small blood vessels of the microcirculation. Begin with vasoconstriction & followed rapidly by vasodilation. Heat & Redness Increase vascular permeability which release proteins in EVS. Swelling & Pain. As fluids moves out of vessels, blood clotting occurs.  Cellular phase (endothelial cell changes), which leads to the migration of leukocytes from the circulation and their activation to eliminate the injurious agent. Adhesion Margination (leukocyte accumulation) Transmigration (leukocyte extend through the vessel wall & migrate into tissue space). Chemotaxis: direct migration of leukocyte to injured tissue.  Phases of Acute Inflammation (pg 312-313) ► Leukocyte Activation & Phagocytosis. ► At the site of injury, Phagocytosis will be triggered. ► Phagocytosis involves 3 steps: ✔ Recognition ✔ Engulfment ✔ Intracellular killing.  Summary: Acute Inflammation: Phases 36 Vascular Phase Cellular Phase Vasoconstriction (Initial) Leukocyte attraction ✔ Recognition Vasodilation ✔ Engulfment Increased Phagocytosis permeability ✔ Intracellular killing. Swelling/ edema The importance for matching of Human Leukocyte Antigens (HLA) types in organ transplantation  Transplantation ► Transplantation can be defined as the “process of taking cells, tissues, or organs, called a graft, from one person and placing them into another person where they take over the normal function of the tissues replaced”. ► For transplantation to be successful, it is essential for the host’s immune system to recognize the graft as “self” rather than “nonself.”  Human Leukocyte Antigens (HLAs) ► Human leukocyte antigens (HLAs) expressed on the surface of cells enable the lymphocytes to ignore the antigen. ► The likelihood of rejection varies indirectly with the degree of HLA similarity that exists between the donor and recipient. ► Matching donor’s HLA with host HLA is very key to avoid Graft/ tissue rejection  HLA ► The human immune system uses HLA’s uniqueness to distinguish self from nonself. ► HLA are responsible for the presentation of “foreign” (antigens) to the immune competent cells. ► T lymphocytes recognize foreign antigens only when it combines with HLA molecules. ► HLA mismatch is considered the main cause of alloreactive T-cell activation, which may followed by graft rejection in solid organ transplantation.  41 The End