Immunologie I DEEL 1
1
,INHOUDSOPGAVE
1 INLEIDING ...................................................................................................................................................... 5
1.1 DEF ................................................................................................................................................................. 5
1.2 HISTORIEK ........................................................................................................................................................ 5
1.3 VACCINATIE ...................................................................................................................................................... 5
2 PATHOGENESE............................................................................................................................................... 6
2.1 ALGEMENE BEGRIPPEN ........................................................................................................................................ 6
2.2 INFECTIEPROCESSEN ........................................................................................................................................... 6
3 VERDEDIGINGSMECHANISMEN ..................................................................................................................... 7
3.1 NATUURLIJKE BARRIÈRES ..................................................................................................................................... 7
3.2 AANGEBOREN EN VERWORVEN IMMUUNSYSTEEM .................................................................................................... 7
3.2.1 Aangeboren immuunstysteem .............................................................................................................. 8
3.2.1.1 cellen van het aangeboren immuunsysteem ................................................................................................... 8
3.2.1.2 Antimicrobiële eiwitten ................................................................................................................................. 10
3.2.1.3 Herkenning patronen op micro-organismen.................................................................................................. 10
3.2.2 Ontsteking ........................................................................................................................................... 11
3.2.2.1 Acute ontstekingsreactie ............................................................................................................................... 11
3.2.2.2 Chemische mediatoren .................................................................................................................................. 11
3.2.2.3 Acute fase reactie .......................................................................................................................................... 12
3.2.2.4 Chronische ontsteking ................................................................................................................................... 13
3.2.2.5 Ontstekingsreactie is betrokken bij vele vormen van afweer ........................................................................ 13
3.2.3 Verworven immuunsysteem ................................................................................................................ 13
3.2.3.1 Begrippen ....................................................................................................................................................... 13
3.2.3.2 Informatiebronnen ........................................................................................................................................ 14
3.3 SAMENVATTING VERWORVEN IMMUUNSYSTEEM: ................................................................................................... 17
4 CELLEN VAN HET VERWORVEN IMMUUNSYSTEEM...................................................................................... 18
4.1 SOORTEN ....................................................................................................................................................... 18
4.1.1 Lymfocyten .......................................................................................................................................... 18
4.1.2 Fagocyten ............................................................................................................................................ 18
4.1.2 Andere ................................................................................................................................................. 18
4.2 LYMFOCYTEN IN DETAIL ..................................................................................................................................... 19
4.3 ONTWIKKELING VAN DIVERSITIET ......................................................................................................................... 21
4.4 ONTSTAAN VAN LYMFOCYTEN............................................................................................................................. 24
4.5 DIFFERENTIATIE VAN DE B-LYMFOCYTEN IN HET BEENMERG ...................................................................................... 26
4.6 DIFFERENTIATIE VAN T-LYMFOCYTEN IN DE THYMUS................................................................................................ 28
4.7 SAMENVATTING CELLEN VAN HET VERWORVEN IMMUUNSYSTEEM.............................................................................. 30
5 MAJOR HISTOCOMPATIBILITY COMPLEX ..................................................................................................... 32
5.1 MHC-KLASSA-I-MOLECULEN .............................................................................................................................. 32
5.2 MHC-KLASSE-II-MOLECULEN ............................................................................................................................. 33
5.3 POLYMORFISME – CO-DOMINANTIE .................................................................................................................... 34
5.4 FUNCTIES MHC-MOLECULEN ............................................................................................................................. 34
5.5 SAMENVATTING MAJOR HISTOCOMPATIBILITY COMPLEX .......................................................................................... 36
6. CELLULAIRE IMMUNITEIT ........................................................................................................................... 37
6.1 T-CELRECEPTOREN ........................................................................................................................................... 37
