Allergies and Hypersensitivity

Question 1

what are allergic reactions (aka hypersensitivity reactions)

Answer 1

• a response to Ags not associated with infection agents
• first exposure causes sensitization (IgE production)
• second exposure causes effector reaction (activation of IgE binding cells)

Question 2

what is Atopy

Answer 2

predisposition to become IgE sensitized

Question 3

Types of hypersensitivity reaction

Answer 3

Type I = immediate hypersensitivity
Type II = cytotoxic hypersensitivity
Type III = immune complex hypersensitivity
Type IV = delayed-type hypersensitivity

Question 4

immune mediators in each type of hypersensitivity reaction

Answer 4

Type I = IgE mediated
Type II = IgG/IgM mediated
Type III = immune complex mediated
Type IV = T-helper or cytotoxic T-cell mediated

Question 5

How do proteases work as a sensitizing agent in hypersensitivity

Answer 5

they break down proteins (barriers) to invade cells

Question 6

what are 5 examples of IgE-mediated reactions to extrinsic antigens (type 1 hyper sensitivity)

Answer 6

• systemic anaphylaxis
• acute urticaria (wheal-and-flare)
• seasonal rhino conjunctivitis (hay fever)
• asthma
• food allergy

Question 7

Besides in an allergic reaction, where might we encounter IgE antigens

Answer 7

parasites

Question 8

IgE mediated allergic diseases - sensitization to an inhaled allergen (1st exposure)

Answer 8

• enzyme Der p1 enters mucosa via tight junctions
• Der p 1 is taken up by DC for presentation and T-cell priming in lymph node
• IgE specific for Der p 1 travels from lymph node to mucosa
• IgE binds receptor on mast cell to trigger degranulation
• Mast cell granule contents cause allergic symptoms

Question 9

what happens on the first contact with an antigen

Answer 9

sensitization - class switching to IgE production

Question 10

IgE mediated allergic diseases - effector mechanism (2nd exposure)

Answer 10

cross-linking of IgE bound to high-affinity receptors on mast cells upon second contact with antigen cause a faster response

Question 11

how does mast cell activation and granule release affect the GI tract

Answer 11

increased fluid secretion and increased peristalsis lead to expulsion of gastrointestinal tract contents - diarrhea and vomitting

Question 12

how does mast cell activation and granule release affect the eyes, nose and airways

Answer 12

decreased airway diameter and increased mucus secretion lead to congestion and blockage of airways, swelling, itching and sneezing

Question 13

how does mast cell activation and granule release affect the blood vessels

Answer 13

increased blood flow and increased permeability leads to increased fluid in tissues and hypotension possibly leads to anaphylactic shock

Question 14

classes of mast cell inflammatory mediators and their examples

Answer 14

enzymes: tryptase, chemise, cathepsin G, carboxypeptidase A
toxic mediator: histamine, heparin
cytokine: IL’s, GM-CSF, TNF-a
chemokine: CCL3
Lipid mediator: prostaglandins, leukotrienes, platelet-activating factor

Question 15

Wheal-and-Flare reaction

Answer 15

swelling and redness from type 1 hypersensitivity
- use the skin prick test to determine possible allergens

Question 16

Systemic anaphylaxis (e.g.from bee venom)

Answer 16

• bee venom penetrates skin and enters the bloodstream
• bee venom encounters mast cells within tissues and crosslinks IgE antibodies
• triggers release of mast cell contents

Question 17

what is Atopic march

Answer 17

the progression of atopic conditions over time, beginning in childhood and continuing into adulthood

Question 18

how genetic factors and the environment intertwine in producing type I reactions

Answer 18

high genetic susceptibility + “hygienic” = atopic
low genetic susceptibility + “less hygienic” = non-atopic

Question 19

type I hypersensitivity treatments

Answer 19

medications that block histamine RELEASE from cells - targets the process not the product

Question 20

mode of action that distinguishes each type of hypersensitivity reaction

Answer 20

type 1: IgE binds to mast cells and granules release contents
type 2: IgG directly attack the cell surface
type 3: antibodies (immune complexes) bind free (soluble) antigens in plasma

Question 21

characteristics of type II hypersensitivity reactions

Answer 21

• occurs when IgG recognize cell surface molecules and bind to them, leading to destruction of cells

Question 22

IgG activity in type II hypersensitivity can lead to…

Answer 22

• opsonization and phagocytosis
• activation of complement on recognized cells
• activation of antibody-dependent cell-mediated cytotoxicity

Question 23

characteristics of type III hypersensitivity reactions

Answer 23

• 1-2 hours onset time
• deposition of immune complexes in tissues causes local inflammatory response known as the Arthus reaction

Question 24

how does IgG cause a type III hypersensitivity reaction

Answer 24

• locally injected antigen in immune individual with IgG antibody
• local immune complex formation activates complement - C5a sensitizes mast cells
• activation of FcyRIII on mast cells induces degranulation and histamine release from mast cells
• local inflammation, increased fluid and protein release, phagocytosis and blood vessel occlusion

Question 25

characteristics of Type IV hypersensitivity reactions

Answer 25

• 24-72 hours onset time
• T-cell mediated (cellular)
• can be either Th1, Th2, cytotoxic T ir T-cell mediated neutrophil inflammation

Question 26

how do T-cells cause a type IV hypersensitivity reaction

Answer 26

• antigen is injected into subcutaneous tissue and processed by local APC
• A TH1 effector cell recognizes antigen and releases cytokines, which act on vascular endothelium
• recruitment of phagocytes and plasma to site of antigen injection causes visible lesion

Question 27

after a macrophage stimulates T1H cells, how do they cause delayed-type hypersensitivity

Answer 27

• release chemokines to recruit macrophages to site of antigen deposition
• release IFN-y to induce expression of vascular adhesion molecules
• release of TNF-a and LT leads to local tissue destruction

Question 28

examples of type III and IV hypersensitivity reactions

Answer 28

type III: serum sickness, arthus reaction
type IV: contact dermatitis by poison ivy, tuberculin test

Question 29

what are inflammatory mediators that participate in hyper sensitivity

Answer 29

histamine, cytokines, PAF

Question 30

when do we develop specific types of allergies

Answer 30

allergic dermatitis: 0-1 years
food allergies: 1-3 years
allergic rhinitis: 4-6 years
Asthma: 6-7 years