Immunologie
Inhoud
Aspecifieke (aangeboren) versus specifieke (verworven) immuniteit ............................ 4
I. Aangeboren immuunrespons.................................................................................. 5
A. Ontstekingsreactie & acute fase respons................................................................ 5
A.1 Ontstekingscytokines ...................................................................................... 8
A.2 Chemokines ................................................................................................. 11
A.3 Vasoactieve molecules .................................................................................. 12
A.3.1 Amines ................................................................................................... 13
A.3.2 Peptiden ................................................................................................. 14
A.3.3 Lipiden ................................................................................................... 15
A.4 Einde van ontstekingsreactie: weefselherstel .................................................. 17
A.4.1 Verandering eigenschappen macrofagen tijdens ontstekingsproces ........... 17
A.4.2 Chronische ontstekingsreactie ................................................................ 17
A.4.3 Acute fase respons ................................................................................. 19
A.4.4 Shock..................................................................................................... 19
B. fagocyten ........................................................................................................... 20
B.1 Macrofagen ................................................................................................... 20
B.1.1 Chemotaxis ............................................................................................ 21
B.1.2 Adhesie .................................................................................................. 21
B.1.3 Opname ................................................................................................. 23
B.1.4 Destructie .............................................................................................. 23
B.1.5 Andere functies....................................................................................... 24
B.2 Neutrofielen.................................................................................................. 25
B.2.1 Chemotaxis ............................................................................................ 25
B.2.2 Adhesie .................................................................................................. 27
B.2.3 Opname & destructie .............................................................................. 28
B.3 Eosinofielen .................................................................................................. 28
B.3.1 Chemotaxis ............................................................................................ 29
B.3.2 Adhesie & opname .................................................................................. 29
B.3.3 Destructie .............................................................................................. 29
B.4 Basofielen .................................................................................................... 29
1
,C. Complement...................................................................................................... 29
C.1 Complementactivatie.................................................................................... 30
C.1.A Klassieke complementactivatie ............................................................... 30
C.1.B Terminale complementactivatie .............................................................. 31
C.1.C MBL complementactivatie ...................................................................... 32
C.1.D Alternatieve complementactivatie ........................................................... 33
C.2 Gevolgen van complementactivatie................................................................ 33
C.2.1 Complement-gemedieerde opsonisatie ................................................... 34
C.2.2 Mediëren ontsteking ............................................................................... 34
C.2.3 Regelen van coagulatiesysteem ............................................................... 35
C.2.4 Erfelijke deficiënties complement ............................................................ 35
C.2.5 Gevolgen van te sterke complement activatie ........................................... 36
C.3 Regulatie van complement activatie ............................................................... 36
C.3.1Overactivatie van complement ................................................................. 38
D. Cytokines .......................................................................................................... 40
D.1 Inleiding ....................................................................................................... 40
D.2 Soorten cytokines ......................................................................................... 41
D.2.1 Interleukines (IL) ..................................................................................... 41
D.2.2 Interferonen (IFN).................................................................................... 41
D.2.3 Cytotoxinen ............................................................................................ 42
D.2.4 Kolonie-stimulerende factoren ................................................................ 43
D.2.5 Transforming growth factor β ................................................................... 43
D.2.6 Chemokines ........................................................................................... 43
D.3 Soorten cytokine-receptoren en signalisatie ................................................... 44
D.3.1 Klasse I cytokinereceptoren (hematopoëtine receptoren) .......................... 45
D.3.2 klasse II cytokine receptoren (interferon receptoren) ................................. 47
D.3.3 TNF-receptor familie .............................................................................. 51
D.3.4 TGFβ receptorfamilie............................................................................... 53
D.3.5 Chemokine receptorfamilie ..................................................................... 54
D.3.6 TLR receptor familie ................................................................................ 54
II. Verworven immuunrespons ................................................................................. 55
A. Lymfocyten ........................................................................................................ 56
B. Antigenen en antigeen presentatie ....................................................................... 60
2
, B.1 Antigenen ..................................................................................................... 60
B.1.1 Soorten .................................................................................................. 60
B.1.2 Epitopen = antigenische determinanten.................................................... 62
B.1.3 Antigeniciteit van een molecule ............................................................... 62
B.1.4 Haptenen ............................................................................................... 65
B.1.5 Kruisreactie ............................................................................................ 65
B.2 Antigeen presentatie...................................................................................... 66
B.2.1 Antigeen-presenterende cellen ................................................................ 66
B.2.2 Presentatie van exogene antigenen........................................................... 70
B.2.3 Presentatie van endogene antigenen ........................................................ 71
C. Major histoncompatibiliteitscomplex ................................................................... 76
