Aims Explain the mechanisms of hypersensitivity reactions. Define anaphylaxis Readings: Abbas & Lichtman, Chapter 11

Aims

• Explain the mechanisms of hypersensitivity reactions.

• Define anaphylaxis

• Readings: Abbas & Lichtman, Chapter 11

Hypersensitivity

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

• Four types of hypersensitivity reactions.

Pathologic immune Mechanism ofType of hypersensitivity mechanism tissue injury

Type I - IgE antibody mast cell immediate hypersensitivity degranulation(hay fever, asthma)

Adapted from Abbas & Lichtman’s Basic Immunology 11-1

Type I

Immediate Hypersensitivity


Type II - IgG or IgM bound to C’ activationantibody-mediated host cells phagocyte cytotoxic or cytolytic reactions activity(HDN, transfusion reactions, abnormalities in autoimmune) membrane

receptor functions


Type II

Antibody-mediated


Type III - Deposition of IgG or C’ activationImmune complex-mediated IgM IC phagocyte activity(Arthus reaction, serum sickness)


Type III

Immune complex-mediated


Type IV - Activation of CD4+ M activation

Delayed hypersensitivity and CD8+ T cells CTL lysis of cells(PPD, contact dermatitis)


Type IV

T cell-mediated

Type I Hypersensitivity“Immediate Hypersensitivity”

• Biologic role in the control of helminth infections (schistosomiasis).

• Reactions include:– Hay fever– Food allergies– allergic asthma– ___________________________________

Predisposing Factors to Type I Reactions

• Type of allergens

• Route of exposure

• Genetic predisposition

• Age

Airborne Allergens

• Low dose antigens.

• Can become airborne due to small size (10-40 µm in diameter).

Pollen

fecal pellets

Dust mite

Adapted from Roitt’s Immunology 15-4

Pathogenesis of Type I

• IgE- mediated– Due to low dose

antigen resulting in CD4+ T cells differentiating into IL-4 producing TH2 cells.

– IL-4 enhances the growth of B cells and induces their class switch from IgM to IgE.

Abbas & Lichtman’s Basic Immunology 11-2


• Initial Exposure• IgE binds to high-affinity Fc receptors on mast cells and

basophils. • Repeat Exposure• Allergen is multi-valent meaning it can bind multiple

IgEs at the same time.• Mast cell and basophil are activated.

Abbas & Lichtman’s Basic Immunology 11-2


• Activated cell releases:• ____________________

– constricts bronchial and intestinal smooth muscle.

– Increases vascular dilation and permeability.

– Causes sneezing, itching (pruritis), and runny nose (rhinorrhea).



• Activated cell releases:• Leukotrienes and

Prostaglandins– generated from membrane

phospholipids.

– Prolonged bronchial constriction.

– Vasodilation.



• Activated cell releases:• Cytokines

– IL-4

– IL-5• Eosinophil activation.

– TNF


Clinical Manifestations of Type 1 Hypersensitivity

• Mild local – “wheal and flare”

• Mosquito bite

– nasal congestion– Pruritis (itching)– Rhinitis– Conjunctivitis– Asthma

Allergic Asthma

• Mast cell activation resulting in:– ________________________________________.– Increased inflammation and mucus.– Chronic bronchospasm.



• Mild systemic– generalized pruritis

(itching)– urticaria (hives)– Nausea– Vomiting– Diarrhea

Roitt’s Immunology 26-2


• Anaphylaxis – Extreme systemic form of Type I hypersensitivity reaction– Immediate reaction (<20 minutes).– Can be local reaction or general leading to fall in blood

pressure due to vasodilation and edema, airway obstruction and broncospasm.



• Severe anaphylaxis - laryngeal edema, hypotension, shock, bronchospasm, cardiac arrhythmia, arrest and death.

– Three possible outcomes that can lead to death:• asphyxiation from laryngeal edema.• suffocation from bronchiolar

constriction/contraction• loss of adequate blood pressure from an

overwhelming edema

Review of Normal Sequence of Events

1 Exposure to allergen2 Th2 activation and IgE production3 IgE binds to mast cell Fc receptors4 2nd exposure to allergen5 Allergen binds to mast cell-associated IgE6 Signal transduction 7 Mediator release (e.g. histamine)8 End organ effects of mediators

Sensitization phase

Activation phase

Effector phase

Management of the Allergic Patient

• Identify the allergen(s):– in vivo challenge tests

– in vitro tests

Management of the Allergic Patient

• Environmental intervention• Pharmacological intervention

– antihistamines– corticosteroids– epinephrine

• Hyposensitization therapy– blocking antibodies – Th2 to Th1 switch– specific suppressor T cells

Type II Hypersensitivity“Antibody-Mediated”

• Caused by _____________________________ antibodies against cell and tissues.

Adapted from Abbas & Lichtman’s Basic Immunology 11-7A

Effector Mechanisms of Type II Hypersensitivity

• Binding of antibody induces inflammation.– By attracting and activating leukocytes.

• Via Macrophages and neutrophils Fc receptors.

– By activating the classical pathway of the complement cascade.

Abbas & Lichtman’s Basic Immunology 11-8A


• Binding of antibody to cells results in opsonization and phagocytosis.– Through phagocytic cells Fc receptor.– Through phagocytic cells C3b receptor.

Abbas & Lichtman’s Basic Immunology 11-8B


• Binding of antibody interferes in normal cell functions.– Binding to receptors resulting in their stimulation

(Graves disease).– Binding to receptors resulting in their inhibition

(Myasthenia Gravis).

Abbas & Lichtman’s Basic Immunology 11-8C

Next Time

• Compare and contrast the ABO and Rho(D) alloantigens.

• Describe an Arthus reaction.• List the cells involved in a DTH response.• Describe ocular immune privilege• Describe the role Anterior Chamber Associated

Immune Deviation (ACAID) is believed to play in an ocular immune response.

• Readings: Abbas & Lichtman, Chapter 11

Objectives

1. Describe the 4 types of hypersensitivity reactions.

1. Similarities & differences

2. Pathogenesis

3. Clinical implications

2. Describe the management of the allergic patient.

Documents

Aims Explain the mechanisms of hypersensitivity reactions. Define anaphylaxis Readings: Abbas & Lichtman, Chapter 11