Hypersensitivity type 2 Flashcards
What is a hypersensitivity type 2 reaction defined as
Destruction of normal tissue/cells by antibody (specifically IgG or IgM) with activation of complement or antibody dependent cell cytotoxicity (using NK cells)
Common examples of hypersensitivity type 2 reactions
Blood transfusion reactions
Hemolytic anemia of newborns
Penicillin induced anemia
Some autoimmune disease
Why are red blood cells commonly affected in type 2 hypersensitivity reactions
Because they do NOT display MHC
Transfusions are performed with
Blood loss
Trauma
Surgery
Low RBC count
How high is the risk of a reaction to a blood transfusion
Species dependent because some species are able to receive “one free” transfusion without a risk of reaction (body has no antibodies/it was never sensitized to another blood type)
What is ACD (acid citrate Dextrose) solution used for
Used in blood collection as an anticoagulant and energy source for red blood cells
Often found in human blood collection packs
What is the formula for ACD solution
Trisodium citrate 22.0g
Citric acid (monohydrate) 8.0g
Dextrose (monohydrate) 24.6g
Distilled water to make it up to 1L
For each 100ml of blood collected, you need ___ml of ACD solution (pH 5.0)
15 ml
Blood group antigens: name often starts with a species code and EA (erythrocyte antigen) followed by a letter or number denoting the order of discovery, what is DEA1.1
DEA: dog erythrocyte antigen
1.1: first allele of antigen 1
A recipient of a blood transfusion may contain pre existing antibody as a result of;
Previous blood exposure or exposure through the diet
The risk of dietary exposure to a blood group antibody is species dependent, who is it often seen in and why
Cattle and some cats
Due to ingesting colostrum with antibodies
What is the mechanism behind a blood transfusion reaction
Pre existing antibody binds to the erythrocyte antigens and activates a complement reaction Causing
Hemolysis
Anaphylatoxin release and mast cell degranulation
Free hemoglobin (can cause secondary damage to the kidneys)
How do you prevent transfusion reactions
Cross matching
The most important cross matching technique is a major cross match, describe this
Using the donors RBCs and the recipients serum
Look for lysis (complement) and agglutination
What is a minor cross match (less important)
Donor serum and recipient RBCs
What are the signs of a mild to moderate transfusion reaction
sweating, salivation, diarrhea vomiting, increased RR/HR
What are the signs of a severe transfusion reaction
Shock Weakness Hyperpnea Hypotension Collapse Death (arrhythmia or apnea)
What are the signs of the recovery phase of transfusion reactions
Hemoglobin from ruptured RBCs eventually converted to bilirubin
Icterus (yellowing) of mucosae and sclera
Describe blood transfusions in cattle
MANY blood types
Blood typing used to check parentage
Transfusions are often incompatible
Some cattle have pre-formed antibodies against foreign RBCs often due to dietary antigens
First transfusions last days to a week
Repeated transfusions needed for the shorter life of RBCs
Dogs have no preformed antibodies against foreign RBCs, they do have many RBC antigens though, what is the major antigen in dogs that causes most problems with transfusions
Only one group, DEA 1 (strong antigen) (there is a card to test this antigen)
DEA 1.1 is a subgroup and the major cause of concern with DEA 1 dogs
40% of dogs are DEA 1.1 positive. They can receive blood from DEA positive AND negative dogs, making them universal blood recipients
if DEA 1.1 (an ideally 1.2) positive dogs are universal recipients, what does that mean for DEA 1.1/1.2 negative dogs
Universal blood donors (don’t need to worry about most dangerous group of antigens)
Greyhounds are universal donors because most are DEA negative
What happens when you transfuse a DEA 1.1 negative dog with a DEA 1.1 positive dog
First transfusion is “free” -it will be okay because there is no preformed antibodies but the body will start to make new antibodies for the next exposure
Transfusion reactions will be seen on subsequent transfusions
This is a common problem in puppies (neonatal isoerythrolysis)
Recommended that you always ____ on subsequent transfusions in breeding bitches
Cross match
Does antigen testing for strong antigens prevent:
Problems on first transfusions: yes
Problems on subsequent transfusions: yes (small risk of incompatibilities from minor antigens)
Does cross matching first transfusion prevent problems with:
First transfusions: yes (test to see if recipient has antibodies to that blood)
Subsequent transfusions: no (you don’t know the blood type, and it doesn’t mean you can use the same blood from the first transfusion because it could have been sensitized from the first transfusion)
