Phagocytes impaired function

Impaired function of phagocytes and deficiency of early components of the classic pathway of the complement system result in increased apoptotic waste. This waste, including nucleosomes and other autoantigens, is formed and altered by the protease of apoptotic cells. They are expressed on the surface of apoptotic blebs and activate bystander dendritic cells. Subsequently the dendritic cells activate helper T cells, which then help B cells to generate high-affinity autoantibodies (Fig. 1). 

As larger amounts of complexes are infused into experimental animals, the rate of clearance slows and vascular lesions appear, presumably as a result of overload (B9, HI, H2). Similar phenomena may occur in man, and impaired clearance has been demonstrated in several diseases associated with manifestations of immune complex deposition including systemic lupus erythematosus (F9, H8, K9, L19, P2), primary biliary cirrhosis (G19), Sjogren s syndrome (H9), and dermatitis herpetiformis (L6). Impaired clearance may be a result of circulatory overload by immune complexes, or a primary defect in mononuclear phagocytic system function may contribute or predispose to immune complex deposition (A15, A16, HI). However, impaired clearance, as currently measured, is neither a prerequisite nor a consistent consequence of immune complex disease. 

B) An increased susceptibility to respiratory infection due to impairment in phagocyte function... 

Edema toxin does not produce major tissue damage. In fact, its major role is to impair phagocyte function (Leppla, 2000). This is consistent with other toxins which fimction to elevate cAMP concentrations. Edema toxin inhibits phagocytosis of spores by human PMNs (O Brien et al, 1985) similar to LF this is in contrast to spores which promote immune cell uptake (see Table 31.1). Increased intracellular cAMP induced by EF inhibits neutrophil chemotaxis, phagocytosis, superoxide production, and microbicidal activity (Crawford et al, 2006 Turk, 2007 O Brien et al, 1985 Friedman et al, 1987 O Dowd et al, 2004 Ahmed et al, 1995). EF has been shown to inhibit TNFa and increase IL-6 production (Hoover et al, 1994). Increased cAMP levels also block LPS-induced activation... 

Steroids also alter important functional activities of lymphocytes and monocytes. This effect is mainly on T lymphocytes and is at least partly due to a decrease in IL-2 production. Other proinflammatory cytokines such as IL-1 and IL-6 are also down regulated (Barnes, 2001 Krensky et al., 2005). The effect on B lymphocytes is less prominent. Steroids also profoundly impair the function of monocytes/macrophages by significantly decreasing their phagocytic ability. Glucocorticoids also increase I B expression, thereby curtailing activation of NF-kB, which increases apoptosis of activated cells (Auphan etal., 1995). 

Liu L, Poon R, Chen L, Frescura AM, Montuschi P, Ciabattoni G, Wheeler A, Dales R (2009) Acute effects of air pollution on pulmonary function, airway inflammation, and oxidative stress in asthmatic children. Environ Health Perspect 117 668-674 Lundborg M, Johard U, Lastbom L, Gerde P, Gammer P (2001) Human alveolar macrophage phagocytic function is impaired by aggregates of ultrafine carbon particles. Environ Res 86 244-253... 

Mice (Mus sp.) fed a zinc-deficient diet of 0.7 mg Zn/kg ration for 40 days, when compared to mice fed a zinc-adequate diet of 36.5 mg Zn/kg, had a reduced growth rate, impaired phagocytic function, increased susceptibility to lead poisoning, and reduced zinc content in blood (0.7mg/L vs. 1.0-1.1) and liver (12.0 mg Zn/kg EW vs. 17.0-19.0). Zinc deficiency during early development affects neural tube development through arrested cell... 

While interference with electron transmission and uncoupling of oxidative phosphorylation have no effect on Ae phagocytic function of polymorphonuclear leucocytes or monocytes they impair the activity of the alveolar macrophage (Karnovsky et al. 1966). 

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