Touro PA Microbiology Lecture 14 Fall 2023.pptx

Immune Deficiency Diseases Hypersensitivity Reactions • Response to antigens (allergens) beyond normal leading to damage • Types of reactions • Anaphylactic: a sever allergic reaction with rapid onset and may cause death in systemic anaphylaxis • Cytotoxic • Immune complex • Delayed cell-mediated...

Immune Deficiency Diseases Hypersensitivity Reactions • Response to antigens (allergens) beyond normal leading to damage • Types of reactions • Anaphylactic: a sever allergic reaction with rapid onset and may cause death in systemic anaphylaxis • Cytotoxic • Immune complex • Delayed cell-mediated Hygiene Hypotheis • Your environment is too clean!!!!!! • Lack of exposure to antigens lowers the body’s immune tolerance • Therefore, hard to cope or deal with harmless antigens Types of Hypersensitivity Type of Reaction Type I (anaphylactic) Type II (cytotoxic) Type III (immune complex) Type IV (delayed cellmediated) Time After Exposure for Clinical Symptoms <30 min 5–12 hours 3–8 hours ≥1 day Type I (Anaphylactic) Reactions • IgE attached to mast cells and basophils • Antigen binds to two adjacent IgE • Mast cells and basophils undergo degranulation, which releases mediators: • Histamine • Leukotrienes • Prostaglandins The mechanism of anaphylaxis. Mast cell or basophil IgE Antigen Granule Histamine and other mediators IgE antibodies, produced in response to an antigen, coat mast cells and basophils. When an antigen bridges the gap between two adjacent antibody molecules of the same specificity, the cell undergoes degranulation and releases histamine and other mediators. The mechanism of anaphylaxis. Mast cells A degranulated mast cell that has reacted with an antigen and released granules of histamine and other reactive mediators Type I (Anaphylactic) Reactions • Systemic anaphylaxis • May result in circulatory collapse and death • Localized anaphylaxis • Hives, hay fever, and asthma A skin test to identify allergens. Preventing Anaphylactic Reactions • Desensitizing injections of antigen • Cause production of IgG, so that IgG antibodies will act as blocking antibodies Type II (Cytotoxic) Reactions • Involve IgG or IgM antibodies and complement • Complement activation causes cell lysis or damage by macrophages The ABO Blood Group System Insert Table 19.2 Hemolytic disease of the newborn. Hemolytic disease Initially during first pregnancy Placenta Rh+ father. Rh– mother carrying her first Rh+ fetus. Rh antigens from the developing fetus can enter the mother's blood during delivery. In response to the fetal Rh antigens, the mother will produce anti-Rh antibodies. RhoGam If the woman becomes pregnant with another Rh+ fetus, her anti-Rh antibodies will cross the placenta and damage fetal red blood cells. Type III (Immune Complex) mediated Reactions • IgG antibodies and antigens form immune complexes that lodge in basement membranes • The complexes are deposited in organs and causes inflammatory damage • Infiltration of immune cells • Tissue damage Type III Hypersensitivities: Immune ComplexMediated • Formation of immune complexes: form when the two arms of an antibody bind identical soluble antigen molecules, linking them • Larger complexes are removed by phagocytes binding to Fc regions • If complexes are small they may remain in circulation or at sites of formation in tissue • Can lodge in blood vessels; activate complement system, which causes inflammation • Seen with rashes, joint pains and symptoms of systemic lupus erythematosus, infective endocarditis, early rubella infection, glomerulonephritis • Complexes can trigger disseminated intravascular coagulation (DIC); clots form in small blood vessels • Leads to organ failure 15 Immune complex–mediated hypersensitivity. Basement membrane of blood vessel Ag Endothelial cell Immune complexes are deposited in wall of blood vessel. Presence of immune complexes activates complement and attracts inflammatory cells such as neutrophils. Neutrophils Enzymes released from neutrophils cause damage to endothelial cells of basement membrane. Type IV (Cell-Mediated) Reactions • Cell mediated • Delayed-type hypersensitivities due to T cells (specifically, CTL) • Slow and are not readily apparent for a day or more • Cytokines attract macrophages and TC cells • Initiate tissue damage The development of an allergy (allergic contact dermatitis) to catechols from the poison ivy plant. Pentadecacatechol molecules Skin protein Dermatitis on arm Pentadecacatechol molecules combined with skin proteins Poison ivy 7–10 days 1–2 days T cells: T memory Sensitization cells: Immune step response (No dermatitis) PRIMARY CONTACT Many active T cells: Disease Dermatitis SECONDARY CONTACT Allergic contact dermatitis. Latex allergy Insert Fig 19.8 Autoimmune Diseases Autoimmune Diseases • Clonal deletion during fetal development ensures self-tolerance • Autoimmunity is loss of self-tolerance Autoimmune Diseases • Cytotoxic: antibodies react with cell-surface antigens • Graves’ disease: increase thyroid hormone production • Antibodies that mimic Thyroid Stimulating Hormone (TSH) • Enlarge Thyroid and bulging eyes • Immune complex: immune complexes of IgM, IgG, and complement deposit in tissues • Systemic lupus erythematosus • Cell-mediated: mediated by T cells • Psoriasis Autoimmune Disease • Results when the immune