This document discusses different types of hypersensitivity reactions and allergies. It describes 4 types of hypersensitivity reactions: Type I is an immediate or anaphylactic reaction mediated by IgE antibodies and mast cells. Type II involves antibody-dependent cytotoxic reactions mediated by IgG and IgM antibodies. Type III reactions are immune complex-mediated responses. Type IV is a cell-mediated reaction involving T cells. The document provides details on the mechanisms, mediators, symptoms and treatments for each type of hypersensitivity reaction.

1. Allergic
OR
Hypersensitivity Reactions
SIRAJUDDIN MOLLA
Research scholar
DEPARTMENT OF PHARMACOLOGY
SPER, JAMIA HAMDARD

2. Index
 Introduction
• Hypersensitivity reaction
• Allergy
 Types of allergens
 Type I hypersensitivity reaction
 Type II hypersensitivity reaction
 Type III hypersensitivity reaction
 Type Iv hypersensitivity reaction

3.  The immune system has vital functions for homeostasis and host defense.
 But exaggerated or misdirect immune response result in tissue injury or
other pathological changes
 This unwanted immune responses, termed as hypersensitivity reactions.
 Require a pre-sensitized (immune) state of the host.
 May be immediate or delayed
 All this happens due to
– release of vasoactive substances
– phagocytosis or lysis of cell
– activation of inflammatory and cytolytic component of complement cell
– cytokines and other mediators
Hypersensitivity Reactions
Introduction

4.  A disorder of the immune system often also referred to as
atopy.
 Strictly, allergy is one of four forms of hypersensitivity and is
called type 1 (or immediate) hypersensitivity.
 Allergic reactions occur to normally harmless
environmental substances known as allergens.
 Reactions are acquired, predictable and rapid.
 It includes eczema, hives, hay fever, asthma, food allergy
and reactions to drugs and the venom of stinging insect
such as wasp and bees
Allergy

5.  Allergens are inciting agents of allergy i.e. The substances capable of
sensitizing the body in such away that an unusual response occurs in
hypersensitive person.
 It may be of biologic, chemical, or of synthetic origin.
 The substance such as pollens, dander's, dust etc. acts as natural
allergens.
 Allergens are protein or glycoprotein .
ALLERGENS

6. 1. Inhalant allergens
2. Ingestant allergens
3. Injectant allergens
4. Contactant allergens
5. Infectant allergens
TYPES OF ALLERGENS

7.  Inhalant allergens are air borne substances as
chemicals, causing respiratory disease,
inflammation in nose and lungs.
 Inhalant allergies caused by environmental factors
such as pollen, pets, house dust mites and
moulds.
 Inflammation in nose & lungs may cause Hay fever
& Asthma.
SYMPTOMS
 Sneezing
 Lacrimation
 Coughing and post nasal
drip
 Itching eyes, nose and
throat.
 Allergic shiner
1. INHALANT ALLERGENS

8.  Allergens which are present in food stuff and swallowed are termed
ingestant (food allergy).
 In food allergy, an immune system response to a food.
 When foods are digested and the nutrients are absorbed, substances
in the food (ingestant allergens) stimulate allergic response. These
reactions cause a number of allergic symptoms.
 Food allergens ordinarily cause GIT symptoms, but they may also
cause
• Skin rash
• Puffed lips and tongue
• Migraine
2. INGESTANT ALLERGENS
• Rhinitis
• Bronchial
asthma

9. Some most common
food allergens
97% of food allergies
are due to only
8 foods

10. 97% of food allergies
are due to only
8 foods
Which are……
Some most common
food allergens

11. Out of this 8 foods, 3 are most likely to cause anaphylaxis.
(a whole body, life-threatening response)

12.  The injectants (injectable preparations and insects) cause
allergy in hypersensitive person.
 The natural sources of injectable allergens are produced by
the sting of bees, hornets and wasps.
 In addition to penicillin products, other injectable that may
cause allergies are liver extract, antitoxins and the glandular
products.
SYMPTOMS
 Itching of the palms of hands and soles of feet
 Erythema
 Peeling of skin
3. INJECTANT ALLERGENS

13.  "Any allergens they produce manifestation of hypersensitivity at the site
of skin or other mucous".
 Aeroallergens, like various pollen grains containing oils, trichomes
various leaves, flowers
 Small fragments of plants tissue carried by smoke originating from
fires, grass fires and burning leaves are also cause for contact
 A Number of plants products used as additives in cosmetics and
perfumes are irritants and cause skin allergy.
 Wool fat in cosmetics, soap and soap powders, plain detergents and
enzyme detergents, nail polishes, hair dye and hair spray are also
included among the major cause of contact dermatitis.
4. CONTACTANT ALLERGENS

