II. Classification Based on the Different Mechanisms of Pathogenesis

 II.  Classification Based on the Different Mechanisms of Pathogenesis

Coombs and Gell (1963) proposed 5 types of hypersensitivity based on the different mechanisms of pathogenesis.  They are the following::


 1. Type I : Anaphylactic hypersensitivity. 

2. Type II  : Antibody - dependent cytotoxic hypersensitivity.  

3.Type III  : Immune complex - mediated 'hypersen sitivity.  

4. Type IV:  Cell - mediated hypersensitivity.  

5. Type V:  Stimulatory hypersensitivity. 

 Of these 5 types, type IV alone is delayed type of hypersensitivity and the other types are immediate type. 

 Type I: Anaphylactic Hypersensitivity  (Anaphylaxis)

 Anaphylaxis is defined as an allergic reaction to an foreign substance to a foreign substance to which it has previously become sensitized resulting from the release of histamine, serotonin and other vasoactive substances. 

 The term anaphylaxis was coined by Richet in 1902 and it means with protection.  The term anaphylaxis comes from the Greek words.  ana = against (without), phylaxis = protection. 

 Anaphylaxis is an immediate type of hypersensitivity. 

 Anaphylaxis is a severe life threatening allergy.  It must be treated as a medical c emergency. 

 In anaphylaxis, antibodies are fixed on the surface of mast cell and basophis in sensitized host.  The antigen combines with the cell fixed antibody, leading to release of pharmacologically active substances (vasoactive amines) which produce the clinical reaction.  They affect the skin, heart and respiratory system.

Factors causing Anaphylaxis

  Anaphylactic reactions are caused when the sensitized animals receive allergens for the second time.

The factors causing anaphylaxis are: 

  • Drugs
  •  Penicillin
  •  Venom
  • Food 
  • Food additives
  •  Egg
  •  Shellfish. 
  • Pollen grains 
  • Temperature- Heat or chillness

 Highlights 

Anaphylaxis 

Anaphylaxis is a life threatening allergic reaction. 

It is an immediate type hypersensitivity.

 It belongs to type I hypersensitivity. 

 It is caused by allergic substances which enter the body for the second time. . 

 When the allergic substance enters the body for the first time, it produces IgE antibodies.

 These antibodies bind to the mast cells and basophils. They do not cause any harm at this time.

 When the same antigen enters the body for the second time, they bind to the antibodies fixed on the mast cells and basophils. ation Fabide 

• This binding of antigen and antibody stimulates the mast cells to produce vasoactive amines. 

 • The vasoactive amines bring about allergic reactions, 

Causes

 • Anaphylaxis is caused by the following factors. Drugs - Penicillin 

• Venom from insect bites or stings of bees, wasps, etc. 

 • Food 

• Food additives 

Egg 

Shellfish Symptoms 

Pollen grains

 Temperature - Heat or chillness. 


 symptoms:

The symptoms of anaphylaxis appear suddenly and quickly within minutes or within an hour.  The symptoms include: 

  • Iching 
  • Hives - Elevation of skin with reddish patches.  
  • Blue tinged skin because of the lack of oxygen. 
  •  Urticaria 
  • Oedema 
  • Swelling of the lips
  •  Swelling of the tongue
  •  Swelling of the throat 
  • Pain in swallowin
  •  Swelling of the conjunctiva
  •  Running nose 
  • Wheezing
  •  Coughing 
  • Vasodilation 
  •  Low blood pressure
  •  Unconsciousness 
  • Abdominal pain 
  • Diarrhoea 
  • Vomiting 
  • Headache 
  • Cardiac arrest - Death 


Diagnosis


  •  Hives 
  • Low blood pressure 
  • Bluish skin 
  • Swelling of lips  and throat
  •  Wheezing
  •  Swelling of the eyes, face, etc. 
  •  Abnormal heart rhythm 
  •  Fluid in the lungs. 


 Control.  

Anaphylaxis can be prevented by avoiding contact with allergens. 

 Treatment

  The following drugs are used for the treatment of anaphylaxis. 

 Epinephrine

 Isoprenaline 

Sodium chromoglycate.  

Symptoms of Anaphylaxis

 Anaphylactic reactions cause the following symptoms .

1. Death: 

When penicillin injection is given to a sensitive person, he shows anaphylactic reactions. There is intense constriction of bronchi and branchi oles Smooth muscles contract and the capillaries dialate. The person begins wheeze "and within minutes, he dies due to asphyxia *. Similar reactions also occur rarely, when a man is stung by bees or wasps.

 2. Diarrhoea and Vomiting:

 These are caused by food allergens. 

3. Urticaria: 

Urticaria is a vascular reaction of the skin marked by slightly cievated patches which are reddish or paler than the surrounding skin. It causes chung. It is caused by certain foods or drugs. 

4. Atopy:

 Atopy literally means out of place or strangeness The term atapy. was coined by Coca (1923). This term is used to refer to naturally oc curring familiar hypersensitivities such as hay fever and asthma. 

The antigens responsible for atopy are called atopens. They may be inhal unts (pollens, house dust, etc.). ingestants (egg, milk, etc.) or contactants. They elicit the production of antibodies of the type IgE These antibodies are called reagin antibodies. 

