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samenvatting hfdst 1-10 infectie en afweer
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samenvatting ptt + lesnota's van hfdst 1-10 (hfdst 7 niet).
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MICROBIOLOGIEInhoud
1. Microbiologie in beweging .......................................................................................................................................... 5
1.1.Introductie ................................................................................................................................................................. 5
1.2. De drie domeinen van het leven .............................................................................................................................. 5
1.3. De kiemtheorie van Koch.......................................................................................................................................... 7
1.4.Interacties tussen species in een niche ..................................................................................................................... 8
1.5.Infectieziekten: impact op de mens en zijn genoom................................................................................................. 9
1.6. Oude, nieuwe, terugkerende pathogenen .......................................................................................................... 9
2.Bacteriën en virussen ..................................................................................................................................................... 10
2.1 bacteriën .................................................................................................................................................................. 10
2.1.1. Situering van de bacteriën ......................................................................................................................... 10
2.1.2. Anatomie van bacteriën: celmembraan, celwand, genoom, andere structuren ...................................... 10
2 .1.3. Metabolisme, celgroei en fenotypische adaptatie .................................................................................... 13
2.1.4. Naamgeving en taxonomie ........................................................................................................................ 16
2.1.5.Genotypische variatie bij bacteriën en typering .............................................................................................. 16
2.2.Virussen ................................................................................................................................................................... 18
2.2.1. Classificatie ................................................................................................................................................ 18
2.2.2. naakt virus VS enveloppe virus .................................................................................................................. 19
2.2.3. DNA VS RNA virus ...................................................................................................................................... 20
2.2.4. Virale levenscyclus ........................................................................................................................................... 20
2.2.5. Aantonen van virussen .............................................................................................................................. 25
3. Antibiotica en virostatica ............................................................................................................................................... 26
3.1. Inleiding .................................................................................................................................................................. 26
3.2. Interactie met bacteriën en gastheer ..................................................................................................................... 27
3.2.1 De gastheer-kiem relatie .................................................................................................................................. 28
3.2.2 Antibiotica en het menselijk lichaam : farmacokinetiek .................................................................................. 28
3.2.3 Antibiotica en bacteriën : farmacodynamiek ................................................................................................... 28
3.3. Het voorspellen van de werkzaamheid in de patiënt ............................................................................................. 29
3.3.1. Het dilutie-antibiogram ................................................................................................................................... 30
3.3.2. Het diffusie-antibiogram ................................................................................................................................. 30
3.4.Het klinisch breekpunt............................................................................................................................................. 30
3.4.1. PK/PD kenmerken van het antibioticum. .................................................................................................. 30
3.4.2. Invloed van lokale omstandigheden, bijzondere eigenschappen van de bacterie of de patiënt. ............. 30
3.5.Overzicht van de antibiotica en hun werkingsmechanisme .................................................................................... 31
3.5.1.Groep 1: Celwandsynthese ............................................................................................................................... 32
3.5.2. Groep 2: antibiotica die inwerken op de eiwitsynthese .................................................................................. 33
3.5.3.Groep 3: antibiotica die inwerken op de nucleïnezuursynthese...................................................................... 35
3.5.4. Groep 4: inhibitie van metabole ‘pathways’ ............................................................................................. 35
3.6.Antibioticaresistentie van bacteriën ....................................................................................................................... 36
3.6.1. Drijvende kracht(en) van resistentie ......................................................................................................... 36
3.6.2. Mechanismen van resistentie.......................................................................................................................... 37
3.6.3. Kinetiek van ontstaan en verspreiding van resistentie ................................................................................... 38
3.6.4. Persisters (en het onderscheid met resistentie-mutanten) ...................................................................... 40
3.6.5. Hoe resistentie voorkomen en inperken? ................................................................................................. 40
3.7. Profylactische gebruik van antibiotica = PREVENTIEF gebruik v antibiotica ..................................................... 41
3.8. Antibiotherapie in de praktijk ............................................................................................................................ 42
1
, 3.8.1. Naar een concrete antibiotherapie: wat komt er zoal bij kijken? ............................................................. 42
3.8.2. Keuze van een antibioticum: hulpmiddelen .............................................................................................. 42
3.8.3. Keuze van een antibioticum : steekkaart en kruistabellen........................................................................ 43
3.9. Middelen tegen virussen ................................................................................................................................... 44
3.9.1. Antivirale middelen (virostatica) grijpen in op de virale levenscyclus ...................................................... 44
3.9.2. Anti-herpes middelen: acyclovir en valacyclovir (valylester prodrug van acyclovir)................................. 45
3.9.3. Antivirale middelen: influenza ................................................................................................................... 46
3.9.4. Antivirale middelen: gecombineerde antiretrovirale therapie (cART) voor HIV ....................................... 47
4. De barrières, de normale flora en de verstoring ervan ............................................................................................. 48