system mistakenly attacks the body’s normal tissues • If self-tolerance is faulty, autoimmune disease may develop • Lymphocytes that react against autoantigens (“self” antigens) are usually eliminated by central tolerance and peripheral tolerance • May stimulate the production of autoantibodies (antibodies against autoantigens) • May activate T cells, resulting in cell damage and inflammation • Sometimes both occur • Autoimmune diseases can be organ-specific or systemic 23 Autoimmune Disease • Causes not entirely clear • Genetic factors • Seen in relatives who share MHC genes • Environmental factors, including infection • Pathogens that evade immune system via mimicry • Deficiency in action or control of cells • Treatment involves managing symptoms and preventing further damage • Anti-inflammatory medications • Stress reduction • Immune-suppressing agents 24 Systemic Autoimmune Diseases • Result from immune response to one or more autoantigens found throughout the body • Rheumatoid arthritis (RA) • Affects connective tissues, often within joints • Can lead to crippling joint destruction • One of the most common autoimmune diseases • Most frequent in women ages 30 to 50 • T cells may accumulate in joints and release inflammatory cytokines • Autoantibodies to substances in the joint fluids form immune complexes causing further damage • Medications used to prevent RA damage target cytokines that trigger an inflammatory response • chaowalit407/iStock/ Getty Images 25 Systemic Autoimmune Diseases 2 • Systemic lupus erythematosus (SLE) • Can affect many different body systems, resulting in a wide range of possible signs and symptoms • Mostly affects women of childbearing age • Multiple mechanisms involved, but a significant factor is the formation of immune complexes in different tissues • Characterized by a variety of destructive autoantibodies that target DNA and other molecules found in cell nuclei • Signs and symptoms of SLE include: fatigue, fever, and rashes, joint pain and swelling • Kidneys or other organs may be damaged • Treatment is aimed at preventing flares, managing symptoms and reducing organ damage 26 Multiple Sclerosis (MS) • Affects the myelin sheath that protects some neurons in the central nervous system • Inflammatory damage associated with the disease compromises nerve impulse conduction • Leading to fatigue and weakness • Eventually complete paralysis in some people • More common in women • Characterized by flares that occur months or years apart • But may be slowly progressing without flares • Disease management involves treating or relieving symptoms during flares, and slowing disease progression 27 Organ-Specific Autoimmune Diseases • Result from autoantigens found only within a specific organ • Graves’ disease causes an over-activation of the thyroid gland (hyperthyroidism) • An autoantibody that binds to the gland’s receptor for thyroid-stimulating hormone (TSH) causing continuous production of thyroid hormones • Treatments include: • Medications that block thyroid hormone synthesis and release • Destruction of thyroid tissue using radioactive iodine • Surgical removal of the thyroid gland Graves Disease • Causes metabolic rate increase resulting in: • weight loss • fatigue • irritability • heat intolerance • rapid heartbeat • Bulging eyes and a goiter (enlarged thyroid gland) may develop • Chris Pancewicz/Alamy Type 1 Diabetes Mellitus • Once called insulin-dependent or juvenile diabetes • Caused by the destruction of pancreatic β cells (produce insulin) by cytotoxic T cells • Insulin allows cells to take up glucose from the bloodstream • Insulin levels decrease • Blood glucose levels increase, draws water from cells and leads to increased thirst and urination • Symptoms include extreme hunger, fatigue, and weight loss • High blood pressure, stroke, blindness, kidney disease, and conditions that lead to the need for limb amputation may result • Treated by insulin injections 30 HLA Reactions HLA Reactions • Histocompatibility antigens: self antigens on cell surfaces • Major histocompatibility complex (MHC): genes encoding histocompatibility antigens • Called, Human leukocyte antigen (HLA) complex: MHC genes in humans Tissue typing, a serological method. Lymphocyte being tested Anti-HLA antibodies attach to HLAs on lymphocyte. HLA Complement and trypan blue dye are added. Cell damaged by complement takes up dye. Reactions to Transplantation • Transplants may be attacked by T cells, macrophages, and complement-fixing antibodies • Transplants to privileged sites do not cause an immune response • Stem cells may allow therapeutic cloning to avoid rejection • Embryonic stem cells are pluripotent • Adult stem or multipotent stem cells have differentiated to form specific cells Grafts • Autograft: use of one’s own tissue • Isograft: use of identical twin’s tissue • Allograft: use of tissue from another person • Xenotransplantation product: use of nonhuman tissue • Hyperacute rejection: response to nonhuman Ag • Graft-versus-host disease can result from transplanted bone marrow that contains immunocompetent cells Immunosuppression • Prevents an immune response to transplanted tissues • Cyclosporine and tacrolimus suppress IL-2 • Mycophenolate mofetil inhibits T cell and B cell reproduction • Sirolimus blocks IL-2 • Basiliximab and daclizumab block IL-2