Which antibody is involved in antibody dependent cytotoxic hypersensitivity?

Type II hypersensitivity, in the Gell and Coombs classification of allergic reactions, is an antibody mediated process in which IgG and IgM antibodies are directed against antigens on cells (such as circulating red blood cells) or extracellular material (such as basement membrane). This subsequently leads to cell lysis, tissue damage or loss of function through mechanisms such as

The activation of the complement system results in opsonization, the agglutination of red blood cells, cell lysis, and cell death.

These reactions usually take between 2 and 24 hours to develop.

Examples[edit]

An example of complement dependent type II hypersensitivity is an acute hemolytic transfusion reaction following transfusion of ABO incompatible blood. Preformed antibody (predominantly IgM) against donor red cell antigens not found in an individual of a particular blood group (e.g. anti-A IgM in an individual with blood group B), bind to the donor red cell surface and lead to rapid complement mediated haemolysis and potentially life-threatening clinical consequences. Complement-dependent type II hypersensitivity can also occur during the transmission of incompatible maternal antibodies to fetal red blood cells causing hemolytic anemia in the fetus, known as erythroblastosis fetalis.

Another example of a complement dependent type II hypersensitivity reaction is Goodpasture's syndrome, where the basement membrane (containing collagen type IV) in the lung and kidney is attacked by one's own antibodies in a complement mediated fashion.

An example of anti-receptor type II hypersensitivity (also classified as type V hypersensitivity) is observed in Graves disease, in which anti-thyroid stimulating hormone receptor antibodies lead to increased production of thyroxine.

However, there are questions as to the relevance of the Gell and Coombs classification of allergic reactions in modern-day understanding of allergy and it has limited utility in clinical practice.

Complement dependent reactions: Antibody is directed against antigen on cells (such as circulating red blood cells) or extracellular materials (basement membrane). The resulting Ag-Ab complexes activate complement (via the classic pathway), leading to cell lysis or extracellular tissue damage.

In the above diagram, a red blood cell has antigen fixed on its surface to which antibody attaches. The attached antibody sets off the complement cascade, which ends with the formation of the "membrane attack complex" of C5-9 which causes lysis of the cell. Other complement components may be generated, such as the opsonin C3b.

Diseases in this complement dependent category include:

• Transfusion reactions: incompatible RBC's or serum is transfused.

• Autoimmune hemolytic anemia: antibody is made against one's own RBC's.

• Erythroblastosis fetalis: maternal IgG crosses the placenta and attaches to fetal RBC's.

• Goodpasture's syndrome: glomerular basement membrane antibody is present.

Antibody-dependent cell-mediated cytotoxicity (ADCC): Low concentrations of IgG or IgE (in the case of parasites) coat target cells. Inflammatory cells such as NK (natural killer) cells, monocytes, and granulocytes then bind to the immunoglobulin Fc receptors and lyse, but do not phagocytize, the target cells.

In the diagram above, a macrophage with Fc receptors on its surface is able to recognize a target cell coated with antibody via the Fc receptor portion of the attached antibody. The macrophage can then demolish the targeted cell by elaboration of proteases.

Examples of ADCC include:

• Transplant rejection

• Immune reactions against neoplasms

• Immune reactions against parasites

Antireceptor antibodies: IgG antibody is directed against receptors in target cells, resulting in complement-mediated destruction of the receptors.

In the diagram above, antibody is directed against acetylcholine receptors at the motor end plate of a muscle, blocking the receptors and diminishing the muscular response. This is the mechanism for muscle weakness in myasthenia gravis.

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In type II (cytotoxic) hypersensitivity, the antibodies produced by the immune response bind to antigens on the patient’s own cell surfaces.

Learning Objectives

• Describe Type II hypersensitivity reactions

Key Points

• The antigens recognized in this way may either be intrinsic (“self” antigen, innately part of the patient’s cells) or extrinsic (adsorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen).
• Mediators of acute inflammation are generated at the site where a foreign antigen is recognized and membrane attack complexes cause cell lysis and death.
• In antibody -dependent cell-mediated cytotoxicity (ADCC), cells exhibiting the foreign antigen are tagged with antibodies ( IgG or IgM) and they are then recognised by natural killer (NK) cells and macrophages which in turn kill these tagged cells.

