Immunological Disorders: Hypersensitivity Type I & II (PDF)

20/1/2025 2 BIOCHEMISTRY & IMMUNOLOGY LEARNING OBJECTIVES IN NURSING (NRS414)...

20/1/2025 2 BIOCHEMISTRY & IMMUNOLOGY LEARNING OBJECTIVES IN NURSING (NRS414) AT THE END OF THE LESSON, STUDENTS ARE ABLE TO EXPLAIN OR IDENTIFY: I. The definition of hypersensitivity. II. Types of cells, antibodies and antigens related to different types of hypersensitivities. III. Mechanism of hypersensitivity type I (allergic reaction). IV. Immunotherapy by the process of desensitization. NRS421 HS240 V. Mechanism of hypersensitivity type II (cytotoxic) HS260 3 4 Overview of Immunological Disorders A condition that results from an inappropriate or Immediate (Type I) Hypersensitivity: Anaphylaxis (Greek inadequate immune response word: Ana = against, phylaxis = protection) results from a prior exposure to a foreign substance called an allergen. Hypersensitivity (allergy): the immune system Cytotoxic (Type II) Hypersensitivity: elicited by antigens on reacts in an exaggerated or inappropriate way to cells, that an immune system recognizes as foreign. a foreign substance Immune complex (Type III) Hypersensitivity: elicited by antigens in vaccines, on microbes, or on a person’s own cells. There are four types of hypersensitivity: Cell-mediated (Type IV) Hypersensitivity: triggered by 1. Immediate hypersensitivity (Type I) exposure to foreign substances from the environment, 2. Cytotoxic hypersensitivity (Type II) infectious disease agents, transplanted tissues, and body’s 3. Immune complex hypersensitivity (Type III) own tissues and cells. 4. Cell-mediated or delayed hypersensitivity Autoimmune disorders represent a form of hypersensitivity in which the body’s immune system responds to its own (Type IV) tissues as if they were foreign. 5 6 Type I Hypersensitivities (Anaphylaxis): Immediate IgE causes immediate (type I) hypersensitivities Characterized by immediate reaction of the sensitized individual Generally within minutes of exposure Tendency to have type I hypersensitivities is inherited Reactions occur in at least 20% to 30% of population Type I reactions can be classified as local anaphylaxis or generalized anaphylaxis Anaphylaxis-name given for IgE-mediated allergic reaction #ADCC: Antibodies-dependent cellular cytotoxicity 1  20/1/2025 7 8 Localized anaphylaxis Most allergic reactions are local anaphylaxis 1. Hives (urticaria) Allergic skin condition characterized by formation of wheal and flare rash. The wheal is an itchy swelling Hives (like a mosquito bite) surrounded by redness (urticaria) 2. Hay fever Allergic condition caused by inhaled antigen. Condition marked by itching teary eyes, sneezing and runny nose 3. Asthma - Respiratory allergy - Allergic mediators attracted to inflamed respiratory tract - Results in increased mucous secretion and bronchi spasm (involuntary muscle contraction) 9 10 11 12 Allergy testing: Possible allergens are placed on point and introduced under a patients skin 2  20/1/2025 13 14 If an individual is hypersensitive, a wheal (white raised area) and flare (reddened area) soon become visible on the skin wheal Flare 15 16 Patch Allergy Test Sensitization occurs when antigen makes contact with some part of body and induces response IgE antibodies bind to receptors on mast cells and basophiles Antigen readily bonds to cells fixed with IgE antibodies Within seconds, mast cells degranulate releasing mediators that initiate immune reaction including hives, hay fever and anaphylaxis 17 18 Antigen / allergen taken up by macrophages and MHC II and APC presents produced APC antigen on MHCII groove The mechanism of immediate (Type I) hypersensitivity Air-borne (Anaphylactic hypersensitivity) Sensitization (1st exposure) substances – pollen, 1. B cells are household activated dust, molds 2. B cells differentiate Venoms into plasma cells from insect which produce stings Antibiotic APC presents antibodies (IgE) antigens to TH Foods against the specific cells allergen 3  20/1/2025 19 - Histamines is produced – dilates capillaries, 20 Armed TH cell secrete increase mucous secretion, stimulates nerves – cytokine (IL-4) that pain and itching drive proliferation and Armed TH cell Cross linking differentiation of B cells causes to plasma cells degranulation in mast cells cytokine and basophils IgE antibodies bind to mass cell receptors – the individual is Cross linking sensitized the IgE Allergen attach to antibodies sensitized mast cells 21 22 Generalized anaphylaxis Rare, but more serious form of IgE-mediated allergy Antigen enters bloodstream and becomes widespread Reactions affect almost entire body Can induce shock Shock is state in which blood pressure too low to supply required blood flow Massive release of mediators causes extensive blood vessel dilation and fluid loss from blood Causes fall in pressure leading insufficient blood flow to vital organ eg brain. Suffocation – marked constriction of the bronchial tubes Fatal within minutes Examples : Bee stings, peanuts, penicillin – cause generalized anaphylaxis 23 24 Treatment of Allergies Immunotherapy Avoid contact with the specific allergen General term for techniques used to modify immune system for favorable effect Desensitization (hyposensitization) is the only Procedure is to inject individual with extremely current available treatment intended to cure an allergy dilute suspension of allergen Called desensitization or hyposensitization Concentration of allergen gradually increased over Very successful against venoms and drug time allergies (e.g. allergic to penicillin) Individual gradually becomes less sensitive Other allergy treatments alleviate