Type II Hypersensitivity Flashcards
Also known as antibody-mediated cytotoxic hypersensitivity.
Type II Hypersensitivity
The immunoglobulins involved in the mechanism of type II hypersensitivity
IgG and IgM
The IgM and IgG are directed against?
Antigens found on the cell surface
The three major effects that can happen wen the antibody binds to a cell
(1) The cell can be destroyed
(2) the function of the cell can be inhibited
(3) the function of the cell can be increased above normal.
Cell damage can occur by several different mechanisms which involve complement as well as antibodies:
(1) Activation of the classical pathway of complement can lead to the formation of the membrane attack complex and cell lysis.
(2) Coating of the cell surface by antibodies can promote opsonization and subsequent phagocytosis of the cells.
3) Cell damage can result from the mechanism of antibody-dependent cellular cytotoxicity (ADCC)
Opsonization can occur through?
Binding of IgG antibody to Fc receptors on macrophages and neutrophils OR binding of cell surface C3b to complement receptors on phagocytic cell
It is mediated through binding of IgG antibody to its corresponding antigen on the target cell and to Fc receptors on macrophages or natural killer cells.
Antibody-dependent cellular cytotoxicity (ADCC)
Clinical examples that involve destruction of cells by type II hypersensitivity includes
- Blood transfusion reactions
- Hemolytic disease of the newborn
- Autoimmune hemolytic anemia.
What will happen when antibody blocks the binding of a physiological ligand to its receptor?
Dysfunction of the cell
An example of autoimmune disease that results to dysfunction of the cell (esp. affects the neuromuscular junctions > muscle weakness)
Myasthenia gravis
Overproduction of cells can result on what autoimmune disorder of the thyroid gland?
Graves’ disease
What hormone is affected in Graves disease?
TSH
An example of cell destruction that results from antibodies combining with heteroantigens.
Transfusion reactions
Major groups involved in transfusion reactions
ABO, Rh, Kell, Duffy, and Kidd systems
Anti-A and anti-B antibodies are naturally occurring antibodies that are also called as
Isohemagglutinins
These are probably triggered by contact with identical antigenic determinants on microorganisms
Isohemagglutinins
The extent of the reactions depends on the following factors (6)
*The temperature at which the antibody is most active
* The plasma concentration of the antibody
* The immunoglobulin class involved
* The extent of complement activation
* The density of the antigen on the RBC
* The number of RBCs transfused40
If a reaction occurs only below 30°C, what is the next step?
Disregard (*because antigen–antibody complexes formed at colder temperatures tend to dissociate at 37°C)
May occur within minutes or hours after receipt of incompatible blood
Acute hemolytic transfusion reactions
Most often associated blood group and antibody in acute hemolytic transfusion rxn
ABO blood group, IgM class
Occurs because of complement activation, resulting in the release of hemoglobin and vasoactive and procoagulant substances into the plasma.
Intravascular hemolysis
Intravascular hemolysis may induce?
Disseminated intravascular coagulation (DIC)
Vascular collapse
Renal failure.
Reactions occur within the first 2 weeks following a transfusion and are caused by an anamnestic response to the antigen to which the patient has previously been exposed
Delayed hemolytic reactions
Antibody responsible for Delayed hemolytic reaction
IgG
Antigens/Blood group involved in delayed hemolytic reaction
Rh, Kell, Duffy, and Kidd blood groups
In, delayed reaction, antibody-coated RBCs are removed extravascularly in what organs?
Spleen and liver
T/F: In delayed hemolytic reaction, intravascular hemolysis does not take place to any great extent because IgG is not as efficient as IgM in activating complement
True
Appears in infants whose mothers have been exposed to blood-group antigens on the baby’s cells that differ from their own
Hemolytic Disease of the Newborn (HDN)
Severe HDN is called
Erythroblastosis fetalis
The mother produces what antibody that can cross the placenta to destroy the fetal rbcs
IgG antibody
Most common antigen involved in severe reactions
D antigen, (RH blood group)
Other antibodies associated with HDN include
anti-c, anti-C, anti-E, anti-e, and less commonly those associated with the Kell, Duffy, and Kidd blood groups
Bilirubin levels above 20 mg/dL are associated with deposition in tissues such as the brain and result in a condition known as
Kernicterus
If serum antibody titrations during the pregnancy indicate a high level of circulating antibody, this can be performed
Intrauterine transfusion
Anti-D immune globulin, called Rhogam, is administered prophylactically at
28 weeks of gestation and within 72 hours following delivery
An example of a type II hypersensitivity reaction directed against self-antigens because individuals with this disease form antibodies to their own RBCs.
Autoimmune Hemolytic Anemia
When the underlying cause of antibody production is unknown; this is referred to as
Idiopathic autoimmune hemolytic anemia
Associated diseases in autoimmune hemolytic anemia may include
- Viral or respiratory infections (infectious mononucleosis, cytomegalovirus, or chronic active hepatitis)
- Immunoproliferative diseases (chronic lymphocytic leukemia and lymphomas)
Drugs that can act as haptens after binding to proteins on the RBC membrane. They can stimulate the production of anti-drug antibodies that destroy the RBCs, primarily through extravascular hemolysis
Penicillins and cephalosporins
Drug that can modify the RBC membrane by facilitating binding of immunoglobulins and complement
Cephalosporin
Drug that can stimulate the production of anti-drug antibodies that bind to the drug to form soluble immune complexes
Quinidine and phenacetin
Drug that can induce hemolytic anemia by stimulating production of autoantibodies against the RBC membrane
Methyldopa
Severity of the hemolysis is affected by what subclass of IgG involved
IgG3 and IgG1
This antibody attaches to B cells and causes a decrease in antibody production. It can use as a treatmnet with warm autoimmune hemolytic anemia
Anti-CD 20 (rituximab)
Can be produced secondary to certain infections, most notably Mycoplasma pneumonia and infectious mononucleosis but also respiratory viruses and HIV
Polyclonal cold agglutinins
Occurs most often after infection with certain viral illnesses, including measles, mumps, chickenpox, and infectious mononucleosis. Px produces a biphasic autoantibody
paroxysmal cold hemoglobinuria
Examples of type II hypersensitivity reactions to tissue antigens include some of the organ-specific autoimmune diseases
Goodpasture syndrome, Hashimoto’s disease, Myasthenia gravis and Insulin-Dependent Diabetes Mellitus
Performed to detect transfusion reactions, HDN, and autoimmune hemolytic anemia. (Coombs discovery in 1945)
Direct Antiglobulin Test (DAT)
Used in the crossmatching of blood to prevent a transfusion reaction. It can either determine the presence of a particular antibody in a patient or type patient RBCs for specific blood group antigens
Indirect Coomb’s test
