PCB 3233 EXAM 4 STUDY GUIDE
Where0does0T-cell0maturation0take0place?0What0are0thymocytes?0-0T-
cell0maturation0takes0place0in0the0thymus.0Thymocytes0are0immature0T0cells0embedde
d0in0epithelia0cell0network0(thymic0stroma)
Be0able0to0understand0some0similarities0and0differences0between0B0cell0and0T0cell0de
velopment.
a.0Examples:0Where0do0they0derive?
0What0cellular0mechanisms0or0processes0are0shared0between0the0two?
0What0comprises0their0cell0lineages?0-0Both0B-cells0and0T-
cells0derive0from0the0bone0marrow0stem0cells0but0the0T-
cell0moves0to0the0thymus0to0mature0while0the0B-
cell0stays0in0the0bone0marrow.0Both0undergo0gene0rearrangement0which0produces0ant
igen0receptors.0T0cells0have0two0lineages.
Regarding0the0initial0stages0of0T-
cell0maturation,0explain0the0direction0of0its0migration0using0"subcapsular0region",0"med
ulla",0and0"cortex"0as0references0in0your0description.0Where0would0you0expect0to0find0
macrophages?0What0about0dendritic0cells?0-0As0the0T-
cell0matures,0it0migrates0from0the0subcapsular0region0of0the0thymus0to0the0inner0corte
x0and0to0the0medulla.0Macrophages0are0found0in0both0the0cortex0and0the0medulla.0De
ndritic0cells0are0found0in0the0medulla.
In0the0thymus,0what0is0the0role0of0macrophages?
0Where0are0Hassal's0corpuscles0found?0-
0Macrophages0remove0the0thymocytes0that0do0not0mature0properly.0Hassal's0corpuscl
es0is0found0in0the0medulla0of0the0thymus0and0it0induces0the0development0of0regulatory
0T0cells.
Evident0from0patient's0who0demonstrate0DiGeorge's0syndrome,0the0development0of0a0f
unctional0T-
cell0repertoire0is0crucial0to0an0individual's0health.0What0causes0DiGeorge's0syndrome?
0Know0the0chromosome0affected.0Identify0what0is0NOT0being0produced0in0this0clinical0
condition,0and0what0further0consequences0are0associated?
0Can0DiGeorge's0syndrome0be0cured?0-
0DiGeorge's0syndrome0is0caused0by0a0deletion0in0chromosome0220where0the0thymus0f
ails0to0develop0and0T0cells0are0absent.0The0lack0of0T0cells0and0thymus0increases0susc
eptibility0to0a0wide0range0of0opportunistic0infections0and0it0resembles0SCID0(severe0co
mbined0immunodeficiency0disease).0Cannot0be0cured.
, The0thymus0is0considered0to0be0completely0developed0before0birth.0However,0its0deter
ioration0results0with0natural0aging,0indicating0that0the0younger0you0are,0the0more0activ
e0it0is.0Knowing0this,0would0you0expect0T-cell0immunity0to0become0defective0overtime?
0Why0or0why0not?
0What0about0in0the0case0of0a0thymectomy0(removal0of0thymus);0would0you0expect0imp
airment0then?0-0T-
cell0immunity0does0not0become0defective0over0age.0The0thymus0just0does0not0develop
0as0many0T-cells0over0time.0T-cells0stay0in0circulation0for0several0years.0T-
cells0do0not0become0defective0even0after0a0thymectomy.
How0does0the0life0of0a0T0cell0differ0from0that0of0a0B0cell?
0Which0lives0longer0and0why0do0you0think0that0is?
0(Hint:0understand0what0"self0renewing"0means0in0this0context)0-0T0cells0are0long-
lived0and0self-
renewing.0T0cells0are0in0circulation0in0the0blood0stream0for0several0months.0Self-
renewing0cells0divide0to0maintain0the0amount0of0cells.
