Hypersensitivity

Question 1

what are the 4 major types of allergy?

Answer 1

Type 1. allergy –> immediate IgE mediated (anaphylactic); i.e. hives, hay fever, asthma. Causes general anaphylaxis which can lead to shock
Type 2. cytotoxic (cell bound antigens) –> transfusion reactions, hemolytic disease of the newborn (HDN) (getting the wrong blood type)
Type 3. Immune complex-mediated (soluble antigens) –> serum sickness, Arthur reaction, SLE (auto-immune reaction where your body makes antibodies against your own body)
Type 4. Delayed cell-mediated –> Tuberculin test for TB exposure and contact hypersensitivity (i.e. poison ivy)

Question 2

Localized Type 1 allergic reaction?

Answer 2

hives, urticaria, allergic rhinitis (inflammation of nasal cavity) and hay fever

Question 3

Systemic Type 1 allergic reaction?

Answer 3

immediate reaction

• life threatening because of impaired breathing due to airway swelling
• uterine cramps, involuntary urination/defecation because smooth mm. contracts
• edema from fluid leaking into tissue spaces (blood vessels dilate and fluid leaks out)
• blood pressure drops and leads to Fatal anaphylactic shock

Question 4

sensitization of type 1 reaction?

Answer 4

sensitization results from classical antigen presentation with T-helper cell involvement and B cell activation (to start producing antibodies for the antigen)

Question 5

Activation of type 1 reaction?

Answer 5

B cells make IgE and it travels in the blood and attaches to the outer membrane of mast cells. The cross linking of at least two IgE molecules bound to Fc receptors on mast cell triggers mast cell/basophil degranulation (release histamine)

Question 6

Two effector phases of type 1 reaction?

Answer 6

1. primary mediators released: histamine, eosinophil chemotactic factor, neutrophil chemotactic factor and proteases
2. secondary mediators released: leukotrienes and prostaglandins

Question 7

What are the 2 roles of histamine and other lipid molecules and cytokines being released from Mast Cells and basophils?

Answer 7

1. increase permeability and dilate blood vessels –> leads to edema and erythema (redness)
2. increase mucus secretion, contract smooth muscle

Question 8

Two forms of treatment for anaphylaxis

Answer 8

1. antihistamines –> block action of histamine
2. epinephrine (epic-pen) –> constricts blood vessels to raise blood pressure, dilates air passages in lungs, and effects smooth muscle [counter acts effects of histamine]

Question 9

ABO Transfusion Reaction

Answer 9

Cytotoxic type 2 hypersensitivity reaction

• this occurs when blood transfusion between people of two different blood types happens
• someone with a type A antigen blood type has antibodies formed for type B, so when the donor cells are type B blood, they carry antibodies for type A
• when the donor cell mixes with the recipient RBC, the anti-A of the donor attacks the A cell of the recipient and complement gets formed leading to hemolysis of RBC

Question 10

Hemolytic Disease of the Newborn (HDN)

Answer 10

Cytotoxic Type 2 hypersensitivity reaction

• this occurs when the mother is RhD negative and her SECOND fetus is RhD positive
• when the mom is RhD negative, it means she has no antibody for RhD in her blood stream, if her first fetus is a RhD positive, then it introduces the positive antigen to the mom’s blood stream and the mom will start to make Anti-RhD+ antibodies in her body (the first baby will not be affected)
• However, when she has a second fetus and its also RhD+, then the mom’s Anti-RhD+ antibodies will begin to attack the RhD+ antigens in the baby, therefore complement pathway gets activated and it causes hemolysis of the baby’s RBC

Question 11

Which antibodies are involved in type 2 reaction?

Answer 11

IgG or IgM

Question 12

How do we prevent Rh sensitization in Hemolytic Disease of the Newborn? [a drug]

Answer 12

Rhogam –> anti-Rh antibodies given before and after delivery to the mom, which rapidly eliminates fetal red blood cells from maternal circulation before B cell activation can occur

Question 13

Type 3 immune complex mediated hypersensitivity

Answer 13

When an Immune Complex (IC) like AB+AG circulate in blood circulation and then deposit in skin, joints and kidney (glomerular basement membrane) [excess amounts of immune complexes - antibody + antigen]

when they deposit, they actually bind to the endothelium lining and then activate the complement pathway which generates chemoattractants for neutrophils - these arrive and then release their granules and enzymes to damage tissue

Question 14

example of type 3 Immune Complex Mediated Hypersensitivity

Answer 14

generalized type –> systemic dissemination of AG-AB (Immune complex) which involves post-streptococcal glomerulonephritis or SLE and rheumatoid arthritis

Question 15

Type 4, delayed cell mediated reaction hypersensitivity

Answer 15

• slow response (takes around 2-3 days) due to previous exposure and has T-memory cells for the antigen
• not antibody mediated, it is mediated by activated macrophages (principal effector cell)
• examples include: contact dermatitis, tuberculin test, and transplant rejection

Question 16

how is type 4 (delayed cell mediated reaction) mediated by activated macrophages (how does the hypersensitivity occur)?

Answer 16

Lytic enzymes that leak from activated macrophages, causes local tissue destruction

CTL (cytotoxic) induced by T-Helper cells may also cause tissue damage

Question 17

What is contact dermatitis?

Answer 17

caused by a delayed cell mediated reaction (type 4 hypersensitivity) –> skin reaction to poison oak and poison ivy where an oil from the plant complexes with skin proteins that are then presented by the skin dendritic cells to the T-Helper 1 cells

Question 18

what are the treatments for contact dermatitis?

Answer 18

corticosteroids

Question 19

what are the treatments for transplant rejection?

Answer 19

immunosuppressive drugs including cortisone