Hypersensitivity Type II Lecture Notes PDF

Block 1.2 lectures 2024-2025 lecture Highlighter key Writer Reviewer...

Block 1.2 lectures 2024-2025 lecture Highlighter key Writer Reviewer Doctor explanation Abbreviation Key information Book >> >> Maryam Alyahya Ali Alkhars Student explaintion 221-222-223 notes References Deleted  College of Medicine Academic Year 2022-23. Title: Hypersensitivity 2 CRN No: Male: 15569, Female: 15581 Block: Block1.2 (Infection and Immunity) Subject/Discipline: Immunology Expert: Dr. Dr.SayedA.Quadri Block Coordinator: Dr.Sayed A.Quadri Learning Objectives Antibody mediated and immune complex diseases (other than IgE) Mechanisms, clinical syndromes and therapy  Type IV hypersensitivity reaction (delayed or T cell-mediated ) Mechanism, clinical syndromes and therapy  Principles of skin tests for the diagnosis of hypersensitivity reactions. Antibody-mediated diseases Type II hypersensitivity Occur if antibody (IgG, IgM) react with antigen on the cell surface “bo antigen” Type 2 is a cytotoxin or cytolytic reaction, type 3 is immune- complex mediated reaction. Both of them are IgG mediated , whether the antigen is a part of the cell membrane or circula “hapten” that Type III hypersensitivity attach to the cell membrane. The antibodies are m autoantibodies and less commonly against foreign “microbial” antigens  Consequences of Complement Activation: In type II, the antigen is present on the tissue —Release of inflammatory products (C3a, or blood cells. C5a), which attract immune cells and amplify the diagram here shows where the antigen is inflammation. present on the tissue, so any antibodies —Opsonization and phagocytosis: Normally, produced against these antigens will result in this helps remove antigens, but in this case, type 2 hypersensitivity reaction it’s not possible because the antigen is fixed in tissue. what are the situations that the antibodies —Membrane Attack Complex (MAC): May are produced against the antigen on the form, causing direct tissue damage. tissue? AUTOIMMUNITY. Frustrated Phagocytosis: Neutrophils bind to Mechanism: Antibodies bind to the antigens IgG antibodies via Fc receptors but cannot on tissue surfaces (shown here in the perform phagocytosis due to the fixed nature extracellular matrix). of the tissue antigen. This leads to complement activation, In frustration, neutrophils release granule primarily through the classical pathway, as contents, including: ROS, Proteolytic enzymes, antigen-antibody complexes are involved and other pro-inflammatory substances. This causes further tissue damage and inflammation. Type II Hypersensitivity: Tissue antigens Antibodiesspecific for tissue antigens deposit on tissues 1 IgG bind to neutrophil and macrophage Fc receptors and activate them 2 Complement system activation Induce inflammation 3 release ROS and lysosomal enzymes. Tissue damage  In another situation of Type II hypersensitivity, the antigen can be Type II Hypersensitivity: Blood cells present on red blood cells (RBCs) rather than on tissues. When antibodies are produced against these antigens, they bind to the RBCs, leading to their destruction. This results in a decreased number of RBCs, ultimately causing anemia ( autoimmune hemolytic anemia ) Antibodiesspecific for blood cells 1 bind to them Opsonizationof blood cells 2 Type III Hypersensitivity: Immune-complex mediated reaction In Type III hypersensitivity, soluble antigens form immune complexes that deposit on blood vessel walls, triggering complement activation, neutrophil recruitment, and the formation of the Membrane Attack Complex (MAC). This leads to inflammation, tissue damage, and vasculitis Antibodiesspecific for soluble antigens bind to them. 1 Immune complexes deposit in blood vessels (through which plasma is filtered at high pressure) 2 Complement activation, inflammation vasculitis 3 3  Type III hypersensitivity Immune complex mediated diseases First, soluble antigens will bind to antibodies forming immune complexes called the antigen-antibody complexes. When they are formed, they could be in different sizes: large, small and intermediate immune complexes most important one is the small complexes, large complexes can be easily identified by the phagocytic cells. Phagocytosis can be done and the large complexes can be easily removed from the blood circulation. Whereas