Immediate hypersensitivity (Type1 hypersensitivity)

Dr.Sreekumar.A.
The Immune Sysyem is made up of a complex network of

Lymphoid organs
Cells
Humoral factors and
Cytokines.

Which enable us to recognize self from nonself or altered self and thereby protection against disease.
Although Vital to survival, immune system is similar to proverbial double edged sword.

· Underactivity causes immunodefeciency states which make us a easy prey to infections and possibly tumours.
· Overactivity leads to allergic and autoimmune diseases.

Disorders of the Immune system.
Pathology related to the immune system falls into four broad general categories.

1)  Hypersensitivty reactions.  e.g:Anaphylaxis.
2)  Autoimmunity – immune responses to self.
3)  Deficiency states. – congenital or acquired.
4)  Amyloidosis.- a disorder of extracellular protein accumulation.

Hypersensitivity Reactions.
Allergy or hypersensitivity was initially defined by Von Pirquet in 1906, as ‘specifically changed reactivity of an host to an agent on a second or subsequent occasion’.

Allergy is now taken to mean a damaging reaction.
Word allergy is derived  from two Greek words.
–   allos (meaning ‘other’).
–   and ergon (meaning ‘action’).

Mechanism.
Exogenous antigens occur in dust,pollens,foods,drugs,microbiological agents,chemicals,blood products etc.

Contact with these antigens lead not only to induction of a protective immune response but also to reactions that can be damaging to tissues.

These hypersensitivity reactions are divided into four general catogories based on the underlying mechanism of immune injury.

They are

•  Type I hypersensitivity  – Immediate hypersensitivity.
•  Type II hypersensitivity – Antibody mediated disorders.
•  Type III hypersensitivity –Immune complex mediated disorders.
•  Type IV hypersensitivity – Cell mediated immune disorders.

In Immediate hypersensitivity ( Type 1 hypersensitivity) the immune response releases
Vasoactive and spasmogenic substances that act on vessels and smooth muscles.
Pro inflammatory cytokines that recruit inflammatory cells.

In antibody mediated disorders (type II hypersensitivity)

• Antibodies participate directly
• In injury to cells promoting their phagocytosis or lysis
• In injury to tissues by inducing  inflammations.
• May also interfere with cellular functions and cause disease without tissue injury.

In Immune complex mediated disorders (type III )

• Antibodies bind antigens and then induce inflammations directly or by activating compliment.
• The leucocytes that are recruited (neutrophils and monocytes) produce tissue damage by release of lysosomal enzymes and generation of toxic free radicals.

In cell mediated immune disorders (type IV )
Sensitized T lymphocytes are the cause of the cellular and tissue injury.

Immediate (Type I ) Hypersensitivity 
Immediate or type I,Hypersensitivty is a rapidly developing immunologic reaction occurring within minutes after the combination of an antigen with antibody bound to mast cells in individuals previously sensitized to the antigen.
These reactions are often called allergy and the antigens are called allergens.It may occur as a local reaction.

Common antigens which cause Type I Hypersensitivity reaction
Pollen
–   Birch tree,Rag weed,Oil seed rape.
Food
–   Eggs,Nuts,Sea food.
Drugs
–   Pencillin,Salicylates.
Insect Products
–   Bee venom,House dust mite.
Animal Hair
–   Cat hair,Dander.

Immediate (Type I ) HypersensitivityIs mediated by immunglobulin E (IgE) antibodies directed against specific antigens(allergens).

Incidence and genetic susceptibility
Some 20-30% of the population exhibit type I hypersensitivity or atopic allergy to common environmental substances.
There is a genetic component to atopic allergy such that if both your parents exhibit this susceptibility you are more than 2 × more likely to do so and if neither parent has manifest allergies you are less than half as likely to when compared to the population as a whole.
Some individuals have multiple and severe allergies, typically both hayfever and eczema; these individuals are termed atopic and frequently have raised total serum IgE levels (10 -100 × normal).
There is a correlation between total [IgE] and atopy.

Mechanism
IgE is produced by B-cells that have previously been stimulated by the antigen.
IgE then attaches to mast cells and basophils, which release primary and secondary mediators upon combination with the antigen.
Type I immediate hypersensitivity occurs within minutes of combination of an antigen with an antibody bound to previously sensitized cell.
Many of these hyper sensitivity reactions have two well defined phases.

The immediate or rapid or  initial response characterized by

• Vasodilatation
• Vascular leakage
• Smooth muscle spasm
• Glandular secretion

These changes become evident by 5 to 30 minutes after exposure and tend to subside within 60 minutes.

§  Primary mast cell mediators that induce the initial rapid response include
–   Biogenic amines.Eg: Histamine
–   Chemotactic mediators.
–   Enzymes.Eg: Chymase,Tryptase.
–   Proteoglycans.Eg: Heparin

Second or Delayed Phase charecterised by

§  Infiltration of tissues with
–   Eosinophils,neutrophils,basophils,monocytes,CD4 +T cells.

§  Tissue destruction in the form of mucosal epithelial cell damage.

The second phase reaction sets in 2 to 24 hours later without additional exposure and may last for several days.
· Driven by
–   Lipid mediators.
Leukotrienes.
Prostaglandins.
Platelet-activating factors.
–   Cytokine mediators recruit and activate inflammatory cells
TNF
Interleukins
Chemokines

Systemic anaphylaxis 
Systemic reaction follows injection of an antigen to which the host has become sensitized.
Typically follows parentral or oral administration of an allergen.
–   Eg :-  Drugs – pencillin.
–   Food – peanuts.
Severity reflects the level of sensitization.
Even a minute doses may induce shock in an appropriate host.
·         Pruritus,urticaria and erythema occur minutes after exposure,followed by bronchoconstriction and laryngeal oedema.This can escalate into laryngeal obstruction,hypotensive shock and death within minutes.

 Local Immediate Hypersensitivity Reactions.
· Exemplified by atopic allergies
· Hereditary predisposition
· Vary depending on portal of entry of the allergen and may take the form of
–   localized cutaneous swelling – hives.
–   nasal and conjuctival discharge.
–   hay fever,bronchial asthma.
–   allergic gastroenteritis.

Diseases due to type 1 Hypersensitivity

• Extrinsic asthma
• Atopic ezcema
• Allergic rhinitis/conjunctivitis
• Food allergies
• Anaphylaxis
• Angio-oedema

Diagnosis

• Typical clinical history.
• Skin-prick test.(wheal and flare reaction).
• Measuring specific IgE in the serum.

Patient Care:  
Prevention:
–  A history of allergic reactions, particularly to drugs, blood, or contrast media, is obtained.
–  The at- risk patient is observed for reaction during and immediately after administration of any of these agents.
–  The patient is taught to identify and avoid common allergens and to recognize an allergic reaction