14.  Allergy caused by the metabolic product of living micro-organism in the
human body.
 The continual presence of certain types of bacteria, protozoa's, molds,
helminths and other parasites in the body of human being are
for chronic infection.
 In such patient bacterial metabolic waste are considered to be infectant
allergens.
5. INFECTANT ALLERGENS
6. Others
Sometimes temperature (cold temp.), radiation may also cause allergy

15. Hypersensitivity Types & Immune Reactants
Gell-Coombs classified the reactions into four types based on the
mechanisms involved and time taken for the reaction-
3 involve antibody
Types Name of Rxn Mediators Attack on Associated disease
Type I: immediate or
anaphylactic
hypersensitivity (allergy)
IgE Mast cell Atopy, Anaphylaxis,
Asthma
Type II: antibody-dependent
cytotoxic
hypersensitivity
IgG and IgM Attack host
antigen
Autoimmune disease
Erythroblast foetalis,
Goodpasture’s
disease
Type III: Immune complex-
mediated
hypersensitivity
Immune complex
(IgG &
complement)
Serum sickness,
Arthus reaction,
Lupus nephritis
One involves antigen specific cells-
Type IV: Cell-mediated or CD4 T-cell Tuberculosis,

16.  Also called immediate or anaphylactic hypersensitivity (simply known as
‘allergy’)
 It is sudden, widespread, potentially severe and life-threatening allergic
reactions(anaphylactic shock).
 The effects may be localised to the nose (hay fever), eye, the bronchial
tree (the initial phase of asthma), the skin (urticaria) or the
tract  atopic disorder
 The reaction usually takes 15 - 30 minutes from the time of exposure to the
antigen
 Begin with a feeling of uneasiness, followed by tingling sensations and
dizziness.
Type I Hypersensitivity

17.  Mediated by
• antibody IgE
• biogenic amines- histamine, adenosine (enhance mast cell mediator
• enzymes- protease, acid hydrolases
 The primary cellular component is the mast cell or basophil and eosinophils
 The reaction is amplified and/or modified by platelets, neutrophils and
eosinophils.
 Some important unwanted effects of drugs include anaphylactic
hypersensitivity responses.
 It has two type of response: local and systemic anaphylaxis
Contd…

18.  Atopy - genetically determined predisposition to develop localized
anaphylactic reactions to inhaled or ingested allergens.
 Family history  chr. 5q31
 With higher serum IgE levels compared to general population
Local anaphylaxis has two phases:
1. Initial response  Vasodilation, vascular leakage, smooth muscle spasm
or glandular secretions  5-30 min. after exposure  subside in 60
minutes
2. Late-phase reaction  2-8 hrs. later without additional exposure to
antigen  More intense infiltration of tissues with eosinophils,
neutrophils, basophils, monocytes & CD4+ T cells  mucosal epithelial
A. Local Anaphylaxis:

19.  Occur after administration of heterologous proteins (e.g. antisera),
hormones, enzymes, polysaccharides & drugs
 Exposure  itching, hives & skin erythema, contraction of resp.
bronchioles + resp. distress, laryngeal edema
B. Systemic anaphylaxis

20.  In these individuals, substances that are not inherently noxious (such as
grass pollen, house dust mites, certain foodstuffs or drugs, animal fur
and so on) provoke the production of antibody, IgE
 IgE has high affinity for its receptor on mast cells and basophils.
 A subsequent exposure to the same allergen cross links the cell-bound
IgE and triggers the release of various pharmacologically active
substances like histamine, PAF, eicosanoids and cytokines.
 Further produce IgE from B-cell
 Cross-linking of IgE Fc-receptor to mast cells increases Calcium influx
in Mast cells and trigger degranulation of mast cells
Mechanism of type I Reaction
Fc (fragment crystallizable) region

21. Mechanism of type I hypersensitivity reaction

22. On blood vessels
 ↑ blood flow & permeability
 ↑ fluid and cells protein in
tissues
 ↑ blood flow to lymph node
Effects
On airway
 ↓ diameter,
 ↑ Mucus congestion,
blockage
On GI
 ↑ fluid secretion,
 ↑ peristalsis
 Expulsion-diarrhea

23.  Skin (prick and intradermal) tests
 Measurement of total IgE and specific IgE antibodies against the
suspected allergens.
 Total IgE and specific IgE antibodies are measured by a enzyme
immunoassay (ELISA).
 Increased IgE levels are indicative of an atopic condition.
Diagnostic tests for
immediate hypersensitivity