Double-Negative0(DN)0thymocytes0vs.0Double-Positive0(DP)0thymocytes:
a.0When/why0are0they0called0DN0thymocytes?
i)0What0cell-surface0proteins0are0expressed?0Which0are0NOT0being0expressed?
ii)0What0is0the0importance0of0Notch010for0these0thymocytes?
b.0When/why0are0they0called0DP0thymocytes?
i)0What0cell-surface0proteins0are0being0expressed0at0this0point?0-
0a.0T0cells0that0express0the0αβ0TCR0but0do0not0express0CD4/CD8/
NK0cell0markers.0This0happens0when0the0progenitor0T0cell0expresses0T-
cell0specific0adhesion0molecule0CD20and0other0molecules0but0not0TCR0complex.
i)0CD20and0CD50are0expressed.0CD40and0CD80are0not0expressed.
ii)0Notch010keeps0the0T-cell0on0the0T-cell0path.
b.0T0cells0that0express0both0CD40and0CD8.
i)0CD2,0CD5,0CD4,0and0CD80are0being0expressed.
The0two0T-cell0lineages:0a:B0and0y:S
a.0which0is0considered0to0be0the0majority?0Which0is0the0minority?
b.0do0the0two0lineages0derive0from0common0DN0or0DP0thymocyte0precusor?0
c.0Which0loci0(a,0B,y,S)0begin0their0rearrangment0roughly0at0the0same0time?
0i.0Understand0"competition"0that's0observed0at0this0point,0and0what0will0be0produced0
as0an0outcome.0(Hint:0depends0on0what0T-
cell0lineage0is0made;0think0about0what0the0result0would0be0if0B0chain0was0made0befor
e0yS0what0is0the0more0frequent0outcome?)0-
0a.0α:β0is0the0majority0and0γ:δ0is0the0minority.
b.0Both0α:β0and0γ:δ0derive0from0double0negative0thymocyte0precursor.
c.0α,0γ,0and0δ0rearrange0at0about0the0same0time.
i)0"Competition"0means0that0depending0on0which0loci0begins0their0rearrangement0first,0
a0particular0lineage0will0arise.
Where0does0T-cell0maturation0take0place?0What0are0thymocytes?0-0T-
cell0maturation0takes0place0in0the0thymus.0Thymocytes0are0immature0T0cells0embedde
d0in0epithelia0cell0network0(thymic0stroma)
Be0able0to0understand0some0similarities0and0differences0between0B0cell0and0T0cell0de
velopment.
a.0Examples:0Where0do0they0derive?
0What0cellular0mechanisms0or0processes0are0shared0between0the0two?
0What0comprises0their0cell0lineages?0-0Both0B-cells0and0T-
cells0derive0from0the0bone0marrow0stem0cells0but0the0T-
cell0moves0to0the0thymus0to0mature0while0the0B-
cell0stays0in0the0bone0marrow.0Both0undergo0gene0rearrangement0which0produces0ant
igen0receptors.0T0cells0have0two0lineages.
Regarding0the0initial0stages0of0T-
cell0maturation,0explain0the0direction0of0its0migration0using0"subcapsular0region",0"med
ulla",0and0"cortex"0as0references0in0your0description.0Where0would0you0expect0to0find0
macrophages?0What0about0dendritic0cells?0-0As0the0T-
cell0matures,0it0migrates0from0the0subcapsular0region0of0the0thymus0to0the0inner0corte
x0and0to0the0medulla.0Macrophages0are0found0in0both0the0cortex0and0the0medulla.0De
ndritic0cells0are0found0in0the0medulla.
In0the0thymus,0what0is0the0role0of0macrophages?
0Where0are0Hassal's0corpuscles0found?0-
0Macrophages0remove0the0thymocytes0that0do0not0mature0properly.0Hassal's0corpuscl
es0is0found0in0the0medulla0of0the0thymus0and0it0induces0the0development0of0regulatory
0T0cells.
Evident0from0patient's0who0demonstrate0DiGeorge's0syndrome,0the0development0of0a0f
unctional0T-
cell0repertoire0is0crucial0to0an0individual's0health.0What0causes0DiGeorge's0syndrome?
