(16) Hypersensitivity Reactions (I & II)

Hypersensitivity reactions refer to adaptive immune responses that occur in ____ or ____ forms and result in disease.

exaggerated, inappropriate

Which hypersensitivity reaction(s) are antibody mediated?

type I, II, III

Which hypersensitivity reaction(s) are cell mediated?

type IV

What kind of hypersensitivity reaction is most immediate?

type I

What kind of hypersensitivity reaction is most delayed?

type IV

What kind of hypersensitivity reaction is mediated by IgG or IgM immune complexes deposited on endothelial cells?

type III

What kind of hypersensitivity reaction is an Arthus reaction?

type III

What kind of hypersensitivity reaction includes blood transfusion reactions? (i.e. mismatched blood types)

type II

What kind of hypersensitivity reaction is an allergic reaction?

type I

What kind of hypersensitivity reaction is PPD (TB skin test)?

type IV

What kind of hypersensitivity reaction includes serum sickness?

type III

What kind of hypersensitivity reaction includes lupus?

type III

What kind of hypersensitivity reaction is mediated by activation of CD4+ and CD8+ T cells?

type IV

What kind of hypersensitivity reaction is mediated by IgE only?

type I

What kind of hypersensitivity reaction is contact dermatitis?

type IV

What kind of hypersensitivity reaction includes autoimmune diseases?

type II

What kind of hypersensitivity reaction is hay fever?

type I

What kind of hypersensitivity reaction is mediated by bound IgG and IgM?

type II

What kind of hypersensitivity reaction is hemolytic disease or the newborn?

type II

If a patient presents with "wheal and flare", nasal congestion, itching, conjunctivitis, asthma, and/or a runny nose, what kind of hypersensitivity reaction are they likely experiencing?

type I

What mediates type I hypersensitivity reactions?

IgE

What is the basic mechanism of tissue injury (via IgE) in type I hypersensitivity reactions?

mast cell degranulation

(basically mast cells release their contents to induce inflammation)

What is the main biologic role of type I (immediate) hypersensitivity reactions?

control of parasitic infections

What are four possible reactions of a type I hypersensitivity response?

hay fever, food allergies, asthma, anaphylaxis

Environmental factors, route of exposure, and age can play a role in making someone susceptible to type I reactions, but what is the largest factor?

genetics

Type I hypersensitivity reactions are mediated by IgE. Remember, IgE is made by B cells in response to what cytokine?

**it enhances the growth of B cells and induces their class switch from IgM to IgE

IL-4

Type I hypersensitivity reactions are mediated by IgE. The antigens involved are larger, so they can't be phagocytosed by APCs. Instead, they directly bind to what kind of T cells?

CD4+ T cells

(induces their differentiation into Th2 cells to secrete IL-4)

Type I hypersensitivity reactions are mediated by IgE. So exposure of a low dose of larger antigens (that can't be phagocytosed very easily by an APC) results in naive CD4+ T cells (that they directly bind to) differentiating into what kind of cells that secrete what?

Th2 cells, IL-4

(antigens bind directly to the CD4+ T cells instead of being presented since they were too large, which causes Th2 to differentiate instead of Th1)

Upon initial exposure of the antigen in a type I hypersensitivity reaction, once IgE is produced upon stimulation of B cells by IL-4 (released by Th2 cells), the IgE binds to high affinity Fc receptors on what kind of cells?

mast cells

(also some basophils)

refers to IgE binding to high affinity Fc receptors of mast cells (and basophils) upon initial exposure of an antigen

**this in itself doesn't trigger a huge response since this is only the FIRST time the immune system has been exposed, and the body is just now learning what this antigen is

sensitization

In a type I hypersensitivity reaction, mast cells are coated in IgE (bound to Fc receptors) upon initial exposure, but there isn't a large-scale immune response mounted this time. However, upon REPEAT exposure, now what happens to activate a bunch of mast cells and basophils?

allergen binds multiple IgEs (which are bound to mast cells and some basophils)

At what point are mast cells and basophils activated in a type I hypersensitivity reaction?

upon repeat exposure after allergen is bound to many IgEs

Once mast cells are activated in a type I hypersensitivity reaction, what 4 things do they release?

histamine, proteases, leukotrienes/prostaglandins, cytokines

Does histamine released from mast cells vesicles (degranulation) in a type I hypersensitivity reaction cause constriction or relaxation of bronchial and intestinal smooth muscle?

constriction

Does histamine released from mast cells vesicles (degranulation) in a type I hypersensitivity reaction cause vasodilation or vasoconstriction?

vasodilation

(plus increased permeability)

3 common symptoms of a type I hypersensitivity reaction upon release of histamine

sneezing, itching (pruritus), runny nose (rhinorrhea)

What is the main reason that activation of mast cells may damage local tissues?

release of proteases

2 types of substances released by activated mast cells that are generated from membrane phospholipids and cause prolonged bronchial constriction & vasodilation

**these enhance the initial effects of histamine!

leukotrienes and prostaglandins

What do mast cells release that enhances the initial effects of histamine?

