- Increased eosinophils (stimulated by

Hypersensitivity: Review Material interleukin-5 and eosinophil chemotactic

factor A [ECF-A)
Introduction - Release of toxic molecules and
inflammatory mediators
Hypersensitivity refers to an enhanced or exaggerated immune
response to an antigen, where the immune response itself is
more harmful than the antigen.

This reaction can result in tissue injury, disease, or even death.

It is influenced by environmental and genetic factors and is

classified by Gell and Coombs into four types:

1. Type I: Anaphylactic Hypersensitivity (Immediate)

2. Type II: Cytotoxic Hypersensitivity (Antibody-
mediated)
3. Type III: Immune Complex Hypersensitivity
(Complex-mediated)
4. Type IV: Delayed Hypersensitivity (T-cell-mediated)

Type I Hypersensitivity: Anaphylactic Reactions

● Mechanism: Cell-bound IgE reacts with an antigen,

leading to the release of active substances such as
histamine, prostaglandins, leukotrienes, and
cytokines.
● Key Reactant: IgE ● Common Conditions: Allergic rhinitis, asthma, food
● Effector Cells: Mast cells and basophils allergies, anaphylaxis, atopic dermatitis
● Affected by: MHC genes - HLA-D (DR-2, DR-4, DR- - Skin: Dermatitis (local skin inflammation)
7) — Swelling and redness (hives/urticaria);
● HLA genes has a role in antigen presentation = if redness spreads = wheal-and-flare
responses to specific antigens reaction
● Variations in gene found in Chromosome 11q (Codes - Respiratory: Bronchoconstriction,
for FcεR) — results to high-affinity to Fc epsilon Bronchospasm
receptor (FcεR1) — Increased chances of IgE binding
- Vasodilation — Increased Permeability —
to cells
Angioedema/Swelling
● Phases:
- Progressive fall of BP (hypotension)
1. Sensitization Phase: Initial exposure to an allergen
triggers B cells to produce allergen-specific IgE, - Shock (Anaphylaxis – most severe type)
which binds to Fcε receptors on mast cells and - Gastrointestinal symptoms
basophils. ● Testing Methods:
○ In vivo: Skin Prick Test, Intradermal Test
IgE production
○ In vitro: RIST (Radioimmunosorbent Assay
for Total IgE), RAST (Radioallergosorbent
Assay for Specific IgE)
● Treatment:
- IgE production (primarily regulated by T ○ Avoidance: Avoiding known allergens is the
Helper 2) normally, there is balance between first line of defense.
TH1 and TH2 activity, but in Type 1 ○ Medications: Antihistamines (H1 blockers),
Hypersensitivity, TH2 is more active corticosteroids, leukotriene receptor
antagonists, and mast cell stabilizers.
2. Activation Phase: Upon re-
○ Emergency Treatment: Epinephrine for
exposure, cross-linking of IgE
anaphylaxis.
causes degranulation, releasing
○ Immunotherapy: Allergen-specific
inflammatory mediators.
immunotherapy to desensitize the immune
system.
○ Biologic Therapy: Omalizumab (anti-IgE
3. Late Phase: Occurs 6-8 hours post-exposure, with monoclonal antibody) for severe allergic
recruitment of eosinophils and more inflammatory asthma.
mediators, worsening symptoms.
- Formation of secondary mediators
(prostaglandin, leukotrienes, cytokines)
MRMU | IMMUNOSERO SY 24-25
Type II Hypersensitivity: Cytotoxic Reactions/ ○ Systemic Lupus Erythematosus (SLE):
Antibody-Mediated Autoimmune disorder affecting multiple
organs.
● Mechanism: Antibodies (IgG, IgM) bind to antigens ○ Rheumatoid Arthritis (RA): Chronic
on cell surfaces, activating complement pathways and inflammation of joints.
leading to cell lysis or opsonization. ○ Sjogren’s Syndrome: Immune attack on
● Key Reactants: IgG, IgM, complement proteins salivary and lacrimal glands.
○ Glomerulonephritis: Immune complex
deposition in kidneys.
○ Farmer’s Lung: Hypersensitivity
pneumonitis from inhaled organic dust.
● Tests: ANA Detection (for SLE and RA), Fluorescent
Staining for immune complexes, Complement Level
Testing

● Examples:
DISCOVERED
BY
Nicolas
○ Hemolytic Disease of the Newborn (HDN): Maurice
Arthus (1903)
Maternal antibodies attack fetal red blood
cells.
○ Transfusion Reactions: Mismatched blood
transfusions cause hemolysis.
○ Autoimmune Hemolytic Anemia (AIHA):
Self-reactive antibodies attack red blood Type IV Hypersensitivity: Delayed/T-Cell
cells. Mediated Reactions
○ Myasthenia Gravis (Inhibitory):
Autoantibodies block acetylcholine receptors ● Mechanism: T-cell activation leads to macrophage
at neuromuscular junctions. recruitment and tissue destruction over 24-72 hours.
○ Graves’ Disease (Stimulating): ● Key Reactants: CD4+ T cells (usually Th1 cells)
Autoantibodies stimulate TSH receptors, ● Key Feature: Granuloma formation to contain
causing hyperthyroidism. pathogens but results in lytic enzyme release and
● Tests: Direct Antibody Testing (DAT), Indirect tissue damage.
Antibody Testing (IAT) ● Examples:
○ Tuberculosis (MTB): Granulomas form to
Type III Hypersensitivity: Immune Complex contain Mycobacterium tuberculosis.
Reactions ○ Leprosy (M. leprae): Chronic granulomatous
inflammation in skin and nerves.
● Mechanism: Soluble antigen-antibody complexes ○ Pneumocystis carinii infections:
deposit in tissues, leading to complement activation, Opportunistic infection in
neutrophil recruitment, and tissue damage. immunocompromised patients.
● Key Reactants: IgG and IgM ○ Leishmaniasis: Parasitic infection leading
● Examples: to chronic skin ulcers.
○ Arthus Reaction: Localized immune ○ Contact Dermatitis: Skin reaction to poison
complex reaction. ivy, metals, hair dye components, and latex.
○ Serum Sickness: Systemic reaction due to
foreign protein exposure.

MRMU | IMMUNOSERO SY 24-25

 ● Tests:
○ Patch Test: Identifies allergens causing
contact dermatitis.
○ Mantoux Test (Tuberculin PPD Test):
Assesses prior exposure to tuberculosis.
○ QuantiFERON-TB Gold Test: Measures
IFN-γ response to MTB antigens.

SUMMARY

MRMU | IMMUNOSERO SY 24-25