the intermediate and the small can not be easily identified and can be larger in number / amount compared to large complexes, further they can escape the identification and as a result, the phagocytic cells going to be overwhelmed, they can not manage the situation. As a result, they get deposited in the basement membrane of blood vessels, particularly in areas with high blood flow, such as the kidneys and synovial joints, leading to glomerulonephritis and arthritis. DR mentioned this as an interesting piece of information, soluble antigens in the blood can come from two sources: Endogenous sources: such as in autoimmune diseases where the immune system attacks self-antigens. Exogenous sources: such as during infections, where foreign antigens are introduced by pathogens platelets aggregated and release vasoactive amines and form micro- thrombi lead to local ischemia Deleted  Immune complex-mediated diseases 1)Arthusreaction: local form due to repeated injections of the same antigen subcutaneously as diabetic receiving repeated insulin injections 2)Serum sickness: systemic form occurs after injection of relatively large doses of foreign serum. Appear 10 days after injection. Manifest by fever, urticarial, arthralgia, LN, ….. 3) Post-steptococcal glomerulonephritis 4)Autoimmune dis. : SLE 5)Certain infection: hepatitis B ….. polyarteritisnodosa Type IV Hypersensitivity: T-cell mediated reaction Type IV hypersensitivity reactions can be mediated by three types of T cells: Th1, Th17, and CD8+ T Th cells differentiate as Th1 cells lymphocytes (cytotoxic T cells). Among these, the Th1- 1 mediated reaction is the most common and significant in causing delayed hypersensitivity. It’s important to remember the functional subsets of T Th1 cells release IFN-γ helper cells: Th1, Th2, and Th17. These subsets are 2 classified based on their cytokine profiles, as each produces different cytokines that result in different functional effects. Macrophage activated. 3 Th1 cells produce IFN-gamma, which will activate macrophages. Activated macrophages enhance their ability to phagocytose by increasing the expression of Toll-like receptors (TLRs) and other innate immune receptors. They also increase their cytolytic activity by producing more reactive oxygen species (ROS) and lysosomal enzymes. Furthermore, macrophages upregulate MHC II 3 expression, improving their capacity for antigen presentation Type IV Hypersensitivity: delayed-type hypersensitivity (DTH) Occurs 24-48 hours after an individual previously exposed to a protein antigen is challenged with the antigen. Takes several hours for effector T-lymphocytes to home at the site of Th1-mediated reactions, as well as other delayed-type antigen respond by secreting cytokines hypersensitivity reactions, are called “delayed” because they typically appear 24-48 hours after antigen exposure. This Characterized by delay occurs because T cells need time to migrate to the site of antigen presence to initiate the immune response. 1.infiltrates of T cells and monocytes in tissues, edema and fibrin T cells migrate to the site of infection to produce the deposition caused by increased vascular permeability immune response, and their migration is guided by selectins (P-selectin, E-selectin, L-selectin) and chemokine receptors. in response to cytokines produced by CD4+ T cells When T cells are activated and differentiated, they undergo changes in receptor expression. They reduce CCR7 expression and increase S1P receptor expression, which is a 2.tissue damage induced by leukocyte products protein found in the blood that helps direct their movement to the site of infection. At the same time, chemokines released at the site of infection, such as C3a, C5a, and (macrophages) that are activated by the T cells. specific cytokines like TNF and IL-4, play a key role in recruiting T cells to the area. T cells migrate from blood vessels to the tissue through a process involving rolling, adhesion, and transmigration across the endothelium, ensuring they reach the site of infection to mediate the immune response. Deleted  Mechanism of Type IV hypersensitivity 1)Cytokine mediated inflammation: mainly by CD4+ T cells CD4+ T cells react and secretes cytokines that recruit and attract lymphocytes, activate macrophages and induce inflammation leading to tissue damage. T helper