typeiihypersensitivityab-2.,...........................................................................

Immunology/hypersensitivity/IGg/Tyoe 2................................................................................................................................................................

1. Type II Hypersensitivity Dr Sara Neha PG SIMS

2. Type II Hypersensitivity refers to an antibody-mediated immune reaction. reactions involve IgG and IgM antibodies These antibodies are directed against cellular antigens, leading to cell damage. So it involves antibody mediated destruction of cells. It is also known as cytotoxic reaction. The killing of cell can occurs by one of the three mechanisms. Activate complement , resulting in an inflammatory response and lysis of the targeted cells, ( Complement mediated lysis of cell) or they can be involved in antibody-dependent cell-mediated cytotoxicity (ADCC) with cytotoxic T cells . or Opsonisation The reaction time is minutes to hours and thus considered as immediate hypersensitivity.

3. Opsonisation ADCC Complement mediated cell lysis the modification of antigens by opsonins (antibody) to make them more accessible to phagocytic cells

4. Type II Hypersensitivity In some cases, the antigen may be a self-antigen, in which case the reaction would also be described as an autoimmune disease . In other cases, antibodies may bind to naturally occurring, but exogenous, cell-surface molecules such as antigens associated with blood typing found on red blood cells (RBCs).

5. Mechanism of Type II Hypersensitivity Reactions The reaction is completed in two phases – sensitization phase and effector phase. A sensitization phase leads to production of antibodies that recognize substances or metabolites that accumulate in cellular membrane structures. In the effector phase , target cells become coated with antibodies which lead to cellular destruction. Antibody bound to a surface antigen can induce the death of the antibody-bound cell by three distinct mechanisms – by activation of the complement system, cell destruction by antibody dependent cell mediated cytotoxicity (ADCC) or by the process of opsonization.

6. Complement system is a system of lytic enzyme which are usually inactive in blood. Enzymes of complement system are activated by antigen-antibody complex. When antibody binds to antigen (microorganism or RBC) they form Ag-ab complex. Ag-ab complex can activate complement system by three different mechanism-classical pathway, alternate pathway and lectin pathway. Activated complement proceeds in cascade mechanism. When complement is activated on the surface of cell (RBC) it causes lysis of cell. Complement mediated lysis of cell

7. Antibody binds with antigen by its Fab portion. However Fc region of antibody has receptor on cytotoxic cells. So, antibody cross link target cell (microorganism or RBC) with cytotoxic cells and promote killing. Most cytotoxic cells contain storage of hydrolytic and digestive enzymes. These enzymes are released on the surface of target cell (MOs or RBC or target cell), killing them. Here antibody itself does not kill or destroy cell but rather mediate killing by presenting antigen to cytotoxic cell. Similarly cytotoxic cell depends upon antibody to bind antigen. So this mechanism is known as Antibody dependent cell mediated cytotoxicity. Antibody dependent cell mediated cytotoxicity (ADCC)

8. When antigen enters into host body, antibodies are produced. Antibody binds to antigen through Fab region. Fc region of antibody remains free. Phagocytic cells such as Neutrophils, macrophages and monocytes have receptors that can bind to Fc region of antibody. The receptor is known as FcR. In this case antibody molecule directly cross links antigen (Microrganism or RBC or target cell) with phagocytic cells. This cross- linkage activates phagocytic cells and increases the rate of phagocytosis. This increased rate of phagocytosis by binding of antibody to antigen is called Opsonization. Opsonization

9. Some examples of Type II Hypersensitivity Transfusion reactions Hemolytic disease of the newborn Autoimmune hemolytic anemia, agranulocytosis, and thrombocytopenia Specific drug reactions Glomerulonephritis Myasthenia gravis, Graves disease, and other autoimmune disorders

10. Common examples Hemolytic transfusion reaction (HTR) -- Transfusion reaction Hemolytic disease of the newborn (HDN) -- Rhesus incompatibility

11. ABO Blood Group Incompatibility The recognition that individuals have different blood types was first described by Karl Landsteiner (1868–1943) in the early 1900s, based on his observation that serum from one person could cause a clumping of RBCs from another. These studies led Landsteiner to the identification of four distinct blood types.