4.1. Inleiding ............................................................................................................................................................. 48
4.2. Barrières tegen micro-organismen .................................................................................................................... 48
4.2.1. The physical barriers that separate the body from its external environment .......................................... 48
4.2.2. Chemische barrière.................................................................................................................................... 49
4.2.3. Barrière-functie: de normale flora en normale anatomie ......................................................................... 49
4.3. Overzicht van de verschillende lichaamsoppervlakken met hun barrières en hun microflora ......................... 50
4.3.1.Huidbarrière ..................................................................................................................................................... 51
4.3.2.Mondholte en bovenste luchtwegen ............................................................................................................... 53
4.3.3.Diepe luchtwegen ............................................................................................................................................. 56
4.3.4. Gastrointestinaal stelsel ............................................................................................................................ 60
4.3.5. Urogenitale slijmvliezen .................................................................................................................................. 62
4.4.Abnormale flora en dysbacteriose .......................................................................................................................... 63
4.4.1.Abnormale flora (kolonisatie) ........................................................................................................................... 63
4.4.2.Dysbacteriose ................................................................................................................................................... 64
4.5. Positieve beïnvloeding van de microflora ......................................................................................................... 65
5.Virulentie en vatbaarheid ............................................................................................................................................... 66
5.1.Kiem-gastheer relatie: begrippen ............................................................................................................................ 66
5.1.1.Infectie ≠ ziekte: kiem-gastheer relatie ............................................................................................................ 66
5.1.2.Partner 1: de kiem ............................................................................................................................................ 67
5.1.3.Virulentie = eigenschap van hoe en in welke mate een kiem ziekte kan veroorzaken.................................... 67
5.1.4. Partner 2: de gastheer ............................................................................................................................... 68
5.1.5.Vatbaarheid ...................................................................................................................................................... 68
5.1.6.Infectie ≠ ziekte: kiem-gastheer relatie ............................................................................................................ 68
5.1.7.Infectie ≠ ziekte: kiem-gastheer relatie op populatie niveau: myxomatose story ........................................... 68
5.1.8. Co-evolutie kiem-host ..................................................................................................................................... 69
5.2.Verloop van een infectie (geïllustreerd met een S. aureus) .................................................................................... 69
5.2.1.Aanhechting ± invasie: entry ............................................................................................................................ 70
5.2.2.Vermenigvuldiging ............................................................................................................................................ 71
5.2.3. Lokale of gegeneraliseerde verspreiding ................................................................................................... 72
5.2.4. Ontwijken afweer ...................................................................................................................................... 75
5.2.5.Vrijkomen uit lichaam: exit............................................................................................................................... 76
5.2.6.Schade aan gastheer, immuunrespons inflammatie ........................................................................................ 77
6.Reservoir en overdracht ................................................................................................................................................. 78
6.1.Exogene versus endogene infectieziekten .............................................................................................................. 78
6.2.Reservoir en overdracht .......................................................................................................................................... 78
6.3.Epidemie .................................................................................................................................................................. 79
6.4.Verplicht aan te geven infectieziekten .................................................................................................................... 79
7.Infectiepreventie en –beheersing (Isabel Leroux-Roels) ................................................................................................ 80
7.1. Infectiepreventie- en beheersing: doorbreken van de infectieketen ............................................................... 80
7.2. Zorginfecties ...................................................................................................................................................... 80
7.3. Overzicht van de pijlers van infectiepreventie en –beheersing ........................................................................ 80
2
, 7.4. Reiniging, desinfectie en sterilisatie .................................................................................................................. 80
7.5. Standaard voorzorgsmaatregelen ..................................................................................................................... 80
7.5.1. Handhygiëne .............................................................................................................................................. 80
7.5.2. Persoonlijke beschermingsmiddelen (PBM) .............................................................................................. 80
7.5.3. Respiratoire hygiëne en hoestetiquette .................................................................................................... 80
7.5.4. Preventie van overdracht van bloedoverdraagbare aandoeningen.......................................................... 80
7.6. Overdrachtsgebonden voorzorgen: isolatiemaatregelen ................................................................................. 80
7.7. Specifieke ziekenhuisbacteriën (MRSA, VRE, MRGN)........................................................................................ 80
7.8. Organisatie van infectiepreventie (ziekenhuishygiëne) in België...................................................................... 80
7.9. Infectiepreventie buiten de ziekenhuizen-zorginstellingen .............................................................................. 80
7.10. Nuttige bronnen ............................................................................................................................................ 80
8. INFLAMMATIE ................................................................................................................................................................ 81
8.1. Aangeboren IS – specifiek IS .............................................................................................................................. 81
8.2. Principes van pathogeenherkenning door het aangeboren immuun systeem ................................................. 82
