IgG class

In this chapter we will discuss immunoglobulins of the IgG class, which is the major type of immunoglobulin in normal human serum, and which has the simplest structure. Each chain of an IgG molecule is divided into domains of about 110 amino acid residues. The light chains have two such domains, and the heavy chains have four. 

Polio is the only disease, at present, for which both hve and killed vaccines compete. Since the introduction of the killed vims (Salk) in 1956 and the live attenuated virus (Sabin) in 1962 there has been a remaikable decline in the incidence of poliomyelitis (Fig. 16.1). The inactivated polio vaccine (TPV) contains formalin-killed poliovirus of all three serotypes. On injection, the vaccine stimulates the production of antibodies of the IgM and IgG class which neutrahze the vims in the second stage of infection. A course of three injections at monthly intervals produces long-lasting immunity to all three poliovirus types. 

Figure 20.10 Digestion of IgG class antibodies with pepsin results in heavy chain cleavage below the disulfide groups in the hinge region. The bivalent fragments that are formed are called F(ab )2. The remaining Fc region normally is severely degraded into smaller peptide fragments.

Human embryo lung fibroblasts infected with a reference laboratory strain of herpes simplex virus (HS V) type 2 were used to detect antibody to HSV type 2 in serum samples. After treatment of cells with serial dilutions of sera, HRP-labeled immunoglobulins to human IgG (class G immunoglobulins) were added and detected with CL substrate [36], In both cases a sharp detection of the specific antibodies was achieved with chemiluminescent assays, which proved more sensitive than the colorimetric immunoperoxidase assays. 

The problem of the immunogenic nature of many human recombinant DNA proteins, and the potential to generate antibodies to a normal human protein, is of special interest to the immunotoxicologist. For example, 3 of 16 patients administered the rDNA-derived interferon-a (clone A) developed antibodies of the IgG class that were undetectable prior to or during therapy (Gutterman et al., 1982). These antibodies were capable of in vitro neutralization of interferon activity, although in vivo neutralization of interferon has not been documented. Since there are several different subtypes of interferon-a s, some contain epitopes not present on their own interferon subtype. Similarly, two patients treated with interferon-/ for many months developed high-titered antibody, which in one case was correlated with an inability of the patient s fibroblasts to produce interferon (Vallbracht et al., 1982). 

In conclusion it can be said that syphilis antibodies ae mainly of the IgM class although smaller concentrations of IgG and perhaps IgA syphilis antibodies are also produced. In gonorrhea, on the other hand, the main antibody produced is of the IgG class. 

Neuroimmunological reactions. The humoral immune response in CNS is different from the immune response usually observed in blood. As a main difference, we find no switch from the IgG-class response to a more speciflc IgG-class response in the course of inflammatory disease. The pattern of intrathecal IgG/IgA/IgM synthesis remains rather constant and depends on the causes, pathophysiology, and localization of the disease process (R4). 

We investigated 53 samples of cerebrospinal fluid (CSF) in patients with neuroborreliosis. The clinical diagnosis of neuroborreliosis was confirmed by positive antibody titers and intrathecal synthesis of immunoglobulins in CSF examined in the IgM and IgG classes by the EFISA method or Western blot or confirmed by direct detection by PCR. 

The availability of purihed antibodies permitted the detailed characterization of the different classes of immunoglobulins with respect to their biosynthesis, metabolism, and composition in plasma (Table 10.2). The most abundant immunoglobulin molecule in serum is IgG. IgG classes 1,2,... 

Isocyanate-induced asthma and hypersensitivity pneumonitis in humans have been reviewed (Baur, 1995 Bernstein, 1996). A case of fatal asthma of a 4,4 -mcthylcncdiphcnyl diisocyanate-scnsitized subject has been described (Carino et al., 1997). Exposure to 4,4 -methylenediphcnyl diisocyanate is a frequent cause of occupational asthma (Liss et al., 1988 Vogelmcicr et al., 1991 Bernstein et al., 1993) but may also induce hypersensitivity pneumonitis (Malo Zeiss, 1982 Vandenplas et al., 1993) and inflammatory upper respiratory tract diseases (Liss et al., 1988 Littorin et al., 1994). Most patients with 4,4 -methylenediphcnyl diisocyanate-induced asthma have elevated levels of IgG-class antibodies towards 4,4 -methylenediphenyl diisocyanate-albumin conjugates in the plasma, while IgE-class antibodies are rare (Liss et al., 1988). 

Currently, 17 mAbs have been approved in the United States (US) for therapeutic use in organ transplant, percutaneous coronary intervention, prophylaxis of respiratory syncytial virus, RA, Crohn s disease, asthma, chronic lymphocytic leukemia (CLL), acute myeloid leukemia, non-Hodgkin s lymphoma, breast cancer, and colorectal cancer. All approved mAbs are of the IgG class 13 human IgG1 one igG4, and two murine IgG2a. Thirteen are intact mAbs, three are conjugated, and one is a Fab fragment (Tables 12.2 to 12.4). 

Five classes of Humans have five different classes of antibody molecule which differ both in immunoglobulins structure and in function. These are called immunoglobulin A (IgA), IgD, IgE, IgG and IgM and each has its own type of heavy chain a, 8, e, y and x, respectively. Thus IgA molecules have two identical a heavy chains, IgD molecules have two identical 8 heavy chains, etc. The human IgG class of antibodies is further divided into four IgG subclasses IgG, IgG2, IgG3 and IgG4, having y, y2, y3 and y4 heavy chains respectively. 

Rheumatoid factors of the IgM and IgG classes have been shown to form immune complexes in serum or joint fluid either by self-association (K17, M4, M26, P13, Sll, W21) or by reaction with native IgG (C4, K17, M4, N5, Sll, W21, W22), and these appear to be the predominant immune complex material in rheumatoid arthritis (C4, Gl, K17, M4, M26, N5, Sll, W21, W22). The primary cause of rheumatoid factor production in rheumatoid arthritis is unknown. However, rheumatoid factors are known to be present in other diseases associated with chronic antigenic stimulation (C14, M14) and can be induced in vitro by stimulation with antigens, autologous aggregated IgG, anti-idiotype reagents, and polyclonal B cell activators such as lipopolysaccharide and Epstein-Barr virus (C4, Dll, F6, F7, Gil, 16, P10, S24). Rheumatoid factors, including IgG rheumatoid factors which form selfassociating intermediate-sized (11-19 S) complexes, play a major role in... 

Concentration in milk and colostrum. The concentration of different Ig classes in milk and colostrum varies considerably according to species, breed, age, stage of lactation, and health status, and is often different from that in blood. In human milk and colostrum, the IgA class comprises about 90% and in blood 15-20% of total Ig, whereas the IgG class is dominant in bovine milk, colostrum and blood (about 60-70% of total Ig). 

Estimation of autoantibodies in CD is based mainly on detection of IgA class immunoglobulins. However, CD is associated with selective IgA deficiency [131]. About 2% of CD patients are IgA deficient in Italy [132, 133] and Ireland [134]. In cases of IgA deficiency, the corresponding IgG antibodies should be evaluated. Indirect immunofluorescent detection of IgG anti-endomysium antibodies has drawbacks due to secondary antibodies against human IgG often nonspecifically binding to connective tissue fibers [135]. However, IgG class antibodies against tTG have shown high specificity for CD in cases of IgA deficiency [136-139],... 

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