L. 32 - Type II Hypersensitivity: Autoimmune and Transfusion Reactions L. 32

What occurs during a Type-II hypersensitivity response?

Pathological antibodies bind directly to antigens on cell surfaces, inducing cell lysis.

Which immunoglobulin isotypes are primarily involved in Type-II hypersensitivity?

Mainly IgM or IgG, but not IgE.

What types of cells can be targeted by antibodies in Type-II hypersensitivity?

Antibodies can attack leukocytes, red blood cells (RBCs), and fixed cells in solid tissues.

What is an autoantibody?

An antibody that binds to self-antigens, potentially leading to autoimmune disease.

Name two examples of Type-II hypersensitivity.

Blood transfusion reactions and hemolytic disease of the newborn.

What are the three mechanisms by which antibodies can induce cell death in Type-II hypersensitivity?

1. Complement activation; 2. Antibody-dependent cell-mediated cytotoxicity (ADCC); 3. Opsonization leading to phagocytosis.

What is hemolytic anemia?

Lytic destruction of RBCs caused by pathological antibodies in Type-II hypersensitivity.

What are the two types of autoimmune hemolytic anemias?

Warm autoantibodies (active at 37°C) and cold autoantibodies (active below 37°C).

What triggers episodes of acute hemolysis in patients with cold autoantibodies?

Exposure to cold temperatures.

What is the cause of alloimmune hemolytic anemias?

Antibodies directed against foreign blood group antigens from transfusions.

What are isohemagglutinins?

Antibodies to A, B, and H antigens that are typically of the IgM isotype.

What are the symptoms of immediate hemolytic transfusion reactions?

Symptoms include hemoglobinuria, bilirubin buildup, fever, chills, nausea, and pain in the lower back.

What distinguishes delayed hemolytic transfusion reactions?

They develop 2-6 days after transfusion and are usually mediated by IgG antibodies.

What is erythroblastosis fetalis?

A severe form of hemolytic disease of the newborn caused by maternal IgG antibodies attacking fetal blood cells.

How can hemolytic disease of the newborn be prevented in subsequent pregnancies?

By administering Rhogam to the mother around 28 weeks of pregnancy and after delivery.

What is drug-induced hemolytic anemia?

Anemia caused by antibodies binding to drugs adsorbed on RBC membranes, leading to complement-mediated lysis.

What is thrombocytopenia?

An abnormally low number of platelets in blood, leading to impaired blood clotting.

What is Goodpasture's syndrome?

An autoimmune disease where autoantibodies target collagen in kidney and lung tissues, causing damage.

What is pemphigus?

An autoimmune disease characterized by blistering of the skin and mucosae due to autoantibodies against adhesion proteins.

What role do antibodies play in the rejection of solid tissue transplants?

Pre-existing alloantibodies against MHC molecules can mediate rapid rejection of transplanted organs.

What causes pemphigus?

Pemphigus is caused by autoantibodies (usually IgG or IgA) that attack adhesion proteins called desmogleins.

What role do desmogleins play in the epidermis?

Desmogleins glue keratinocytes together to form intact upper epidermal layers and mucosal epithelial cells to form mucosae.

What is the standard treatment for pemphigus?

Corticosteroid administration is the standard treatment.

What characterizes Type III hypersensitivity?

Type III hypersensitivity is characterized by the formation of immune complexes that can lead to tissue damage.

What happens when immune complexes are deposited in tissues?

They can recruit complement components and neutrophils, causing tissue damage from granules released by these cells.

What is the Arthus reaction?

The Arthus reaction is a localized immune complex-mediated reaction that occurs within 4-8 hours after antigen injection, leading to tissue damage and inflammation.

What are the symptoms of serum sickness?

Symptoms include fever, weakness, generalized vasculitis, edema, erythema, lymphadenopathy, arthritis, and sometimes glomerulonephritis.

What is the primary mechanism of Type IV hypersensitivity?

Type IV hypersensitivity is purely cell-mediated, primarily involving the action of effector T helper cells, cytotoxic T lymphocytes, and macrophages.

Who first described the delayed-type hypersensitivity reaction?

Robert Koch first described the delayed-type hypersensitivity reaction when studying Mycobacterium tuberculosis.

What is the time frame for the onset of Type IV hypersensitivity reactions?

Type IV hypersensitivity reactions typically occur 24-72 hours after exposure to the sensitizing antigen.

What are the two phases of the delayed-type hypersensitivity response?

The two phases are the sensitization phase and the effector phase.

What occurs during the sensitization phase of DTH?

The sensitization phase involves initial exposure to an antigen, leading to activation and clonal expansion of antigen-specific T helper cells.

What is a granuloma, and how can it form?

A granuloma is a nodule-like mass that can form from a prolonged DTH response, often due to activated macrophages.

How is a DTH reaction detected?

A DTH reaction is detected through a skin test by injecting antigen intradermally, resulting in a characteristic skin lesion if positive.

What is contact hypersensitivity?

Contact hypersensitivity, or contact dermatitis, is a secondary immune response to small, chemically reactive molecules that bind to self-proteins in the skin.

What are some examples of agents that can cause contact hypersensitivity?

Examples include poison ivy, poison oak, hair dyes, nickel salts, latex, drugs like penicillin, and cosmetics.

What is the consequence of large immune complexes in the bloodstream?

When large immune complexes are formed, they can lead to tissue damage due to inefficient clearance by phagocytic cells.

What is the role of complement fixation in Type III hypersensitivity?

Complement fixation leads to the production of anaphylatoxins like C3a and C5a, which attract more neutrophils and macrophages.

What can deposition of immune complexes in blood vessels cause?

Deposition of immune complexes on blood vessel walls can cause vasculitis.

What can immune complex deposition in joints lead to?

It can lead to arthritis when immune complexes are deposited in the synovial membrane.

What is the relationship between antigen and antibody in serum sickness?

In serum sickness, when antigen levels exceed antibody levels, smaller immune complexes form that are not cleared and can cause tissue damage.

What is the role of cytokines in the effector phase of DTH?

In the effector phase, TH1 cells secrete cytokines that activate macrophages and other inflammatory cells.

What is a common treatment for chronic DTH reactions?

Corticosteroid treatment is commonly used to manage chronic delayed-type hypersensitivity reactions.