8.2.1. Positieve herkenning: herkenning van pathogenen door het immuunsysteem (aangeboren IS)............. 82
8.2.2. Negatieve herkenning: herkenning van pathogenen door het immuunsysteem (aangeboren IS) ........... 82
8.2.3. Vragen van een wachtwoord (aangeboren IS) .......................................................................................... 82
8.2.4. Detectie van schade aan de lichaamscellen (aangeboren IS) .................................................................... 83
8.3.Inflammatie ≠ infectie Chronische inflammatie -> weefselschade ........................................................................ 83
8.3.1 Pathogenen beschadigen weefsel op verschillende manieren ........................................................................ 83
8.3.2 pathogenen exploiteren verschillende compartimenten die op verschillende manieren worden verdedigd 83
8.3.1 faryngitis : reactie vd gastheer (inflammatie) staat op voorgrond .................................................................. 84
8.3.2 Inflammatie tgv GOF (GAIN OF FUNCTION) mutatie in inflammatie machinerie ............................................ 84
8.4.Pathogen/damage recognition ................................................................................................................................ 85
8.4.1.Het Complementsysteem en factor C3 ............................................................................................................ 85
8.4.2. Pathogen recognition receptor: TLR ................................................................................................................ 88
8.4.3. Pathogen recognition receptor: cytoplasmatische NOD receptoren .............................................................. 88
8.4.4. Pathogen recognition receptor: NLR en inflammasomen ............................................................................... 89
8.4.5. RNA en DNA sensors: Pathogen recognition receptor voor virussen en bacteriën ........................................ 89
8.5.Inflammatie ............................................................................................................................................................. 90
8.5.1 Kenmerken........................................................................................................................................................ 90
8.5.2. Inflammatie en Cytokine storm Septische Shock ............................................................................................ 91
8.5.3. Inflammatie en bloedstolling ........................................................................................................................... 91
8.5.4. Inflammatie en botresorptie ........................................................................................................................... 92
8.5.5. Genezing, chronische Inflammatie en fibrose ................................................................................................. 92
8.5.6 Systemische effecten van inflammatie............................................................................................................. 93
8.6.Effector mechanismen van het innate/aangeboren immuun systeem................................................................... 95
8.6.1. Monocyt/macrofaag ........................................................................................................................................ 95
8.6.2. Neutrofielen (neutrofiele granulocyten) ......................................................................................................... 95
8.6.3. Natural killer cells (NK) and innate lymphoid cells ......................................................................................... 97
8.6.4. Defensines ....................................................................................................................................................... 97
8.6.5. Interferonen .................................................................................................................................................... 97
8.6.6. celautonoom mechanisme: autofagie ............................................................................................................ 98
8.6.7. celautonoom mechanisme: AID/APOBEC........................................................................................................ 98
9. specifieke immuniteit : Ig, TCR en HLA .......................................................................................................................... 99
9.1. Principes van adaptief immuunsysteem................................................................................................................. 99
9.2. Structuur antilichamen ......................................................................................................................................... 102
9.3. Functie van antilichamen...................................................................................................................................... 104
9.4. De B en T celreceptor ........................................................................................................................................... 106
3
, 9.5. Genereren van miljarden verschillende receptoren (T en B) .............................................................................. 107
9.5.1 (re)genereren van B-cel receptoren ............................................................................................................... 107
9.5.2 (re)generatie van Tcel receptoren .................................................................................................................. 108
9.6. Veranderen van immuunglobuline isotype en somatische hypermutatie ........................................................... 109
9.7. Majeur Histocompatibiliteitslocus of HLA ............................................................................................................ 112
9.8. Antigen-presentatie en herkenning door TCR ..................................................................................................... 118
9.9: Waarom is er alloreactiviteit (Tcel) ?.................................................................................................................... 118
9.10: ERFELIJKHEID VAN auto-immuniteit? ................................................................................................................. 119
10. aanmaak en selectie van B en T cellen ...................................................................................................................... 120
10.1. Ontwikkeling van B cellen ................................................................................................................................... 120
10.1.1. Fase 1: samenstellen van het repertoire ................................................................................................. 121
10.1.2. Fase 2: negatieve selectie ........................................................................................................................ 123
10.1.3. Fase 3/4: positieve selectie/recirculatie .................................................................................................. 124
10.1.4. Fase 5: ontmoeten van het antigeen ....................................................................................................... 124
10.1.5. Fase 6: immuniteit ................................................................................................................................... 125
10.2.Ontwikkeling van T cellen .................................................................................................................................... 126
10.2.1. Fase 1: samenstellen van het repertoire ................................................................................................. 127
10.2.2. Fase 2: positieve selectie ......................................................................................................................... 128
10.2.3. Fase 3: negatieve selectie ........................................................................................................................ 129
10.2.4. Fase 4-6: recirculatie, ontmoeten van het antigeen, immuniteit ........................................................... 130
10.3 Intermezzo: HLA polymorfisme ........................................................................................................................... 132
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