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Unformatted text preview: Topic 20 N. meningitidis (The Meningococcus) AND MENINGITIS 1) Describe in general terms the different types of disease caused by N. meningitidis and N. gonorrhoeae. 1. The Pathogenic Neisseria-human pathogens that cause purulent infection a) N. gonorrhoeae- usually a localized infection of the genital tract that provokes a strong inflammatory response b) N. meningitidis- an extracellular, invasive pathogen that causes severe and dramatic life- threatening infections: 1) acute meningitis- the most common cause of meningitis worldwide 2) sepsis- called meningococcemia a) fulminant meningococcemia (purpura fulminans)- The Waterhouse-Friderichsen syndrome 2) Describe the morphology and Gram-stained characteristics of N. meningitidis. Morphology- Gram negative cocci that resemble paired kidney beans 3) Describe the virulence factors of this pathogen and indicate the role of each in pathogenesis. Cell Surface Structures that are virulence factors (and antigenic) a) Pili- mediate attachment b) Outer membrane proteins- define 20 serotypes; function as afrimbrial adhesins (like the gonococcal Opa family of proteins) c) Polysaccharide capsule- major virulence factor- antiphagocytic 1) Defines 9 serogroups (serologic groups) based on the antigenicity of the capsules. (Each serogroup (A,B,C,D,X,Y,Z,W-135, 29E) has a unique polysaccharide composition) 2) Most important serogroups A,B,C,Y and W-135 a) Types A and C- associated with epidemic disease b) Type B- associated with sporadic cases of disease; most common serotype in the U.S., where epidemics are rare 3) Capsular polysaccharides are shed into the blood and CSF during active disease 4) Purified capsular vaccine-contains A,C,Y and W-135 capsular serotypes. 5) The serogroup B capsule is poorly immunogenic; biochemical composition is a form of polysialic acid (identical to a host cell carbohydrate structure) Molecular Mimicry: a) Organisms evade the specific immune response because their antigens are not recognized as foreign b) Any immune response that is induced potentially cross-reacts with human tissues, resulting in disease. The capsule of serogroup B cross-reacts with human neuronal tissues d) Endotoxin-Lipooligosaccharides (LOS) rather than LPS; blebs are shed from the organisms during growth in vivo . *LPS= Lipid A, Core oligosaccharide, repeating O-antigen polysaccharide; LOS= lacks the repeating O-antigen polysacchardies. The oligosaccharide component is relatively short, but exhibits considerable antigenic variation 1) The LOS of meningococcus is used as a serological typing system- separates trains into 12 immunotypes 2) LOS is a potent endotoxin-important contributor to disease- especially sepsis; responsible for adrenal cortical necrosis 3) LOS is the target antigen for bactericidial antibody made by the host 2) Other Virulence Factors: e) IgA1 protease- to survive on the mucosal surfaces with contain IgA, meningococci secrete IgA1 protease that attacks the hinge regions- creating Fab and Fc fragments...
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- Fall '09