2. Autoantibody structure

An antibody molecule and also autoantibody are include of four polypeptide chains; composed of a pair of identical heavy (H) and light (L) chains. Molecular weight of light chain is 25 kDa and heavy chain is 50–70 kDa. The four chains joint together as a Y shaped. Each light chain is bound to one heavy chain, and the two heavy chains are bound to each other by disulfide bonds between two cysteine amino acid.

The antigen-binding site of chains that diverse at different antibody is called as the variable (V) regions and composed of amino acid N-terminal domains of the heavy and light chains. The part next to the V region is called the constant (C) region. A light chain is made up of one V and one C region, and a heavy chain has one V and three (at IgG, IgA) or four (at IgM, IgE) C regions. Each of them is 110 amino acids in length and fields into a characteristic threedimensional shape called immunoglobulin (Ig). There are three hypervariable regions or CDRs at each variable region of the heavy chain (VH) and of the light chain (VL) which is just 6–10 amino acids in length. CDR3 is the greatest variability of three hypervariable region, at the junction of the V and C regions [4, 5] Figure 1.

Fab fragment (fragment antigen binding) is composed of a bonded whole light chain (with one V and one C region) and a heavy chain's V and first C region and recognizes the antigen. The Fc fragment (fragment crystalline) is the remaining region of heavy chain. Each antibody

Structure, Physiology, and Functions of Autoantibodies http://dx.doi.org/10.5772/intechopen.76020 15

Figure 1. Structure of an antibody molecule (IgG).

Failure of immunologic tolerance may cause the development of autoimmune response and

The cause of autoimmune diseases is an association of genetic tendency and environmental factors cause alteration the immune regulatory genes by diver's mechanisms as epigenetics. In autoimmune diseases pathogenesis, both cellular (as in multiple sclerosis) and humoral (as in systemic lupus erythematosus (SLE)) type of the adaptive immune system takes a role. An

In most of autoimmune diseases, the autoantibodies could been found but not all. Even in some autoimmune diseases, the autoantibodies signify not autoimmune disease risk, but also the level of the autoantibodies signifies the severity. By autoantibodies, we can understand

Autoantibodies are self-reactive antibodies. The self-antigens may be found in all cell types (e.g. chromatin, centromeres) and those autoimmune diseases is systemic or be highly specific for a specific cell type in one organ of the body (e.g. thyroglobulin in cells of the thyroid gland) and those autoimmune diseases is organ-specific. The self-antigens can be in proteins, nucleic acids, carbohydrates, lipids structure [16]. Immune tolerance is succeed by various mecha-

An antibody molecule and also autoantibody are include of four polypeptide chains; composed of a pair of identical heavy (H) and light (L) chains. Molecular weight of light chain is 25 kDa and heavy chain is 50–70 kDa. The four chains joint together as a Y shaped. Each light chain is bound to one heavy chain, and the two heavy chains are bound to each other by

The antigen-binding site of chains that diverse at different antibody is called as the variable (V) regions and composed of amino acid N-terminal domains of the heavy and light chains. The part next to the V region is called the constant (C) region. A light chain is made up of one V and one C region, and a heavy chain has one V and three (at IgG, IgA) or four (at IgM, IgE) C regions. Each of them is 110 amino acids in length and fields into a characteristic threedimensional shape called immunoglobulin (Ig). There are three hypervariable regions or CDRs at each variable region of the heavy chain (VH) and of the light chain (VL) which is just 6–10 amino acids in length. CDR3 is the greatest variability of three hypervariable region, at the

Fab fragment (fragment antigen binding) is composed of a bonded whole light chain (with one V and one C region) and a heavy chain's V and first C region and recognizes the antigen. The Fc fragment (fragment crystalline) is the remaining region of heavy chain. Each antibody

autoimmune response does not inevitably signify the autoimmune disease [5, 6].

immunologic tolerance failure and pathogenesis mechanisms [7–15].

nisms, occurred at both central and peripheral organs.

disulfide bonds between two cysteine amino acid.

junction of the V and C regions [4, 5] Figure 1.

then autoimmune disease [4, 5].

14 Autoantibodies and Cytokines

2. Autoantibody structure

contains two identical Fab fragments and one Fc fragment. The hinge region is located in the middle of the Fab and Fc regions and is very bending so helps the two Fab fragment getting closer to antigen far away. The C-Terminal end of the heavy chain of bound antibodies can terminate with or without anchoring in the cell membrane, but the C-Terminal end of the light chain terminates freely without attaching the cell membrane [4, 5].

There are two types of light chains according to C region, called κ and λ. Their functions are same. 60% of antibodies are κ chains and 40% are λ chains There are five types of heavy chains also according to C region, called μ, δ, γ, ε and α. Every combination of heavy chain and light chain is available. Antibodies are classified and entitled according to their heavy chains types (IgM, IgD, IgG, IgE and IgA) [4, 5].