6.1.1 Cytotoxische T-cellen (Tc of CTL) ......................................................................................................... 37
6.1.2 T-helper cellen (Th cellen) .................................................................................................................... 37
6.2 CELLULAIRE IMMUUNRESPONS............................................................................................................................ 38
6.2.1 CD4+ Th-lymfocyten oefenen functie uit d.m.v. cytokinen .................................................................. 41
6.2.2 CD8+ cytotoxische T-lymfocyten .......................................................................................................... 43
6.2.3 CTL belangrijk voor afweer tegen tumorcellen .................................................................................... 44
6.2.4 Cellen verantwoordelijk voor cellulair immunologisch geheugen: centrale en effectorgeheugencellen
...................................................................................................................................................................... 45
2
, 6.2.5 Verschillende mechanismen regelen duur en omvang cellulaire respons ........................................... 45
6.3 SAMENVATTING CELLULAIRE IMMUNITEIT.............................................................................................................. 45
7. HUMORALE IMMUNITEIT ........................................................................................................................... 47
7.1 ANTILICHAMEN (AL)......................................................................................................................................... 47
7.2 INDELING........................................................................................................................................................ 47
7.3 HUMORALE IMMUUNRESPONS ........................................................................................................................... 48
7.3.1 Affiniteit en aviditeit --> bepalen sterkte interactie tussen AG en AL .................................................. 48
7.3.2 Volledige activatie en differentiatie rijpe B-lymfocyten vereist twee signalen .................................... 49
7.2.3 Activatie van B-lymfocyten door koolhydraten ................................................................................... 51
7.2.4 Transcriptiefactoren bepalen of geactiveerde B-lymfocyten uitrijpen tot plasmacellen of
differentiëren tot geheugenlymfocyten ........................................................................................................ 51
7.2.5 Affiniteitsrijping tijdens humorale immuunrespons ............................................................................ 51
7.2.5.1 Dimere en polymere AL ................................................................................................................................. 52
7.2.5.2 Isotype switching ........................................................................................................................................... 52
7.2.6 Activatie B-lymfocyten door AG-specifieke CD4+ effector-Th-lymfocyten in secundair lymfoïde
organen ........................................................................................................................................................ 53
7.4 VERDELING EN FUNCTIE VAN IMMUNOGLOBULINEN IN HET LICHAAM .......................................................................... 53
7.4.1 IgM ...................................................................................................................................................... 54
7.4.2 IgG ....................................................................................................................................................... 55
7.4.3 IgA ....................................................................................................................................................... 55
7.4.4 IgD ....................................................................................................................................................... 55
7.4.5 IgE ........................................................................................................................................................ 55
7.5 PRIMAIRE EN SECUNDAIRE HUMORALE IMMUUNRESPONS ........................................................................................ 56
7.6 REGULATIE VAN DE HUMORALE IMMUUNRESPONS .................................................................................................. 57
7.7 FUNCTIES VAN DE B-LYMFOCYT ........................................................................................................................... 58
7.8 SAMENVATTING HUMORALE IMMUNITEIT ............................................................................................................. 58
8 HET COMPLEMENTSYSTEEM ........................................................................................................................ 60
8.2 KLASSIEKE ACTIVERINGSROUTE ............................................................................................................................ 60
8.3 MANNOSEBINDEND-LECTINEROUTE ..................................................................................................................... 61
8.4 ALTERNATIEVE ROUTE ....................................................................................................................................... 61
8.5 ACTIVATIE VAN COMPLEMENTFACTOR C3 ............................................................................................................. 62
8.6 COMPLEMENT STIMULEERT ONTSTEKINGSREACTIE ................................................................................................... 62
8.7 SAMENVATTING COMPLEMENTSYSTEEM................................................................................................................ 63
9 CYTOKINEN .................................................................................................................................................. 64
9.1 TUMORNECROSEFACTOR-Α (TNF-Α ) EN INTERLEUKINE-1 (IL-1) ............................................................................... 64
9.3 INTERLEUKINE-2 (IL-2) ..................................................................................................................................... 65
9.4 INTERLEUKINE-3 (IL-3) ..................................................................................................................................... 65