C.1 Polygenie en polymorfisme ............................................................................ 77
C.2 MHC klasse I moleculen ................................................................................ 79
C.3 MHC klasse II moleculen ............................................................................... 81
D. T cel receptor (TCR) ............................................................................................ 82
D.1 Inleiding ....................................................................................................... 82
D.2 T cel receptordiversiteit ................................................................................. 84
E. Weefsels van het immuunsysteem ....................................................................... 86
E.1 Bron van cellen van het immuunsysteem: het beenmerg .................................. 86
E.2 Primaire lymfoïde organen ............................................................................. 86
E.2.1 Thymus .................................................................................................. 87
E.2.2 Bursa van Fabricius ................................................................................. 88
E.2.3 Peyerse platen ........................................................................................ 89
E.2.4 Beenmerg ............................................................................................... 89
E.3 Secundaire lymfoïde organen ......................................................................... 89
E.3.1 Lymfeknopen .......................................................................................... 90
E.3.2 Milt ........................................................................................................ 93
E.3.3 Andere secundaire lymfoïde organen ........................................................ 94
F. T lymfocyten populaties ....................................................................................... 95
F.1 CD8+ T lymfocyten (cytotoxische T-cellen, CTLs) en NK cellen .......................... 95
F.2 CD4+ T lymfocyten (helper T cellen, Th cellen) ................................................. 98
F.2.1 Th1-cellen ............................................................................................... 98
F.2.2 Th2-cellen ............................................................................................... 99
3
, F.2.3 Th17 cellen ............................................................................................100
F.2.4 Tfh cellen, folliculaire T cellen ..................................................................100
F.2.5 Treg cellen, regulatorische T cellen ..........................................................101
G. T en B cel activatie .............................................................................................102
G.1 T cel activatie ...............................................................................................102
G.1.1 T cel receptorcomplex ............................................................................102
G.1.2 Signaalcascade van plasmamembraan naar celkern ................................104
G.1.3 Beëindigen van T cel activatie .................................................................106
G.2 B cel activatie ..............................................................................................106
G.3 Inhibitoren van T cel signalisatie → potentiële therapeutische doeleinden .......108
G.3.1 Transplantaties ......................................................................................108
G.3.2 B cel lymfoma’s .....................................................................................109
G.3.3 Mastceltumoren ....................................................................................109
Aspecifieke (aangeboren) versus specifieke
(verworven) immuniteit
Fase van Tijd na infectie Belangrijke Resultaat
immuunrespons stappen/processen
4
Inhoud
Aspecifieke (aangeboren) versus specifieke (verworven) immuniteit ............................ 4
I. Aangeboren immuunrespons.................................................................................. 5
A. Ontstekingsreactie & acute fase respons................................................................ 5
A.1 Ontstekingscytokines ...................................................................................... 8
A.2 Chemokines ................................................................................................. 11
A.3 Vasoactieve molecules .................................................................................. 12
A.3.1 Amines ................................................................................................... 13
A.3.2 Peptiden ................................................................................................. 14
A.3.3 Lipiden ................................................................................................... 15
A.4 Einde van ontstekingsreactie: weefselherstel .................................................. 17
A.4.1 Verandering eigenschappen macrofagen tijdens ontstekingsproces ........... 17
A.4.2 Chronische ontstekingsreactie ................................................................ 17
A.4.3 Acute fase respons ................................................................................. 19
A.4.4 Shock..................................................................................................... 19
B. fagocyten ........................................................................................................... 20
B.1 Macrofagen ................................................................................................... 20
B.1.1 Chemotaxis ............................................................................................ 21
B.1.2 Adhesie .................................................................................................. 21
B.1.3 Opname ................................................................................................. 23
B.1.4 Destructie .............................................................................................. 23
B.1.5 Andere functies....................................................................................... 24
B.2 Neutrofielen.................................................................................................. 25
B.2.1 Chemotaxis ............................................................................................ 25
B.2.2 Adhesie .................................................................................................. 27
B.2.3 Opname & destructie .............................................................................. 28
B.3 Eosinofielen .................................................................................................. 28
B.3.1 Chemotaxis ............................................................................................ 29
B.3.2 Adhesie & opname .................................................................................. 29
B.3.3 Destructie .............................................................................................. 29
B.4 Basofielen .................................................................................................... 29
1
,C. Complement...................................................................................................... 29
C.1 Complementactivatie.................................................................................... 30
C.1.A Klassieke complementactivatie ............................................................... 30
C.1.B Terminale complementactivatie .............................................................. 31
C.1.C MBL complementactivatie ...................................................................... 32
C.1.D Alternatieve complementactivatie ........................................................... 33
