3.1.1. Antibody responses to T-independent antigens

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

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

#### 3.1.2. Antibody responses to T-dependent antigens

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

Stimulations of two or more protein antigens lead at least three changes in B lymphocytes to improve the interaction of these B cells with helper T lymphocytes.

The changes are:

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.

Property IgM IgG IgA IgD IgE Heavy chain type μ γα δΕ % of total immunglobulin in serum 9 75 15 0.2 0.004 Structure Monomer or pentamer Monomer Monomer or dimer Monomer Monomer Molecular weight (1000) 900 150 170 or 400 180 190 Complement fixation ++ ++ — —— Cross the placenta — ++ — —— Allergic response — —— — ++ Antigen receptor at B cell ++ — — + — Secretoral response — — ++ — —

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

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

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].

Antibodies are responsible for the humoral type of adaptive immune responses, glycoprotein

Antigens can directly bind to antigen receptors of specific B lymphocytes. The type of reversible bond is non-covalent as; electrostatic attraction, hydrogen bonds, Van der Waals-, charge interactions and hydrophobic forces. Membrane–bound antibodies (IgM and IgD type) work

part of the receptor and remains attached to the IgA-dimer [4, 5, 17].

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

produced B lymphocytes by antigens [4, 5, 17].

3. Physiology of autoantibody

structure and produced by B lymphocytes.

3.1. Physiology of antibody

16 Autoantibodies and Cytokines


The T cell activation by B cell requires antigen recognition and co-stimulation:

1. Antigen recognition: B lymphocytes work as antigen-presenting cells (APCs); B lymphocytes may bind, internalize and process the antigen protein, and present multiple different peptides of that protein to T lymphocyte.

stimulate self-reactive T cells which react with self-antigens in the tissue [4]. Some peptide antigens of microbes are similar to self-antigens, so leads to cross-reactions; called as molecular mimicry [6]. For example; the antibodies against Porphyromonas gingivalis; a periodontal pathogen were increased before RA onset and had a relation with RA [20–23].

Structure, Physiology, and Functions of Autoantibodies http://dx.doi.org/10.5772/intechopen.76020 19

Sun lights can trigger lupus diseases. Many drugs as procainamide, hydrocarbon pristine, hydralazine, chlorpromazine, methyldopa, quinidine, minocycline and nitrofurantoin can trigger autoimmunity or autoimmune disease through ANAs and ANCAs. Many chemical agents include heavy metals as mercury, gold, and cadmium, pesticides, herbicides, hydrazine can

In organ-specific autoimmune diseases, such as thyroiditis, type 1 diabetes mellitus and primary biliary cirrhosis, autoantibodies can be stimulated by infection of the target organ, through molecular mimicry [16, 24]. In systemic autoimmune diseases, such as systemic lupus, autoantibodies can be triggered by genetic factors. For example; a nuclear autoantibodies produced by antigenic drive from excessive release of death cells antigens and enhanced by

The immune system can differentiate self from non-self [5]. Immunologic tolerance is lack of response to self-antigens that encounter with lymphocytes [6]. The recognition of self is a special set of immune events that all constituents of the organism take a role and may be interrupted by environmental and genetic factors [25–29]. There are three possible immune responses according to antigen type, after antigen encounter with the lymphocytes which has

1. Active immune response: Due to the active lymphocytes and antigen type is called immu-

2. Tolerance: Due to inactive or killed lymphocytes and antigen type is called tolerogenic. For

Microorganism Related autoimmune diseases

Streptococcus pyogenes Rheumatoid fever Escherichia coli Primary biliary cirrhosis Shigella spp. Reiter syndrome Hepatitis B Multiple sclerosis Coxsackie B4 Type 1 diabetes mellitus

Cytomegalovirus Scleroderma

Microorganisms related autoimmune diseases are listed in Table 2.

trigger autoimmunity [5].

intrinsic abnormalities in B or T cells [16, 24].

3.3. Production of autoantibody

the receptors for a specific antigen;

example, self-antigens

Table 2. Infections related with autoimmune diseases.

nogenic. For example, most of non-self-antigens

3.3.1. Immunologic tolerance

2. Co-stimulation: The helper T cells are stimulated by B7 molecules as co-stimulator expressed by B cells.

CD40 ligand (CD40) and cytokines are expressed by CD4+ helper T lymphocytes after activation. CD40 ligand; a surface protein delivers the co-stimulatory signal in B cells and interacts with CD40 on the surface of B lymphocytes. Attachment of CD40 and cytokines stimulate B cell clonal expression and antibody production. Class switching and affinity maturation are also stimulated by helper T lymphocytes [4, 5, 19].

After B lymphocytes proliferation and differentiation into antibody-secreting plasma cells, the antibodies enter the blood through lymphoid follicle. Some plasma cells move to bone marrow, live at the bone marrow for months or years and continue to produce antibodies afterwards antigen is removed. These antibodies supply a rapid response when they meet with same antigen. The humoral immune response decreases physiologically by time because of programmed B cell death. But a small number of activated cells differentiate into memory cells, which "freeze" in a state for a very long time [4, 18, 19]. When the body encounter with the same antigen, the memory cells quickly change into antibody-secreting plasma cells and produce immunoglobulins. The two advantages of memory cells;

1. Shorter reaction day: instead of five or more days, it takes one or two.

2. B memory cells differentiate with class switch and somatic hypermutation so in case of reinfection, only memory cells with higher affinities and class switch are selected which are completely same with the B cell receptors of the original infection. Recurring antigen stimulation causes to helper T lymphocytes increase consecutively antibody increase with heavy chain class switching and affinity increase [17, 19].
