Hypersensitivity Reactions

Shanes Faculty, DOBT, JNC, Bangalore - 95

Immune reactions offer protection against infectious agents, their metabolites and other harmful substances in a healthy individual.

But in some cases, immune response instead of providing protection, may lead to deleterious reactions inducing extensive damage or even death to the host. Such injurious reactions are commonly termed as hypersensitivity.

Definition of hypersensitivity reactions

Hypersensitivity reactions is a state of altered reactivity in which body reacts with an exaggerated immune response to what is perceived as a foreign substance (or antigen).

Hypersensitivity reaction is found in immunologically sensitized individual after subsequent contact with same antigen resulting in exaggerated or lethal process of immunity.

This can be localized to one area or generalized and may include: rash, itching, hives, swelling, difficulty breathing, and/or low blood pressure.

Hypersensitivity is also termed as allergic reactions.

The concept of hypersensitivity was introduced by two French scientists Paul Portier and Charles Richet. They found that localized reactions of bathers in Mediterranean to stings to Portuguese man of war (jelly fish) was due to toxins.

Antigens causing hypersensitivity reactions are referred as “allergens”.

The initial contact with antigen leading to synthesize of B or T lymphocytes in a sensitized individual is known as “sensitizing or priming dose”.

The second contact with the same specific antigen resulting in hypersensitivity reactions are called as “shocking dose”.

Types of hypersensitivity reactions

On the basis of time taken to develop the effector molecules during the course of reactions.

◦ Immediate hypersensitivity reactions: appears and recedes rapidly, induced by antigens or haptens through any route, antibody mediated reactions. Ex: anaphylaxis, atopy, hemolytic diseases, autoimmune

diseases, Arthus reactions and Serum sickness.

◦ Delayed hypersensitivity reactions: appears slowly and lasts longer, induced by infections or injection of antigen or hapten intradermally or by skin contact, cell mediated reactions etc.

Ex: Contact dermatitis, Tuberculin reactions.

Gell and Coombs classification of

hypersensitivity reactions P. G. H. Gell and R. R. A. Coombs revised the

classfication of hypersensitivity reactions based on mechanisms of pathogeneiss into five types:

1. Type I (IgE mediated or anaphylactic hypersensitivity reactions.

2. Type II (Cytotoxic) hypersensitivity

3. Type III (immune complex mediated ) hypersensitivity reactions.

4. Type IV (Delayed or cell mediated) hypersensitivity

5. Type V (Stimulatory) hypersensitivity.

This reactions occur when an antigen (allergen) attaches with IgE on the surface receptors of mast cells and basophiles.

A subsequent exposure to the same antigen (allergens) cross link to the cell bound IgE and initiate the release of various pharmacologically active mediators leading to clinical manifestations.

This reactions takes usually within 15 – 20 minutes, so it is a immediate hypersensitivity reactions.

Slide 7.9

Activation of mast cells in type I hypersensitivity and release of their mediators. ECF, eosinophil chemotactic factor; NCF, neutrophil chemotactic factor; PAF,

platelet-activating factor. (From Robbins Basic

Pathology ,2003）

http://www.youtube.com/watch?v=UfLAwO4_NTQ&feature=related

http://www.theimmunology.com/animations/IgE%20Mediated%20(Type%20I)%20Hypersensitivity.htm

for hypersensivity reactions 3 http://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter33/animation_quiz_3.html

for hypersensitivity reactions 2 http://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter33/animation_quiz_5.html

Allergy reactions: http://www.youtube.com/watch?v=y3bOgdvV-_M

Histamine: occurs in granules of mast cells and basophils. Release of histamine results in vasodilation increased capillary permeability and smooth muscle contraction. Ex: Allergic rhinitis (hay fever), Urticaria and Angioderma.

Leukotrienes: these are slow reacting substances do not occur in preformed state, but produced during reaction. Shows increased vascular permeability and smooth muscle contraction. Ex: Asthama.

Eosinophil chemotactic factor (ECF): this is tetra peptide that exists in preformed state in mast cell granulation, it attracts eosinophils play prominent role in immediate allergic reactions.

Prostaglandins and thromboxanes: these are closely related to leukotrienes. Helps in aggregation of platelets.

