Hypersensitivity

Reactions
 Hypersensitivity
Exaggerated immune response to common
innocuous antigens that causes damage to
the host
Results in tissue injury or other
pathophysiological changes
Occurs when an already sensitized
individual is re-exposed to the same foreign
substance
Have sensitization phase and effector phase
Gell & Coombs Classification: Based on Mechanisms involved and
time taken to develop
Type I Hypersensitivity
 IgE cross-linkage initiates degranulation

• Once cross-linkage of
antigen has occurred,
intracellular signaling
result in mast cell
degranulation
• Increased Ca++ influx
• Cooperation among
protein and lipid kinases,
phosphatases,
rearrangement of the
cytoskeleton
 Type I Hypersensitivity

Two phases:
1. Initial response: because of
preformed mediators present in
granules of mast cells
 Vasodilation, vascular leakage,
smooth muscle spasm or
glandular secretions
 5-30 min. after exposure 
subside in 60 minutes
2. Late-phase reaction: Newly
synthesized mediators like LTs,
PGs in mast cells
 2-8 hrs. later without additional
exposure to antigen
 More intense infiltration of
tissues with eosinophils,
neutrophils, basophils,
monocytes & T cells
 With mucosal epithelial damage
 Type 1 Hypersensitivity: Localized or Systemic

 Localized Hypersensitivity Reactions

○ Allergic Rhinitis
Most common, “hay fever”
○ Asthma
Triggered like hay fever but doesn’t happen in nasal cavity,
happens in lower respiratory tract
○ Food allergies
Hives, vomiting
○ Atopic dermatitis
Allergic eczema
SYSTEMIC ANAPHYLAXIS
• Quick systemic reaction 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
• Dilation of blood vessels: Drop in blood pressure
• Contraction of Smooth muscles
• Edema, Shock like condition
• Death in extreme conditions
Atopy genetic predisposition to
develop localized anaphylactic
reactions to inhaled or ingested
allergens
• family history promotes allergy
development
• With higher serum IgE levels
compared to general population
 Type I Hypersensitivity

DIAGNOSIS:
1.History
2.Skin prick test: Wheal & flare (+)
3.Blood eosinophilia
4.RAST (Radioallergosorbent assay)
Clinical Methods to detect Allergy

• Skin testing
• Checking serum level of
IgE
 Type I Hypersensitivity

TREATMENT:
1.Aviodance of the allergen
2.Pharmalogic Intervention: Cromolyn Sodium
(prevents degranulation), Theophylline
(Increased cAMP), Anti-histamine (first phase
only), Corticosteroids (late phase reaction),
Epinephrine (for anaphylaxis)
3.Immunologic Intervention: Hyposensitization
(Treg cells, IgG) to induce tolerance; no IgE
production, Administration of altered allergen
(Ragweed Pollen)
Type II (Ab mediated Cytotoxic Hypersensitivity)

Cytotoxic reactions as the cells are damaged

directly by action of antibody and complement.
IgG or IgM class of antibodies are involved in
these reactions.
Mechanism: Binding of a specific antibody
directly to an antigen on the surface of a cell
cause lysis of that cell through invoking of
Complement pathways or by phagocytosis or
ADCC (by MQs & NK cells).

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 Examples of Type II Hypersensitivity

• Transfusion Reactions
• Rh Incompatibility Reactions
• Hemolytic disease of new born
• Autoimmune reactions: Autoimmune hemolytic
anemia, Purpura
• Drug induced reactions: Chloramphenicol in
some cause leucopenia
• Anti-receptor antibody disease: Myasthenia
grevis (Ach), TSH (Hyperthyroidism)
 Type III (ICM) Hypersensitivity

Mechanism of Type III Hypersensitivity

 Antigens combines with antibody within circulation and

form immune complex

 Wherever in the body they deposited, they activate

compliment system

 Polymorphonuclear cells are attracted to the site

(chemokines C5a)