24. 1. Antihistamines which block histamine receptors - diphenhydramine,
hydroxyzine and
promethazine
2. Chromolyn sodium inhibits mast cell degranulation by inhibiting Ca2+
influx.
3. Leukotriene receptor blockers - montelukast, zafirlukast and zileuton
4. inhibitors of the cyclooxygenase pathway - aspirin
5. Bronchodilators (inhalants) for bronchoconstriction - salbutamol, salmeterol,
formoterol
6. Inhinbitors for cAMP-phosphodiesterase – dipyridamole, sildenafil,
theophylline
Treatments

25.  Also called antibody-dependent cytotoxic hypersensitivity
 Immune system (antibodies) targets tissue-specific antigens present on the
surface of host cell or other tissue components that are (or appear to be)
foreign
 Host cells or proteins altered by drugs are sometimes mistaken by the
immune system for foreign organisms and evoke antibody formation.
 Examples, some drugs alter neutrophils  agranulocytosis of platelets
 leading to thrombocytopenic purpura.
 The antigens are normally endogenous, sometimes it may exogenous
Type II hypersensitivity

26.  These type II reactions are also implicated in some types of
autoimmune disease (e.g. Hashimoto’s disease, haemolytic
anaemia, Rh disease of the new born.
 The lesion contains antibody, complement and neutrophils
 The reaction time is minutes to hours.
 Primarily mediated by antibodies of the IgM or IgG classes and
complement
 Antibody (IgG) mediates cell death
 This reaction characterised by tissue damage.
Contd…

27. There are three type of mechanism involved in type II reaction
1. Antibody and Complement-mediated destruction
2. Antibody-Dependent Cell-mediated Cytotoxicity (ADCC)
3. Antibody-mediated target cell dysfunction
Mechanism of type II reaction

28. Mechanism 1
 Antibody-complement that mediate lysis
 Antibody (IgM, IgG) + antigen on cell surface  activation of
complement system  formation of MAC (membrane attack
component)  tissue damage
1. Antibody and Complement-mediated destruction

29. 1. Antibody and Complement-mediated destruction

30. 1. Antibody and Complement-mediated destruction

31.  Occurs when target cell are too large and not possible to
phagocytised.
 Cells exhibiting the foreign antigen are tagged with antibodies (1gG or
IgM).
 Ab + Ag  activation of NK cell  bind to Fc fragment of IgG  cell
lysis without phagocytosis  kill these tagged cells
2. Antibody-Dependent Cell-mediated Cytotoxicity (ADCC)
Mechanism II

32. 2. Antibody-Dependent Cell-mediated Cytotoxicity (ADCC)

33. 2. Antibody-Dependent Cell-mediated Cytotoxicity (ADCC)

34. Mechanism III
 Antibodies directed against cell surface receptors  impair or
dysregulate function
 Example:
• Myasthenia gravis - acetylcholine receptors
• Goodpasture's syndrome - type IV collagen
• Pernicious anaemia - intrinsic factor
• Acute rheumatic fever - antibodies vs. Streptococcal antigens
cross- react
3. Antibody-mediated target cell dysfunction

35. 3. Target cell dysfunction – Graves disease

36. 3. Target cell dysfunction –
myasthenia gravis

37. 3. Target cell dysfunction – pernicious
anaemia

38. 3. Target cell dysfunction – pernicious
anaemia

39. Diagnostic tests include
• Detection of circulating antibody against the tissues involved
• The presence of antibody and complement in the lesion (biopsy)
by immunofluorescence.
Treatment
 anti-inflammatory – aspirin, Ibuprofen, naproxen, diclofenac,
celecoxib
 immunosuppressive agents – Cyclophosphamide (it is very efficient
in the therapy of systemic lupus erythematosus, autoimmune
Diagnostic tests and Treatment

40.  It is a immune complex-mediated hypersensitivity, occurs when
antibodies react with soluble antigens which is not attached to the organ
involved.
 The antigen-antibody complexes can activate complement and stimulate
the release of inflammatory mediators.
 An experimental example of this is the Arthus reaction that occurs if a
foreign protein is injected subcutaneously into a rabbit or guinea pig
with high pre-existing circulating concentrations of antibody.
 The reaction may take 3 - 10 hours after exposure to the antigen, the area
becomes red and swollen because the antigen–antibody complexes
precipitate in small blood vessels and activate complement.
Type III hypersensitivity reaction

41.  Neutrophils are attracted and activated by C5a  generate
toxic O2 species  secrete enzymes.
 Mast cells are also stimulated by C3a to release mediators.
 Damage caused by this process is involved in serum sickness,
which occurs when antigen persists in the blood after
sensitization, causing a severe reaction, as in the response to
mouldy hay (known as farmer’s lung).
 Also occurs in certain types of autoimmune kidney and
arterial disease, skin, blood vessels, joints (e.g., rheumatoid
arthritis)
mouldy hay
Contd…
Farmer's lung is a type of hypersensitivity pneumonitis that is
caused by precipitants such as moldy hay or straw.