9.5 INTERLEUKINE-4 (IL-4) EN INTERLEUKINE-5 (IL-5) ................................................................................................. 65
9.6 INTERLEUKINE-6 (IL-6) ..................................................................................................................................... 65
9.7 INTERLEUKINE-12 (IL-12) ................................................................................................................................. 65
9.8 INTERLEUKINE-15 (IL-15) ................................................................................................................................. 65
9.10 CHEMOKINEN CXCL8 (IL-8) EN CCL2 (MCP-1) ................................................................................................. 65
9.11 INTERFERON (IFN) ......................................................................................................................................... 66
10 MONOKLONALE ANTILICHAMEN ............................................................................................................... 67
10.1 PRODUCTIE MONOKLONALE ANTILICHAMEN TEGEN BEPAALD AG ............................................................................. 67
10.2 SOORTEN MONOKLONALE AL ........................................................................................................................... 68
11 INFECTIES EN INFECTIEZIEKTEN.................................................................................................................. 69
11.1 AFWEER TEGEN EXTRACELLULAIRE BACTERIËN ...................................................................................................... 69
11.2 AFWEER TEGEN INTRACELLULAIRE BACTERIËN ...................................................................................................... 70
11.3 AFWEER TEGEN INTRACELLULAIRE VIRUSSEN ........................................................................................................ 70
11.4 AFWEER TEGEN SCHIMMELS ............................................................................................................................. 71
11.5 PARASIETEN .................................................................................................................................................. 72
3
, 11.6 MICRO-ORGANISMEN EN PARASIETEN ONTSNAPPEN AAN HET I.S. (= EVASIE) ............................................................. 73
11.6.1 Evasie door AG variatie (verandering van AG opmaak) .................................................................... 73
11.6.2 M.o. produceren eiwitten die antilichamen kunnen afbreken of inactiveren .................................... 75
11.6.3 Bacteriën en virussen produceren eiwitten die complement-activatie remmen ............................... 75
11.6.4 Interferentie met antigeenpresentatie maakt virussen onzichtbaar voor herkenning door T-
lymfocyten .................................................................................................................................................... 75
11.6.5 Virale homologen van cytokinen en cytokinereceptoren en andere eiwitten onderdrukken de
antivirale immuniteit .................................................................................................................................... 76
4
1
,INHOUDSOPGAVE
1 INLEIDING ...................................................................................................................................................... 5
1.1 DEF ................................................................................................................................................................. 5
1.2 HISTORIEK ........................................................................................................................................................ 5
1.3 VACCINATIE ...................................................................................................................................................... 5
2 PATHOGENESE............................................................................................................................................... 6
2.1 ALGEMENE BEGRIPPEN ........................................................................................................................................ 6
2.2 INFECTIEPROCESSEN ........................................................................................................................................... 6
3 VERDEDIGINGSMECHANISMEN ..................................................................................................................... 7
3.1 NATUURLIJKE BARRIÈRES ..................................................................................................................................... 7
3.2 AANGEBOREN EN VERWORVEN IMMUUNSYSTEEM .................................................................................................... 7
3.2.1 Aangeboren immuunstysteem .............................................................................................................. 8
3.2.1.1 cellen van het aangeboren immuunsysteem ................................................................................................... 8
3.2.1.2 Antimicrobiële eiwitten ................................................................................................................................. 10
3.2.1.3 Herkenning patronen op micro-organismen.................................................................................................. 10
3.2.2 Ontsteking ........................................................................................................................................... 11
3.2.2.1 Acute ontstekingsreactie ............................................................................................................................... 11
3.2.2.2 Chemische mediatoren .................................................................................................................................. 11
3.2.2.3 Acute fase reactie .......................................................................................................................................... 12
3.2.2.4 Chronische ontsteking ................................................................................................................................... 13
3.2.2.5 Ontstekingsreactie is betrokken bij vele vormen van afweer ........................................................................ 13
3.2.3 Verworven immuunsysteem ................................................................................................................ 13