C.2 Gevolgen van complementactivatie................................................................ 33
C.2.1 Complement-gemedieerde opsonisatie ................................................... 34
C.2.2 Mediëren ontsteking ............................................................................... 34
C.2.3 Regelen van coagulatiesysteem ............................................................... 35
C.2.4 Erfelijke deficiënties complement ............................................................ 35
C.2.5 Gevolgen van te sterke complement activatie ........................................... 36
C.3 Regulatie van complement activatie ............................................................... 36
C.3.1Overactivatie van complement ................................................................. 38
D. Cytokines .......................................................................................................... 40
D.1 Inleiding ....................................................................................................... 40
D.2 Soorten cytokines ......................................................................................... 41
D.2.1 Interleukines (IL) ..................................................................................... 41
D.2.2 Interferonen (IFN).................................................................................... 41
D.2.3 Cytotoxinen ............................................................................................ 42
D.2.4 Kolonie-stimulerende factoren ................................................................ 43
D.2.5 Transforming growth factor β ................................................................... 43
D.2.6 Chemokines ........................................................................................... 43
D.3 Soorten cytokine-receptoren en signalisatie ................................................... 44
D.3.1 Klasse I cytokinereceptoren (hematopoëtine receptoren) .......................... 45
D.3.2 klasse II cytokine receptoren (interferon receptoren) ................................. 47
D.3.3 TNF-receptor familie .............................................................................. 51
D.3.4 TGFβ receptorfamilie............................................................................... 53
D.3.5 Chemokine receptorfamilie ..................................................................... 54
D.3.6 TLR receptor familie ................................................................................ 54
II. Verworven immuunrespons ................................................................................. 55
A. Lymfocyten ........................................................................................................ 56
B. Antigenen en antigeen presentatie ....................................................................... 60
2
, B.1 Antigenen ..................................................................................................... 60
B.1.1 Soorten .................................................................................................. 60
B.1.2 Epitopen = antigenische determinanten.................................................... 62
B.1.3 Antigeniciteit van een molecule ............................................................... 62
B.1.4 Haptenen ............................................................................................... 65
B.1.5 Kruisreactie ............................................................................................ 65
B.2 Antigeen presentatie...................................................................................... 66
B.2.1 Antigeen-presenterende cellen ................................................................ 66
B.2.2 Presentatie van exogene antigenen........................................................... 70
B.2.3 Presentatie van endogene antigenen ........................................................ 71
C. Major histoncompatibiliteitscomplex ................................................................... 76
C.1 Polygenie en polymorfisme ............................................................................ 77
C.2 MHC klasse I moleculen ................................................................................ 79
C.3 MHC klasse II moleculen ............................................................................... 81
D. T cel receptor (TCR) ............................................................................................ 82
D.1 Inleiding ....................................................................................................... 82
D.2 T cel receptordiversiteit ................................................................................. 84
E. Weefsels van het immuunsysteem ....................................................................... 86
E.1 Bron van cellen van het immuunsysteem: het beenmerg .................................. 86
E.2 Primaire lymfoïde organen ............................................................................. 86
E.2.1 Thymus .................................................................................................. 87
E.2.2 Bursa van Fabricius ................................................................................. 88
E.2.3 Peyerse platen ........................................................................................ 89
E.2.4 Beenmerg ............................................................................................... 89
E.3 Secundaire lymfoïde organen ......................................................................... 89
E.3.1 Lymfeknopen .......................................................................................... 90
E.3.2 Milt ........................................................................................................ 93
E.3.3 Andere secundaire lymfoïde organen ........................................................ 94
F. T lymfocyten populaties ....................................................................................... 95
F.1 CD8+ T lymfocyten (cytotoxische T-cellen, CTLs) en NK cellen .......................... 95
F.2 CD4+ T lymfocyten (helper T cellen, Th cellen) ................................................. 98
F.2.1 Th1-cellen ............................................................................................... 98
F.2.2 Th2-cellen ............................................................................................... 99
3
, F.2.3 Th17 cellen ............................................................................................100
F.2.4 Tfh cellen, folliculaire T cellen ..................................................................100
F.2.5 Treg cellen, regulatorische T cellen ..........................................................101
G. T en B cel activatie .............................................................................................102
G.1 T cel activatie ...............................................................................................102
G.1.1 T cel receptorcomplex ............................................................................102
G.1.2 Signaalcascade van plasmamembraan naar celkern ................................104
G.1.3 Beëindigen van T cel activatie .................................................................106
G.2 B cel activatie ..............................................................................................106
G.3 Inhibitoren van T cel signalisatie → potentiële therapeutische doeleinden .......108
G.3.1 Transplantaties ......................................................................................108
G.3.2 B cel lymfoma’s .....................................................................................109
G.3.3 Mastceltumoren ....................................................................................109
Aspecifieke (aangeboren) versus specifieke
(verworven) immuniteit
Fase van Tijd na infectie Belangrijke Resultaat
immuunrespons stappen/processen
4