symptoms but do not cure the disorder 4  20/1/2025 25 26 Normal allergic reaction -Natural exposure to an allergen causes helper T cells stimulate B cells that mature in plasma cells to make IgE Desensitization antibodies (Hyposensitization) - After binding to mast cells, a second allergen exposure causes degranulation - Histamines are produced 27 29 Denatured allergen prevents B cells from maturing into plasma cells to make IgE antibodies. Plasma cells are producing IgG Type II Hypersensitivities: The IgG bind to incoming allergen and attach to mast Cytotoxicity cells. No degranulation, no histamines produced 30 Type II Hypersensitivities: Cytotoxic Type II Hypersensitivities:Cytotoxic Antibodies react with cell surface antigens causing cell injury or death Cells can be destroyed in type II reactions through activation of the complement system or by antibody- dependent cellular cytotoxicity (ADCC) Examples of type II hypersensitivities are Transfusion reactions Hemolytic disease of the newborn 5  20/1/2025 32 33 Transfusion Reactions Normal human red blood cells have genetically determined surface antigens (blood group systems) that form the basis for different blood types Transfusion reaction: can occur when matching antigens and antibodies are present in the patient’s blood at the same time A and B antigens which determine the ABO blood group system 34 35 Type II Hypersensitivities: Cytotoxic Transfusion reactions Transfusion reactions A person's serum has no IgM antibodies against the antigens present on his or her own red blood Normal red blood cells have different surface cells. antigens If a sensitized patient receives red blood cells with a different blood cell antigen during a blood Antigens differ from person to person transfusion, IgM antibodies cause a Type II People are designated type A, B, AB or O hypersensitivity reaction against the foreign antigen. Transfused blood that is antigenically different The foreign RBC are agglutinated (clumped), can be lysed by recipient immune cells complement is activated, and hemolysis (rupture of blood cells) occurs within the blood vessels. Cross-matching blood is used to ensure Symptoms of a transfusion reaction include compatibility between donor and recipient fever, low blood pressure, back and chest pain, nausea, and vomiting. IgM antibodies cause type II reactions Transfusion reactions can usually be prevented Symptoms include low blood pressure, pain, by careful cross-matching of donor and recipient blood group antigens so that the correct blood nausea and vomiting type can be selected for transfusion. 36 37 Blood typing and transfusions Blood Transfusion Reaction https://youtu.be/dKTKftGHnmo 6  20/1/2025 38 39 Type II Hypersensitivities: Cytotoxic Hemolytic disease of the newborn Basis of disease is incompatibility of Rh factor between mother and child Rh factor RBC cell surface antigen Rh positive = Rh antigen present Rh negative = Rh antigen missing Anti-Rh antibodies form in Rh negative mother pregnant with Rh positive fetus First Rh positive fetus unharmed Second Rh positive fetus provokes strong secondary immune response IgG antibodies of secondary response cross placenta causing extensive damage to fetal red blood cells 40 41 Hemolytic Disease of the Newborn Erythroblastosis fetalis In addition to the ABO blood group, red blood cells can have Rh antigens Rh positive: blood with Rh antigens Rh negative: blood without Rh antigens Sensitization occurs when an Rh-negative woman carries an Rh-positive fetus and produces anti-Rh antibodies if it again encounters the Rh antigen 42 43 Cytotoxic (Type II) Hypersensitivity Specific antibodies react with cell surface antigens interpreted as foreign by the immune system Leading to phagocytosis, killer cell activity, or complement-mediated lysis Cause and Effect of Hemolytic Disease of the Newborn Cells to which the antibodies are attached, as well as surrounding tissues, are damaged because of the resulting inflammatory response 7  20/1/2025 44 45 a) The fetus of an Rh- mother may inherit paternal genes for Rh antigen and b) The mother makes a primary In Rh incompatibility, an Rh- mother who is carrying have Rh+ blood. During response to Rh antigens and an Rh+ child has no problems during the first delivery of a first Rh+ baby develops memory cells for anti- induce anti-Rh antibody in Rh antibodies pregnancy, because the fetal blood cells do not enter the mother the mother's system to cause an immune response. During childbirth, some blood always escapes from the placenta. If it is left in the mother's body, her immune system responds to it, creating antibodies and memory cells. In subsequent pregnancies, her antibodies enter the fetus' body and begin to destroy the fetal red blood cells. 46 47 separate Child affected by hemolytic disease caused by Rh incompatibility 49 Enlarged liver and spleen caused by the efforts of those organ to remove damage red blood cells 8  20/1/2025 50 51 How Is Rh Incompatibility Treated? If a pregnant woman has the potential to develop Rh incompatibility, doctors give her a series of two Rh immune-globulin shots Questions: during her first pregnancy. What would be the reaction when the Rh+ She'll get: mother have a Rh– fetus? 1. The first shot around the 28th week of pregnancy 2. The second shot within 72 hours of giving birth 52 53 An Rh- fetus has no Rh antigens to induce antibody creation in either an Rh- or Rh+ mother. Hemolytic disease of Newborn (HDN) https://youtu.be/4hCzGhQPrzk The fetal immune system is not yet developed enough to create antibodies to the mother's Rh+ antigens, so no problem is created. 54 ANY QUESTIONS? 9