3.2.3.1 Begrippen ....................................................................................................................................................... 13
3.2.3.2 Informatiebronnen ........................................................................................................................................ 14
3.3 SAMENVATTING VERWORVEN IMMUUNSYSTEEM: ................................................................................................... 17
4 CELLEN VAN HET VERWORVEN IMMUUNSYSTEEM...................................................................................... 18
4.1 SOORTEN ....................................................................................................................................................... 18
4.1.1 Lymfocyten .......................................................................................................................................... 18
4.1.2 Fagocyten ............................................................................................................................................ 18
4.1.2 Andere ................................................................................................................................................. 18
4.2 LYMFOCYTEN IN DETAIL ..................................................................................................................................... 19
4.3 ONTWIKKELING VAN DIVERSITIET ......................................................................................................................... 21
4.4 ONTSTAAN VAN LYMFOCYTEN............................................................................................................................. 24
4.5 DIFFERENTIATIE VAN DE B-LYMFOCYTEN IN HET BEENMERG ...................................................................................... 26
4.6 DIFFERENTIATIE VAN T-LYMFOCYTEN IN DE THYMUS................................................................................................ 28
4.7 SAMENVATTING CELLEN VAN HET VERWORVEN IMMUUNSYSTEEM.............................................................................. 30
5 MAJOR HISTOCOMPATIBILITY COMPLEX ..................................................................................................... 32
5.1 MHC-KLASSA-I-MOLECULEN .............................................................................................................................. 32
5.2 MHC-KLASSE-II-MOLECULEN ............................................................................................................................. 33
5.3 POLYMORFISME – CO-DOMINANTIE .................................................................................................................... 34
5.4 FUNCTIES MHC-MOLECULEN ............................................................................................................................. 34
5.5 SAMENVATTING MAJOR HISTOCOMPATIBILITY COMPLEX .......................................................................................... 36
6. CELLULAIRE IMMUNITEIT ........................................................................................................................... 37
6.1 T-CELRECEPTOREN ........................................................................................................................................... 37
6.1.1 Cytotoxische T-cellen (Tc of CTL) ......................................................................................................... 37
6.1.2 T-helper cellen (Th cellen) .................................................................................................................... 37
6.2 CELLULAIRE IMMUUNRESPONS............................................................................................................................ 38
6.2.1 CD4+ Th-lymfocyten oefenen functie uit d.m.v. cytokinen .................................................................. 41
6.2.2 CD8+ cytotoxische T-lymfocyten .......................................................................................................... 43
6.2.3 CTL belangrijk voor afweer tegen tumorcellen .................................................................................... 44
6.2.4 Cellen verantwoordelijk voor cellulair immunologisch geheugen: centrale en effectorgeheugencellen
...................................................................................................................................................................... 45
2
, 6.2.5 Verschillende mechanismen regelen duur en omvang cellulaire respons ........................................... 45
6.3 SAMENVATTING CELLULAIRE IMMUNITEIT.............................................................................................................. 45
7. HUMORALE IMMUNITEIT ........................................................................................................................... 47
7.1 ANTILICHAMEN (AL)......................................................................................................................................... 47
7.2 INDELING........................................................................................................................................................ 47
7.3 HUMORALE IMMUUNRESPONS ........................................................................................................................... 48
7.3.1 Affiniteit en aviditeit --> bepalen sterkte interactie tussen AG en AL .................................................. 48
7.3.2 Volledige activatie en differentiatie rijpe B-lymfocyten vereist twee signalen .................................... 49
7.2.3 Activatie van B-lymfocyten door koolhydraten ................................................................................... 51
7.2.4 Transcriptiefactoren bepalen of geactiveerde B-lymfocyten uitrijpen tot plasmacellen of
differentiëren tot geheugenlymfocyten ........................................................................................................ 51
7.2.5 Affiniteitsrijping tijdens humorale immuunrespons ............................................................................ 51
7.2.5.1 Dimere en polymere AL ................................................................................................................................. 52
7.2.5.2 Isotype switching ........................................................................................................................................... 52
7.2.6 Activatie B-lymfocyten door AG-specifieke CD4+ effector-Th-lymfocyten in secundair lymfoïde
organen ........................................................................................................................................................ 53
