Type II and II hypersensitivity Flashcards
Type II reactions: Antibody-dependent cellular cytotoxicity
Antibody is directed against a cell surface or tissue antigen
Antibody interacts with complement or effector cells (macrophages, neutrophils, NK cells) to damage the target.
Antibodies link the effector cells to the target cells via the effector cell Fc receptor
Antibodies on target cells interact with C1 of the complement classical pathway
activation and destruction of the target.
C3b and C3d are deposited on the target cells and act as recognition units
for effector cells with complement receptors
Opsonins increase the phagocyte’s capacity to produce reactive oxygen
intermediates and to destroy pathogens, as well as increases their ability to produce immuno-pathological damage in hypersensitivity
Antibodies binding to Fc receptors on phagocytes stimulates them to
release arachidonic acid, the precursor for prostaglandin and leukotrienes
involved in inflammation.
Most pathogens are destroyed by a combination of oxygen metabolites,
radicals, ions, enzymes, altered pH, etc. inside the phagolysosomes.
Target tissue cannot be ingested (completely engulfed) by phagocytes.
Sensitized targets attacked by phagocytes are damaged by the release of
the cellular contents (enzymes) by the frustrated effector cell.
Transfusion
Definition: Transfer of blood from a donor to a recipient
Function: Used to replenish erythrocytes (or other cells) that the recipient
has lost as a result of injury or disease.
Major blood groups in RBC transfusion reactions are ABO, Rhesus, Kell,
Duffy, Mn
Blood groups
Type A individuals make antibodies to the B carbohydrate antigen
Type B individuals make antibodies to the A carbohydrate antigen
Type O individuals make antibodies to the A & B antigens.
Type AB individuals make neither Anti A nor Anti B
Antibodies to blood groups antigens are present in all individuals after infancy and are believed to be the result of exposure to microbial flora.
Transfusion reactions occur within minutes after receiving mismatched blood and result in
Hypotension (low blood pressure)
Shock (secondary to inflammatory action of complement components)
Liver and kidney toxicity due to products of lysed red cells (hemoglobin
and bilirubin). Breakdown products of hemoglobin fever, chills, nausea, vomiting &
lower back pain. Sometimes transfusion reactions develop over days or weeks Long term transfusion reactions may be due to blood group antigens
other than ABO
Treatment for transfusion reaction
Discontinue transfusion
Maintain urine flow
Give diuretic
Hemolytic disease of the newborn (HNB)
Appears in newborn infants when an Rh- mother has been sensitized to
Autoimmune hemolytic anemia:
Occurs when patients produce antibodies to their own red cells.
Detected by Coombs tests
Drug induced reactions to blood components
Drugs adsorb to the RBC membrane and antibody is made to the drug-cell
membrane complex. (Complement is activated progressive anemia from red cell destruction)
antigen D on the red cells of an Rh+ fetus. Maternal IgG antibody crosses the placenta and reacts with fetal red cells
causing destruction of the red cells (hemolytic anemia) & impaired platelet
function (Erythroblastosis fetalis). This is fatal if untreated First infants generally can be carried to term but subsequent infants are
affected After the birth of the first Rh+ baby, a normally slightly leaky placenta
allows Rh+ erythrocytes to enter the mother’s blood and elicit a memory
immune response thus resulting in maternal IgG antibody against the
infant’s red cells. Rhogam (antibody directed to the Rh antigen) is now given to Rh- mothers
at the time of delivery in order to prevent production of maternal anti RhD
antibodies. It binds to fetal erythrocytes which have entered the mothers
circulation and results in the red cells being cleared before a maternal
immune response is triggered.
Autoimmune hemolytic anemia:
Occurs when patients produce antibodies to their own red cells.
