Virulence factors of N.meningitidis (Pizza M et al. 2014):
Adhesins: Adhesins or adhesion molecules allow the pathogen to bind to epithelial cells. They induce internalization, allowing the pathogen to overcome this barrier by the intracellular route.
Receptor for human transferrin: N. meningitides is not capable of forming siderophores. However, iron is essential for the growth of these bacteria. Instead, they form receptor proteins for transferrin. These have a stronger affinity for iron than transferrin. This affinity allows them to take over and process iron ions from transferrin in the organism.
Endotoxins: N. meningitides produces endotoxins that are capable of triggering the cytokine cascade, causing fever, coagulopathy, and shock. These toxins are toxic cell wall components, such as lipopolysaccharide (LPS) and others. These endotoxins activate macrophages, which secrete TNF-alpha. This leads to fever, toxic vasculitis, disruption of the coagulation system and bleeding.
IgA prote ases: IgA proteases cleave IgA immunoglobulins and inhibit the action of protective antibodies.
Polysaccharide capsule: A capsule protects the pathogen from phagocytosis and complementopsonization. The nature of the capsule surface prevents the formation of a functional convertase and the membrane-attack complex. This makes efficient C3b-mediated opsonization impossible.
Phase variation and antigenic variance: Phase variation, i.e. switching on and off of specific genes associated with antigenic variance (of surface molecules) plays an important role in meningococcal virulence. It can lead to abrupt changes in the phenotype and thus its antigenicity(antigenic mimicry).
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Immunity in M. meningitis: Elimination of the disease is complicated by the enormous diversity and antigenic variability of the pathogen, Neisseria meningitidis, one of the most variable bacteria in nature(Caugant A et al.2014).For natural immunity to meningococci, colonization with non-pathogenic N. lactamica and non-related but immunologically similar bacteria could be important.
Deficiencies in the complement system: The complement system and antibodies against the capsule (in B meningococci also against membrane proteins) play a critical role in the immune defense of invasive meningococcal disease, as activated complement leads to bacterial death by direct lysis or by opsonization and phagocytosis.
Individuals who undergo recurrent attacks of Neisseria infection have a high prevalence of familial deficiencies of terminal complement factors (see Immune Deficiencies Primary (Complement Deficiencies) below). This deficit results in the inability to form the membrane-attacking complex (C5-C9). However, the prevalence of terminal complement factor deficiency in the general population is very low (about 0.03%). On the other hand, approximately 50% of all affected individuals undergo meningococcal infection at some point in their lives. Patients with complement factor deficiency tend to have infections with the rarer serogroups W-135, X, Y, Z, and 29E.
Properdin Deficit: Individuals with properdin deficiency, a sex-related inherited disorder, have functional classical complement activation but impaired alternative activation. More than half of males in this group develop meningococcal disease, and the course is often fulminant with a fatal outcome.
Individuals with hypogammaglobulinemia, primary isolated IgM deficiency, or functional/organic asplenia are also at increased risk for sporadic meningococcal disease or for severe disease courses (see Waterhouse-Friderichsen syndrome below).