2. Dr Sonal Saxena, MD
Director Professor and Head of the Department of Microbiology
Maulana Azad Medical College,
New Delhi
and
Dr Amala A Andrews, MD
Maulana Azad Medical College,
New Delhi
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3. INTRODUCTION
Hypersensitivity refers to the undesirable injurious
consequences in a sensitised host following contact with
specific antigens
Allergy refers to all immune processes harmful to the host
such as hypersensitivity and autoimmunity
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4. CLASSIFICATION
Based on time
Immediate
Delayed
Based on mechanism (Coombs and Gell)
Type I (immediate anaphylactic hypersensitivity)
Type II (cytolytic/cytotoxic hypersensitivity)
Type III (immune complex-mediated hypersensitivity)
Type IV (delayed type T-cell mediated
hypersensitivity)
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5. Table 16.1 Distinguishing features of immediate and
delayed types of hypersensitivity
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CLASSIFICATION
6. Table 16.2 Types of hypersensitivity reactions and their
features
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CLASSIFICATION
7. TYPE I
(ANAPHYLACTIC
HYPERSENSITIVITY)
Within minutes after exposure to the antigen
Mediated by IgE and involves degranulation of mast cells or
basophils.
Occurs in two forms:
- Anaphylaxis: Acute, potentially fatal with systemic
manifestation
- Atopy: Chronic or recurrent, non-fatal and typically localised
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8. TYPE I
(ANAPHYLACTIC
HYPERSENSITIVITY)
Anaphylaxis
Acute, fatal, systemic
Sensitizing dose Shocking dose
Mediated by cytotropic IgE antibody
Antigen combining with IgE bind to mast cells and
basophils leading to degranulation and release of
biologically active substances
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9. ANAPHYLAXIS:
SIGNS AND
SYMPTOMS
Usually caused by drugs and insect stings
Occurs in seconds
Itching of the scalp and tongue
Flushing of the skin
Difficulty in breathing
Nausea, vomiting, abdominal pain and diarrhea
Hypotension, loss of consciousness and death
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10. TYPES OF
ANAPHYLAXIS
1. Cutaneous anaphylaxis
Antigen given intradermally to a sensitised host
Local wheal-and-flare response (local
anaphylaxis)
2. Passive cutaneous anaphylaxis (PCA)
- In vivo method
- To detect antibodies that can passively lead to
cutaneous anaphylaxis
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11. TYPES OF
ANAPHYLAXIS
3. Anaphylaxis in vitro
Schultz–Dale phenomenon
Intestinal/uterine muscle strips from sensitised guinea
pigs, held in a bath of Ringer’s solution will contract
vigorously on the addition of the specific antigen to the
bath
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12. MECHANISM OF ANAPHYLAXIS
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Fig. 16.1 Type I reaction: Immediate anaphylactic hypersensitivity reaction mediated
by IgE (Source: https://openstax.org/books/ microbiology/pages/19-1
hypersensitivities-19-3)
13. MECHANISM
OF
ANAPHYLAXIS
Pharmacological mediators
Primary mediators
◦ Histamine
◦ Serotonin (5-hydroxytryptamine)
◦ Chemotactic factors
◦ Enzymatic mediators
Secondary mediators
◦ Platelet-activating factor (PAF)
◦ Leukotrienes and prostaglandins
◦ Cytokines, bradykinin and other kinins
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14. ANAPHYLAXIS
Treatment
Prompt
0.5 mL of a 1-in-1000 solution, subcutaneously or
intramuscularly
Anaphylactoid reaction: The intravenous injection of
peptone, trypsin and certain other substances provokes a
clinical reaction resembling anaphylactic shock; this is
termed an anaphylactoid reaction
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15. ATOPY
Genetically determined familial hypersensitivities
Hay fever and asthma
Antigens commonly involved
◦ Environmental inhalants like pollens and house dust
◦ Ingestants like eggs and milk
◦ Contact allergens
Preponderant IgE response
Symptoms depends on portal of entry: E.g., conjunctivitis,
rhinitis, gastrointestinal symptoms and dermatitis
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16. DETECTION OF TYPE I
HYPERSENSITIVITY
Skin test
RAST
Radioimmunosorbent test (RIST)
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Fig. 16.2 (a)Skin test to demonstrate
immediate hypersensitivity, and (b) wheal-
and-flare reaction on the forearm seen in
an individual allergic to pollen, and cat fur;
seen within 30 minutes of injecting minute
doses of the allergens (Source: Dr Reba
Kanungo, personal collection)
17. TREATMENT OF
TYPE 1
HYPERSENSITIVITY
Acute anaphylaxis or allergy
Epinephrine (adrenalin)
Antihistamines (block H1 and H2 receptors)
Corticosteroids (reduce histamine levels).
