General pathology
Lecture no 12
TODAY’S
TOPIC
HYPERSENSITIVITY
REACTIONS
HYPERSENSITIVITY REACTIONS
• 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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HYPERSENSITIVITY REACTIONS
• I (Immediate Hypersensitivity)
• II (Antibody Mediated Hypersensitivity)
• III (Immune-Complex Mediated
Hypersensitivity)
• IV (Cell-Mediated Hypersensitivity)
TYPE I (IMMEDIATE) HYPERSENSITIVITY
• Also called allergic reactions, or allergies
• Antiges will react with fixed antibodies
• ANTIBODIES: IgE
• CELLS: Mast cells and basophills
• The antigens that stimulate it are called
allergens
• (i.e. House dust, Pollens, Cosmetics, Insects,
Clothing and Drug)
• Exposure may be ingested, inhalation,
injection or direct contact.
• Type I hypersensitivity reactions can be
systemic (e.g., systemic anaphylaxis) or
localized to a specific target tissue or organ
(e.g., allergic rhinitis, asthma).
PATHOGENESIS
ON FIRST EXPOSURE
• Ag will enter into the body (7 days are required
to form Ab)
• IgE will be synthesized
• Attach on basophills and mast cells
• Sensitization of mast cells.
ON 2 EXPOSURE
nd
EARLY PHASE
• Starts within 5-30 min of Ag entry/ exposure and
will persist for 1 hr/60 min
• Cross linking of IgE Ab on sensitized mast cells and
basophils
• Release of histamine
• MAST cell DEgranulation, vasodilatation, vascular
leakage, smooth muscle spasm
LATE PHASE
• Within 2- 8 hrs of Ag exposure
• Persists for several days
• Role of araquidonic acid metabolites (leucotriens)
• Eosinophils, PMNs, T-Cells
CLINICAL MANIFESTATIONS
• Dyspnea
• Broncospasm
• Wheezes, ronchi ANAPHYLAXIS
• Increased bronchal secretions
• Abdominal cramps
• Diarrhea
• Itchy erythematous rash
• Hyperthermia
• Hypotension
• CLINICAL EXAMPLES OF TYPE I
HYPERSENSITIVITY
– Anaphylaxis,
– allergies,
– bronchial asthma (atopic forms)
TYPE II (CYTOTOXIC)
HYPERSENSITIVITY
• Ag is fixed
• Antibody free
• IgG
PATHOGENESIS:
1. Complement system activation (role of MAC)
2. Antibody dependant cell mediated cytotoxicity
3. Antibody dependent cellular dysfunction
TYPE II (CYTOTOXIC) HYPERSENSITIVITY
Type II hypersensitivity involves IgG or IgM
antibody-mediated
IgM or IgG immunoglobulin react with cell-
surface antigens to activate the complements
system and produce direct damage of the sell
surface.
Transfusion reactions and hemolytic disease
of the newborn are examples of type II
hypersensitivity.
Type II Hypersensitivity
MECHANISMS:
Complement-Dependent Reactions
Source: Robbins PATHOLOGIC
BASIS OF DISEASE
Type II Hypersensitivity
MECHANISMS:
Complement-Dependent Reactions
1. Transfusion reactions
2. Erythroblastosis fetalis
3. Autoimmune hemolytic anemia,
agranulocytosis, thrombocytopenia – (+)
antibodies vs own blood cells
4. Pemphigus vulgaris – Ab’s vs.
desmosomes
5. Drug reactions
Type II Hypersensitivity
MECHANISMS:
Antibody-Dependent Cell-Mediated
Cytotoxicity (ADCC)
Source: Robbins PATHOLOGIC BASIS OF DISEASE .
Type II Hypersensitivity
MECHANISMS:
Antibody-Mediated Cellular Dysfunction
• Antibodies directed against cell surface
receptors impair or dysregulate
function
Source: Robbins PATHOLOGIC BASIS OF DISEASE
Type II Hypersensitivity
MECHANISMS:
Antibody-Mediated Cellular Dysfunction
1. Myasthenia gravis – acetylcholine
receptors
2. Goodpasture’s syndrome – type IV
collagen
3. Pernicious anemia – intrinsic factor
4. Acute rheumatic fever – antibodies vs.
Streptococcal antigens cross-react with
heart
Type III (Immune Complex–Mediated)
Hypersensitivity
Type III hypersensitivity is also known as immune complex
hypersensitivity.
The reaction may take 3 - 10 hours after exposure to the
antigen (as in Arthus reaction).
The reaction may be general (e.g., serum sickness) or may
involve individual organs including or other organs.
Antigens causing immune complex mediated injury are:
Exogenous
Endogenous
Mechanism of Type III
Hypersensitivity
Antigens combines with antibody within
circulation and form immune complex
Wherever in the body they deposited
They activate complement system
Polymorphonuclear cells are attracted to
the site
Result in inflammation and tissue injury
Type III Hypersensitivity
Source: Robbins PATHOLOGIC BASIS OF DISEASE 6th ed.
Type III (immunocomplex)
hypersensitivity
• Antigen/Antibody “Complexes”
– Kidney (Glomerular Basement Membrane)
– Blood Vessels
– Skin
– Joints
• Common Type III Diseases
– SLE (Lupus),
– Poly(Peri)arteritis Nodosa,
– Poststreptococcal Glomerulonephritis,
– Arthus reaction (hrs),
– Serum sickness (days)
The crippling distortion of joints
characteristic of rheumatoid arthritis
The characteristic facial rash of systemic
lupus erythematosus
TYPE IV (DELAYED OR CELL-MEDIATED)
HYPERSENSITIVITY
Delayed hypersensitivity is a function of T Lymphocytes,
not
antibody.
It starts hours (or Days) after contact with the antigen and
often
lasts for days.
It can be transferred by immunologically committed
(Sensitized) T cells, not by serum.
Principal pattern of immunologic response to variety of
intracellular microbiologic agents
i.e.: Mycobacterium Tuberculosis
Viruses
Fungi
Parasites
MECHANISM OF TYPE IV
HYPERSENSITIVITY
Activated T Lymphocytes
Release of cytokines and macrophage
activation
T-cell mediated cytotoxicity
TYPE IV HYPERSENSITIVITY
• Tuberculin Skin Reaction
• Graft rejection
• GRANULOMA FORMATION
• CONTACT DERMATITIS
SUMMARY
• I Acute allergic reaction
• II Antibodies directed against cell surfaces
• III Immune complexes
• IV Delayed Hypersensitivity (Tb skin test)
