Allergy and Hypersensitivity

Question 1

What is hypersensitivity?

Answer 1

Hypersensitivity is an immune disorder caused by an inappropriate response to antigens that are not necessarily pathogens.

Question 2

How does hypersensitivity result?

Answer 2

Hypersensitivity results from inappropriately vigorous innate and/or adaptive immune responses to antigens.

Question 3

How many classes of hypersensitivity are there?

Answer 3

There are four classes of hypersensitivity.

Question 4

How do the classes of hypersensitivity differ?

Answer 4

The classes of hypersensitivity differ by the immune molecules and cells that cause them, as well as the way they induce damage.

Question 5

How is allergy defined?

Answer 5

Allergy is defined as a damaging immune response by the body to a substance (allergen) to which it has become hypersensitive.

Question 6

What are the consequences of allergy?

Answer 6

Allergy triggers unnecessary increases in vascular permeability and inflammation, which can lead to tissue damage with little benefit.

Question 7

What are local allergic responses?

Answer 7

Local allergic responses are characterized by symptoms restricted to the site where the antigen interacts with the body. Examples include asthma, atopic dermatitis, and food allergies.

Question 8

What is anaphylaxis?

Answer 8

Anaphylaxis is a systemic (whole-body) response that occurs if the same antigens are more widely disseminated throughout the body.

Question 9

How quickly can anaphylactic shock become fatal?

Answer 9

Anaphylactic shock can be fatal within 2-4 minutes of exposure to the antigen.

Question 10

What is atopy?

Answer 10

Atopy refers to a predisposition to an immune response against diverse antigens and allergens, leading to the overproduction of immunoglobulin E (IgE). This increased likelihood of developing a hypersensitivity reaction.

Question 11

What is an allergen?

Answer 11

An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body.

Question 12

How do IgE antibodies recognize an antigen?

Answer 12

IgE antibodies recognize an antigen via their variable region.

Question 13

What type of receptors do IgE antibodies bind to?

Answer 13

IgE antibodies bind to one of two types of Fc receptors (FcR) via their constant regions.

Question 14

Which cells express the FcεRI receptor and are the main mediators of allergy symptoms?

Answer 14

Mast cells, basophils, and eosinophils express the FcεRI receptor and are the main mediators of allergy symptoms.

Question 15

What initiates signaling cascades in mast cells and basophils during an allergic response?

Answer 15

Cross-linking of FcεRI receptors by allergen/IgE complexes initiates signaling cascades that resemble those initiated by antigen receptors.

Question 16

What is the result of signaling in mast cells and basophils during an allergic response?

Answer 16

Signaling results in mast cell/basophil degranulation with the release of inflammatory mediators.

Question 17

What type of hypersensitivity reaction is allergy?

Answer 17

Allergy is a type I hypersensitivity reaction that is mediated by IgE antibodies.

Question 18

Under normal circumstances, when do individuals produce IgE antibodies?

Answer 18

Individuals without allergies generally produce IgE antibodies only in response to parasitic infections.

Question 19

What characteristic does an allergen need to have in order to cause cross-linking?

Answer 19

The allergen needs to be multivalent (have multiple epitopes) in order to cause cross-linking.

Question 20

What is degranulation?

Answer 20

Degranulation is a cellular process that releases antimicrobial, cytotoxic, or other molecules from secretory vesicles called granules found inside some cells.

Question 21

What is the initial cause of bronchial and tracheal smooth muscle contraction in the asthmatic response?

Answer 21

The initial contraction of bronchial and tracheal smooth muscles is mediated by histamine, typically within minutes of release as a result of mast cell degranulation.

Question 22

What other effects does histamine binding to the H1 receptor have in the asthmatic response?

Answer 22

Binding of histamine to the H1 receptor also induces increased vascular permeability and mucous secretion.

Question 23

What enzyme released during degranulation leads to the release of leukotrienes and prostaglandins in the asthmatic response?

Answer 23

Phospholipase released by degranulation initiates enzymatic breakdown of phospholipids in the plasma membrane, eventually leading to the release of leukotrienes and prostaglandins.

Question 24

What is the consequence of the release of leukotrienes and prostaglandins in the asthmatic response?

Answer 24

The release of leukotrienes and prostaglandins triggers further bronchoconstriction, increased vascular permeability, and mucous secretion.

Question 25

When does the early response of the asthmatic response occur?

Answer 25

The early response occurs within minutes of allergen exposure.

Question 26

What triggers the late-phase reaction in the asthmatic response?

Answer 26

Hours after the early response has subsided, inflammatory mediators already released trigger the late-phase reaction.

Question 27

What is the role of cytokines released from mast cells in the asthmatic response?