Detected by Coombs tests
o Warm reactive antibodies (react with antigen at 37˚C) usually
against Rh CDE antigens
o Cold reactive antibodies (react with antigen below 37˚C) mediated
by complement. The antibody is against the Ii (adult I or fetal i)
antigen in “cold agglutinin disease”. Patients with lymphoma make
monoclonal cold agglutinin IgM antibodies that are the product of
an abnormal clone. In some cases idiopathic cold agglutinin
disease can progress to malignant lymphoma, thus patients require
close long term follow up care. (Low titers of cold agglutinins can
occur following M. pneumoniae, Epstein-Barr virus (EBV),
cytomegalovirus (CMV)). Acute post infectious syndromes usually
resolve spontaneously. In chronic idiopathic disease the severity of
symptoms must be weighed against the potential long term effects
of chemotherapeutic or immunosuppressive agents.
Drug induced reactions to blood components
Drugs adsorb to the RBC membrane and antibody is made to the drug-cell
membrane complex. (Complement is activated progressive anemia from red cell destruction)
Drug antibody complexes adsorb to the cell via adherence or Fc receptor Drugs adsorb to cells and break self tolerance causing antibody to be
made to self antigen
Hyper-acute Graft Rejection
Occurs when a transplant recipient has preformed antibodies directed
against the graft Recipient antibodies react immediately against antigens exposed on the
grafted organ
Major effectors are neutrophils and platelets interacting with the sensitized
cells via Fc, C3b and C3d receptors
Examples of Type II Hypersensitivity diseases
A. Goodpasture’s syndrome: Antibody is made to the glycoprotein of the
glomerular basement membrane. IgG antibody (50% fix complement) Linear fluorescence pattern.
B. Myasthenia Gravis: extreme weakness is associated with antibody to
the ACh (acetylcholine) receptors on the surface of muscle membranes. Antibodies block binding of ACh to the receptors so the effect of the ACh is reduced thus the muscle contracts weakly. Anti IgG and complement are involved.
Type III hypersensitivity reactions
Mediated by formation of immune complexes & complement activation.
Complement split products serve as immune effector molecules vasodilation and chemotactically attract neutrophils.
Tissue damage occurs from the accumulation of neutrophils and the
release of lytic enzymes, or by the terminal membrane attack complex. Healthy tissue in the vicinity is also damaged.
Categories of immune complex diseases:
The combined effect of low grade persistent infections together with weak
antibody response chronic immune complex formation which eventually deposits in tissue (kidney).
Examples
o Chronic hepatitis B infection o Post streptococcal glomerulonephritis
Autoimmune diseases (auto-antigen and auto-antibody complex deposited
in kidney, joints & skin) Example: Systemic lupus erythematosus Inhaled antigen (mold, plant, animal antigens, fungi) complexes with
specific antibody and is deposited in lungs Examples
o Farmer’s lung o Pigeon fanciers disease
Type III inflammatory mechanisms
Trigger complement system (C5a, C3a, C4a, anaphylatoxins) and cause
release of vasoactive amines from mast cells and basophils, increasing vascular permeability.
Anaphylatoxins are chemotactic for neutrophils
Macrophages at the site release cytokines (TNF-Tumor necrosis factor)
Platelets interact with complexes via Fc receptors causing aggregation
and microthrombosis. PMNs (neutrophils) release lytic enzymes which damage underlying red
cells.
Serum sickness
Circulating immune complexes deposit in the blood vessel walls and
tissue leading to increased permeability, and inflammatory diseases such as glomerulonephritis and arthritis
Symptoms: fever, weakness, generalized vasculitic rashes with edema,
erythema & lymphadenopathy. Symptoms are related to the quantity of immune complexes formed, the size of the complexes and the tissue of deposition.
Arthus Reaction
Animals are immunized repeatedly until they have high titers of antibody
. Further injection of antigen subcutaneously or intradermally a reaction The reaction occurs around the walls of local blood vessels where antigen
is encountered. Depending on the amount of antigen injected, there is
marked redness, edema and hemorrhage at the injection site that is
maximal 4-8 hrs afterwards & wanes by 48 hours. Deposition of the complexes in the vessel wall is followed by infiltration of
neutrophils and intravascular clumping of platelets. After 24-48 hrs neutrophils are replaced by mononuclear cells and
subsequently plasma cells. Complement activation is essential for attraction of neutrophils which are
important in this reaction. Examples
o Farmer’s lung o Extrinsic allergic vasculitis o Rarely occurs after diphtheria or tetanus immunization