 Result in inflammation (anaphylatoxins)and tissue injury

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 Type III Hypersensitivity

Antigens Associated with Immune Complex

Disorders
ANTIGEN CLINICAL MANIFESTATION
EXOGENOUS
Infectious agents:
Bacteria: Y. enterocolitica Arthritis
Streptococci GN, Infective endocarditis
T. pallidum Glomerulonephritis
Viruses: Hep. B, CMV Polyarteritis nodosa
Parasites: Plasmodium Glomerulonephritis
Schistosoma
Fungi: Actinomycetes Farmer’s lung

ENDOGENOUS
Nuclear antigens SLE
Immunoglobulins Rheumatoid arthritis
Tumor antigens Glomerulonephritis
 Type III (ICM) Hypersensitivity

Immune Complex Diseases:

 Arthus reaction
 Serum Sickness
 Hypersensitivity Pneumonitis
 Glomerulonephritis
 Rheumatoid Arthritis
 Systemic Lupus Erythematosus

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 Type III Hypersensitivity

SERUM SICKNESS
• Patient forms antibodies to xenogeneic
Ig administered during passive immune
therapy regimens

ARTHUS REACTION
• Seen when boosters are administered to
individuals who already possess high
antibody titers to vaccine molecules
• Localized area to tissue necrosis 
edema, hemorrhage, ulceration
• Develop over a few hours
 Type III (ICM) Hypersensitivity

Rheumatoid arthritis

 Immune complexes deposited in the joint

» Results in release of inflammatory chemicals
» The joints begin to break down and become
distorted

 Trigger not well understood

 Treated with anti-inflammatory drugs

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The crippling distortion of joints characteristic of rheumatoid arthritis
 Type III (ICM) Hypersensitivity
Systemic lupus erythematosus
Autoantibodies against DNA result in immune complex
formation
Many other autoantibodies can also occur
» Against red blood cells, platelets, lymphocytes,
muscle cells
Trigger unknown
 Immunosuppressive drugs reduce autoantibody
formation
Glucocorticoids reduce inflammation

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The characteristic facial rash of systemic lupus erythematosus
Type IV Hypersensitivity

Cell-mediated delayed type hypersensitivity

Initiated by antigen specific sensitized T
lymphocytes
Principal pattern of immunologic response
to intracellular microbiologic agents
(particularly Mycobacterium tuberculosis)
as well as viruses, fungi, protozoa &
parasites
 Type IV Hypersensitivity
Mechanism: When a particular antigen is
presented by APC to naïve Th cell, it enhances
proliferation of antigen specific Th1 cells &
various cytokines. These cytokines attract the
MNCs and activate them. It is the enhanced
no. of MNCs and their activities that create the
major feature of this type of reaction.
 Type IV
Sensitization phase and Effector phase of DTH
Two forms:
1.Delayed-type hypersensitivity
 Mediated by CD4 T cells
 1st exposure to Ag  CD4 T cells
+ class II MHC  differentiation
of naïve CD4 T cells to TH1 cells
 release of IL-12, IFN-, IL-2,
TNF & lymphotoxin
 Tuberculin skin test, contact
dermatitis, granulomatous
inflammation
2.T Cell-Mediated Cytotoxicity
 Mediated by CD8+ T cells
 Sensitized CD8+ T cells kill
antigen-bearing target cells
 Graft rejection, virus infections,
tumor immunity
Type IV – contact dermatitis
Allergic contact dermatitis
 Type IV (Cell Mediated) Hypersensitivity

Tuberculin like reaction

• An injection of tuberculin PPD into the skin causes

reaction in individual exposed to tuberculosis or
tuberculosis vaccine
• Used to diagnose contact with antigens of
M. tuberculosis
» No response when individual not infected or
vaccinated
» Red, hard swelling develops in individuals previously
infected or immunized after 48 hours
» Montoux test, Johnin test

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A positive tuberculin test
Granulomatous Hypersensitivity: Prolonged DTH can lead to formation of
granuloma. Ex: T.B., Leprosy
Thanks