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Virulence, Adherence, & Antigenic Diversity
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INITIAL PATHOGEN-HOST INTERACTIONS
Host must make contact with its environment exchange air ingest food eliminate waste HOST DILEMMA PREVENTION OF MICROBIAL ENTRY VS CONTACT WITH ENVIRONMENT
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PATHOGENS CAPITALIZE ON POINTS OF ENTRY
DIGESTIVE TRACT RESPIRATORY TRACT UROGENITAL TRACT CONJUNCTIVA HOST POSSESSES DEFENSE MECHANISMS TO PREVENT ENTRY MECHANICAL CLEANSING e.g. blinking & peristalsis
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pilC pilE opa capsule opc Adherence Adherence Invasion
Serum resistance Adherence Invasion
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a bacterial defense against host’s mechanical cleansing
ADHERENCE a bacterial defense against host’s mechanical cleansing HOST CELL RECEPTOR bacterium BACTERIAL ADHESIN PILI OMPs host cell requires two factors host receptor bacterial adhesin
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surface protein structure
ADHESIN surface protein structure 1) pilus (fimbria) - for attachment at a distance 2) non-fimbrial adhesin (outer membrane protein) - for intimate attachment
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pili flagella
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ADHESIN DIVERSITY HOST RANGE ENVIRONMENTAL CONDITIONS
SPECIFIC ADHESIN FOR SPECIFIC HOST RECEPTOR ex. N. GONORRHEA (VAGINA vs RECTUM) ENVIRONMENTAL CONDITIONS ex. Uropathogenic E. COLI (PYELONEPHRITIS ISOLATES) EXPRESS TYPE 1 PILI – (Bladder) LIQUID TYPE P PILI – (Kidney) SOLID SURFACE
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VARYING ADHESIN COMPOSITION
ADHESIN DIVERSITY MEDICAL IMPORTANCE NEISSERIA GONORRHEA AVOID IMMUNE SYSTEM BY VARYING ADHESIN COMPOSITION
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Majority with one antigen
Minority with different antigen
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majority killed by immune response subpopulation avoids immune response
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Subpopulation multiplies
New subpopulation
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ANTIGENIC VARIATION
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MECHANISMS OF ANTIGENIC VARIATION
each N. gonorrhea cell possesses genetic information for a large number of variant pilin proteins thus, each cell can produce progeny that synthesize pili that exhibit different epitopes than did its parent
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} PILIN GENE ORGANIZATION pilE pilS pilE - expressed due to promoter
pilS - silent genes due to i) lack of promoter ii) incomplete pilS genes same orientation as pilE } A B C A promoter pilE pilS
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upon the sequence of pilE
Antigenicity depends upon the sequence of pilE } A A B C A } pilS pilE B A B C B
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MECHANISMS i) gene conversion ii) transformation
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Gene Conversion pilS = endogenote A B C A type A pilus A B C
type B pilus recombination
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Transformation Lysed Donor Recipient pilS = exogenote B A C
recombination A B C C Recipient type C pilus
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Antigenic possibilities are infinite
D X X B B/C B/C B/C/D
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