The tendency to develop atopy is genetically determined. Atopy therefore in families. Al l human beings are capable of forming reagin antibody small amount, but in atopics, the reagin antibodies are produced in large amount.

About 10% of persons have this tendency to overproduce reagin. It has et reparted that bottle feed babies tend to develop atopy in later life more him than breast feed babies. 

 The atopic allergy is due to the production of IgE artibodies which in tum is due to the deficiency of IgA antibodies. Thus IgA deficiency may predispose to atopy 

The symptoms of atopy include conjunctivitis in the eyes, rhinitis in the trafors tract, dermatitis in the skin, urticaria, vomiting, diarrhoea, etc.


 Mechanism of Anaphylaxis 


The culprit of anaphylactic hypersensitivity is one type of immunoglobulin cailed IgE antibody. When a person receives the allergens (antigens) for the first time, the aller gens get attached to the B cells. The allergens stimulate the B cells to proliferate plasma cells. The plasma cells make IgE antibodies. The IgE antibodies are called reagins and they are made by people who are allergic. The reaginie antibodies have a strong affinity for fixation to mast cells or basophils in skin or mucous surfaces. 

The IgE antibodies produced for the first time, get attached to the surfact receptors of mast cells with the help of their Fc fragment. This reaction would not harm the person and the person is now said to be immunized or sensitized for that particular antigen. 

 As this initial contact with antigen leads to the priming of the B cells, this is known as sensitizing or priming dose. 

 Subsequent contact with the allergen causes manifestations of hyper sensitivity. This is known as shock - dose. 

 When the animal is exposed to the same antigen for the second time the animal would be in danger. The IgE antibodies attached to the surface of mas cells, bind with the antigens.  The allergens cross - link * the IgE antibodies at tached to the mast cells. Antigens B cell (Pollen) Plasma cell IgE Antibodies Mast cell .Sara obligation 

This cross - linking of IgE antibodies triggers the mast cells and a series of enzymatic reactions occur inside the mast cells.  As a result the mast cells lease granules, 

The phenomenon of releasing of granules from mast cells is called degranu lation.  These granules contain substances like histamine, serotonin, heparin, These substances are the primary cause for anaphylaxis.  are of two types, namely: 

The manifestations of anaphylaxis are due to the mediators.  The mediators

 Primary mediators 

Secondary mediators, 

The primary mediators include histamine, serotonin, heparin, etc.  They are released from the granules of mast cells and basophils.  They bring about their action quickly and immediately.  

The secondary mediators are produced by leukocytes upon the stimulant of mast cells.  They act slowly.  They include slow reacting substance of anaphylaxis (SRS - A), prostaglandins, leukotrienes, platelet activating factor (PAF), etc.  

In addition to the above mediators, complement activation releases and phylatoxins. 

 Symptoms

 The symptoms of anaphylaxis appear suddenly and quickly within minutes or within an hour.  The symptoms include:. 

  •  .  Itching 
  • Hives - Elevation of skin with reddish patches.
  •   Blue tinged skin because of the lack of oxygen. 
  •  Urticaria 
  • Oedema 
  • Swelling of the lips 
  • Swelling of the tongue
  •  Swelling of the throat 
  •  Pain in swallowing
  • Swelling of the conjunctiva
  •  Running nose 
  • Wheezing 
  • Coughing 
  • Vasodilation
  •  Low blood pressure
  •  Headache Cardiac arrest - Death

Prevention and Treatments


 Anaphylactic hypersensitivity can be prevented and treated in the follow ing methods:
 1. Avoiding Contact with Allergens: Anaphylaxis can be prevented by avoiding contact with allergens. 

2. Desensitization:

 The hypersensitivity can be prevented by the admin traction of graded doses of allergen.

 3. Hyposensitivity: 

Anaphylactic reactions are caused by IgE antibodies However IgG antibody blocks the IgE antibody. The IgG antibodies divert the allergen from contact with mast cell - IgE antibody complex and thus prevent allergy. 

4. Stabilizing Mast Cells: 

The anaphylactic reactions are caused by this triggering of mast cells. Mast cell triggering can be prevented by giving drugs like isoprenaline and sodium chromoglycate. Isoprenaline binds to the surface receptors of mast cells and thus the mast cells are stabilized. Sodium chromoglycate can stabilize the lysosemal membrane, even mast cells during cross - linking of antigen and IgE. 

5. Inhibition of Histamine Receptors: 

Antihistamines suppress anaphylaxis. Antihistamines do not prevent the release of histamines from mast cells but they inhibit the receptor for histamine on the cell surface. 

 6. Blocking the Release of Histamines: 

The derivatives of adrenergic drugs and theophyllin derivatives block the release of amines from mast cells indirectly. They influence the mast cells to stimulate adenocyclase and raise CAMP and thereby stabilize lysosomal membrane and block the release of amines. These drugs also influence the smooth muscles for relaxation, a reverse of anaphylactic reactions. Steroids and chromoglycate also inhibit the release of amines from mast cells. Both these drugs stabilize the lysosomal membrane and inhibit the release of amines from mast cells.







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