12. Transfusion reaction A patient may require a blood transfusion because they lack sufficient RBCs ( anemia ). For instance, if a person with type B blood receives a transfusion of type A blood, their anti-A antibodies will bind to and agglutinate the transfused RBCs. In addition, activation of the classical complement cascade will lead to a strong inflammatory response, and the complement membrane attack complex (MAC) will mediate massive hemolysis of the transfused RBCs. The debris from damaged and destroyed RBCs can occlude blood vessels in the alveoli of the lungs and the glomeruli of the kidneys. Within 1 to 24 hours of an incompatible transfusion, the patient experiences fever, chills, pruritus (itching), urticaria (hives), dyspnea, hemoglobinuria (hemoglobin in the urine), and hypotension (low blood pressure). In the most serious reactions, dangerously low blood pressure can lead to shock, multi-organ failure, and death of the patient.

13. Figure- A type II hypersensitivity hemolytic transfusion reaction (HTR) leading to hemolytic anemia. Blood from a type A donor is administered to a patient with type B blood. The anti-A isohemagglutinin IgM antibodies in the recipient bind to and agglutinate the incoming donor type A red blood cells. The bound anti-A antibodies activate the classical complement cascade, resulting in destruction of the donor red blood cells.

14. Hemolytic disease of the newborn (HDN) Rhesus incompatibility (Rh hemolytic disease) If an Rh− woman carries an Rh+ baby to term, the mother’s immune system can be exposed to Rh+ fetal red blood cells . This exposure will usually occur during the last trimester of pregnancy and during the delivery process. If this exposure occurs, the Rh+ fetal RBCs will activate a primary adaptive immune response in the mother, and anti-Rh factor IgG antibodies will be produced. IgG antibodies are the only class of antibody that can cross the placenta from mother to fetus; however, in most cases, the first Rh+ baby is unaffected by these antibodies because the first exposure typically occurs late enough in the pregnancy that the mother does not have time to mount a sufficient primary antibody response before the baby is born. If a subsequent pregnancy with an Rh+ fetus occurs, however, the mother’s second exposure to the Rh factor antigens causes a strong secondary antibody response that produces larger quantities of anti-Rh factor IgG. These antibodies can cross the placenta from mother to fetus and cause HDN, a potentially lethal condition for the baby.

15. When an Rh− mother has an Rh+ fetus, fetal erythrocytes are introduced into the mother’s circulatory system before or during birth, leading to production of anti-Rh IgG antibodies. These antibodies remain in the mother and, if she becomes pregnant with a second Rh+ baby, they can cross the placenta and attach to fetal Rh+ erythrocytes. Complement-mediated hemolysis of fetal erythrocytes results in a lack of sufficient cells for proper oxygenation of the fetus. (b) HDN can be prevented by administering Rho(D) immune globulin during and after each pregnancy with an Rh+ fetus. The immune globulin binds fetal Rh+ RBCs that gain access to the mother’s bloodstream, preventing activation of her primary immune response.

16. Drug induced hemolytic anemia This drug induced hemolytic anemia is an example of Type II hypersensitivity reaction. Certain drugs such as penicillin, cephalosporin and streptomycin can absorb non-specifically to protein on surface of RBC forming complex similar to hepten-carrier complex. In some patients these complex induce formation of antibodies, which binds to drugs on RBC and induce complement mediated lysis of RBC and thus produce progressive anemia

17. Cell Destruction due to Autoantigens Antibodies to a variety of self antigens such as basement membranes of lung and kidney (Goodpasture’s Syndrome), the acetylcholine receptor (Myasthenia Gravis) and erythrocytes (Autoimmune Hemolytic Anemia) can result in tissue damaging reactions.

18. Autoimmune Hemolytic Anemia

19. Myasthenia gravis

20. An example of a cytotoxic reaction is thrombocytopenia. In this disease, antibody molecules are elicited by certain drug molecules. The antibodies unite with antigens on the surface of thrombocytes (platelets), and with complement activation, the thrombocytes are destroyed. The result is an impaired blood-clotting mechanism. Thrombocytopenia

21. Another example of the cytotoxic reaction is agranulocytosis. In this immune disorder, antibodies unite with antigens on the surface of neutrophils. As these cells are destroyed with complement activation, the capacity for phagocytosis is reduced. Agranulocytosis