Hunter-Type II Hypersensitivity Flashcards by michelle granstrom

Again, what is the immune reactant in Type II hypersensitivity reactions?

IgG

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What is the nature of the antigen in Type II rxns?

cell or matrix associated antigen

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What is the effector mechanism with Type II rxns?

it involves FCR+ cells (phagocytes, NK cells)

there is binding to cells in the blood & tissue to form an immune response against your own tissues.

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What are some examples of Type II hypersensitivity reactions?

Immunohemolytic Anemias
Microbial cross-reactions with host tissues (e.g. rheumatic fever)
Autoantibodies to self-proteins on cells or intracellular matrix
Autoantibodies that block or stimulate cell surface receptors

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What are some examples of immunohemolytic anemias?

Transfusion Reactions (ABO Mismatch)
Drug-induced (e.g. penicillin)
Hemolytic Disease of the Newborn

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autoimmune hemolytic anemia

Give the target antigen, mechanism of disease, and clinicopathologic manifestation.

Target antigen: RBC membrane protein (Rh blood group antigens–I antigen)
Mechanism: opsonization & phagocytosis of RBCs
Manifestation: hemolysis, anemia

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Autoimmune Thrombocytopenic Purpura

Give the target antigen, mechanism of disease, and clinicopathologic manifestation.

Target Antigen: Platelet Membrane Proteins
Mechanism: opsonization & phagocytosis of platelets
Manifestation: bleeding

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Pemphigus Vulgaris

Give the target antigen, mechanism of disease, and clinicopathologic manifestation.

Target Antigen: proteins in epidermal intercellular junctions (cadherins)
Mechanism: antibody-mediated activation of proteases, disruption of intercellular adhesions
Manifestation: skin vesicles (bullae)

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Vasculitis caused by ANCA

Give the target antigen, mechanism of disease, and clinicopathologic manifestation.

Target Antigen: Neutrophil granule proteins, presumably released from activated neutrophils
Mechanism: neutrophil degranulation & inflammation
Manifestation: Vasculitis

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Goodpasture syndrome

Give the target antigen, mechanism of disease, and clinicopathologic manifestation.

Target Antigen: Noncollagenous protein in basement membranes of kidney glomeruli and lung alveoli
Mechanism: Complement- and Fc receptor–mediated inflammation
Manifestation: nephritis, lung hemorrhage

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Acute rheumatic fever

Give the target antigen, mechanism of disease, and clinicopathologic manifestation.

Target Antigen: Streptococcal cell wall antigen; antibody cross-reacts with myocardial antigen
Mechanism: inflammation, macrophage activation
ManifestatioN: myocarditis, arthritis

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Myasthenia Gravis

Give the target antigen, mechanism of disease, and clinicopathologic manifestation.

Target Antigen: Ach receptor
Mechanism: Antibody inhibits acetylcholine binding, down-modulates receptors
Manifestation: muscle weakness, paralysis

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Graves Disease (hyperthyroidism)
Give the target antigen, mechanism of disease, and clinicopathologic manifestation.

Target Antigen: TSH receptor
Mechanism: Antibody-mediated stimulation of TSH receptors
Manifestation: hyperthyroidism

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Type II Diabetes

Give the target antigen, mechanism of disease, and clinicopathologic manifestation.

Target Antigen: insulin receptor
Mechanism: antibody inhibits binding of insulin
Manifestation: hyperglycemia, ketoacidosis

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Pernicious Anemia

Give the target antigen, mechanism of disease, and clinicopathologic manifestation.

Target Antigen: intrinsic factor of gastric parietal cells
Mechanism: neutralization of intrinsic factor, decreased absorption of Vit B12
Manifestation: abnormal erythropoiesis, anemia

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Describe the process by which an antibody against self would destroy a free floating self cell.

You have antibody for some pathogen that cross reacts with self tissue.
Perhaps complement plays a role.
The antibody binds to the cell.
C3b is deposited on the host cell.
Phagocytic cells react to this opsonized cell & eat it up!