Key Terms

• macrophages: A type of white blood cell that targets foreign material, including bacteria and viruses.
• dendritic cells: Dendritic cells are immune cells that function to process antigen material and present it on the surface of other cells of the immune system. They act as messengers between innate and adaptive immunity.
• cytotoxic hypersensitivity: In type II hypersensitivity, the antibodies produced by the immune response bind to antigens on the patient’s own cell surfaces.

In type II hypersensitivity (or cytotoxic hypersensitivity), the antibodies produced by the immune response bind to antigens on the patient’s own cell surfaces. The antigens recognized in this way may either be intrinsic (“self” antigen, innately part of the patient’s cells) or extrinsic (adsorbed onto the cells during exposure to some foreign antigen, possibly as part of infection with a pathogen). These cells are recognized by macrophages or dendritic cells, which act as antigen-presenting cells. This causes a B cell response, wherein antibodies are produced against the foreign antigen.

Figure: Complement death: A complement protein attacking an invader.

An example of type II hypersensitivity is the reaction to penicillin wherein the drug can bind to red blood cells, causing them to be recognized as different; B cell proliferation will take place and antibodies to the drug are produced. IgG and IgM antibodies bind to these antigens to form complexes that activate the classical pathway of complement activation to eliminate cells presenting foreign antigens (which are usually, but not in this case, pathogens). That is, mediators of acute inflammation are generated at the site and membrane attack complexes cause cell lysis and death. The reaction takes hours to a day. The membrane attack complex (MAC; ) is typically formed on the surface of pathogenic bacterial cells as a result of the activation of the alternative pathway and the classical pathway of the complement system, and it is one of the effector proteins of the immune system. The membrane-attack complex (MAC) forms transmembrane channels. These channels disrupt the phospholipid bilayer of target cells, leading to cell lysis and death.

Another form of type II hypersensitivity is called antibody-dependent cell-mediated cytotoxicity (ADCC). Here, cells exhibiting the foreign antigen are tagged with antibodies (IgG or IgM). These tagged cells are then recognised by natural killer (NK) cells and macrophages (recognised via IgG bound (via the Fc region) to the effector cell surface receptor, CD16 (FcγRIII)), which in turn kill these tagged cells.

Autoimmune diseases resemble type II-IV hypersensitivity reactions. They differ from hypersensitivity reactions in that the antigens driving the immune process are self-antigens rather than non-self as in hypersensitivity reactions. Below are some examples of Type II hypersensitivity-like autoimmunity.

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12.4C: Type II (Cytotoxic) Reactions is shared under a CC BY-SA 4.0 license and was authored, remixed, and/or curated by LibreTexts.

What antibodies are released in antibody mediated cytotoxic hypersensitivity?

A type II, or cytotoxic, hypersensitivity reaction occurs when IgG or IgM antibodies bind to an antigen on the surface of a cell and cause other immune cells and complements to attack it, leading to the cell's destruction.

What are the antibodies involved in a Type II cytotoxic hypersensitivity reaction?

A type II hypersensitivity reaction is also called a cytolytic reaction because the damage is mediated by hapten-specific antibodies which are capable of triggering cytotoxicity in the target cell. The antibodies involved in a type II reaction are both IgM and IgG, with the latter type predominating.

Which antibody is involved in hypersensitivity reaction?

Immediate hypersensitivity reactions are predominantly mediated by IgE, IgM, and IgG antibodies.

What is an example of a cytotoxic hypersensitivity reaction?

Figure: Complement death: A complement protein attacking an invader. An example of type II hypersensitivity is the reaction to penicillin wherein the drug can bind to red blood cells, causing them to be recognized as different; B cell proliferation will take place and antibodies to the drug are produced.