Introduction to

Hypersensitive reactions By

Deepika Rana1601

M.Sc. Microbiology (3rd sem)M.D. University, Rohtak

Introduction • The immune response uses multiple strategies to reduce

damage to self by turning off responses when pathogen is cleared and avoiding reactions to self antigens.

• However, these checks and balances can break down, leading to immune-mediated reactions that are more detrimental than protective.

• Some immune-mediated disorders are caused by a failure of immune tolerance.

• Others are caused by an inappropriately vigorous innate and/or adaptive response to antigens that pose little or no threat.

Hypersensitivity -Exaggerated immune response that causes damage to the individual. Immediate hypersensitivity (types I, II, and III) is mediated by antibody or immune complexes, and delayed-type hypersensitivity (type IV) is mediated by TH cells.

• Primary mediator is the adaptive immune system T & B lymphocytes

• Damage is mediated by the same attack mechanisms that mediate normal immune responses to pathogen.

Young girl sneezing in response to flowers.[Brand New Images/Getty Images]Allergy: A type I hypersensitive reaction

•Two French scientists, Paul Portier and Charles Richet, were the first to recognize and describe hypersensitivities for which Richet was subsequently awarded the Nobel Prize in Physiology or Medicine in 1913.

•As part of their studies to the stings of Physalia physalis, they demonstrated that the toxic agent in the sting was a small protein. They reasoned that eliciting an antibody response that could neutralize the toxin may serve to protect the host.

Paul Portier

Charles Richet

•Therefore, they injected low doses of the toxin into dogs to elicit an immune response, and followed with a booster injection a few weeks later.

•However, instead of generating a protective antibody response, the unfortunate dogs responded immediately to the second injection with vomiting, diarrhoea, asphyxia, and death.

•Richet coined the term “anaphylaxis ,” derived from the Greek and translated loosely as “against protection” to describe this overreaction of the immune system, the first description of a hypersensitivity reaction.

Multiple types of hypersensitivity reactions

• Immediate hypersensitivity reactions result in symptoms that manifest themselves within very short time periods after the immune stimulus resulting from antibody-antigen reactions.

• Hypersensitivity reactions that take hours or days to manifest themselves are referred to as delayed- type hypersensitivity (DTH) reactions resulting from T-cell reactions.

• Type I• Type II• Type III• Type IV

___________________________________Type I, II and III Antibody Mediated

Type IV Cell Mediated

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Classification of Hypersensitivity

• Different immune mechanisms give rise to distinct hypersensitivity reactions, two immunologists, P. G. H. Gell and R. R. A Coombs, proposed a classification scheme to discriminate among the various types of hypersensitivity.

• Type I hypersensitivity reaction are mediated by IgE

antibodies, and include many of the most common allergies to, respiratory allergens, such as pollen and dust mites.

• Type II hypersensitivity reactions result from the binding of IgG or IgM to the surface of host cells, which are then destroyed by complement- or cell-mediated mechanisms.

• Type III hypersensitivity reactions, antigen-antibody complexes deposited on host cells induce complement fixation and an ensuing inflammatory response.

• Type lV hypersensitivity reactions result from inappropriate T-cell activation.

Commonly called allergy

In type 1 hypersensitivity, B-cells are stimulated (by CD4+TH2 cells) to produce IgE antibodies specific to an antigen. The difference between a normal infectious immune response and a type 1 hypersensitivity response is that here the antibody is IgE instead of IgA, IgG, or IgM.

The antigens that stimulate it are called allergens (i.e. House dust, Pollens, Cosmetics, Insects, Clothing and Drug)

Exposure may be through ingestion, inhalation, injection or direct contact.

Type I hypersensitivity reactions can be systemic (e.g., systemic anaphylaxis) or localized to a specific target tissue or organ (e.g., allergic rhinitis, asthma).

Type I (Immediate) Hypersensitivity

Cytotoxic

Type II hypersensitivity involves IgG or IgM antibody-mediated

IgM or IgG immunoglobulin react with cell-surface antigens to activate the complements system and produce direct damage of the cell surface.

Transfusion reactions and hemolytic disease of the newborn are examples of type II hypersensitivity.

Type II (Cytotoxic) Hypersensitivity

Type III hypersensitivity is also known as immune complex hypersensitivity.

The reaction may take 3 - 10 hours after exposure to the antigen (as in Arthus reaction).

The reaction may be general (e.g., serum sickness) or may involve individual organs.

Antigens causing immune complex mediated injury are:

ExogenousEndogenous

Type III (ICM- Immune Complex–Mediated) Hypersensitivity

Immune Complex Diseases-

Hypersensitivity Pneumonitis- Hypersensitivity pneumonitis is an inflammation of the alveoli within the lung caused by hypersensitivity to inhaled organic dusts. Sufferers are commonly exposed to the dust by their occupation or hobbies.

Glomerulonephritis- Glomerulonephritis (GN) is inflammation of the glomeruli, which are structures in your kidneys that are made up of tiny blood vessels. These knots of vessels help filter your blood and remove excess fluids. If glomeruli are damaged, kidneys will stop working properly and one can go into kidney failure.

Rheumatoid Arthritis- Rheumatoid arthritis (RA) is a long-lasting autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest.

Systemic Lupus Erythematosus- Systemic lupus erythematosus (SLE), also known simply as lupus, is an autoimmune disease in which the body’s immune system mistakenly attacks healthy tissue in many parts of the body. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face.

Delayed hypersensitivity is a function of T Lymphocytes, not antibody.

It starts hours (or Days) after contact with the antigen and often lasts for days.

It can be transferred by immunologically committed (Sensitized) T cells, not by serum.

Principal pattern of immunologic response to variety of intra cellular microbiologic agentsi.e.: Mycobacterium Tuberculosis

Type 1 diabetes mellitus is an example where Tc cells attack pancrealtic islet cells

In Hashimoto thyroiditis Tc cells attack thyroid epithelial cells.

Type IV (Delayed or Cell Mediated) Hypersensitivity

The use of Type 5 is rare. These conditions are more frequently classified as Type 2, though sometimes they are specifically segregated into their own subcategory of Type 2.

Instead of binding to cell surfaces, the antibodies recognise and bind to the cell surface receptors, which either prevents the intended ligand binding with the receptor or mimics the effects of the ligand, thus impairing cell signaling.

As its mechanisms do not destroy target cells, they are responsible for induction of organ/tissue dysfunctions only most of authors prefer it to be and independent, the 5th type of hypersensitivity reactions.

Some clinical examples: Graves' disease, Myasthenia gravis

Type V(Antibody mediated stimulatory) Hypersensitivity

REFERENCESKuby Immunology 7th edition 2013 Chapter-15 Allergy, Hypersensitivities, and ChronicInfl ammationhttp://www.healthline.com/health/glomerulonephritis#Overview1 https://en.wikipedia.org/wiki/Hypersensitivity_pneumonitis http://www.healthline.com/health/systemic-lupus-erythematosus http://www.slideshare.net/pervezali5283/hypersensitity-and-types-of-hypersensitivit

y-i-ii-iii-iv

Thankyou