Hypersensitivity
(Allergy)
Dr. Megha Y Pawar
Introduction
Immune response is generally beneficial to the host but sometimes it may be
harmful.
Sensitized individual may respond to subsequent antigenic stimuli in heightened or
exaggerated manner leading to tissue damage, diseases and even death of the
individual. This type of response is termed as Hypersensitivity Or Allergy.
Introduction
❑ Hypersensitivity – Undesirable injurious consequences in the sensitised host
–following contact with specific antigens
❑ Allergy – All immune processes harmful to the host, such as hypersensitivity and
autoimmunity
❑ Increased resistance is called immunity and increased susceptibility is called
hypersensitivity.
❑ Hypersensitivity reaction – Contact with antigen (allergen)
❑ Sensitising or priming dose – Initial contact sensitises - priming of appropriate B
or T cells
❑ Shocking dose– Subsequent contact with allergen– manifestations of
hypersensitivity
Classification
Immediate hypersensitivity
Delayed hypersensitivity
Feature Immediate Type Delayed Type
1. Onset & Duration Appears & recedes rapidly Appears slowly in 24-72 hrs & lasts longer
2. Immune Response Antibody mediated Cell mediated (T-lymphocytes)
3. Passive Transfer Possible with serum Cannot be transfer with serum but possibly
with lymphocytes
4. Desensitisation Easy but short lived Difficult but long lasting
5. Induction Antigens or haptens by any By antigen injected intradermally or skin
route contact
Immediate hypersensitivity (B cell or antibody mediated)
Anaphylaxis
Atopy
Antibody mediated cell damage
Arthus phenomenon
Serum sickness
Delayed hypersensitivity (T cell mediated)
Infection (tuberculin)
Contact dermatitis
Coombs and gel classification (1963)
Type 1 – Anaphylactic (IgE or regain-dependent)
Type 2 – Ab-mediated cytotoxic hypersensitivity
Type 3 – Immune complex-mediated hypersensitivity
Type 4 – Delayed or cell-mediated hypersensitivity
Type 5 - Stimulatory hypersensitivity
Type I, II & III – depends on interaction of Ag with humoral Abs – Immediate
Type
❑ Type IV – mediated by T- lymphocytes – develops in 24-72 hrs – Delayed
hypersensitivity
Type 1: Anaphylactic (IgE or regain-dependent)
❑ It is an IgE mediated immediate type of hypersensitive reaction.
❑ The term was coined by Richet.
❑ Example: Anaphylactic shock
❑ Antibodies (cytotropic IgE antibodies) fixed on surface of tissue cells (mast cells
and basophils) in sensitised individuals
❑ Antigen + cell fixed antibody - release of pharmacologically active substances –
clinical reaction
❑ Two forms
1) Anaphylaxis – acute, potentially fatal, systemic
2) Atopy – chronic or recurrent, non-fatal, localised
Regain antibodies: not produced against bacteria or virus but against cells
1. Anaphylaxis – acute, potentially fatal, systemic
❑ Classical immediate hypersensitivity
Features
❑ Induced by - antigen and haptens
❑ Interval of 2-3 weeks between sensitising dose and shocking dose
❑ Sensitised individuals remain so for long periods of time
Clinical effects – due to
❏ Smooth muscle contraction
❏ Increased vascular permeability
Organs affected - ‘target tissues’ or ‘shock organs’
Humans – symptoms and signs
❏ Itching of scalp and tongue
❏ Flushing of skin
❏ Difficulty in breathing - bronchospasm
❏ Nausea, vomiting, abdominal pain, blood in stool
❏ Acute hypotension, loss of consciousness
Type I reaction
Types Of Anaphylaxis
1. Cutaneous anaphylaxis:
❑ Small shocking dose of antigen – intradermally
❑ Sensitised host – wheal and flare response
❑ Wheal – pale central area of puffiness
❑ Flare – surrounding the wheal – hyperaemia and erythema
2. Passive cutaneous anaphylaxis:
❑ Sensitive in vivo method – detection of antibodies
❑ Small volume of antibody injected intradermally into normal animal
❑ Antigen with Evan’s Blue – injected intravenously 4-24 hours afterwards
Types Of Anaphylaxis
3. Anaphylaxis in vitro (Schultz-Dale phenomenon)
❑ Isolated tissue – intestinal or uterine muscle strips from sensitised guinea pig
❑ Held in a bath of Ringer’s solution
❑ Contract vigorously on addition of specific antigen to the bath named Schultz-Dale
phenomenon
2. Atopy- chronic or recurrent, non-fatal, localised
❑ Coca - 1923 – naturally occurring familial hypersensitivities
❑ Typically – hay fever and asthma
❑ Antigens – inhalants (e.g.- pollen, house dust), Ingestants (e.g.– eggs, milk) & Drugs
❑ Contact allergens – skin and conjunctiva exposed
❑ Atopens – not good antigens when injected parenterally
❑ Induce IgE antibodies, ‘reagin’ antibodies
❑ Atopic sensitisation – developed spontaneously following natural contact with
atopens.
