1. HYPERSENSITIVITY REACTIONS
Immunopathology & Molecular biology
Dheeraj Kumar
BMLT 6 SEM
Hypersensitivity
Immune Response is generally a Protective Process, but it may Sometimes be injuries to the host.
which Just eliminates the antigens without Causing any damage to the host. However, at time this
Response leads to exaggerated inflammatory Response which Causes extensive tissue damage.
Definition
Hypersensitivity refers to a Condition in which Immune response results in excessive reaction
leading to tissue damage disease or even death in the Sensitized host.
Classification
Coombs and Gell (1963) classified hypersensitivity reactions into four major types.
1. immediate (Antibody Mediated)
Type I (Anaphylactic Reaction)
Type II (Cytotoxic Reaction)
Type III (Immune Complex)
2. Delayed (Cell Mediated)
Type IV (Delayed)
1. Immediate hypersensitivity Reaction
These reactions occur immediately, within few minutes to few hours of antigen Contact as a result
of abnormal humoral response (antibody mediated).
Type I (Anaphylaxis Reaction)
Type I hypersensitivity reaction is Production of IgE by Sensitized B Cell following contact with an
allergen which induces mast Cell degranulation.
2. The acute Potentially fatal, Systemic form Called anaphylaxis and the recurrent non-fatal localized
form Called atopy.
Mechanism of Type I Hypersensitivity
This reaction occurs into two Phase.
1. Sensitization Phase
2. Effector Phase
1.Sensitization Phase
These occur when an individual is exposed for the first time to the Sensitization or Priming dose of
an allergen.
The allergen is processed by the antigen presenting Cell and activate TH Cell which Secrete
interleukin.
IL-4 induces the B Cell to differentiate into IgE Producing Plasma Call and memory Cell.
Secreted IgE migrate to the target Sites and Coat on the Surface of mast cell and basophil.
The FC Region of IgE binds to high affinity Fc receptor present on mast cell Surface.
Such Sensitized mast Cell (Coated with IgE) will be waiting for interaction with the antigenic
challenge.
3. 2.Effector Phase
When the Same allergen is introduced (shocking dose) it directly Contact with the fab region of IgE
coated on mast cells.
Allergen bound to IgE triggers the mast cells activation and degranulation.
Granules within the mast cell and basophil are released chemical mediators. (Histamine, Serotonin,
prostaglandins, leukotrienes).
Chemical mediator act on various tissue leading to increased permeability of blood vessels, Vascular
and Smooth muscle Contraction, Vasodilation.
Type II Hypersensitivity reactions (Cytotoxic Reaction)
Type II hypersensitivity or Cytotoxic Reaction affects a variety of organs and tissues.
The reaction is mediated by antibodies of the IgG or rarely IgM.
Reaction time is minute to hr.
Cell Lysis result due to: -
The fc region of antibody bound with antigen Can ag and ab Complex activate Complement system.
Activated Complement will lead to Cell Lysis.
Antibody depended Cellular Cytotoxicity (ADCC).
IgG Ab Can Coat on the target Cell by interacting with the surface Ag through fab region.
4. The fc portion of IgG in turn binds to fc receptors. on various effectors Such as NK, macrophages.
neutrophil ex- tumor Cells, graft Cell. Parasites.
Type III hypersensitivity Reaction (Immune Complex mediated)
Type III hypersensitivity Reaction develop as a result of excess formation of immune Complexes (Ag-
Ab Complexes).
Which initiates an inflammatory response through activation of Complement System Leading to
tissue injury.
The reaction may take 3-10 hr. after exposure to the Ag.
Ag-Ab immune Complex IgG mediated.
The Ag may be -
Exogenous: - bacterial, viral, Parasitic
Endogenous- Autoimmunity
It is mediated by Soluble immune Complex.
Mechanism of Type III hypersensitivity reaction
Ag Combines with ab within Circulation and form immune Complex wherever in the body they
deposited.
They activate the Complement System. (C3a and C3b).
Compliment System attract & activate neutrophil which release inflammatory Chemicals (lytic
enzyme) which Cause extensive tissue damage.
5. Causes of Immediate hypersensitivity Reaction
✓ Transfusion reaction (ABO incompatibility).
✓ Rh incompatibility (Hemolytic disease of the newborn).
✓ Autoimmune disease (hemolytic Anemia, Thrombocytopenia.
✓ Drugs induce reaction.
2. Delayed hypersensitivity Reaction
Delayed hypersensitivity Reaction is an immunologic reaction that is mediated primarily by T cells
and monocytes and presents hours to days after the antigen crosses into the skin.
Type IV Hypersensitivity Reaction
Type 4 hypersensitivity reaction differs from other types in various ways. It is delayed type (occur
after 48-72hr. of Ag exposure).
It is Cell mediated (T Cell).
Mechanism of type IV hypersensitivity Reaction
Mechanism done in two phases.
1.Sensitization Phase
2.Effector Phase
1.Sensitization Phase
It occurs after 1-2 weeks of Ag exposure.
During this period the APC (Antigen presenting Cell) Process and Present along with MHC II to the
helper Cell.
Most T cells are derived from TH 1 Cell but occasionally other T- cell (CD8, CD4).
2.Effector Phase
T Cell directly Contact with Ag & secrete Cytokines.
Which attract & recruit Various inflammatory Cell ex - Macrophages.