Serotonin: found in mast cells and platelets, released during anaphylaxis. Increased vascular permeability, capillary dilation and smooth muscle contraction are caused by serotonin.

a nonspecific exaggerated physiologic response which involves a vascular response and a cellular response by phagocytic cells to infection/injury

Mildest may be only edema. Reaction is triggered by mast cells, basophils. If inflammatory cells are present, many are eosinophils

OPSONIZATION - - coating of Antibody and/or complement to facilitate phagocytosis • ex. of opsonins - C3b, C4b, C5b, fibronectin, leukotrienes, immunoglobulins (i.e. IgG) • engulfment - achieved through amoeboid motion. Final structure is called vacuole or phagosome.

• degranulation and digestion

Animation of Phagocytosis by Enhanced Attachment (Opsonization)

① Urticaria and angioneurotic edema ② Asthma ③ Hay fever ④Insect allergy: serious or fatal

anaphylaxis may follow. Edema of larynx, with airway obstruction may occur.

Cytolytic or cytotoxic reactions (1) Mechanism: ① Complement-dependent reactions Transfusion reactions Erythroblastosis fetal Autoimmune hemolytic anemia Certain drug reactions

② Antibody-dependent cell-mediated

cytotoxicit (ADCC).

May be relevant to:

Graft rejection

The destruction of targets too large to be

phagocytosed, such as parasites or tumor

cells.

③Antibody-mediated cellular dysfunction

Myasthenia gravis: muscle weakness

Graves’ disease: hyperthyroidism

Slide 7.10

Schematic illustration of three different mechanisms of antibody-mediated injury in type Ⅱ hypersensitivity. A, Complement-dependent reactions that lead to lysis of cells or render them susceptible to phagocytosis.

(From Robbins Basic Pathology ,2003）

Slide 7.11

Antibody-dependent cell-mediated cytotoxicity (ADCC). IgG-coated target cells are killed by cells that bear Fc receptors for IgG (e.g., NK cells,

macrophages). . (From Robbins Basic Pathology ,2003）

Slide 7.12

Antireceptor antibodies disturb the normal function of receptors. In this example, acetylcholine receptor antibodies impair neuromuscular

transmission in myasthenia gravis. (From Robbins Basic Pathology ,2003）

(1) Reaction types

① Arthus reaction

② serum sickness

③ Collagen diseases

① Acute glomerulonephritis

② Systemic lupus

erythematosus

③ Necrotizing angiitides

④ Rheumatoid arthritis

⑤ Progressive systemic sclerosis

⑥ Dermatomyositis etc.

Slide 7.13

Schematic illustration of the three sequential phases in the induction of systemic type Ⅲ (immune complex) hypersensitivity. (From Robbins Basic Pathology ,2003）

Slide 7.14

Schematic representation of the pathogenesis of immune complex-mediated tissue injury. The morphologic consequences are depicted as boxed areas. . (From Robbins Basic Pathology ,2003）

Slide 7.15

Immune complex vasculitis. The necrotic vessel wall is replaced by smudgy, pink

“fibrinoid” (Dr. Trace Worrell)

(From Robbins Basic Pathology ,2003）

Delayed hypersensitivity reaction (1) Tissue reaction: Consist of

parenchymal destruction associated with perivascular lymphocytic and macrophage reaction.

① Chronic active hepatitis

② Viral exanthem

③ Contact dermatitis

④ Graft rejection

⑤ Inflammatory bowel disease.

Slide 7.16

Delayed hypersensitivity in the skin. Immunoperoxidase staining reveals a predominantly perivascular cellular infiltrate that marks positively with anti-CD4

antibodies. ( Dr. Louis Picker) .

(From Robbins Basic Pathology ,2003）

Slide 7.17

A section of a lymph node shows several granulomas, each made up of an aggregate of epithelioid cells and surrounded by lymphocytes. The granuloma in the center shows several multinucleate giant cells. ( Dr. Trace Worrell)

(From Robbins Basic Pathology ,2003）

Slide 7.18

Schematic illustration of the events that give rise to the formation of granuloma in type Ⅳ hypersensitivity reactions. Note the role played by T cell-derived

cytokines. . (From Robbins Basic Pathology ,2003）

Advise of the Day

To Be Continued…