Concepts of hypersensivity should be well versed to all medical personnel to understand its implications. I have made it very simple to all readers to understand the same
Normally the immune system plays an important role in protecting the body from microorganisms and other foreign substances. If the activity of the immune system is excessive or overreactive, a hypersensitivity reaction develops. The consequences of a hypersensitivity reaction may be injury to the body or death.
Normally the immune system plays an important role in protecting the body from microorganisms and other foreign substances. If the activity of the immune system is excessive or overreactive, a hypersensitivity reaction develops. The consequences of a hypersensitivity reaction may be injury to the body or death.
Immediate or Type I hypersensitivity is a rapid immunological reaction occurring in a previously sensitized individual that is triggered by the binding of an antigen to IgE antibody on the surface of mast cells.
Type II Hypersensitivity-Antibody mediated cytotoxic HypersensitivityAnup Bajracharya
Type II Hypersensitivity is antibody-mediated immune reaction in which antibodies (IgG or IgM) are directed against cellular or extracellular matrix antigens with the resultant cellular destruction, functional loss, or damage to tissues.
Through this presentation you will be able to learn detailed information about hypersensitivity reactions, its type and clinical manifestation of all types of hypersensitivity reactions and related diseases.
A. There are three types of immunological disorders
1. Hypersensitivity
2. Autoimmune disease
3. Immunodeficiency
B. Hypersensitivity reactions to usually harmless substances are often called allergies or allergic reactions
Immediate or Type I hypersensitivity is a rapid immunological reaction occurring in a previously sensitized individual that is triggered by the binding of an antigen to IgE antibody on the surface of mast cells.
Type II Hypersensitivity-Antibody mediated cytotoxic HypersensitivityAnup Bajracharya
Type II Hypersensitivity is antibody-mediated immune reaction in which antibodies (IgG or IgM) are directed against cellular or extracellular matrix antigens with the resultant cellular destruction, functional loss, or damage to tissues.
Through this presentation you will be able to learn detailed information about hypersensitivity reactions, its type and clinical manifestation of all types of hypersensitivity reactions and related diseases.
A. There are three types of immunological disorders
1. Hypersensitivity
2. Autoimmune disease
3. Immunodeficiency
B. Hypersensitivity reactions to usually harmless substances are often called allergies or allergic reactions
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Defecation
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Normal defecation is painless, resulting in passage of soft, formed stool
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FLATULENCE
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FECAL INCONTINENCE
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1. Type 1 hypersensitivity reaction
(allergy)
Dr. Prathyusha
PG in ENT Narayana Medical College
NELLORE
2. once upon a time………
• Menes, the first
Egyptian pharaoh ruled
about 3100 BC.
• The plate of his empty
tomb appears to show a
wasp or hornet
• suggest that Menes died
from a wasp sting ?.
3. 100 yrs ago…..
• An young paediatrician understood that the function of the immune
system should be rationalized
• NOT in terms of exemption of disease
• but in terms of change of reactivity.
• He coined a new word to represent such an idea….ALLERGY
(“unfortunately used as a slang in our day today life”)
• In his own words….
• “the first contact of the immune system with
an antigen changes the reactivity of the
individual on the second and subsequent
contacts, this change (or allergy) can induce a
4. • Clemens Peter von Pirquet
(May 12, 1874 – February 28, 1929)
• Austrian scientist and pediatrician
• Patients who were injected with horse serum or
smallpox vaccine had quicker, severe reactions
to second injections.
• The collection of symptoms resulting from
serum injections, he gave the name serum
5. He is none other than ….
Pirquet during those
days……
6. Meanwhile…..
• Two French scientists, Paul Portier and Charles Richet,
investigated the violent stings of jellyfish.
• concluded that the reaction was the result of toxins.
• Used isolated jellyfish toxins as vaccines and injected to
dogs.
• with subsequent booster doses dogs had asphyxia and
vomiting and diarrheas
• This overreaction was termed as anaphylaxis by them
• Anaphylaxis (opposite to prophylaxis )
• Richet was subsequently awarded the Nobel Prize in
7.
8.
9.
10. First of all hypersensitivity
• Exaggerated or misdirected immune response
• Results in tissue injury or other pathophysiological
changes
• Occurs when an already sensitized individual is re-exposed
to the same foreign substance
• May be immediate or delayed
16. Characteristics of an antigen
• Small 15-40,000 MW proteins.
• Specific protein components
• Often enzymes.
• Low dose of allergen
• Mucosal exposure.
• Most allergens promote a Th2 immune response
17. Prior Sensitization
required…………..
• the allergen stimulates the production of allergen-
specific IgE antibodies by
plasma cells in susceptible individuals.
• The allergen-specific IgE attaches itself to the surface of
mast cells in various
tissues and basophils in the blood in a process known
as sensitization.
18. Macrophage and exposure of an
antigen• Antigen-presenting cells fall into two categories:
• professional
• non-professional.
• Those that express MHC class II molecules
Co-stimulatory molecules
Pattern recognition receptors are
• The non-professional APCs express MHC class I molecules.
Professional A
19.
20.
21. Activation of T helper cell
• T cells cannot recognize and DO NOT respond to, 'free' or
soluble antigen.
• The APC involved in activating T cells is usually a
macrophage
• the T cells recognize and respond to antigen that has been
processed and
presented by cells via carrier molecules like MHC
molecules.
22.
23.