Atopic persons can be treated by desensitisation
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18. TYPE II
REACTIONS:
CYTOLYTIC AND
CYTOTOXIC
Antigenic determinants on the surface of cells
or
Free antigen or hapten absorbed on to cell surfaces
Activation of IgG (or rarely IgM) antibodies
Complement activation
Cytotoxic or cytolytic effects
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19. TYPE II REACTIONS: CYTOLYTIC AND
CYTOTOXIC
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Hemolytic anemia, agranulocytosis and thrombocytopenic purpura
Erythroblastosis fetalis, transfusion reactions
Autoimmune and drug-induced hemolytic anemia
Pernicious anemia
Autoimmune thrombocytopenic purpura , myasthenia gravis
20. TYPE II
REACTIONS:
CYTOLYTIC AND
CYTOTOXIC
Antibody-dependent cell cytotoxicity (ADCC)
Cytotoxic cells may be stimulated by the antigen–
antibody complex
Stimulatory type
Type V hypersensitivity
Subtype of type II
IgG binds to the cell surface antigen receptors
Graves’ disease
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21. TYPE III REACTIONS: IMMUNE COMPLEX-MEDIATED
HYPERSENSITIVITY
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Stimulate an inflammatory reaction
Immune complex formation and deposition
Complement activation
Antigen and antibody combine
22. TYPE III REACTIONS:
IMMUNE COMPLEX-
MEDIATED
HYPERSENSITIVITY
Types
i) Serum sickness: Systemic
form
ii) Local Type III reaction
Arthus reaction
Autoimmune disorders
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Fig. 16.3 Type III reaction (mechanism of
immune complex-mediated
hypersensitivity)
23. ANTIBODY
DEPENDENT
ENHANCEMENT
• Antibodies to a number of viruses cause enhanced virus
entry and replication in some cells
• Virus–antibody immune complexes interact with cells
bearing complement or fc receptors
• Internalisation of the virus is enhanced, leading to
increasing infection
• This results in exacerbation of viral disease
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24. TYPE IV REACTIONS:
T CELL-MEDIATED
HYPERSENSITIVITY
(DELAYED TYPE)
Delayed cell-mediated immune response
Provoked by
◦ Intracellular microbial infections
◦ Hapten-like simple chemicals applied on the skin
Induced by sensitised T cells (Tdth, Th1, Th2, Tc)
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25. UNIVERSITIES PRESS PVT LTD.
TYPE IV REACTIONS: T CELL-MEDIATED
HYPERSENSITIVITY
Types
1. Tuberculin (infection)
Prior infection or immunisation shows positive tuberculin test
Cutaneous basophil hypersensitivity: A local reaction resembling the tuberculin
response produced by the intradermal injection of some protein antigens
2. Contact dermatitis: Contact with chemicals such as nickel and chromium, dyes,
dinitrochlorobenzene, drugs such as penicillin, plant allergen and toiletries
26. TYPE IV
REACTIONS: T
CELL-MEDIATED
HYPERSENSITIVITY
Mechanism of contact dermatitis
Langerhans’ cells capture hapten along with the
modified tissue proteins to draining lymph nodes
Present processed antigen along with MHC molecules to
T cells
The sensitised T cells to the skin site release various
lymphokines
Th1 cells secrete IFN-γ and IL-2activate macrophages
and other lymphocytes
Activated Tc cells mediate the killing of target cells
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27. TYPE IV REACTIONS: T
CELL-MEDIATED
HYPERSENSITIVITY
Symptoms of contact dermatitis
- Macules and papules to vesicles
- Break down, leaving behind raw, weeping areas
Detection using ‘patch test’
- Allergen is applied to the skin
- Itchiness in 4–5 hours, and local reaction
- From erythema to vesicle or blister formation, after
24–28 hours
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