HYPERSENSITIVITY REACTION - SECOND MBBS STUDENTS - UNDERGRADUATE STUDENTS - MEDICAL COLLEGE - POWERPOINT

1. HYPERSENSITIVITY
REACTIONS
Dr. SOMESHWARAN RAJAMANI, MBBS, MD
Assistant professor, Department of Microbiology,
Karpagam Faculty of medical sciences and Research.

2. Immunity – protective – overcome infectious
agents (antigens) and toxins
Immune response – may also be injurious to
host
Sensitised individual respond to specific
antigenic stimuli in an inappropriate or
exaggerated manner
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3. In protective part of immunity – antigen is
the focus of attention and what happens to it
Example: Bacteriolysis, Toxin neutralization
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4. In hypersensitivity antigens are of little
concern and often innocuous or bland
substances such as serum proteins or pollen
Hypersensitivity is concerned with what
happens to host as a result of immune
reaction
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5. Injurious consequences in the sensitized host,
following contact with specific antigens.
Deals with injurious aspect of heightened and
exaggerated immune response leading to
tissue damage, disease or even death
Concerned with what happens to the host
rather than what happens to the antigen.
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6. 12/17/2015
Essentials for Hypersensitivity
Contact with allergen
Sensitizing/priming dose
Induction of AMI/CMI
Shocking dose
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7.  TRADITIONAL CLASSIFICATION
 COOMB AND GELL (1963) CLASSIFICATION
Traditional classification is based on the time required for a sensitized
host to develop clinical reactions on re-exposure to the specific antigen
Coomb and Gell classification is based on mechanism of pathogenesis
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8.  IMMEDIATE HYPERSENSITIVITY: (B cell or antibody
mediated)
Anaphlaxis
Atopy
Antibody mediated damage
Arthus phenomenon
Serum sickness
 DELAYED HYPERSENSITIVITY
Infection (Tuberculin) type
Contact dermstitis type 12/17/2015 8

9. IMMEDIATE HYPERSENSITIVITY DELAYED HYPERSENSITIVITY
Appears and recedes rapidly Appears slowly and lasts longer
Induced by antigens or haptens by any route Antigen or hapten intradermally or with
Freund’s adjuvant or by skin contact
Circulating antibodies present and responsible for
reaction; ‘antibody mediated’ reaction.
Circulating antibodies may be absent and not
responsible for reaction; ‘cell mediated’ reaction
Passive transfer possible with serum Cannot be transferred with serum; but possible
with T cells or transfer factor
Desensitisation easy, but short-lived Difficult, but long-lasting
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10.  (4 types)
1. Type l : IgE mediated
2. Type ll : Cytolytic & Cytotoxic
3. Type lll : Immune complex
4. Type lV : Delayed hypersensitivity
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11. Atopy
Anaphylaxis
Arthus reaction
Serum sickness
Autoimmune anemia
Hemolytic disease of newborn
Grave’s disease
Myasthenia gravis
Contact dermatitis
Tuberculin reaction
Schwartzmann reaction
Cutaneous basophil
hypersensitivity
I III
II
IV
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Type of
reaction
Clinical syndrome Time required for
manifestation
Mediators
Type l Anaphylaxis
Atopy
Minutes IgE: histamine & other
pharmacological agents
Type ll Ab mediated damage-
thrombocytopenia,
hemolytic anemia
Variable : hours to
days
IgG : Igm, C
Type lll Arthus reaction
Serum sickness
Variable : hours to
days
IgG : Igm, C, leucocytes
Type lV Tuberculin
Contact dermatitis
Hours to days T cells; lymphokines;
macrophages
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 IgE dependant/ Reagin , mediated
 Occur in 2 forms:
1. Anaphylaxis – acute, potentially fatal, systemic
form.
2. Atopy – chronic or recurrent, non fatal, localized
form.
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Ana- without, Phylaxis-protection
Classical immediate hypersensitivity reaction
Sensitization
Most effective when Ag is introduced parenterally
Minute quantities are enough
Interval of 2-3 weeks needed between sensitizing &
shocking dose
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15. Once sensitized it remains so for long time
Shocking dose most effective by IV route then
IP, then SC then ID
The shocking Ag must be same or similar to
Sensitizing Ag
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16.  Mechanism: Cytotropic IgE – IgE antibodies
bound to surface of mast cells and basophils
FcER receptors analogous to TCR is present
in these cells
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17. Schultz Dale phenomenon:
Intestinal or uterine muscle strips – from
sensitized guinea pigs – kept in a bath of ringer’s
solution – contarct vigorously on addition of
specific antiserum
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18. Primary mediators:
Histamine, Serotonin, Chemotactic factors
Secondary mediators:
Prostaglanins and Leukotrienes, Platelet activating
factor (PAF)
Others:
anaphylatoxins, bradykinin
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19. Theobald-Smith phenomenon:
Guinea pigs - Sublethal load of sea anemones –
toxin - immune
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20. Intravenous Trypsin or peptone - HS
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21. B
cell
Histamine,
tryptase,
kininegenase, ECFA
Leukotriene-B4, C4, D4,
prostaglandin D, PAF
Newly
synthesized
mediators
TH2
Sensitization against allergens and
type-I hypersensitivity
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22. 12/17/2015
Type I Reactions
Humans –
 Itching of scalp & tongue, flushing
of skin, difficulty in breathing,
nausea, vomiting, diarrhea, acute
hypotension, loss of consciousness,
death (rare)
 Causes
 Serum therapy, antibiotics,
insect stings
 Treatment
 Adrenalin 0.5 ml (1 in 1000
solution) SC/IM repeated up to
2 ml in 15 min
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CUTANEOUS (LOCAL)
ANAPHYLAXIS
 Follows I.D. injection (small shocking dose) – a local
wheal & flare response is seen.
 Wheal – central pale area of puffiness due to edema
 Flare - surrounds wheal, caused by hyperemia and
subsequent erythema.
Uses : - Testing for hypersensitivity
 Precaution – Keep adrenalin injection ready to combat
severe fatal reaction.
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ATOPY
 Refers to naturally occurring familial
hypersensitivities of human beings :
- Hay fever
- Asthma
 Antigens involved in atopy can be
1. Inhalants – pollen, house dust
2. Ingestants – eggs, milk
3. Contact allergens.
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Type-I hypersensitivity
The common allergy
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1. Skin tests (ID injection )
- with allergens like pollen, cat or dust mite
Children - 3x3 mm wheal
Adults – 4x4 mm wheal +ve test
takes 5 -15 mins to develop, persist for 30 mins or more
– IMMEDIATE RESPONSE.
2. Radioallergosorbent test (RAST)
- to measure the levels of Ig E in serum. 26

