2. Type III (caused by immune complexes):

Testing of autoantibodies is diagnostic criteria in many diseases. But, also autoantibodies could be detected in healthy individuals [79]. Since isotype/subclass and glycosylation pattern is critical for the pathogenic potential of a particular antibody, it could be helpful for the diagnostic analysis. Pathogenic autoantibodies could be produced either by continuous formation of short-lived plasma cells or through the formation of long-lived plasma cells, or both [80]. Therapeutic treatment available nowadays could suppress B cell activation and short-lived

By contrast, mice with FcγRIIb knocked out spontaneously develop a lupus like disease [71]. Different isotypes antibodies have different affinities for the four FcγRs. IgG2a has higher affinity for FcγRIV, leading to inflammatory responses, whereas IgG1 selectively engages FcγRIIb, leading to inhibitory responses [30]. There is a similar relationships with human FcγRs and that the ability to protect or induce inflammation will change according to the

7. Removal of cell debris: Natural autoantibodies takes role in the removal of cell debris during inflammation, and autoantibodies to inflammatory cytokines have protective functions against

Immune responses can cause tissue injury and disorders called as hypersensitivity diseases. Hypersensitivity is a term of excessive or aberrant immune responses [4]. Tissue damage in autoimmune diseases can occur through several mechanisms, which are similar to three of the

Antibodies against cell and tissue may cause tissue and disease. IgM and IgG antibodies activate the phagocytosis of cells by binding to complement and Fc receptor- mediated leukocyte [4]. The reactions are caused by antibodies against self-protein antigens. Autoantibodies generated against cell surface antigens/extracellular matrix proteins may be cytotoxic (type IIA) or agonistic/antagonistic (type IIB). Autoantibodies to cell surface antigens may initiate cell destruction by complement- mediated lysis (cell destruction), phagocytosis, or antibodydependent cell-mediated cytotoxicity (ADCC) [5]. At Table 5, some examples of antibody-

Antibody-mediated activation of proteinase, disruption of

intercellular adhesion

Erythrocytes membrane antigen Opsonization and phagocytosis of erythrocytes

1. Type II (caused by autoantibodies reactive with cell surface or matrix antigens):

Myasthenia gravis Acetylcholine receptor Antibody inhibits acetylcholine binding

plasma cell, while do nothing to long-lived plasma cells [81].

isotype of the autoantibody and FcγR engaged.

4.2. Mechanisms of autoimmune tissue injury

classical types of hypersensitivity reactions [5]:

Disease Target antigen Mechanism

Pemphigus vulgaris Proteins in intercellular junction of epidermal cell

mediated diseases are given.

Table 5. Antibody-mediated diseases.

Autoimmune hemolytic anemia

inflammation [82].

28 Autoantibodies and Cytokines

Autoantibodies can bind to circulating antigens and form immune complexes that deposit in vessels, tissues and cause tissue injury. Injury is mainly due to leukocyte recruitment and inflammation [4]. Autoantibodies can cause disease by forming immune complexes with the circulating antigens. Immune complex formation is a normal process to remove antigens and to phagocyte through Fc or complement receptors so are prevented their deposition. The efficiency of uptake of immune complexes by either Fc receptors or CR1 is proportional to the number of IgG molecules associated in the complex [5]. At Table 6, some examples of immune complex mediated diseases are given.

3. Type IV (delayed-type hypersensitivity, mediated by T cells):

T cell-mediated disease is caused by CD4 T lymphocytes or by killing of host cells by CD8 CTLs [4]. T cells recognize protein antigen-presenting cells in the context of class II major histocompatibility complex (MHC) molecules and produce the cytokines interferon γ (IFN-γ), interleukin 3 (IL-3), tumor necrosis factor (TNF) α, TNF-β, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Elaboration of "TH1 (a subset of helper T cells) cytokines" leads to macrophage recruitment and activation, enhanced expression of adhesion molecules, and increased production of monocytes by the bone marrow [5]. At Table 7, some examples of T cell-mediated diseases are given.


Table 6. Immune complex mediated diseases.


Table 7. T cell-mediated diseases.
