What is Hypersensitivity | Hypersensitivity reactions | allergen | common allergic conditions

Hypersensitivity reactions-

• Allergy means hypersensitivity.

• it is defined as abnormal immune response to a chemical or physical agent, that is called allergen.
• these are caused by the activity of the immune system detrimental ( tend to cause harm) to the host in response to exposure of the antigens to the immune cells of the body.

✓allergic reactions /
    immunological hypersensitivity reactions-
• during the first exposure to an allergen, the immune system does not produce any reactions in the body.
* Initial exposure or sensitization to the allergen is required for the reactions. 

• but subsequent exposure to the allergen causes inflammatory responses. These reactions are called allergic reactions or immunological hypersensitivity reactions.

• these reactions may be innate or acquired.
• these reactions are mostly mediated by antibodies.
In some conditions T-cells are involved.
✓common symptoms-
- sneezing
- itching
- skin rashes
✓ common allergic conditions-
- food allergy
- bronchial asthma
- urticaria/ hives ( skin rashes)
- allergic rhinitis

✓allergens-
• Any substance that produces the allergy.
• it may be an antigen or a protein or any other type of substance.
• even physical agents can develop allergy.

> Allergens are introduced by-
a. Contact-       chemical substance
b. Inhalation- pollen grains
c. Ingestion-    food
d. Injection- .  Drug

√ common allergens- 
1. Food substance-
- wheat
- egg
- milk
- chocolate
2. Inhalants-
- pollen grains
- fungi
- dust
--smoke
- perfume
- dis-agreeable odor
3. Drugs-
- Aspirin
- antibiotics
4. Physical agent
- cold and heat
- light
- pressure
- radiation
5. Contactants
- chemical substance
- metals
- animals
- plants

✓{ Hypersensitivity reactions}
These are classified into five types-

1. Type 1 (anaphylactic reaction)
2. Type 2 (cytotoxic reaction)
3. Type 3 (antibody mediated reaction)
4. Type 4 (cell mediated reaction)
5. Type 5 ( stimulatory or blocking reaction)

TYPE 1 HYPERSENSITIVITY REACTION
1. Type 1
   • Anaphylactic reaction
   • immediate type
• commonly referred as allergy.
*it is also called immediate hypersensitivity reaction because it develops within few minutes of exposure to an allergen.

• it is defined as a rapidly developing immunological reaction occurring within minutes after the combination of an antigen with antibody bound to mast cells in individuals previously sensitize to the antigen.
* Anaphylactic reactions are mediated by IgE.
IgE also called Reagins or sensitizing antibodies.
° the first state is stage of sensitization followed by the exposure resulting in development of symptoms

✓[Important features of Type 1    hypersensitivity reaction]~

° the clinical features are usually seen during the second time antigen exposure subsequent to sensitization or priming.
° histamine is responsible for early clinical features because it is performed mediator.
° IL-4 is responsible for secretion of IgE from the B cells.
° IL-5 is the most potent eosinophil activating cytokines.
° PAF(platelet activating factor) is the major mediator of the late phase reaction.

} Process of allergic reactions-

a• when the body is exposed to an allergen the immunoglobin is produced.
b• immunoglobin bind with surface receptor of mast cells and circulating basophils.
c• mast cells are granulated cells found in connective tissue and below the mucous membrane in throat , lungs and eyes.
d• during subsequent exposure of the body to allergen,  allergan immunoglobinE (IgE) reaction take place.
e• this leads to degranulation of mast cells and basophils and release of chemical mediators such as histamine.
f• the chemical mediators produced the hypersensitivity reactions.

@ most serious reactions are
~ fall in BP due to vasodilatation
~ obstruction of air passage and difficulty in breathing due to bronchoconstriction and
~ shock

Examples of type 1 hypersensitivity reactions-

•bronchial asthma
•allergic rhinitis
•hay fever
•food Allergy
•atopic dermatitis
•urticaria

*Casoni test for hydatid cyst disease

TYPE 2 HYPERSENSITIVITY REACTION
> Cytotoxic reaction

• cytotoxic reactions involve mainly immunoglobin G ( IgG antibody).
• some times IgM and IgA antibodies are also involved.
• type 2 hypersensitivity is mediated by antibodies directed toward endogenous
 or exogenous antigen present on cell surfaces or extracellular Matrix.
• the disease developed due to cytotoxic reactions are hemolytic disease of newborn in case of Rh incompatibility and autoimmune hemolytic anaemia.

✓examples of type 2 hypersensitivity reaction

My.          - Myasthenia gravis
Blood .    - Blood transfusion reactions
Group .  - Graves disease/Goodpasture syndrome
Is .           - ITP /  Insulin resistant diabetes
R .           - Rheumatic fever
H .           - Hyper acute graft rejection
Positive .- Pernicious anemia/Pemphigus vulgaris

TYPE III HYPERSENSITIVITY REACTION
IMMUNE COMPLEX DISEASE
ANTIBODY MEDIATED REACTION

•  excess amount of antibodies like IgG or IgM are produced in this type.
• it is characterized by formation of antibody about five days after introduction of the antigen.
• the antigen antibody complexes are precipitated and deposited in localized areas like
~ joints causing arthritis
~ heart causing myocarditis
~ glomeruli of kidney causing glomerulonephritis.
* A small or intermediate immune complexes are most pathogenic.
* The large complexes are rapidly removed by the macrophages.

•immune Complex mediated inflammation is seen in10 days after antigen Administration and results in the development of vasculitis ,Arthritis , Glomerulonephritis.
*the blood vessels show intense neutrophilic infiltration and necrotising vasculitis having the presence of fibrinoid necrosis.

Examples of type 3 hypersensitivity-
• reactive arthritis
• serum sickness
• post streptococcal Glomerulonephritis(PSGN)
• SLE / lupus ( systemic lupus erythematosus)
• type 2 lepra reaction
• arthus reaction
• farmer's lung
•hypersensitivity pneumonitis
• polyarteritis nodosa (PAN)

TYPE 4 HYPERSENSITIVITY REACTION

>Cell mediated reaction
>Delayed hypersensitivity reaction
>Slow type of hypersensitivity reaction

• it is mediated by CD4+ T-cells and direct cell cytotoxicity mediated by CD8+ T-cells.
• it is found in allergic reactions due to bacteria ,virus and fungi.
• also seen in contact dermatitis caused by chemical allergens and during rejection of transplanted tissues.

* Tuberculosis skin test / Mantoux test
An example of type 4 reaction is delayed reaction after intra dermal injection of tuberculin in persons who are previously affected by tuberculosis.

@the important feature of delayed type hypersensitivity reaction is the involvement of T-lymphocytes rather than antibodies.

Examples of type 4 hypersensitivity reactions-

• tuberculin reaction
• lepromin test
• multiple sclerosis
• chronic graft rejection
• contact dermatitis
• Type 1 lepra reaction
• tumor immunity
• resistance to viral infection
• sarcoidosis

TYPE 5 HYPERSENSITIVITY REACTION

Stimulatory reaction
Blocking reaction
• It is seen in autoimmune disease like Graves disease (stimulatory reactions) and Myasthenia Myasthenia gravis ( blocking reactions)

Graves disease
~ the excess secretion of thyroid hormone leads to Graves disease
•normally TSH combines with surface receptors of thyroid cells and causes synthesis and secretion of thyroid hormones.
• the secretion of thyroid hormone can be increased by thyroid stimulating antibodies (TSAB).
• thyroid stimulating antibodies are produced by plasma cells (B lymphocytes).

Myasthenia gravis
It is due to the development of IgG autoantibodies.