Describe the process by which an antibody against self would destroy a bunch of tissue.

Antibody against self is bound to the self tissue. It opsonizes it. The neutrophil comes over w/ the Fc receptor & binds. Can’t do phagocytosis so it does “frustrated phagocytosis” & injects its killing agents into the tissue. Results in lots of inflammation & tissue injury.

Describe antibody mediated cellular dysfunction.

antibody binds to a receptor.
blocks NT.
Antibody stimulates the receptor without hormone–over-activity
Ex: Myasthenia Gravis & Grave’s Disease

What are the 2 mechanisms by which natural antibodies to AB antigens destroy foreign RBCS?

Mechanism #1: Phagocytosis–Fcr+ phagocytes bind & eat up.

Mechanism #2: Complement Activation–lysis & RBC destruction

Describe drug-induced immunohemolytic anemia.

RBC surface proteins modification by the penicillin “hapten”
Presentation of penicillin-modified RBC peptides to CD4 T cells
B cells receive T cell help and begin to produce anti-penicillin antibodies
Antibodies bound to penicillin-modified RBC cause their destruction either by phagocytosis, or less often complement-mediated hemolysis

A 72-year-old woman with osteoarthritis suffered acute hemolysis after her right hip was replaced. She had no evidence of splenomegaly and no lymphadenopathy to suggest an underlying malignancy. No explanation was found for the episode; warm and cold antibody tests were negative. She remained well until she had the other hip replaced 2 years later, when she again developed hemolysis soon after the anesthetic, as well as after the revision 7 months later. Her serum was found to react with red cells coated with the cephalosporin used at the time of anesthetic induction.
What does this patient have?
What is the proper treatment?

cephalosporin-induced hemolytic anemia (type II hypersensitivity)
**she had an MHC molecule capable of presenting drug-modified peptides–>gave her an IgG response
Avoid the antibiotic.
Get a medialert bracelet.
Tested for cross-reactivity with penicillin

What is alloimmunization?

this is when 2 genetically different people interact…mom & baby.
Ex: Rh- mom w/ several Rh+ babies.

When is it a risk that a mom is Rh-?

not with her first baby

but with her second baby if she got any RBCs from the first child during delivery she could have antibodies against Rh+

Maternal Ig__ anti-Rh antibodies cross placenta and cause ______________.

IgG!

hemolysis of fetal RBCs, can result in severe anemia & fetal heart failure & massive edema (hydrops fetalis).

If an infant survives the attack of its mom's anti-Rh antibodies...what could still be a problem for him?

could be that during the hemolysis of his blood...lots of bilirubin was released. Could have brain damage from these heme metabolites

What is the direct Coombs test?

Rh- mom & Rh+ daughter. Take blood from the baby's umbilical cord (invasive). If this blood has mom's Anti-Rh antibodies bound to it...then it will bind the rabbit anti-human antibody. This will cause agglutination that will show up in a titer to show the severity.

What is the indirect Coombs test?

Rh- mom & Rh+ daughter. Take maternal serum w/ anti-Rh antibodies. Add Rh+ RBCs (not from the fetus so not invasive). Add rabbit anti-human antibody. If there is antibody, it will bind the RBC & will bind the rabbit & will agglutinate. It will show up in a titer to show the severity.

PATIENT HISTORY: Mrs. Waymarsh was 31-years-old when she became pregnant for the third time. She was known to have blood group A, Rh- red cells. Her husband was also type A but Rh+. Their first-born child, a male, was healthy. During her second pregnancy Mrs. Waymarsh was noted to have an indirect Coombs titer at a 1:16 dilution of her serum. The fetus was followed closely and the delivery of a healthy baby girl was induced at 36 weeks of gestation. It was 5 years later when Mrs. Waymarsh became pregnant again. CLINICAL FINDINGS: At 14 weeks gestation her indirect Coombs titer was 1:8 and at 18 weeks 1:16. Amniotic fluid was obtained at 22, 24, 27, and 29 weeks of gestation and was found to have increasing amounts of bilirubin (indicating fetal RBCs were being hemolyzed). At 29 weeks of gestation a blood sample was obtained from the umbilical vein and found to have a hematocrit of 6.2% (normal 45%). What might be an appropriate treatment?