42.  Type III hypersensitivity is also implicated in lupus erythematosus (a
chronic, autoimmune inflammatory disease).
 This reaction may be the pathogenic mechanism of diseases caused by
many microorganisms
 Mediated by soluble immune complexes - mostly of the IgG and sometimes
IgM and complement (C3a, 4a and 5a).
 Both exogenous (chronic bacterial, viral or parasitic infections) and
endogenous (non-organ specific autoimmunity) antigens can cause it.
 The damage is caused by platelets and neutrophils
Contd…

43. Mechanism of type
III reaction
Lumen of blood vessel

44. Diagnosis involves
• Tissue biopsies for deposits of IgG or IgM and complement by
immunofluorescence.
• The presence of immune complexes in serum and depletion in the
level of complement
• Polyethylene glycol-mediated turbidity to detect immune complexes.
Treatment
• anti-inflammatory agents- aspirin, Ibuprofen, naproxen, diclofenac,
celecoxib
Diagnosis and Treatment

45.  Its also known as cell-mediated or delayed type hypersensitivity
reaction.
 The prototype of type IV hypersensitivity is the tuberculin reaction, a local
inflammatory response seen when proteins derived from cultures of the
tubercle bacillus are injected into the skin of a person who has been
sensitised by a previous infection or immunisation.
 The reaction takes 2 to 3 days to develop.
 An ‘inappropriate’ cell-mediated immune response is stimulated and
accompanied by infiltration of mononuclear cells and the release of
various cytokines.
 Cell-mediated hypersensitivity is also the basis of the reaction seen in some
Type IV hypersensitivity

46.  It is also important in the skin reactions to drugs or industrial chemicals.
chemical (termed a hapten) + proteins (in the skin)  ‘foreign’
substance  evokes the cell-mediated immune response.
 In essence, inappropriately deployed T-cell activity underlies all types of
hypersensitivity, it only initiates types I, II and III, and being involved in
both the initiation and the effector phase in type IV.
 These reactions are the basis of pathogenesis of many clinically important
group of autoimmune and infectious diseases.
• tuberculosis, leprosy, blastomycosis (fungal infection),toxoplasmosis
(a parasitic disease).
• granulomas due to infections and foreign antigens.
• contact dermatitis (poison ivy, chemicals, heavy metals, etc.)
Contd…

47.  Can be classified into three categories depending on the time of onset and
clinical and histological presentation
Type Reaction
time
Clinical
appearance
histology Antigen and site
Contact 48-72 hr eczema lympocytes followed by
macrophage edema of
epidermis
Epidermal (organic
chemicals, poisons
ivy, heavy metals etc)
Tuberculin 48-72 hr Local
induration
lympocytes, monocytes,
macrophages
intradermal
(tuberculin lepromin,
etc
Granulom
a
21-28 days Hardening macrophages,
epitheoid and giant
cells, fibrosis
persistent antigen or
foreign body
(tuberculosis, leprosy,
etc.)
Contd…

48.  TH1 release cytokines to activate vascular endothelium
 Cytokines activate macrophages and cause release of more cytokines
and chemokines
 Activated macrophages to produce chemotactic factor, interleukin-2,
interferon-gamma (IFN-y), Tumour necrosis factor (TNF), cytotoxin
etc.
 Transform macrophages into giant multinucleated cell, which
eventually becomes necrotic
Mechanism of type IV reaction

49. Mechanism of type IV reaction

50. Diagnostics
 Diagnostic tests in vivo include delayed cutaneous reaction (e.g.
Montoux test) and patch test (for contact dermatitis).
 In vitro tests for delayed hypersensitivity include mitogenic response,
lympho-cytotoxicity and IL-2 production.
Treatments
 Corticosteroids and other immunosuppressive agents -
Cyclophosphamide
 Immunosuppressive drugs and/or glucocorticoids are routinely employed
to treat such disorders.
Diagnostics and Treatments
Its cytotoxic effect is mainly due to cross-linking of strands of DNA
and RNA, and to inhibition of protein synthesis.

52.  RANG AND DALE'S PHARMACOLOGY, HP RANG, JM RITTER, RJ FLOWER
AND G. HENDERSON, 8TH EDITION, ELSEVIER LTD., 2016
 https://karger.com/iaa/article-abstract/180/4/291/168203/Recent-
Advances-in-Clinical-Allergy-and-Immunology/2019
 https://www.slideshare.net/harshi12345/natural-allergens-238855791
 https://www.slideshare.net/rx_sonali/allergy-hypersensitivity
 http://www.alcit.in/allergy-situation-in-india/
References