cells:TH1…….. IFN-gamma, TH17 ……recruit ofleucocytes Tissue damage is caused by products of activated macrophages as hydrolytic enzymes , O2 intermediates, nitric oxide and pro-inflammatory cytokines ( TNF, IL-1, IL-6) 2) T cell mediated killing of host cells: by cytotoxic CD8+ T cells Autoimmune diseases include both CD4 , CD8 T cells  The Th1-mediated reaction is primarily a response to persistent infections that cause chronic inflammation. This chronic inflammation is driven by macrophages and T lymphocytes, resulting in a prolonged immune response. Over time, this leads to the accumulation of T lymphocytes, macrophages, and fluid at the site of the antigen, causing edema. Each site of antigen presence exhibits three key features:n Accumulation of T lymphocytes, Accumulation of macrophages and Accumulation of fluid. These accumulations result in induration, a physical sign of delayed hypersensitivity. Induration refers to an area of the skin that feels slightly harder upon palpation, caused by the buildup of immune cells and fluid at the site of inflammation. T cell mediated diseases 1) Type 1 (insulin dependent ) Diabetes Mellitus. 2) Autoimmune diseases as Rheumatoid Arthritis, Multiple sclerosis, inflammatory bowl diseases. 3) Contact dermatitis: due to contact with chemical substances or drugs Act as haptensand attach to body proteins. The tuberculin skin test is a diagnostic test for tuberculosis. A small amount of tuberculin protein is injected into the skin, and the reaction is checked after 4) Tuberculin skin test , brucillin, lepromin, candidin…… 24-48 hours. If the person has TB, T lymphocytes and macrophages will accumulate at the site, causing 5) Granulomatous lesionsin chronic infections by intracellular induration. This reaction indicates prior exposure or infection with TB. organisms that resist destruction by macrophages as T.B, leprosy, schistosomiasis forming giant cell and granuloma. 6) Superantigenmediated diseases (toxic shock syndrome) polyclonal T cell activation “non specific binding” ……. Production of large amounts of inflammatory cytokines…….. Syndrome similar to septic shock  Skin allergy test Deleted Skin prick test:pricking the skin with a needle or pin containing a small amount of the allergen. Skin scratch test: a deep dermic scratch is performed with help of the blunt bottom of a lancet. Skin scrape Test: a superficial scrape is performed with help of the bovelof a needle to remove the superficial layer of the epidermis. Intradermic test: a tiny quantity of allergen is injected under the dermis with a hypodermic syringe. Patch test: applying a patch to the skin, where the patch contains the allergen  Immediate reaction tests: Skin testing on arm Deleted “ prick, scratch and scrape tests” Skin prick test : safest and easiest, moderately sensitive Intradermal test: more sensitive, high risk of false positive reactions or risk of anaphylaxis  Deleted Delayed reaction tests: “Patch tests and photopatchtests” Allergen is fixed on the back of patient for 1-2 days and result read after 1 day and 2-3 days. Skin “ non cleaned with alcohol , not treated, no infection” , hypoallergic tape for fixation Photopatchis a modification in which after one day the patch is removed skin is irradiated with UV light. When photo-allergic reactions are suspected  Deleted Precautions 1) Skin tests should be performed after a time interval of reaction that allows resolution of symptoms. “3 weeks but not more than 3 months”. 2) Non irritant concentrations are used. “ some drugs have known recommended concfor skin tests” 3) Medical history of subject to avoid medications that interfere the skin testing as histamine, corticosteroids, antidepressants. 4) Physical examination and history for high risk patients as infection, pregnancy, non compliance to procedure  Deleted 5) Must be prepared to deal with potential emergency situation. 6) Sequence of test procedures: prick test prior to intradermal test..then patch test. Also photopatchtest if suspected photo induced reactivity. 7) Timing of reading : prick and intradermal tests read after 15-20 min. late reading after 24h, 48h. Patch test is read after 48h, 72h. Additional reading after 7 days. 8) A negative test does not conclusively rule out an allergy 9) Positive control “histamine”, negative control “no allergen”  team Wishes you the best