Antibody-dependent, cell-mediated cytotoxicity

Large granular lymphocytes, not belonging to either the T- or B-cell lineage. Natural killer (NK) cells are considered part of the innate defense system since, in contrast to cytotoxic T-cells, they are able to kill certain tumor cells in vitro without prior sensitization. The basal activity of NIC cells increases dramatically following stimulation with type I IFNs. In addition, NK cells display Fc-receptors for IgG and are important mediators of Antibody-Dependent-Cell-mediated-Cytotoxicity (ADCC). 

NK cells possess a receptor for Fc/and this enables them to adhere to target cells coated in antibody with the resultant destruction ofthat cell. This phenomenon is known as antibody-dependent cell-mediated cytotoxicity (ADCC). This was attributed to a separate cell population known as killer (K) cells but these have now been shown to be in effect NK cells. 

Trinchieri G, De March M. Antibody-dependent cell-mediated cytotoxicity in humans. II. Energy requirement. J Immunol 1975 115(l) 256-260. 

ADCC Antibody-dependent cell-mediated cytotoxicity... 

ADCC Antibody Dependent Cell mediated Cytotoxicity... 

IgG Immunoglobulin G is present in lymph fluid, blood, cerebrospinal fluid and peritoneal fluid. It is composed of 2 y chains of 50 kDa and 2 L chains (k or ) of 25 kDa with a total molecular weight of 150 kDa. The functions of IgG include agglutination and formation of precipitate, passage through placenta and thus conferring immunity to fetus, opsonization, antibody-dependent cell-mediated cytotoxicity (ADCC), activation of complement, neutralization of toxins, immobilization of bacteria and neutralization of virus. 

Fig. 9.3. Immunoglobulin E (IgE) and mast cell activation are important components of the mammalian response to cestode infections (ADCC, antibody dependent cell-mediated cytotoxicity Ag, antigen EO, eosinophils Feel, high affinity receptor for Fc portion of IgE LTs, leukotrienes Mac, macrophages NO, nitric oxide PGs, prostaglandins TNFa, tumour necrosis factor alpha).

Iannello A, Ahmad A. Role of antibody-dependent cell-mediated cytotoxicity in the efficacy of therapeutic anti-cancer monoclonal antibodies. Cancer Metastasis Rev. 2005 24 487M-99. 

In humans, there are five isotypes of antibodies, IgG, IgA, IgD, IgE, and IgM, which are defined by the structures of their heavy chains and their abilities to form multimers (Figure 10.1) [8], IgG is the most abundant isotype present in serum with average serum concentrations ranging from 0.5 to 9mg/ml depending on the IgG subtype. This is followed by IgA (3mg/ml), IgM (1.5mg/ml), IgE (0.05 mg/ml), and IgD (trace). Each antibody isotype has unique functions. Critical functions of IgG include opsonization, complement activation, antibody-dependent cell-mediated cytotoxicity (ADCC), passive immunity, and regulation of B cells. Both IgM and IgD act as antigen receptors on naive B cells, and soluble, multimeric forms of IgM are involved in complement activation. IgA is involved in mucosal and passive neonatal immunity, while IgE is involved in immediate hypersensitivity [8],... 

G22. Gravagna, P., Gianazza, E., Arnaud, P., Neels, M., and Ades, E. W., Modulation of the immune response by plasma protease inhibitors. II. Alpha 2-macroglobulin subunits inhibit natural killer cell cytotoxicity and antibody-dependent cell-mediated cytotoxicity. Scand. J. Immunol. 15, 115-118 (1982). 

A subfamily of disintegrin and metalloproteinase with thrombospondin motifs Antibody-dependent cell-mediated cytotoxicity as in NK cells attacking antibody-coated cells... 

Dickinson AM, Shenton BK, Alomran AH, Donnelly PK, Proctor SJ. Inhibition of natural killing and antibody-dependent cell-mediated cytotoxicity by the plasma protease inhibitor alpha 2-macroglobulin (alpha 2M) and alpha 2M protease complexes. Clin Immunol Immunopathol 1985 36 259-5. 

IgE antibodies have the unique ability to bind with high affinity to Fc<-RI receptors on mast cells and basophils, and induce degranulation and cytokine secretion by these cells when they are cross-linked by antigen. In addition to its central role in the patht nesis of atopic disorders, it has been speculated that IgE-mediated mast cell degranulation may have a role in the expulsion of gut and respiratory traa parasites. IgE may also have a role in eosinophil killing of parasites by IgE-mediated antibody-dependent cell-mediated cytotoxicity. Despite these observations, it is unclear whether IgE plays an indispensable role in protection against disease. 

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