MICROBIOLOGIE
Inhoud
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
4
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller Studentjegeneeskunde. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $12.35. You're not tied to anything after your purchase.