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Hypersensitivity

Type 1 Type 2 Type 3 Type 4

(IgE mediated/anaphylactic ) (IgG mediated/cytotoxic) (Immune complex (Cell mediated)
mediated)
Onset Immediate (sec-hrs ) Immediate Immediate Delayed (days)
Requires Yes Yes (Ag-Ab complex Yes(Ag-Ab complex No
antibodies involving particulate matter deposition)
such as RBC, bacterial cell Body produces anti-dsDNA
wall etc.) in SLE and RA
Manifestations Systemic and localized anaphylaxis, hay fever, Hemolytic transfusion Serum sickness, necrotizing Contact dermatitis, tubercular
(signs and asthma, hives/urticaria, eczema reactions, HDN, autoimmune vasculitis, rheumatoid lesions, GVHD
symptoms) hemolytic anemia, arthritis, Granuloma formation – Increase
Goodpasteur syndrome glomerulonephritis, SLE WBC in an area (Delayed Inflm)

Causative Allergens/atopic antigens
agent  Atopy- inherited tendency to have an
immune reaction to a natural
substance
Sensitization MHC class II is utilized by APCs and is reacted
phase upon by CD-4 T-helper cells (TH2)  Release
of cytokinesB cell becomes plasma cell to
produce specific IgE
Effector phase IgE are bounded to FcεRI (receptors of mast
cells and basophils)
 Presence of allergens allow cross
linkages of IgE  degranulation of
mast cells  Release of histamine and
other regulators
 Primary mediators
o Histamine, heparin, ECF, NCF,
proteases
 Secondary mediators
o Platelet activating factors,
prostaglandin, leukotriene
(LT-B4)
Blood transfusion reactions,
Drug reactions, Rh factor
incompatibility
Activation of complement
Effector molecules: MAC
NO CYTOKINE
INVOLVEMENT
-If the immune complex is
formed directly on the cell,
ADCC is activated Lysis
Soluble antigen
Activation of complement
Effector molecules:
Neutrophil
Deposition of immune
complexes
• Tissue damage
• Inflammation (Edema)
• Recruitment of cells
Intracellular pathogen –
bacteria/parasite/virus
Contact antigen induction –
poison ivy(urushiol), oak tree,
cosmetics(hair dye)
APC(Dendritic cells) phagocytize
the intracellular pathogen Use
MHC class II  Present to CD
4(TH1)Release cytokines
Peripheral Lymph. Release GM-
CSF and IL-3
 Monocyte to Macrophage (INF-
γ and TNF β activates
macrophage)  Engulf substances
Activation of resting macrophage
and TH1
Increase # of WBC in a local area
(includes CD 8)
Formation of induration called
granuloma

Note: See Table 43.1 found on page 3 for the mechanism

of the hypersensitivity reaction
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Side notes Leukotrienes and prostaglandins came from Classical pathway is initiated Tissue Damage Discovered by Robert Koch
arachidonic acid  End result: Cell  Phagocytes cannot
Pathways may converge to: lysis, opsonization, engulf target cells, Does not require antibodies and
cyclo-oxygenaseProstaglandin inflammation granules and complement activation
5-lipoxygenase Leukotriene ADCC- antibody dependent lysosomal contents
cell cytotoxicity are released
Experiment:  Autoimmunity Arthus reaction
Passive cutaneous hypersensitivity reaction (coating of normal  Localized type 3
 Kustner: Wheal and flare formation cells) – NK cell reaction
recognition  Local injection of
antigen
Treatment 1. Immunotherapy
Results: Downregulation of TH2; Upregulation
of TH1 and T-regulatory cells
2. Anti-IgE monoclonal antibodies
Example: Omalizumab - 1st Anti-IgE
monoclonal antibody approved by USFDA
Tests In vivo skin test (cutaneous and intradermal) DAT- detect sensitized cells Primary( EIA,Fluorescent Patch test-gold standard in dx of
+ result: Wheal and flare formation in vivo staining) and secondary contact dermatitis (48 hrs;peak-
In vitro test serologic tests ( Passive 72hrs)
1. Total IgE via RIST agglutination)
2. Ag specific IgE via RAST Mantoux test/ tuberculin test
- Use 0.1ml purified protein
derivative from M. leprae (Wheal
and Flare formation); Granuloma
>/= 15mm- Present infection
>/= 10 mm- Past exposure
<=5 mm – Negative

Types of RIST ( Radioimmunosorbent test)

Competitive Noncompetitive

Solid phase Contains anti-IgE ( nonspecific ) Contains anti-IgE

Antibodies Patient IgE vs Radiolabeled IgE Patient IgE

 Both will compete for the anti-IgE site
Principle The antibody with the highest concentration in the solid phase Patient IgE + anti IgE Incubate and wash (to remove
are those that are bound to the anti-IgE nonreactive antibodies)  Add radiolabeled anti-IgE that would
bind to the patient IgE  Wash and incubate

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Measurement Radioactivity can be measured through the radiolabeled IgE
that is bound to the anti IgE in the solid phase
Interpretation Radioactivity measured is indirectly proportional to the
patient’s total IgE (Inverse relationship)
Diagram
Radioactivity can be measured through the radioisotope that is
bound to the patient IgE
Radioactivity measured is directly proportional to the patient’s
total IgE

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