Institute for Microbiology, Medical Faculty of Masaryk University Institute for Microbiology, Medical Faculty of Masaryk University and St. Anna Faculty Hospital in Brno and St. Anna Faculty Hospital in Brno Miroslav Votava, Vladana Woznicová Miroslav Votava, Vladana Woznicová FACTORS OF PATHOGENICITY FACTORS OF PATHOGENICITY AND VIRULENCE – II AND VIRULENCE – II Lecture for 2nd-year students Lecture for 2nd-year students April April 20 20 th th , 200 , 200 9 9
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Institute for Microbiology, Medical Faculty of Masaryk University Institute for Microbiology, Medical Faculty of Masaryk University and St. Anna Faculty Hospital in Brno and St. Anna Faculty Hospital in Brno
Miroslav Votava, Vladana WoznicováMiroslav Votava, Vladana Woznicová
FACTORS OF PATHOGENICITYFACTORS OF PATHOGENICITYAND VIRULENCE – II AND VIRULENCE – II
Lecture for 2nd-year studentsLecture for 2nd-year studentsApril April 2020thth, 200, 20099
Ability to overcome the defence – AAbility to overcome the defence – A
A) Ability to overcome the A) Ability to overcome the innateinnate immunity immunity: :
To To resistresist complement complement to to inhibitinhibit complement activation complement activation to to protectprotect one‘s own surface one‘s own surface
To To resistresist phagocytosis phagocytosis not not to allowto allow being engulfed being engulfed to to survivesurvive inside the phagocyte inside the phagocyte
To To interfere withinterfere with the the cytokine cytokine functionfunction
Ability to resist complementAbility to resist complement
Inhibition of complement activation Inhibition of complement activation capsule – shielding surface molecules capsule – shielding surface molecules (meningococci, pneumococci) (meningococci, pneumococci) activation inhibitors (gonococci – addition of sialic activation inhibitors (gonococci – addition of sialic
acid to terminal acid to terminal saccharidessaccharides, , many many viruses, viruses, E. coli E. coli and and S. pyogenes – S. pyogenes –
production of regulation factor H, production of regulation factor H, S. pyogenes S. pyogenes and and P. aeruginosa P. aeruginosa – – enzymes enzymes splitting C3b a C5a)splitting C3b a C5a)
Protection of the surfaceProtection of the surface (salmonellae and (salmonellae and E. coliE. coli in in S phase, flagella of motile bacteria)S phase, flagella of motile bacteria)
Ability to resist complement Ability to resist complement →→ sseroresistance eroresistance
http://inst.bact.wisc.edu
Ability to resist phagocytosis – IAbility to resist phagocytosis – I
1. 1. NNot to allow being engulfedot to allow being engulfed
formation of formation of capsulecapsule ( (mostmost importan important!t!))
agents of meningitis and pneumonia agents of meningitis and pneumonia ((N. meningitidis, H.N. meningitidis, H. influenzae, E. coli, influenzae, E. coli, S.S. pneumoniae,pneumoniae, K. pneumoniaeK. pneumoniae))
http://www.coll-outao.qc.ca
Ability to resist phagocytosis – II Ability to resist phagocytosis – II
2. 2. To survive inside the phagocyteTo survive inside the phagocyte
blockade of phagolysosome formation blockade of phagolysosome formation ((CChlamydia, hlamydia, MMycobacteriycobacteriumum, , LLegionella, egionella, TToxoplasmaoxoplasma) )
escape from phagosome escape from phagosome ((RRickettsia, ickettsia, SShigella, higella, LListeria, isteria, LLeishmania, eishmania, TTrypanosomrypanosomaa))
production of antioxidants production of antioxidants (staphylococci, gonococci, meningococci)(staphylococci, gonococci, meningococci)
Ability to overcome the defence Ability to overcome the defence – B– B
B) B) Ability to overcome the Ability to overcome the acquiredacquired immunity: immunity:
Always an attempt to Always an attempt to avoid antibodiesavoid antibodies or immuneor immune lymphocyteslymphocytes::
to reproduce quickly to reproduce quickly (respiratory viruses, diarrhoeal (respiratory viruses, diarrhoeal agents, agents, malarialmalarial plasmodia) plasmodia)
attempt toattempt to deceive deceive immune systemimmune system
to hide itselfto hide itself
to change one‘s to change one‘s own own antigensantigens
to induce toleranceto induce tolerance
attempt to attempt to suppress immune reactionsuppress immune reaction
Ability to deceive the immune Ability to deceive the immune system – Isystem – I
• To hide itself To hide itself in ganglions in ganglions (HSV, VZV) (HSV, VZV) on intracellular membraneson intracellular membranes (HIV, adenov.) (HIV, adenov.) in infectious focuses in infectious focuses ((M. M. tbctbc, echinococci) , echinococci) in privileged in privileged sites sites (agents of mucosal (agents of mucosal infections, infections, T. T. gondii gondii inin eye, retroviruses eye, retroviruses in cellular in cellular genome)genome)
2. To induce the immune tolerance2. To induce the immune tolerance(CMV, rubella v., leishmaniae, cryptococci, (CMV, rubella v., leishmaniae, cryptococci, maybe even HIV)maybe even HIV)
Ability to deceive the immune Ability to deceive the immune systemsystem – II – II
3. 3. To change antigens of one‘s ownTo change antigens of one‘s own
antigenic mimicry antigenic mimicry ((S. pyogenes, T. pallidum,S. pyogenes, T. pallidum,M. pneumoniaeM. pneumoniae))
antigenic camouflage antigenic camouflage (schistosomes – (schistosomes – blood proteins, staphylococci – protein blood proteins, staphylococci – protein A, A, streptococci – protein G, CMV – streptococci – protein G, CMV – βmG)βmG)
Ability to deceive the immune Ability to deceive the immune systemsystem – III – III
4. 4. To suppress immune reactionTo suppress immune reactioninvasion into the immune system invasion into the immune system (HIV, m(HIV, measleseasles
virus) virus) interference in cytokine formation interference in cytokine formation ((M. lepraeM. leprae, , protozoa) protozoa) production of production of superantigenssuperantigens (staphylococci, (staphylococci, streptococci) streptococci) production of proteases production of proteases (meningococci, (meningococci, gonococci, haemophili, gonococci, haemophili, pneumococci) pneumococci) binding Fcbinding Fc fragment fragment of IgG of IgG (staphylococci, (staphylococci, streptococci, HSV)streptococci, HSV)? ? (influenza virus, HBV, EBV)(influenza virus, HBV, EBV)
Toxicity – I Toxicity – I
DamageDamage by by direct effect of infectious agent direct effect of infectious agent
Cellular death Cellular death lysis by toxins, viruses, immune lymphocytes lysis by toxins, viruses, immune lymphocytes apoptosis (HSV, shigellae) apoptosis (HSV, shigellae)
Metabolic injury Metabolic injury – influence of exotoxins– influence of exotoxins
Mechanical causes Mechanical causes (schistosomal eggs, (schistosomal eggs, P. jiroveciiP. jirovecii, , pseudomembranes in diphtheria) pseudomembranes in diphtheria)
The most frequent cause of death The most frequent cause of death → → septic shock septic shock triggered by triggered by endotoxinsendotoxins
G G –– : lipopolysaccharide : lipopolysaccharide G + : teichoic acid + peptidoglycan G + : teichoic acid + peptidoglycan
Injury as a Injury as a result of defence reactionsresult of defence reactions
b) b) Injuries caused Injuries caused by specific immune reaction by specific immune reaction (immunopathological consequences of (immunopathological consequences of hypersensitivityhypersensitivity))