There is five antibody isotypes with different functions and physical and biological properties, summarized in Table 1.

1. IgM: Heavy chain type is μ. It has pentamere structure with five Fc fragments where complement binds. The antigen+ pentamere antibody+ complement bound to five Fc complex starts strong complement activation and is removed by phagocytic cells or complement mediated lysis. So IgM plays critical role in neutralization but it has relatively low affinity and cannot penetrate into cells/tissues because of the pentamere structure. Half-life of IgG is approximately 10 days [4, 5].

2. IgG: Heavy chain type is γ. It has monomere structure and penetration rate is high e.g. penetare through the placenta There are four classes of IgG: G1, G2, G3 and G4. 65% of total IgG is G1. G1 and G3 activate complement system if the antigen is protein structure and the protein antigens are removed by phagocytic cells. G2 and G4 play role if the antigen is


as antigen receptors of B lymphocytes (BLR) and can bind to antigens in proteins, lipids, carbohydrates and nucleic acids structures. T lymphocytes can react antigens just in protein structure. For an antigen-presenting cells (APC), there is not any necessity to present antigens to B lymphocytes. Epitopes antigens recognized by T cells are narrow linear peptides from 8 to

Structure, Physiology, and Functions of Autoantibodies http://dx.doi.org/10.5772/intechopen.76020 17

After binding of antigens to the receptors that are membrane- bound antibodies; IgM and IgD type, B lymphocyte become activated. The clonal expansion which means proliferation of antigen specific cells follows the activation of B lymphocytes and they differentiate into antibody-secreting effector cells. The specificity of the naïve B cell membrane-bound antibody receptors is same with the secreted free antibodies. During their differentiation period, some B cells may differentiate to produce antibodies with different heavy chain classes (or isotypes) called as heavy chain class (isotype) switching. After switching, different effector functions can be monitored. Repeated exposure to an antigen leads to the production of antibodies with

Antibodies responses are classified into two based on the requirement for T cell help; as

If the structure of antigens is non-protein as polysaccharides, lipids, nucleic acids and others antibody responses evoke without the helper T cells participation. These non-protein antigens

For immunoglobulin receptor mediated signal transduction in B lymphocytes, the bringing together of two or more antigen molecules in an aggregate (cross-linking), or repeating epitopes of one antigen molecule is needed for antigen binding to membrane bound antibody of the B cell. Multivalent epitope (multiple identical epitopes) as in polysaccharide and lipid antigen can make cross-link many antigen receptors on a specific B cell consequently stimulate

Most soluble protein antigens cannot make cross-link because they do not contain multivalent epitope so cannot stimulate their proliferation and differentiation of B lymphocytes. Antigen-

Stimulations of two or more protein antigens lead at least three changes in B lymphocytes to

increasing capacity to bind the antigen; called as affinity maturation [4, 18].

cannot bind to MHC molecules consequently cannot be detected by T cells.

proliferation, differentiation and antibody production of B lymphocytes [4, 19].

presenting cells process and helper T lymphocytes remember the protein [5].

improve the interaction of these B cells with helper T lymphocytes.

20 amino acids [4, 16, 17].

T-independent or T-dependent

3.1.1. Antibody responses to T-independent antigens

3.1.2. Antibody responses to T-dependent antigens

1. Increased expression of B7 co-stimulator, 2. Increased expression of cytokine receptor

3. Reduced expression of chemokine receptors.

The changes are:

Table 1. Physical, biological properties and functions of immunoglobulins.

carbohydrate structure. Half-life of IgG is approximately 21 days. Since IgG has high affinity and high molar concentrations in plasma, it makes neutralization [4, 5, 17]. It also makes opsonization because of γ receptors of phagocytes. If N-terminal end is N-acetyl glucosamine, the IgG act as pro-inflammatory and if there is sialic acid then act as anti-inflammatory.

3. IgA: Heavy chain type is α. It has monomere or mostly dimere structure which consists of two basic units joined by a J chain. There are two classes of IgA: A1 and A2. IgA1 is in the serum while IgA2 is in secretions as; colostrum, salivary, eye tear, respiratory, digestion and genital and make neutralization of antigens at the mucosal sites. A2; secretory IgA (sIgA) is protected from lytic enzymes in the digestion tract by secretory component (SC) which is a part of the receptor and remains attached to the IgA-dimer [4, 5, 17].

4. IgD: Heavy chain type is δ. It has monomere structure. There are two classes of IgD: soluble and bound IgD. While function in immunology of soluble IgD is not known yet, IgD that bound on the cell membrane of newly produced B lymphocytes with IgM, activates of newly produced B lymphocytes by antigens [4, 5, 17].

5. IgE: Heavy chain type is ε. It has monomere structure. IgE plays role in parasitic infections and allergic reactions by binding to specific IgE receptors on mast cells and basophiles [4, 5].
