Our body has a defense system (immune system) ensuring its integrity.
It defends it against exogenous aggressions (microorganisms) and monitors pathological cell proliferation. To accomplish this task, it has natural (innate, non-specific) and other adaptive (acquired or specific) control mechanisms. The latter are provided by effectors which recognize antigens in a specific way.
What are immunoglobulines?
Immunoglobulins are serum glycoproteins from mammalian interstitial fluid that are produced by B cells (membrane immunoglobulin) or by plasma cells (soluble immunoglobulin). In general, it is produced following specific antigenic stimulation. Immunoglobulins produced after antigen stimulation or those having corresponding antigens are called ANTIBODIES.
CLASSES AND SUBCLASSES OF IMMUNOGLOBULINS
In mammals, there are five classes of immunoglobulins (IgG, IgM, IgA, IgE and IgD) which differ in their Phi, the half-life, the number of constant domains and the role of the constant parts. The classes and subclasses are terminated by the types of heavy chains; each of these chains is encoded by a different gene.
1/ Immunoglobulin G (IgG)
it is a glycoprotein made up of two heavy chains (γ) and two light chains (κ or λ). It represents 70 to 75% of total immunoglobulins with a concentration of 10 to 18 g / l. She
includes four subclasses: IgG1, IgG2, IgG3 and IgG4 and which represent 66%, 23%, 7% and 4% of IgG respectively. The difference between them lies in the hinge region and in the number of disulfide bridges.
Half of these immunoglobulins are 21 days, except for IgG3 which is 7 days. Their sedimentation constant is 7 S and with a PM of 146 Kd. IgG (1,2,3) fix the complement. Only IgG1 and IgG3 which can cross the placenta. The γ chain consists of 3 constant domains and a variable. But all light chains are only formed from two domains, a constant and a variable.
2/ Immunoglobulin A (IgA)
it is a glycoprotein in two forms, a monomeric form consisting of two heavy chains (α) and two light chains (κ or λ) and represents 80% of serum IgA. The second form is predominant in secretions (milk, saliva …). It is dimeric of 385 Kd and 11 S. it contains the chain J of 15 Kd plus a secretory component of 70 Kd. IgA groups two subclasses:
IgA1 which is found, above all, in serum form and IgA2 which is found, above all, in secretory form. The concentration of serum IgA is 1 to 4.5 g / 1. They do not fix the complement and do not cross the placenta. The α chain consists of 3 constant domains and a variable.
3/ Immunoglobuline M (IgM)
it is a glycoprotein of 900 Kd and 19 S. Usually, it is pentameric and made up of 10 heavy chains (μ) and 10 light chains (κ or λ) identical. It represents 10% of serum immunoglobulins. The subunits are linked together by disulfide bridges and the chain J (junction). The μ chain contains four constant domains and one variable. The membrane IgM is monomeric containing an additional hydrophobic sequence which allows it to anchor to the cytoplasmic membrane. This molecule constitutes the specific receptor for the antigen on the B lymphocyte (BCR). It is associated with two molecules Igα (CD79a) and Igβ (C79b) which are responsible for signal transduction after antigenic stimulation.
4/ Immunoglobulin D
it is a glycoprotein consisting of two heavy chains (δ) and two light chains q (κ or λ) identical. It represents 10% of serum Ig. It exists in two forms; the serum form which is soluble and the membrane form which constitutes, with the membrane IgM, the BCRs of mature B lymphocytes. It is the most sensitive to proteolysis.
The heavy chains δ only bind to each other by a disulfide bridge. It is 184 kd, 7 S and a half-life of 3 days. The serum concentration is 0.05 to 0.4 g / l. the heavy chain has three constant domains and one variable.
5/ Immunoglobulins E
it is 190 Kd and 8S glycoprotein with a half-life of 3 days. It consists of two heavy chains (ε) and two light chains (κ or λ). Its serum concentration is 0.003 g / l. Most IgE are found to be fixed on basophils and mast cells by receptors specific to the constant part (RFCεI). It does not fix the complement and does not cross the placenta. It is a thermolabile Ig.
an immunoglobulin can induce an adaptive immune response (production of antibodies). So it has the properties of an antigen. The antibodies produced are directed against the various antigenic determinants located on the constant part or the variable part. There are three groups of antigenic determinants of light chains or heavy chains defining the isotype, allotype and idiotype.
1- Isotype: it is the properties of antigenic determinants which define the classes and subclasses of immunoglobulins of the same species. It is carried by the constant part.
2 – Allotype: it is the properties of antigenic determinants which differentiate different individuals within the same species. It is carried by the constant part.
3 – Idiotype: it is the properties of antigenic determinants which differentiate immunoglobulins of the same isotype and of same allotype in an individual. It is carried by the variable part.
An immunoglobulin molecule consists of a variable part, represented by the Fab fragment which constitutes the site of attachment of the antigen to the antibody; the latter is called the PARATOPE. So the variable part is responsible for the recognition of the antigen and the reaction with it. The constant party represented by the FC plays several roles:
(1) Activation of the complement (IgG1, IgG2, lgG3).
(2) binding to receptors carried by cells derived from the hematopoietic line (cytophilia or cytotropy).
IgG have three receptors: RFCγI or CD 64, RFCγII or CD 32 and RFCγIII or CD 16. They mainly fix IgG l and IgG 3. They are expressed by monocytes, macrophages, polynuclear, NK and CTL. IgEs have two receptors: RFCε I which is expressed by mast cells and basophils and RFCεII or CD23 which is expressed by the majority of blood cells (monocyte; polynuclear, lymphocytes, platelets …).
(3) the catabolism of immunoglobulins whose speed is regulated by Fc and more precisely by CH2.
(4) certain isotypes of immunoglobulins have the property of crossing cells (trans cytosis). IgA is secreted in exocrine secretions and IgG is secreted in the interstitial fluid.
The first contact of the antigen With the organism activates the immune cells (T and B lymphocytes) and induces a primary immune response which is characterized by:
- The latency phase lasts several days
- The Ig level is slightly increased and then declines rapidly
- The isotype is IgM
The second contact induces a secondary immune response which is characterized by:
- The latency phase is very short
- the Ig level is very high
- the isotype is IgG especially with also IgA and IgM
-Search for soluble or particulate antigens (invitro)