HYPERSENSITIVE REACTION (HSR) 

Immune response that have deleterious effect resulting in tissue damage are called as hyper sensitivity. The reaction  within humoral branch are called as immediate hypersensitivity which manifest its symptoms within minutes.
These are of 3 types-
1. Type I          2. Type II                 3. Type III

Hypersensitivity reaction with in cell mediated branch show its symptoms to a delay of two days following Ag exposure. *It is delayed type hypersensitivity.


Immediate Hypersensitivity-
In immediate hypersensitivity reaction different isotypes induce different immune effector molecules.
 IgE induces mast cell degranulation
 IgM & IgG induces hypersensitivity reaction by activating complement system.

Type I : initiation time 2 to 30 min
In this type hypersensitivity IgE molecules bound to mast cells & basophils get sensitized by cross linking through allergen molecules which induces degranulation in respective cell. Upon degranulation of both Mast cell and basophils, they secrete various allergic mediators.
Receptors for IgE binding on mast cells and basophils are of two types:-
1. Fc εR  I --- high affinity     2. Fc εR II---- low affinity

Type II HSR
This is also called as antibodies mediated cytotoxic HSR.
In this reaction cytotoxic cells with Fc receptors bind to Fc portion of antibodies on target cell and promote the killing. Binding of antibodies to the surface of the cell can result in:
o Phagocytosis of the cell
o Lysis of the cell
o Damage to molecules on the cell surface (e.g., myasthenia gravis)
o Activation of cell-surface receptors (e.g., thyrotoxicosis)
Initiation time for such reaction is 5 to 8 hrs.

Type III HSR
Whenever the antigen- antibody complexes get deposited very near to site of antigen entry or these complexes flow in blood, they will develop localized and systemic reaction respectively. In such reaction complement split products will causes Mast cell degranulation and consequent increase in local vascular permeability.
Such type of reaction will take 2-8 hrs to get initiated.


Type IV Delayed type of reaction:---  such type of HSR has initiation time – 24 to 72 hrs. These are the important reaction against bacteria and parasites that can live intra cellular. In this HSR cell mediated branch of immune system will sensitized Tdth  which will induce release of various cytokines. The net effect of these cytokines is to cause an accumulation and activation of macrophages which will leads to localized non specific destruction of cell and so intracellular pathogens are also get cleared.

THE COMPLEMENT SYSTEM

The complement system plays a major role in host defence and the inflammatory process.
Complement consists of a complex series of at least 15 proteins that normally are functionally inactive in plasma. They are present in normal serum and are thus a part of the innate immunity defences of the body.
1. Complement cascade:  Complement  is activated sequentially in a cascading manner. Each protein activating the protein that directly follows it in the sequence. Complement proteins are not antibody, but the cascade is activated by antibody.
2. Activation of the complement cascade: Have widespread physiologic and pathophysiologic effects. It causes lysis of erythrocytes in haemolytic anemia, sensitizes foreign particles to phagocytosis and causes release of histamine from mast cells.

Features of the system

 The complement system consists of some 30 proteins circulating in blood plasma.
 Most of these are inactive until
 They are cleaved by a protease which, in trun.
 Converts them into a protease
 Thus many components of the system serve as the substrate of a prior component and then as an enzyme to activate a subsequent component.
Complement proteins begin to appear in fetal circulation during the first 13 weeks gestation and are present in neonate at 50% to 60% of adult levels.
The presence of complement proteins before antibody in fetal development suggests that these proteins were the main protection against microbes before the evolutionary development of antibodies.

Three pathway of complement activation:

1) Classical pathway
2) The alternative pathway
3) Lectin pathway

CLASSICAL PATHWAY

The classical pathway triggered by activation of the C1 complex.
1). The C1 complex  is trimolecular  complex. it contains three polypeptides- C1q, C1r,and C1s held together by calcium ions. With the removal of the calcium. C1 breaks down into its three subunits and lose activity.
A. C1q is the portion of the C1 molecule that attaches first to immunoglobulin and initiates complement activation.
B. C1r, when activated , cleaves the proenzyme C1s
C. C1s, when , activated, becomes another serine protease, referred to as C1 esterase because of its esterase activity.
2). C1s cleaves C4 into C4a and C4b.
3).Once bound to the C4b molecule. The next component becomes susceptible to enzymatic attack by the C1s serine protease.
 C2b is activated to become the third serine protease in cascade. It substrates are C3 and Cs.
 Formation of the C4b2a complex, (C3 convertase) requires magnesium ions.
Circulating C3 binds to C4b portion of C4b2a complex to make C5 convertase (C4b2a3b complex). Which is the first component of membrane attack pathway.

complement pathway