24. Activated T cell
• Stimulate B cells and their proliferation to plasma
cells
• Stimulates other T helper cells
30. Isotype switching requires
• B cell class switch to IgE requires T cell help:
• CD40L and IL-4 or IL-13 (Th2 cytokines)
• The propensity to make an IgE response to
• environmental antigens varies among individuals
31. After Ig E production
• IgE produced by plasma cells is rapidly taken up
• by FcεRI
• Tissue mast cells and
• Circulating basophils
• (serum τ½~2 days; compare to IgG~21 days)
32.
33. IgE receptor
• The high-affinity IgE receptor, also known as FcεRI,
• FcεRI is a tetrameric receptor complex consisting of
• one alpha (FcεRIα - antibody binding site),
• one beta (FcεRIβ - which amplifies the downstream signal),
• and two gamma chains (FcεRIγ - the site where the
downstream signal initiates) connected by two disulfide
bridges.
34.
35. Secondary exposure to allergen
• Mast cells are primed with IgE on surface.
• Allergen binds IgE and cross-links to activate
• signal with tyrosine phosphorylation,
• Ca++ influx,
• degranulation
• release of mediators
36.
37.
38.
39.
40. • Secondary mediators
• Mediators formed after activation
• Leukotrienes
• Prostaglandins
• Th2 cytokines- IL-4, IL-5, IL-13, GM-CSF
41. LOCAL ANAPHYLAXIS
• Two phases:
• Initial response
• Vasodilation, vascular leakage, smooth
muscle spasm or glandular secretions
• 5-30 min. after exposure
• subside in 60 minutes
42. • 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
43. SYSTEMIC ANAPHYLAXIS
• Occur after administration of
• heterologous proteins (e.g. antisera),
• hormones,
• enzymes,
• polysaccharides & drugs
• itching, hives & skin erythema
• contraction of resp. bronchioles + resp. distress
laryngeal edema
44.
45. • Continuation of sensitization cycle
• Mast cells control the immediate response.
• Eosinophils and neutrophils drive late or chronic
response.
• More IgE production further driven by
• Activated Mast cells, Basophils, Eosinophils.
46. Role of eosinophils
• Continuation of sensitization cycle
• Eosinophils
• Eosinophils play key role in late phase reaction.
• Eosinophils make – enzymes,
• cytokines (IL-3, IL-5, GM-CSF),
• Lipid mediators (LTC4, LTD4, PAF)
• Eosinophils can provide CD40L and IL-4 for B cell
activation.
51. genetic mapping of atopy individuals
• One locus, on chromosome 5q,
• linked to a region that encodes a variety of
cytokines, including IL-3, IL-4, IL-5, IL-9, IL-13,
and GM-CSF.
• A second locus, on chromosome 11q
• linked to a region that encodes the chain of the
high-affinity IgE receptor.
• atopy is multigenic
• other loci to be identified
52. Lab Diagnosis of Allergy
• Skin Prick Test
• Liquid with allergen are
injected with tiny needle
either directly or by affixing
a patch
• after 24 to 72 hours to see
if a reaction occurs.
• If the skin reacts, a red,
raised area (called a wheal)
can be observed, indicating
sensitization to that allergen.
53.
54.
55. • The panel chosen should be based on the patient's clinical
history, as with skin testing.
56. Ig E blood levels
• IgE Blood Test
• specific immunoglobulin E (IgE) antibodies in the blood
that are produced by the body’s immune system when an
allergen is present
57. In Vitro Testing
• patients with affected skin, such as dermatographism or
atopic dermatitis.
• safer option if the patient is at risk for anaphylaxis
• Immunoassays are often referred to as radioallergosorbent
(RAST) testing, but that term is outdated because radiation
is rarely used today.
• Current methods include enzyme-linked immunosorbent
assay (ELISA)
• fluorescent enzyme immunoassays (FEIA)
• Chemiluminescent immunoassays,
58. A solid-phase immunoassay
• allergen bound to a matrix. The patient’s serum is added
and the antibodies bind to the allergen.
• All serotypes (IgG, IgM, IgA, and IgE) will bind if they
recognize the allergen.
• A secondary anti-IgE antibody is used to identify if IgE is
bound.
• The report is a quantitative value in kIUA/L or in arbitrary
divisions into classes I-VI. Asymptomatic sensitization is
common below class III (< 3.5 kIUA/L).[7]
59. • The accuracy of immunoassays varies
with the system used and the quality of
the allergen.
• There is good predictive value (>90%) for
pollens of grass, trees, dust mites, and
cats, whereas
• less accurate results may be obtained from
venoms, weeds, latex, dogs, and molds
• If results are equivocal, further evaluation
can be done by means of skin testing and,
if indicated, a challenge to the allergen.
60. Patch Testing
• chronic eczematous conditions contributing to a delayed-
type hypersensitivity reaction.
• contact dermatitis to jewelry containing nickel.
• food allergies in eosinophilic esophagitis and some drug
allergies
• The most common patch techniques are the individual Finn
chamber or the thin-layer rapid-use epicutaneous (TRUE)
test.
61. Other tests with no clinical significance
• cytotoxic tests,
• provocation-neutralization,
• electrodermal testing,
• applied kinesiology,
• iridology, and hair analysis.
62. Bibliography
• The Pathophysiology, Diagnosis and Treatment of
Allergic Rhinitis Allergy Asthma Immunol Res.
2010 April;2(2):65-76.
• The history of the idea of allergy J. M. Igea Allergy
2013; 68: 966–973.
• Hypersensitivity Mechanisms: An Overview
www.columbia.edu/itc/hs/medical/pathophys/immun