Hypersensitivity II Flashcards
Hypersensitivity reactions type II
Also termed cytotoxic or cytolytic hypersensitivity
Not really a hypersensitivity, more an appropriate immune response to antigen, but where antigen is inappropriately situated on surface of cells
Mechanisms: complement mediated cytolysis (CMC), antibody-dependent cell mediated cytotoxicity (ADCC)
ADCC mechanism
Antibodies (host IgG or IgM) bind to target cells and direct effector cells via Fc receptors
Effector cells include macrophages, neutrophils, eosinophils, NK cells
Effector cells while destroying target cells will also release granule contents to destroy connective/ supporting tissue
CMC mechanism
Antibodies (IgG and IgM) can bind to target cells and activate C1 from the classical complement pathway
Also opsonised target cells can adhere effector cells (e.g. phagocytes) via the presence on the latter of complement receptors e.g. receptor for C3b
Also C3a and C5a may induce type I hypersensitivity
Type II hypersensitivity
Damage mediated by specific IgG or IgM
Origins of specific antibody response
Hapten response (destruction of RBCs due to immune response); molecular mimicry (raised antibody levels start to damage other cells in the body); idiopathic- loss of self tolerance (generate antibodies we shouldn’t against our own cells)
Hapten
Mostly results in haemolytic anaemias, when platelets and granulocytes become target cells also leads to thrombocytopenia and granulocytopenia
Mechanism: drug molecules bound to surface of target cell serve as a hapten for the generation of a reactive antibody, triggering CMC or ADCC
Also drug binding may lead to breakdown of self-tolerance, antobodies are generated that react against self-cell surface proteins
Generally when drug administration is stopped the adverse immune response will stop
Molecular mimicry (rheumatic fever)
Rheumatic fever- some antigens have similarity to proteins present on heart valves»_space;> causes antibodies to attack heart valves
Occurs following an infection of the throat by Streptococcus pyrogenes
Idiopathic- loss of self-tolerance (autoimmunity) e.g. blocking auto-antibodies
Myasthenia gravis- Progressive muscle weakness caused by auto-antibodies against ACh receptors on motor end plates of neuromuscular junctions
Interferes with neuromuscular transmission, may lead to reduction in number of receptors as a result of increased endocytosis
Causes failure of muscle to respond to normal neural impulses
Treatment- anticholinesterases prolong action of ACh
Idiopathic e.g. destructive auto-antibodies
Hashimoto’s disease (autoimmune hypothyroidism)
Antibodies bind to thyroid proteins and damage tissues, antibodies raised against TPO, destroy cells that express proteins
Clinically- causes lethargy and depression, destruction of thyroid cells and T-cell lymphocytic infiltration against TPO and thyroglobulin, treat with thyroxine replacement
Type II seen with erythrocytes as the target cells- rejection
Blood transfusion reactions: ABO antigens comprise a surface erythrocyte carbohydrate moiety (substance H)
Group A and B blood modify substance H
Group O blood does not modify substance H
Serum antibodies against erythrocyte antigens may occur naturally without prior exposure to foreign blood or be induced over days and weeks after contact has occurred
IgM is the most common antibody class directed against ABO antigens
ABO transfusion reaction
Antibody response to BAO system antigens is usually IgM
Causes agglutination, complement activation and intravascular haemolysis, destruction of RBCs can lea to circulatory shock, released contents of RBCs can lead to kidney necrosis
Clinically: fever, hypotension, nausea and vomiting, haemoglobineamia and haemoglobinuria, renal failure
Haemolytic disease of the newborn part 1
Blood with the Rhesus antigen is Rh +, blood without it is Rh -
A problem can occur in Rh- women carrying Rh+ babies
During the first pregnancy the mother becomes sensitized by her babies Rh+ red blood cells that have passed through the placenta into her blood stream, causing the mother to form anti-Rh antibodies
These IgG antibodies can cross the placenta during future pregnancies
If the mother becomes pregnant again with a Rh+ baby, her antibodies will cross the placenta and destroy the baby’s red blood cells
Haemolytic disease of the newborn part 2
The baby becomes anaemic and hypoxic and brain damage and death can occur if blood transfusions are not done before birth
One or two blood transfusions are usually done after birth where the baby’s Rh+ blood is removed and replaced by Rh-