7.4 VERDELING EN FUNCTIE VAN IMMUNOGLOBULINEN IN HET LICHAAM .......................................................................... 53
7.4.1 IgM ...................................................................................................................................................... 54
7.4.2 IgG ....................................................................................................................................................... 55
7.4.3 IgA ....................................................................................................................................................... 55
7.4.4 IgD ....................................................................................................................................................... 55
7.4.5 IgE ........................................................................................................................................................ 55
7.5 PRIMAIRE EN SECUNDAIRE HUMORALE IMMUUNRESPONS ........................................................................................ 56
7.6 REGULATIE VAN DE HUMORALE IMMUUNRESPONS .................................................................................................. 57
7.7 FUNCTIES VAN DE B-LYMFOCYT ........................................................................................................................... 58
7.8 SAMENVATTING HUMORALE IMMUNITEIT ............................................................................................................. 58
8 HET COMPLEMENTSYSTEEM ........................................................................................................................ 60
8.2 KLASSIEKE ACTIVERINGSROUTE ............................................................................................................................ 60
8.3 MANNOSEBINDEND-LECTINEROUTE ..................................................................................................................... 61
8.4 ALTERNATIEVE ROUTE ....................................................................................................................................... 61
8.5 ACTIVATIE VAN COMPLEMENTFACTOR C3 ............................................................................................................. 62
8.6 COMPLEMENT STIMULEERT ONTSTEKINGSREACTIE ................................................................................................... 62
8.7 SAMENVATTING COMPLEMENTSYSTEEM................................................................................................................ 63
9 CYTOKINEN .................................................................................................................................................. 64
9.1 TUMORNECROSEFACTOR-Α (TNF-Α ) EN INTERLEUKINE-1 (IL-1) ............................................................................... 64
9.3 INTERLEUKINE-2 (IL-2) ..................................................................................................................................... 65
9.4 INTERLEUKINE-3 (IL-3) ..................................................................................................................................... 65
9.5 INTERLEUKINE-4 (IL-4) EN INTERLEUKINE-5 (IL-5) ................................................................................................. 65
9.6 INTERLEUKINE-6 (IL-6) ..................................................................................................................................... 65
9.7 INTERLEUKINE-12 (IL-12) ................................................................................................................................. 65
9.8 INTERLEUKINE-15 (IL-15) ................................................................................................................................. 65
9.10 CHEMOKINEN CXCL8 (IL-8) EN CCL2 (MCP-1) ................................................................................................. 65
9.11 INTERFERON (IFN) ......................................................................................................................................... 66
10 MONOKLONALE ANTILICHAMEN ............................................................................................................... 67
10.1 PRODUCTIE MONOKLONALE ANTILICHAMEN TEGEN BEPAALD AG ............................................................................. 67
10.2 SOORTEN MONOKLONALE AL ........................................................................................................................... 68
11 INFECTIES EN INFECTIEZIEKTEN.................................................................................................................. 69
11.1 AFWEER TEGEN EXTRACELLULAIRE BACTERIËN ...................................................................................................... 69
11.2 AFWEER TEGEN INTRACELLULAIRE BACTERIËN ...................................................................................................... 70
11.3 AFWEER TEGEN INTRACELLULAIRE VIRUSSEN ........................................................................................................ 70
11.4 AFWEER TEGEN SCHIMMELS ............................................................................................................................. 71
11.5 PARASIETEN .................................................................................................................................................. 72
3
, 11.6 MICRO-ORGANISMEN EN PARASIETEN ONTSNAPPEN AAN HET I.S. (= EVASIE) ............................................................. 73
11.6.1 Evasie door AG variatie (verandering van AG opmaak) .................................................................... 73
11.6.2 M.o. produceren eiwitten die antilichamen kunnen afbreken of inactiveren .................................... 75
11.6.3 Bacteriën en virussen produceren eiwitten die complement-activatie remmen ............................... 75
11.6.4 Interferentie met antigeenpresentatie maakt virussen onzichtbaar voor herkenning door T-
lymfocyten .................................................................................................................................................... 75
11.6.5 Virale homologen van cytokinen en cytokinereceptoren en andere eiwitten onderdrukken de
antivirale immuniteit .................................................................................................................................... 76
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