The lectin pathway

Activation of C2 and C4 produces the C3 convertase and, via the same reactions sequences of the classical pathway, leads to formation of the MAC. 

Complement deficiencies are associated with several diseases. Alternative pathway deficiencies are rare, but when they exist more than one-half of factor D or properdin-deficient individuals suffer from Neisseria infections of which 75% are fatal. Individuals with deficiencies in the MAC components, e.g., C5, C6, Cl, and C8, are also susceptible to infection with Neisseria. Deficiencies in C1, C4, and C2 are associated with systemic lupus erythematosus and glomerulonephritis. Hereditary angioedema, a disease characterized by recurrent submucosal and subcutaneous edema, is caused by a deficiency in Cl inhibitor. Complexes and interactions similar to those of the complement system are also characteristic of the clotting system (Chapter 36). 

Cytokines are a group of cell-derived proteins or peptide molecules that transmit signals between cells of the 

An annotated list of some of the cytokines involved in immune system modulation is given in Table 35-4. The rapid development of cytokine biology, however, guarantees that such tables are likely to be incomplete the moment that they are created and, more importantly, inaccurate in some respects. Internet sites exist that update cytokine 

Immunological memory, i.e., B cells and T cells that are poised for rapid antibody formation and antigen destruction, provides the molecular basis for the successful use of vaccines. In vaccination, the stimulation of B- and T-cell clones leads to formation of antibodies to the foreign proteins. Differentiation of some of the B cells that recognize the antigen into memory cells provides the mechanisms for resisting subsequent infections. 

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Although, as with human disease, complement deposition is not conspicuous in the vasculitic lesions, multiple experimental observations indicate that complement activation has an important pathogenic role in this model (64,65). Depletion of complement with Cobra venom factor completely prevents the development of glomerulonephritis and vasculitis after injection of MPO-IgG or transfer of anti-MPO splenocytes (64). Injection of anti-MPO IgG into mice with knockout of various complement genes demonstrates that the alternative complement pathway, but not the classic pathway or the lectin pathway, is required for anti-MPO IgG mediated disease induction (64). Specifically, C4-/- mice with blockade of the classic pathway and the lectin pathway develop disease that is same as in wild type mice, whereas C5-/-mice with blockade of all pathways and factor B -/- mice with selective blockade of the alternative pathway are completely protected from disease induction. In accord with an important role for complement, the CS-inhibiting monoclonal antibody (BB5.1) prevents the induction of glomerulonephritis in mice after injection of anti-MPO IgG and LPS (65). Even when the anti-C5 antibody is administered a day after the anti-MPO, there is a marked reduction in disease induction. 

In its central projections the vomeronasal pathway, distinguished by a unique lectin-affinity, ascends to an accessory olfactory bulb, while dorsal and ventral pathways supply the dorsal and ventral regions of the main olfactory bulb (Saito and Taniguchi, 2000). The AOS (but not the MOS) of salamanders displays considerable diversity in the... 

Lectin pathway, stimulated by binding to a lectin. Lectins belong to a family of proteins called collectins, which are present in blood and bind to bacteria. One lectin, known as the mannose binding lectin (MBL), binds to a sequence of mannose sugars that are part of the carbohydrate on the cell surface of some bacteria. It is the lectin-bacteria complex that activates one of the complement proteins. The components of the pathway are prefixed with a C and a number. 

The reactions that take place in the complement system can be initiated in several ways. During the early phase of infection, lipopoly-saccharides and other structures on the surface of the pathogens trigger the alternative pathway (right). If antibodies against the pathogens become available later, the antigen-antibody complexes formed activate the classic pathway (left). Acute-phase proteins (see p. 276) are also able to start the complement cascade lectin pathway, not shown). 

The classical complement pathway reqnires activation by circulating antibodies, IgM or IgG (specific immnne response), while the alternative and lectin pathways can be activated in the absence of antibody (non-specific immnne response). 

Schrag, J.D., Procopio, D.O., Cygler, M., Thomas, D.Y. and Bergeron, J.J. (2003) Lectin control of protein folding and sorting in the secretory pathway. Trends Biochem. Sci. 28, 49-57. 

It appears that the two receptor cell layers in the vomeronasal epithelium relate directly to the rostral/caudal division of the accessory olfactory bulb. In mice and rats, apical and basal receptor cell layers differ in their pattern of projections to the accessory olfactory bulb. The apical, Gaj2-expressing cells project to the rostral half of the accessory olfactory bulb, and the basal, Ga -expressing cells project to the caudal half (Jia Halpern, 1996). The boundary between these two areas matches that described in the lectin- and antibody-labeling studies. Further, the output cells of the accessory olfactory bulb appear to arborize predominantly or exclusively within either the rostral or the caudal portion, suggesting that the two halves of the accessory olfactory bulb may form separate functional pathways carrying information solely or mainly from each of the two receptor families (Jia, Goldman Halpern, 1997). 

Matsushita M, Fujita T. Ficolins and the lectin complement pathway. Immunol Rev 2001 180 78-85-... 

Fujita T, Matsushita M, Endo Y. The lectin-complement pathway—its role in innate immunity and evolution. Immunol Rev 2004 198 185-202. 

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