Answer 27

Cytokines released from mast cells increase the expression of adhesion molecules on endothelial cells, facilitating the influx of neutrophils, eosinophils, and helper T cells.

Question 28

What is involved in Type II hypersensitivity reactions?

Answer 28

Type II reactions involve antibody-mediated destruction of cells by antibody classes other than IgE, such as IgG or IgM.

Question 29

What are the three mechanisms by which antibody bound to the target cell can trigger destruction?

Answer 29

Activation of the complement cascade.
Antibody-dependent cell-mediated cytotoxicity (ADCC).
Antibody bound to the target cell attracts and activates phagocytic cells that kill by the process known as opsonization.

Question 30

What happens in transfusion reactions?

Answer 30

Antigens (carbohydrates) on transfused blood cells generate antibodies in people with a different blood group lacking those antigen(s), resulting in intravascular hemolysis.

Question 31

What is the cause of hemolytic disease of the newborn?

Answer 31

Maternal IgG specific for fetal Rhesus (Rh) antigens cross the placenta and destroy fetal red blood cells if the mother is Rh- and the father is Rh+.

Question 32

How does malaria contribute to hemolysis?

Answer 32

Red blood cells pick up antigens from the P. falciparum parasite, and antibodies trigger hemolysis.

Question 33

What triggers drug-induced hemolytic anemia?

Answer 33

Red blood cells that have bound drug molecules (or metabolites) can trigger antibody responses, such as to penicillin.

Question 34

Why can’t extensive immune complexes of antibody and antigen always be cleared by phagocytes?

Answer 34

Extensive immune complexes of antibody and antigen cannot always be cleared by phagocytes due to peculiarities of the antigen itself or disorders in phagocytic machinery.

Question 35

What can happen when immune complexes are not cleared and remain in the body?

Answer 35

Uncleared immune complexes can induce degranulation of mast cells and inflammation triggered by complement activation, as well as attraction and activation of neutrophils at the site of the immune complex.

Question 36

What are the consequences of immune complex deposition in tissues and capillary beds?

Answer 36

Immune complexes deposited in tissues and capillary beds can induce more innate immune activity, blood vessel inflammation (vasculitis), and tissue damage.

Question 37

What specific conditions can result from immune complex deposition in the kidney and joints?

Answer 37

Deposition of immune complexes in the kidney can lead to glomerulonephritis, and in the joints, it can lead to arthritis.

Question 38

Is Type IV hypersensitivity mediated by antibodies?

Answer 38

No, Type IV hypersensitivity is purely cell mediated, not antibody mediated.

Question 39

What is required for the development of Type IV hypersensitivity?

Answer 39

Type IV hypersensitivity requires T cells to be sensitized to the antigen during the sensitization phase, followed by cytokine production, inflammation, and recruitment of macrophages during the effector phase upon subsequent re-exposure to the antigen.

Question 40

When do symptoms appear in Type IV hypersensitivity?

Answer 40

Symptoms appear 24-48 hours after re-exposure, hence the name “Delayed-type” hypersensitivity.

Question 41

What are some examples of conditions associated with Type IV hypersensitivity?

Answer 41

Examples of Type IV hypersensitivity include contact dermatitis (e.g., poison ivy, nickel ions, hair dyes), granulomas associated with tuberculosis and other intracellular pathogens (bacteria, viruses, fungi, multi-cellular parasites), and graft rejection.

Question 42

What happens during the sensitization phase of Type IV hypersensitivity?

Answer 42

During the sensitization phase, the initial contact with the antigen presented by an antigen-presenting cell triggers the activation, clonal expansion, and differentiation of T helper cells bearing appropriately shaped T cell receptors. Cytokines are secreted by these activated T cells.

Question 43

What happens during the effector phase of Type IV hypersensitivity?

Answer 43

During the effector phase, upon re-exposure to the antigen, the sensitized T cells produce various cytokines and chemokines, attracting and activating macrophages and other non-specific inflammatory cells. This perpetuates the immune response, and symptoms typically appear around 24-48 hours after re-exposure.

Question 44

What are common allergic causes of cough?

Answer 44

Hypersensitivity reactions, such as Type I allergies, are common causes of coughing.

Question 45

What should be considered when evaluating a cough?

Answer 45

While hypersensitivity reactions can cause coughing, it is important to consider that a cough may also be a symptom of a serious underlying disease. Other potential causes of coughing include medication, idiopathic (unknown cause), or psychogenic (psychological cause).

Question 46

What are “red flags” associated with coughing?

Answer 46

Red flags are signs and symptoms found in the patient’s history and clinical evaluation that may indicate a serious underlying pathology. They require further investigation to rule out any serious conditions associated with the cough.