SYMPTOMS
❑ Conjunctivitis, rhinitis, gastrointestinal symptoms and dermatitis
– following exposure through eyes, respiratory tract, intestine or skin, respectively
Prausnitz and Kustner (PK) reaction
❑ IgE – homocytotropic
❑ Only human IgE can fix to surface of human cells
❑ Prausnitz and Kustner 1921 reported that if serum from Kustner who had atopic
hypersensitivity to certain species of cooked fish was injected intravenously into
Prausnitz, Wheal and flare reaction in a few minutes.
Type 2: Ab-mediated cytotoxic hypersensitivity
Antigenic component is either a part of tissue cell, or a microbial product or a drug
attached to cell wall.
❑ Combination of IgG with the antigenic determinants on cell surface
❑ Leading to cytotoxic or cytolytic effects
Type 2: Ab-mediated cytotoxic hypersensitivity
Examples:
❑ Lysis of RBCs by anti erythrocyte antibodies.
❑ Lysis of platelets by autoantibodies - autoimmune thrombocytopenia.
❑ Alternatively free antigen or hapten – absorbed on cell surfaces- combined antigen or
hapten with corresponding antibody leads to cell damage
❑ Drug such as penicillin, sulfonamide, quinidine, sedormid, etc. attach to the surface of
cells such as RBC, neutrophils or platelets.
❑ Causes change in antigenicity, inducing antibody synthesis, which causes cryptotoxic
reaction.
Type II reaction
Type 3: Immune complex-mediated hypersensitivity
It is characterized by deposition of antigen-antibody complexes in tissues
activation of complement infiltration of polymorphonuclear leucocytes
tissue damage.
Examples
I. Arthus reaction
II. Serum sickness
I. Arthus Reaction: Localised- Relative antibody excess
❑ Arthus (1903) observed that when rabbits were repeatedly injected
subcutaneously with normal horse serum:
❏ Initial injections – no effect
❏ Later injections - local reaction - edema, induration and haemorrhagic necrosis
❑ Tissue damage due to formation of antigen-antibody precipitates; causes
complement activation and release of inflammatory molecules
❑ Leads to increased vascular permeability, infiltration of site with neutrophils
❑ Leucocyte platelet thrombi - reduce blood supply and lead to tissue necrosis
2. Serum Sickness: Generalised-Relative antigen excess
❑ Systemic form of type III hypersensitivity
❑ Appears 7-12 days following a single injection of a high concentration of foreign
serum
❑ Example: Diphtheria antitoxin
❑ Formation of immune complexes (foreign serum and antibody) deposited on
endothelial lining of blood vessels causing inflammatory infiltration
❑ Immune complex diseases are –post-streptococcal glomerulonephritis, hepatitis B,
malaria) disseminated malignancies and autoimmune conditions
Type 4: Delayed or cell-mediated hypersensitivity
❑ Mediated by sensitized T- lymphocytes – releases lymphokines – effect on
macrophages, leucocytes & tissue cells.
❑ In this reaction there is an appreciable delay between the exposure to Ag and the
development of symptoms.
Examples
I. Tuberculin(infection) type
II. Contact dermatitis type
1. Tuberculin (Infection) Type
❑ Small dose of tuberculin injected intradermally in individual sensitised to
tuberculoprotein (by infection or immunisation)
❑ An erythema & swelling occurs at the site of injection within 48-72 hrs.
❑ Purified protein derivative (PPD)- active material of tubercle bacilli use
❑ Tuberculin test – Indication of the state of delayed hypersensitivity
2. Contact Dermatitis Type
❑ Delayed hypersensitivity- due to skin contact with chemicals- metals, drugs, dyes.
❑ Sensitisation requires percutaneous absorption
❑ Sensitised T cells - skin site - contact antigen – release lymphokines
❑ Lesions- macules, papules, vesicle-eczematous dermatitis
❑ Hypersensitivity detected by ‘patch test’
Type 5: Stimulatory hypersensitivity
❑ This causes excessive secretion of thyroid hormone that leads to thyrotoxicosis.
Example
Grave’s disease
❑ Thyroid hormones are produced in excess quantity
❑ Long acting thyroid stimulating (LATS) antibody is an autoantibody to thyroid
membrane antigen.
❑ LATS combines with a TSH receptor on thyroid cell surface
❑ Results in excessive secretion of thyroid hormone
SHWARTZMAN REACTION
❑ Schwartzman (1928) – Injected Culture filtrate of S. typhi intradermally in rabbit
❑ Same filtrate injected Followed intravenously after 24 hours
❑ Initial (preparatory) dose – characteristically endotoxin- accumulation of leucocytes-
releases lysozyme enzyme- damage capillary walls.
❑ Intravenous (provocative) dose – bacterial endotoxin- intravascular clotting- leading
to necrosis of vessel walls & haemorrhage.
❑ Haemorrhagic necrotic lesion develops at the site of intradermal inoculation, known
as Schwartzman Reaction