**triggers prolonged bronchial constriction & vasodilation

leukotrienes and prostaglandins

3 cytokines released by mast cells

**generally function to lure more WBCs to site of reaction to stimulate inflammation

IL-4, IL-5, TNF-a

What is IL-5 mostly responsible for when released by mast cells in a type I hypersensitivity reaction?

eosinophil activation

phase of type I hypersensitivity reaction that includes exposure to allergen, Th2 activation and IgE production, and IgE binding to mast cell Fc receptors

sensitization phase

phase of type I hypersensitivity reaction that includes repeat exposure to allergen, allergen binding to mast cell associated IgE, and signal transduction

activation phase

phase of type I hypersensitivity reaction that includes mediator release and end organ effects of those mediators

effector phase

What 4 respiratory effects can a type I hypersensitivity reaction have to cause allergic asthma?

bronchoconstriction, inflammation, increased mucus secretion, chronic bronchospasm

We know that some of the local effects of a type I hypersensitivity reaction includes a "wheal and flare" rash, nasal congestion, itching, conjunctivitis, asthma, and/or a runny nose...but what are some clinical systemic manifestations of a type I reaction? (5)

generalized pruritis, hives, nausea, vomiting, diarrhea

What is the most severe form of a type I hypersensitivity reaction?

anaphylaxis

extreme systemic form of a type I hypersensitivity reaction that is immediate and can be initiated by a local or general/systemic reaction, leading to a drop in BP to vasodilation and edema, airway obstruction, and bronchospasm

anaphylaxis

What 3 immediate effects of a severe anaphylactic reaction make it so dangerous?

laryngeal edema, bronchoconstriction, decrease in BP

Type I hypersensitivity:

1. Exposure to allergen

2. ____ cell activation and [Ig] production

3. Ig binds to Fc receptors on [these cells]

4. 2nd exposure to allergen

5. Allergen binds to bound Ig on those cells

6. Signal transduction

7. Release of mediators, such as ____

8. End organ effects of mediators

Th2, IgE, mast cells, histamine

method of identifying allergens that can induce a type I reaction in which allergen is injected into the skin, and you wait to see if there's a reaction

in vivo (intradermal test)

method of identifying allergens that can induce a type I reaction in which you draw blood and add different allergen to different samples to see if IgE is produced (general term + specific test)

in vitro, RAST

method of allergy management in which Th2 cells are induced to switch into Th1 cells, producing blocking antibodies of a different isotype so that a bunch of IgE isn't bound to mast cells

**can also stimulate specific suppressor/regulatory T cells to induce tolerance

hyposensitization (or desensitization) therapy

What mediates type II hypersensitivity reactions?

bound IgG or IgM

(bound to self cells)

What are IgG and IgM antibodies in type II reactions formed against?

cell and tissue antigens (including self antigens)

What is the basic mechanism of tissue injury (via bound IgG or IgM) in type II hypersensitivity reactions?

complement activation, phagocyte activity, abnormalities in membrane receptors

In a type II hypersensitivity reaction, binding of antibodies (NOT IgE, usually IgG or IgM) induces inflammation. How is this done via other leukocytes? (i.e., which ones, via what molecules)

attracting and activating macrophages and neutrophils via Fc receptors

In a type II hypersensitivity reaction, binding of antibodies (NOT IgE, usually IgG or IgM) induces inflammation. How is this done via the complement cascade?

activation of classical pathway

(damage by MAC, or also makes opsonins/b fragments)

Binding of antibodies to cells in a type II hypersensitive reaction results in what two processes occurring to the antigen?

opsonization, phagocytosis

(mostly due to classical complement pathway, also ADCC)

What two receptors on phagocytic cells contribute to opsonization and phagocytosis of an antigen via binding of antibodies?

Fc receptor, C3b receptor

In addition to inducing inflammation, binding of antibodies in a type II hypersensitivity reaction interferes in normal cell functions. What is an example of an autoimmune disease in which antibodies bind and result in stimulation of the cells?

Graves disease

(TSH receptors are stimulated by antibodies to make more thyroid hormone)

In addition to inducing inflammation, binding of antibodies in a type II hypersensitivity reaction interferes in normal cell functions. What is an example of an autoimmune disease in which antibodies bind and result in inhibition of the cells?

myasthenia gravis

(ACh receptors are inhibited by antibodies to result in muscle weakness)

What mediates type III hypersensitivity reactions?

IgG or IgM immune complexes (deposited on endothelial cells)

What is the basic mechanism of tissue injury (via IgG or IgM ICs) in type III hypersensitivity reactions?

complement activation, phagocyte activity

What mediates type IV hypersensitivity reactions?

T cells

(activation of CD4+ and CD8+ T cells)

What is the basic mechanism of tissue injury (via T cells) in type IV hypersensitivity reactions?

macrophage activation, lysis of target cells

Which of the following does NOT characterize immediate hypersensitivity?

A. It is mediated by T cells.

B. It involves IgE antibodies.

C. It occurs within 20 minutes of exposure to the allergen.

D. It usually involves allergic responses to inhaled or ingested allergens.

E. It includes hay fever, asthma, and hives.

A

The inflammatory agent _____ is released from mast cells during a type I hypersensitivity reaction.

A. IgE

B. IL-4

C. IL-1

D. histamine

D

____ refers to the life-threatening allergic phenomenon characterized by severe hypotension and profound bronchial constriction due to the presence of large amounts of chemical mediators in the blood released from mast cells and basophils in response to a particular allergen.

A. autoimmunity

B. hypersensitivity

C. anaphylaxis

D. immunodeficiency

C