Hypersensitivity

Question 1

Major mediators of Type I hypersensitivity

Answer 1

IgE and Mast Cells or Eosinophils

Question 2

Types of hypersensitivity reaction

Answer 2

Question 3

Major mediators of Type II hypersensitivity

Answer 3

Autoreactive IgG/IgM and sometimes effector mediators of IgG (neutrophils, macrophages)

Question 4

Major mediators of Type III hypersensitivity

Answer 4

Immune-complex-forming antibodies against soluble antigens, complement, and chronic inflammatory cells recruited to sub-endothelial immune-complex deposits.

Question 5

Major mediators of Type IV hypersensitivity

Answer 5

CD4 and CD8 T cells and downstream effector cells driven by T-cell-derived cytokine production

Question 6

Atopy

Answer 6

Presdisposition to developing allergies. Sometimes used synonymously with allergy.

Question 7

Sensitization phase of allergy

Answer 7

Activation of Th2 and IL-4-secreting Tfh cells, which lead to ε heavy chain class-switching and IgE production in B cells. The IgE produced then binds to the surface of mast cells, basophils, and eosinophils via FcεRI.

Question 8

Distinct phases of Type I hypersensitivity

Answer 8

The immediate effects are mediated by mast cell degranulation, but there is also a late-phase reaction.

This late-phase reaction happens several hours following exposure and is the characterized by infiltration of neutrophils and eosinophils in response to the mast cell signals. It is these cells which are the culprit in tissue damage associated with repeated bouts of allergic reactions.

Question 9

Development of an allergy diagram

Answer 9

Question 10

Kinetics of allergy

Answer 10

Question 11

Genes with variants that predispose to development of allergies

Answer 11

IL-4

IL-4R

IL-13

IL-5

Filaggrin

Question 12

Filaggrin

Answer 12

Protein required for barrier protection in skin. Mutations predispose to development of allergies early in life, especially atopic dermatitis.

Question 13

FcεRI signaling

Answer 13

Question 14

Principal cells involved in late-phase reaction

Answer 14

neutrophil

eosinophil

Th2

Question 15

Late-phase reactions are stimulated by. . .

Answer 15

. . . IL-4 and TNF-α derived from mast cell degranulation.

Question 16

Most of the actual tissue damage associated with allergy is caused by. . .

Answer 16

. . . eosinophil-derived proteases cleaving structural proteins.

Question 17

hay fever

Answer 17

Allergic reaction to inhaled antigens, such as ragweed pollen antigens. This results in allergic sinusitis and rhinitis, initiated by mast cells in the nasal mucosa.

Increased mucus production and late-phase inflammation occur as a result of mast cell degranulation and Th2 activation locally.

Question 18

food allergy

Answer 18

Ingested antigens trigger intestinal mast cell activation. Results in increased peristalsis which may cause diarrhea and vomitting.

More severe symptoms such as anaphylaxis may occur if the antigens are absorbed and become systemic.

Question 19

asthma

Answer 19

Characterized by difficulty breathing, wheezing, coughing, and airway obstruction in response to a respiratory allergen which activates bronchial mast cells.

Question 20

chronic asthma

Answer 20

In chronic cases of asthma, baseline eosinophilia of the airway is common, and mucus production in the airway is ramped up. Bronchial smooth muscle also hypertrophies and thus becomes hyper-reactive to various stimuli.

May be IgE-dependent or -independent, in which case cold or exercise may trigger asthma attacks.

Question 21

Anaphylaxis

Answer 21

Systemic reaciton characterized by rapid edema in various tissues, including the larynx, and precipitous drop in blood pressure (anaphylactic shock), as well as bronchoconstriction.

A result of systemic mast cell degranulation.

Question 22

Treatment for anaphylaxis

Answer 22

Epinephrine to contract vascular smooth muscle and relieve shock symptoms, as well as acting as a bronchodilator to counter bronchoconstriction symptoms.

Question 23

Treatments for asthma

Answer 23

Corticosteroids, leukotriene antagonists, and β adrenergic receptor agonists.

Question 24

Cromolyn

Answer 24

Inhibits mast cell degranulation

Question 25

Isotypes of antibody which bind to Fcγ receptors on neutrophils and macrophages and promote activation

Answer 25

IgG1 and IgG3

Question 26

Pernicious anemia

Answer 26

Anemia caused by B₁₂ deficiency resulting from either diet or loss of intrinsic factor.

May be autoimmune in origin, if the immune system targets parietal cells for destruction or neutralizes intrinsic factor.

Question 27

Type II vs Type III Hypersensitivity manifestations

Answer 27

Type II will usually be tissue localized depending on the antigens involved.

Type III will manifest as systemic vasculitis and will focus around tissues with turbulent flow that are susceptible to IC deposition, such as synovial joints and kidneys.

Question 28

Serum sickness

Answer 28

First discovered Type III hypersensitivity disease. Occurs following administration of antiserum. Produces ciruclating immune complexes which then mediate disease.

This may result from host antibodies and injection of foreign antigen within the blood as well. Some humanized mAbs may also serve as antigens for serum sickness ICs.

Question 29

Arthus reaction

Answer 29

A localized form of Type III hypersensitivity. Induced by subcutaneous administration of protein antigen. Results in local IC formation and local vasculitis.

In a small percentage of vaccine recipients who have previously been vaccinated or already have antibodies against the vaccine antigen, a painful swelling that develops at the injection site represents a clinically relevant Arthus reaction.

Question 30

In human immune complex diseases, the antibodies may be specific for ___.

Answer 30

In human immune complex diseases, the antibodies may be specific for self antigens or microbial antigens

Question 31

Systemic lupus erethymatosus as a Type III hypersensitivity disease

Answer 31

In systemic lupus erythematosus, immune complexes of anti-DNA antibodies and DNA can deposit in the blood vessels of almost any organ, causing vasculitis and impaired blood flow, leading to a multitude of different organ pathologies and symptoms

Question 32

Example of bacterial antigen-induced Type III hypersensitivity from Microbiology

Answer 32

Poststeptococcal glomerulonephritis

Question 33

Where does delayed-type hypersensitivity get its name?

Answer 33

Because it occurs 24 to 48 hours after an individual previously exposed to a protein antigen is re-challenged with the antigen (i.e., the reaction is delayed). The delay occurs because it takes several hours for circulating effector T lymphocytes to home to the site of antigen challenge, respond to the antigen at this site, and secrete cytokines that induce a detectable reaction.

Question 34

Example of a purposefully induced Type IV Hypersensitivity reaction with clinical utility

Answer 34

Purified protein derivative tests

Think 48-72 hour followup appointments to read a tuberculosis PPD test.