0Know0the0chromosome0affected.0Identify0what0is0NOT0being0produced0in0this0clinical0
condition,0and0what0further0consequences0are0associated?
0Can0DiGeorge's0syndrome0be0cured?0-
0DiGeorge's0syndrome0is0caused0by0a0deletion0in0chromosome0220where0the0thymus0f
ails0to0develop0and0T0cells0are0absent.0The0lack0of0T0cells0and0thymus0increases0susc
eptibility0to0a0wide0range0of0opportunistic0infections0and0it0resembles0SCID0(severe0co
mbined0immunodeficiency0disease).0Cannot0be0cured.
, The0thymus0is0considered0to0be0completely0developed0before0birth.0However,0its0deter
ioration0results0with0natural0aging,0indicating0that0the0younger0you0are,0the0more0activ
e0it0is.0Knowing0this,0would0you0expect0T-cell0immunity0to0become0defective0overtime?
0Why0or0why0not?
0What0about0in0the0case0of0a0thymectomy0(removal0of0thymus);0would0you0expect0imp
airment0then?0-0T-
cell0immunity0does0not0become0defective0over0age.0The0thymus0just0does0not0develop
0as0many0T-cells0over0time.0T-cells0stay0in0circulation0for0several0years.0T-
cells0do0not0become0defective0even0after0a0thymectomy.
How0does0the0life0of0a0T0cell0differ0from0that0of0a0B0cell?
0Which0lives0longer0and0why0do0you0think0that0is?
0(Hint:0understand0what0"self0renewing"0means0in0this0context)0-0T0cells0are0long-
lived0and0self-
renewing.0T0cells0are0in0circulation0in0the0blood0stream0for0several0months.0Self-
renewing0cells0divide0to0maintain0the0amount0of0cells.
Double-Negative0(DN)0thymocytes0vs.0Double-Positive0(DP)0thymocytes:
a.0When/why0are0they0called0DN0thymocytes?
i)0What0cell-surface0proteins0are0expressed?0Which0are0NOT0being0expressed?
ii)0What0is0the0importance0of0Notch010for0these0thymocytes?
b.0When/why0are0they0called0DP0thymocytes?
i)0What0cell-surface0proteins0are0being0expressed0at0this0point?0-
0a.0T0cells0that0express0the0αβ0TCR0but0do0not0express0CD4/CD8/
NK0cell0markers.0This0happens0when0the0progenitor0T0cell0expresses0T-
cell0specific0adhesion0molecule0CD20and0other0molecules0but0not0TCR0complex.
i)0CD20and0CD50are0expressed.0CD40and0CD80are0not0expressed.
ii)0Notch010keeps0the0T-cell0on0the0T-cell0path.
b.0T0cells0that0express0both0CD40and0CD8.
i)0CD2,0CD5,0CD4,0and0CD80are0being0expressed.
The0two0T-cell0lineages:0a:B0and0y:S
a.0which0is0considered0to0be0the0majority?0Which0is0the0minority?
b.0do0the0two0lineages0derive0from0common0DN0or0DP0thymocyte0precusor?0
c.0Which0loci0(a,0B,y,S)0begin0their0rearrangment0roughly0at0the0same0time?
0i.0Understand0"competition"0that's0observed0at0this0point,0and0what0will0be0produced0
as0an0outcome.0(Hint:0depends0on0what0T-
cell0lineage0is0made;0think0about0what0the0result0would0be0if0B0chain0was0made0befor
e0yS0what0is0the0more0frequent0outcome?)0-
0a.0α:β0is0the0majority0and0γ:δ0is0the0minority.
b.0Both0α:β0and0γ:δ0derive0from0double0negative0thymocyte0precursor.
c.0α,0γ,0and0δ0rearrange0at0about0the0same0time.
i)0"Competition"0means0that0depending0on0which0loci0begins0their0rearrangement0first,0
a0particular0lineage0will0arise.
