Hypersensitivity Reactions

Question 1

What is Type I hypersensitivity?

Answer 1

IgE antibody response to an antigen

First exposure: T_H2 cells release IL-4
IL-4 drives B cells to produce IgE in response to antigens
Antigen-specific IgE binds to Fce receptor on mast cells

Second exposure: Larger amounts of IgE bind to mast cells causign acute release of mast cell contents, causing allergic reaction

Question 2

What is the difference between T_H1 and T_H2 CD4+ T cells?

Answer 2

Th1: TCR binds to MHCII molecules on macrophages containing bacteria; CD40L (on Tcell) binds to CD40 on APC leading to release of cytokines including:
IFN-y
GM-CSF
TNF-a
Fas ligand

Th2: Same binding molecules, but bind to Bcells presentign specific antigens, leading to release of:
IL-4
IL-5
IL-15
–> Primary Tcell involved in Ab production

Question 3

What causes the clinical signs of Type I hypersensitivity?

Answer 3

Due to a memory response (primary exposure and activation of Th2 cells leading to IgE class switching does cause clinical signs)

• *Repeated exposure to allergen causes:**
• Secretion of IgE by plasma cells
• Binding of IgE to FcRe
• Crosslinking of Ag between IgE molecules
• Activation of Mast cells or Basophiles

Immediate hypersensitivity reaction is due to vasoactive amines, lipid mediators

Late-phase reponse (2-4hrs post exposure) is due to cytokines

Question 4

What casuses the wheal and flare of allergy diagnostic skin tests?

Answer 4

Early release of histamine and vasoactive amines from mast cells and basophils

Question 5

What types of disorders are caused by Type I hypersensitivity?

Answer 5

Allergic rhinitis

Asthma

Anaphylaxis

Question 6

What is Type II Hypersensitivity?

Answer 6

IgG-mediated direct antibody fixation to tissue

–> this antibody fixation triggers the complement system and marks cells for NK cell lysis or macrophage phagocytosis

Question 7

What type of hypersensitivity is Transfusion reactions to blood groups? How does it work?

Answer 7

Type II hypersensitivity

• Antibodies are made against specific blood types, leading to those Abs binding to antigen + RBCs when transfused with the wrong blood

–> These blood cells are lysed and phagocytosed, leading to a hemolytic anemia

Question 8

What is Type III hypersensitivity? What are the two types?

Answer 8

Immune complex mediated hypersensitivity

1. Generalized: when immune complexes are formed in the blood and deposited in tissues
   (i. e. Kidney Glomerulonephritis)
2. Localized (Arthus reaction): when immune complexes are deposited near site of antigen entry
   (i. e. insect bite or antigen injection)

Question 9

What are the three phases of generalized immune complex disease?

Answer 9

1. Immune complex formation

2. Immune complex deposition

3. Complex-mediated inflammation

–> commonly found in kidney glomerulonephritis

Question 10

How are the host cells destroyed in Type II and III hypersensitivity?

Answer 10

Innate host defense mechanisms:

• *Type II:** Injury caused by antitissue antibody
• Complement and Fc receptor mediated recruitment and activation of inflammatory cells
• *Neutrophils and macrophages** injure tissue through phagocytosis, excretion of enzymes, ROSs

Type III: Injury caused by Immune complex tissue deposition
- Again, Complement and FcR recruitment
Neutrophils release of granules, enzymes, and ROSs

Question 11

What is Type IV hypersensitity?