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Involve activation of complement by IgG or
IgM binding to an antigenic cell.
Antigenic cell is lysed.
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Type II Hypersensitivity
Role of complement and phagocytes
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 Reactions against blood cells & platelets
1. Incompatible blood transfusion.
2. Hemolytic disease of the newborn.
3. Autoimmune hemolytic anemias,
thrombocytopenia.
• Reactions against Tissue Antigens
1. Myasthenia gravis & LATS in Grave’s disease
2. Pemphigus vulgaris 29

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Type II hypersensitivity induced by
exogenous agents
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 Involve reactions against soluble antigens
circulating in serum.
 Usually involve IgA antibodies.
 Antibody-Antigen immune complexes are deposited
in organs, activate complement, and cause
inflammatory damage.
 Glomerulonephritis: Inflammatory kidney damage.
 Occurs when slightly high antigen-antibody ratio is
present.
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APC
TH2
B cell
Sensitization for Type III hypersensitivity
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Immune Complex Mediated Hypersensitivity
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Systemic form of type lll HS.
Appears 7-12 days following the injection of large
doses of foreign serum (Diphtheria antitoxin).
ICs are deposited on the endothelial lining of blood
vessels in various parts of the body.
Features – fever, LN pathy, splenomegaly, arhthritis,
glomerulonephritis, endocarditis, rashes, abdominal
pain, nausea & vomiting.
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Serum sickness
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Local reaction consisting of edema, induration &
hemorrhage.
Followed by repeated SC injection with a foreign
serum/ normal horse serum.
Intense local reaction – edema, induration,
hemorrhagic necrosis
Reaches peak after 4 - 10 hrs, disappears by 48
hrs.
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 Takes more than 12 hrs to develop.
 Involve CMI reactions.
 Provoked by intracellular microbial infections or
haptens like simple chemicals
 Varieties of Delayed HS :
1. Contact 48-72 hrs
2. Tuberculin 48-72 hrs
3. Granulomatous 21-28 days
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 Eczematous reaction at the point of
contact with an allergen, like
1. Metals – nickel, chromium
2. Simple chemicals – dyes
3. Drugs – Penicillin
• Cells involved in Contact HS
1. Langerhans cells
2. Keratinocytes
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Lesions – vary from macules & papules to vesicles that
break down leaving behind raw weeping areas
Detected by ‘Skin Patch Test’
* Allergen is applied to the skin under an
adherent dressing.
* Itching appears in 4- 5 hrs.
* Local reaction after 24- 48 hrs: Erythema
to vesicle or blister formation 40

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Clinical & Patch test appearance of contact
hypersensitivity
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Tuberculin Type Hypersensitivity
Tuberculin type –
 ID inoculation of PPD in sensitized
individual leads to induration &
inflammation in 48-72 hrs. This is not
the same as skin test done for Type I
hypersensitivity.
 Used for diagnosis / exclusion of
diagnosis of many bacterial / fungal /
parasitic / viral and autoimmune
diseases.
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Leprosy
Tuberculosis
Schistosomiasis
Sarcoidosis
Crohn’s disease
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Not an immune reaction
Pertubation in factors affecting intravascular
coagulation
Ex: Waterhouse Freiderichsen syndrome
Meningococcal septicemia
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Type-IVType-IIIType-IIType-Icharacteristic
Comparison of hypersensitivity reactions
TB test,
poison ivy,
granuloma
farmers’
lung, SLE
pemphigus,
Goodpasture
hay fever,
asthma
examples
antibody IgE IgG, IgM IgG, IgM none
antigen exogenous cell surface intracellularsoluble
response
time
15-30 min. Min.-hrs 3-8 hours 48-72 hours
or longer
appearance Weal & flare Lysis &
necrosis
Erythema
& edema
Erythema &
induration
baso- and
eosinophils
Ab and
complement
histology PMN and
complement
Monocytes &
lymphocytes
T-cellsantibodyantibodyantibodytransfer with
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48. Hypersensitivity – injurious
4 types – Type I, II, III, IV
I, II, III – Immediate
IV- Delayed
Differences between immediate and delayed HS
Examples for Type I, II, III and IV HS
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49. THANK YOU
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