TREATMENT: Upon finding that the fetus was profoundly anemic, 85 ml of type O, Rh- packed RBCs were transfused into the umbilical vein. At 30.5 weeks of gestation another sample of umbilical vein blood was obtained; the hematocrit was 16.3%. The fetus was transfused again with 75 ml of type O Rh- packed RBCs. The fetus was examined at weekly intervals for the appearance of hydrops and none was observed. At 33.5 weeks of gestation the hematocrit of an umbilical vein sample was 21%, so another 80 ml of type O, Rh- packed RBCs was transfused. At 34.5 weeks gestation it was determined that the fetus was sufficiently mature to sustain extrauterine life without difficulty; labor was induced and a normal female infant was born. The hematocrit in the umbilical vein blood was 29%. The baby did well and no further therapeutic measures were undertaken.

How can a fetus receive a blood transfusion?

thru their umbilical vein in the placenta. Thank goodness!

1. Rh antigens are so sparsely scattered on the RBC surface that IgG molecules bound to these antigens are too separated to bind C1q. Therefore complement-mediated hemolysis cannot be invoked to explain hemolytic disease of the newborn. By what mechanism are the RBCs destroyed?

RBCs destroyed by phagocytosis. Baby has active phagocytes.

2. When an Rh- woman is ABO compatible with her husband, the risk of Rh alloimmunization is 16%. When they are ABO incompatible the risk falls to 7%. How would you explain this difference?

When mom & dad have same ABO—higher risk to alloimmunization of Rh. Opposite blood types risk falls. If the baby happens to be incompatible with mom on ABO…the likelihood is that those RBCs will have natural antibodies from mom that will remove those cells before mom becomes alloimmunized. There are also immunohemolytic diseases associated with ABO.

3. Why were Rh- RBCs used for the intrauterine transfusion?

So that if the baby has mom's anti-Rh antibodies, they won't bind the RBCs & destroy the fetal hematocrit.

4. The hematocrit of Mrs. Waymarsh’s baby gradually returned to normal 6 weeks after birth. Why would it take 6 weeks?

When the baby is born it still has the anti-Rh antibodies. 2 half lives of 3 weeks and you are pretty much done.

If you suspect hemolytic disease of the fetus, a Type ____ hypersensitivity...what is the procedure that you should follow?

Type II Hypersensitivity Use Coombs Test to determine if Rh- mother has anti-Rh antibodies Human immunoglobulin specific for Rh D antigen (Rhogam) Given at 28 weeks gestation and again within 72 hrs of delivery to Rh- women Anti-Rh antibodies opsonize Rh+ fetal RBCs for phagocytosis and prevent alloimmunization

Describe what happens in post-streptococcal rheumatic fever.

Antibodies to Streptococcal M Antigens Cross-React with Antigens on Heart and Synovial Tissue This happens b/c Group A Streptococcal M proteins share epitopes with proteins found in synovium, heart muscle, and heart valve.

What kind of damage occurs in post-strep rheumatic fever? What is the treatment & prognosis?

Molecular mimicry contributes to the arthritis, carditis, and valvular damage. **Treatment with NSAIDS, corticosteroids, and antibiotics Prognosis depends mostly on the severity of the initial carditis.

A 10-year-old boy presents with a migratory polyarthritis, arthralgia, and a fever of 38.5° C. Upon examination, a pericardial rub, aortic murmur, and cardiac enlargement were noted. His history was significant for a streptococcal pharyngitis 3 weeks before that was diagnosed by a rapid strep test. His mother noted that she stopped the antibiotics that were prescribed after 5 days because her son was feeling much better. What does this child have? What would be a good treatment for him?

The boy met the Jones criteria for a diagnosis of post-streptococcal rheumatic fever. He was treated with aspirin and prednisolone, and penicillin V.