True or false
Cross matching tells you the blood type of the animal
FALSE
it tells you if the recipients blood will react to the donors serum
Antigen testing tells you what
Blood type
Describe transfusions in horses
Many blood groups but only 2 are important
No preformed antibody unless previously exposed (one free transfusion)
Risk of reactions is like dogs except multiparous pregnant mares have a higher risk
Describe blood transfusions in cats
Low incompatibility risk in North American domestic cats
Transfused RBCs last about 5 weeks
Describe the blood groups of cats
Follow and non standard system, There is one gene with 3 alleles
a is dominant and gives blood type A
b is recessive, bb cats are type B blood
c is rare and gives type AB blood
99% of all North America domestic cats are the same blood type (A)
Siamese and Burmese -all type A
Persian and Himalayan are mixed, either A or B
UK cats: 40% are type A and 60% are type B
Most cats possess IgM antibodies against type A antigens even though no previous transfusions probably due to
Dietary antigens
A blood transfusion to a type B cat from a type A cat is destroyed in
Hours
Some type A cats possess low amounts of antibody against Type B antigens, resulting in
Less severe transfusion reactions
What is neonatal isoerythrolysis (AKA hemolytic disease of new borns)
Results a from ingesting colostrum rich with antibodies Against the neonates RBCs (antibody causing the problem is passively transferred)
Common problem in horses and mules, occasionally seen in cats dogs and sheep
Describe how neonatal isoerythrolysis occurs in horses foals and mules
Occurs when:
- stallion has a different blood group (antigens) from the mare
- foal inherits some of these antigens from the dad and therefore has a different blood type from the mare
Aa and Qa antigens cause the most problems (others are weaker)
Dam is sensitized due to leakage of the foal blood from placental bleeding or at foaling or during previous transfusions and starts to make antibodies
Foal ingests colostrum from the mare that has antibodies against its blood type
What breed of horses is neonatal isoerythrolysis especially common in
Thoroughbred mares that have had multiple foals
Affects 1% of foals
Describe how a mule is created? Can it be the reverse situation
Mule: female horse and male donkey cross (large genetic difference making these animals sterile) there is a 10% rate of neonatal isoerythrolysis occurring with the birth of mules
Very rare in reverse (male horse and female donkey) very unlikely it will survive, if it does it’s called a Hinny
What are the signs of hemolytic anemia when the foal ingests colostrum with antibodies
Initially pale and then icteric mucous membranes
May show hemoglobinuria
Weakness
Lethargy
Shock
Death
How do you test for neonatal isoerythrolysis
PCV (mild: 0.15 to 0.25 L/L)
(severe: <0.15 L/L)
Jaundiced foal agglutination test: mares colostrum with foals RBCs (agglutination is positive)
Test mares blood during pregnancy for rising titers of antibodies against Aa or Qa antigens
How do you treat neonatal isoerythrolysis
Prevent or stop colostrum ingestion for at least 36h (colostrum production will stop and give time for foal to correct anemia and make more RBCs)
Feed colostrum from another mare (best) or given serum from an unrelated horse
Blood transfusion if PCV <0.15 L/L (convenient source is washed RBCs from the dam (takes out serum)) (equine RBCs clump and separate from serum with time so this is easy)
Describe neonatal isoerythrolysis in cats
Also called Fading Kitten Syndrome
Rare in north America more common in the UK (more type B cats)
Most likely seen when a blood group B queen is mated with a blood group A tom
Chance of this occurring is small if the queen is A and Tom is B
Describe how neonatal isoerythrolysis occurs in cats
Blood type B queen x blood type A Tom
Queen with be genotype bb
Tom will be genotype ab or aa
Offspring will be
1) if Tom is ab: ab or bb (type a or b)
2) is Tom is aa: ab (type a)
Blood group A offspring at risk of this disease from the A antibody in the colostrum
What are the signs of fading kitten syndrome
Icterus
Weakness
Paleness
Describe type 2 drug hypersensitivities
Drug or it’s break down products bind to cells making them antigenic (labels cells as pathogenic and the body attacks them)
Penicillin associated hemolytic anemia is rare but occasionally seen in
Horses
Describe vaccines grown in tissue
Cattle killed BVD vaccine is grown on kidney cells
Contains potent adjuvant (causes an increased immune response)
Causes stimulated anti MHC antibody production
Antibody transferred to calves in colostrum and causes pancytopenia