What type of hypersensitivity reaction is serum sickness?
type III
What is a type III hypersensitivity reaction?
Type III hypersensitivity is an immune complex-mediated reaction in which an antigen-antibody complex lodges in tissue, activating complement, and attracting phagocytes that cause tissue damage. (IgG)
What is the immune reactant for a type III hypersensitivity reaction ?
IgG anitbody
What is the antigen for a type III hypersenstivity reaction?
soulable antigen (univalent)
What is the effector mechanism for a type III hypersenstivity reaction?
complement FcR+ cells
What initiated the type III reaction in the case study?
intravenous administration of a large dose of the antigen (penicillin)
What is the general reason a type III reaction occurs?
excess antigen with fewer anitbodies (which are soluable)
Where do the soluble complexes end up?
they are taken up by endothelial cells and deposited into tissue
What does the depositing of the complexes in tissue lead to?
activation of the complement pathway and subsequent release of C3a and C5a
What is the function of C3a?
a potent stimulator of histamine release from mast cells
What is the function of C5a?
Chemotaxis for neutrophils and induce mast cell degranulation
What is the ultimate result of the high anitgen:low anitbody complexes?
vascular permeability, diapedesis, upregulation of lectins and selectins, WBC recruitment, inflammatory response, platelet mediated clots leading to blood vessels bursting
What can a high intravenous dose of a drug lead to?
vasculitis, nephritis, arthritis
What can a subcutaneous dose lead to ?
Arthus reaction
What can an inhaled dose lead to?
farmer's lung (alveolar/capillary interface decrease)
What is the normal respiration rate of a human?
20 breaths per minute
Was the boy's respiration rate increased?
yes (68)
What is the normal heart rate of a human?
60-80 beats/min
Was the boy's heart rate elevated?
yes (120)
Should lungs be seen on x-ray?
no they are soft tissue
What doe it mean if lung tissue is opague?
indicates fluid or mass
What does fluid in the lungs indicate?
pneumonia
What does elevated WBC but normal immature forms of neutrophils mean?
bacterial infection that is not overwhelming
The opaquness of one lobe lead to the diagnosis of what?
lobular pneumonia
How was the bacterial cause of the pneumonia diagnosed?
sputum and blood cultures
What was the bacterial cause of the pneumonia?
streptococcus pneumoniae (pneumonococcus)
Describe Streptococcus pneumoniae
Gram+;
Encapsulated; can develop into meningitis
True or false: IV administration is a systemic approach
true
Why did the patient feel better on the fourth day of treament?
there was a high antigen content, but the antibodies were not activated to be secreted in high concentrations yet
Why was the treatment switched from ampicillin to penicillin?
the s. pneumonia cultured was sensitive to penicillin
true or false: on the 9th day of treatment, the patient was feeling better and was going to be released
true
What were the patients symptoms on day 10?
hives, swollen face, tightening airway, swollen, painful ankles, enlarged spleen, and swollen lymphnodes
What treatment was administered on the 10th day?
anti-histamine benedryl, B2-adrenergic albuterol, and penicillin was discontinued
How does an antihistamine function?
the drug bind H1 receptors which prevent histamines from binding and thus vasopermaiility and smooth muscle contraction is inhibited
What is B2 adrenergic drug like albuterol?
helps the patient breath by dialating the airways
What do the large lymphnodes and enlarge spleen indicate?
a systemic problem
what is the function of the spleen?
filters pathogenic organisms from the blood
What were the doctor's differential diagnoses for the patient?
serum sickness or menigitis
Why do the lymphocyte results in the profile make sense?
the lymphnodes are enlarged indicating that clonal selection and expansion are occuring
true or false: plasma cells were present in blood smears
true
What do the plasma cells in the blood smear indicate?
the activation of B cells and the potential synthesis of IgG leading to type II reaction
Describe the erythrocyte sedimentation rate test?
whole blood is centrifuged in order to determine if coagulation between acute phase proteins and antigens
What is the normal erythrocyte sedimentation rate?
20 mm/hr
What did the patients increased erythrocyte sedimentation rate indicate?
more acute phase proteins were present, more coagulation, and more inflammation
What was the result of the total serum complement level test?
the C1q and C3 levels were decreased
Why were the C1q and C3 levels decrease?
because the reservoir naturally in the blood were utilized
Why did the patient develop urticaria and swollen/painful joints?
the immune complexes were lodging in the skin capillaries and joints leading to vessel leakage, swelling, and vasodilaiton
As the size of the complexes increase what can occur?
2 or more IgGs can bind leading to the classical complement pathway
Why was the patient put on benadryl and naproxen?
the erythrocyte sedimentation and total serum complement tests indicated serum sickness
What occured after benedryl and naproxen were used?
the patients hives were worse and they developed neurologic symptoms and purpuric rashes developed
What was the purpose of naproxin?
inhibits prostaglandin formation which decreased pain by preventing enzymes cox 1 and cox 2)
What are purpuric rashes caused by?
hemorraging of the blood vessel
What was the purpose of the CT scan?
to rule out menigitis caused by a infectious brain lesion
What was the purpose of the CSF analysis ?
to rule out mengitis
What things would have indicated mengitis on a CSF anaylsis?
increased protein, decreased glucose, and increased WBCs
Why might mengitis have developed?
streptococcus pnemoniae can cross the BBB and penicillins cannot
What was the purpose of the ECG?
showed decreased blood flow to the posterior part of the brain ( the cause of neurologic signs)
Why was there a decreased amount of blood flow to the brain?
the body's blood vessels became leaky and they hemmoraged all over the body due to complement fixing and clotting
What was the purpose of the skin biopsy?
to identify the edema around the dermis capillaries and lymphocyte infiltration
What did immunoflorenses of the skin biopsy show?
deposition of IgG and C3
What did the immunofloruscent test confirm?
Type III reaction
What was the patient sent home on?
prednisone and benedryl
What is the function of prednison?
upregulates production of NFkappaB inhibitor where decreases lymphocyte maturation and proliferation)
What two tests were completed 2 weeks after dicharge?
skin test and Ras test
What was the skin test and what was its purpose?
small amounts of the penicillin antigens were injected under the skin in order to determine if there was immediate mast cell degranulation as a result of reloaded IgEs
What did the skin test rule out?
type I reaction
What is the Ras test?
insoluable beads are coated with antigen and the PT's serum is run over the beads to determine if there are any IgE's in the blood. Radioactive anti-Fc IgE are then added and the radioactivitiy is recorded
What did the negative ras test proof?
the reaction was not type I
What two drug types were the patient's parents told not to given?
penicillins or cephalosporins which are structurally similar
What test was most important in determining that the PT was suffering from an immune complex disorder?
total serum proteins were decreased
What caused the acute phase reaction?
IL-1 and IL-6 secreted from macrophages that took up original antigen leading to more complement proteins and inflammatory proteins
What is the big concept of type III reactions?
univalent complexes form when there are excessive antigens and fewer IgG anitbodies. The complexes get absorbed in endothelial cells leading to deposition. 2 or more IgGs leads to the classical pathway and C3 and C5a lead to mast cell degranulaiton. Blood