Lecture

 16  –  Review  Questions  

 
Slide  3:  
1. What  accounts  for  the  fact  that  different  people  are  susceptible  to  different  
diseases?  
Differences  in  the  capacity  to  generate  different  cytokines  including  IL-­‐4  

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2. What  type  of  cytokine  mutations  result  in  susceptibility  to  infections  that  
would  normally  be  killed?  

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3. Decreased  TH1  cytokines  (IFN  gamma  and  IL-­‐12)  or  increased  TH2  or  TH17  
cytokines  result  in  susceptibility  to  infection  by  pathogens  normally  killed  by  

o.
macrophages  
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Slide  4:  
1. Formalin  fixed  vaccines  primarily  give    TH2  cytokines,  and  skewing  of    CD4  T  
cell  responses  away  from  production  of  protective  _TH1  cytokines.  
o

 
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Slide  6:  (will  cover  later)  

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Slide  7:  
1. Describe  how  different  pathogenic  infections  can  lead  to  different  Th  
responses.  
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2. Name  one  cytokine  that  DCs  release  in  response  to  an  intracellular  infection?    
IFN  gamma  

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 3. Which  type  of  response  (Th1  or  Th2)  does  this  elicit?  
TH1  
4. Name  one  cytokine  that  DCs  release  in  response  to  an  extracellular  infection?  
Histamine  
5. Which  type  of  response  (Th1  or  Th2)  does  this  elicit?  
TH2  
Slide  8:  
1. Which  type(s)  of  DCs  can  activate  naïve  CD4  T  cells  (LN  resident  or  
migratory)?  
Both  
Migratory  DC  pick  up  Ag  in  periphery  and  migrate  to  LN,  LN  resident  DC  pick  
up  Ag  from  FDC  
Slide  9:  
1. What  are  the  two  models  for  DC  maturation  (i.e.  how  are  they  different)?    
(hint:  think  about  the  immature  DC,  does  it  require  a  specific  antigen  to  
become  a  specific  Th  stimulator?)  

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  Model  1:  immature  DC  can  become  TH  1  or  TH2  stimulation  DC  cells  

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Model  2:  immature  DC  are  already  committed  to  becoming  mature  TH1  or  

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TH2  stimulating  DC  cells  
Slide  10:  

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1. Which  type(s)  of  response  (Th1  or  Th2)  do  CD8α+  cells  elicit?  CD8α-­‐  cells?  
ou urc
TH1  TH2  
2. Once  a  CD4  (Th)  cell  has  differentiated,  how  does  it  act  on  future  CD4  cells  in  
terms  of  their  differentiation?  
o

Cytokines  produced  by  T  cells  block  differentiation  into  alternative  TH  cell  
Slide  11:  
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1. Which  is  a  stronger  influencer  of  Th  differentiation:  Cytokines  or  

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Costimulatory  molecules?  
Different  types  of  ac#vated  DC  express  different  costimulatory  proteins  
 
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BUT  -­‐  costimulation  skewing  of  CD4  responses  is  less  absolute  than  cytokines  –  
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balance  between  different  costimulatory  signals  results  in  biased  production  of  
different  cytokines  and  skewing  to  different  TH  responses  
 
Slide  12:    
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1. Fill  in  the  following  table  outlining  CD4  T  cell  differentiation  including  which  
Th

cytokine  induces  which  transcription  factors,  which  cell  type  results,  and  
what  cytokines  that  cell  type  releases:  
Cytokine  from  DC   Transcription   Type  of  CD4  T  cell   Cytokine(s)  
factor   produced  
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IL-­‐12   T-­‐bet   TH1   IFN  gamma  

IL-­‐4   GaTA3   TH2   IL-­‐4,  IL-­‐5,  IL-­‐13  
IL-­‐6  IL-­‐23   RoR  gamma  t   TH17   IL-­‐17A,  IL-­‐17F,IL-­‐6  
IL-­‐6   MAF,  FOXP3-­‐   TFH   IL-­‐21  
TGF  Beta   FOXP3-­‐   TReg   TGF  beta  

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Slide  13:  
1. Describe  the  function(s)  of  the  following  types  of  CD4  T  cells:  
a. Th1:  
IFN  gamma,  macrophage,  intracellular  bacteria,  dead  intracellular  
bacteria  
b. Th2:  
IL-­‐4,  IL-­‐5,  IL-­‐13,  eosinophil,  mast  cell,  plasma  cell  
c. Th17:  
IL-­‐17,  fibroblasts,  epithelial  cells,  chemokines,  neutrophils  
d. Tfh:  
B  cell,  IgM,  IgG,  B  cells,  plasma  cell,  isotyoe  switching,  affinity  
maturation  
e. Treg:  
Inhibit,  immature  dendiritic  cell,  lack  of  T  cell  activation  
Slide  14:  

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1. What  are  the  4  types  of  T  helper  cells  naïve  CD4  T  cells  can  differentiate  into?  

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TH  1,  TH17,  Treg,  TH2  

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2. What  controls  which  type  of  Th  cell  naïve  CD4  T  cells  differentiate  into?  
Signals  from  DC  and  innate  cells    

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3. How  is  this  process  a  positive  feedback  mechanism?  
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Differentiation  results  in  production  of  cytokines  that  further  activate  same  
kinds  of  cells  that  initiated  that  response  
Slide  15:  
o

1. Describe  the  general  pathway  for  cytokine  signal  transduction:  

a. Cytokine  binding  to  receptor  recruits  _Jak  Proteins  
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b. Jak  proteins  phosphorylate  _each  other,    and  Cytokine  receptor    

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c. STAT  proteins  dimerize  and  translocate  to  the  nucleus  and  act  as  
transcription  factors  
Slide  16:  
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1. Which  cytokine  receptor(s)  does  IL-­‐2  promote  expression  of?  Which  type(s)  
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of  Th  cells  does  this  cause  differentiation  of?  

IL-­‐2  induces  STAT5,  which  promotes  IL-­‐12R  (TH1),  IL-­‐4R  (TH2),  and  IL-­‐2R  
(Treg)  signaling    
2. Which  cytokine  receptor(s)  does  IL-­‐2  suppress  expression  of?  Which  type(s)  
is

of  Th  cells  does  this  suppress  differentiation  of?  

Th

suppresses  IL-­‐6R  (TH17).  

3. Why  does  all  of  the  above  occur?  
Different  cytokine  signals  result  in  activation  of  different  transcription  
factors  that  direct  expression  of  different  types  of  cytokines  in  the  T  cells.  
sh

Slide  17:  
1. Describe  what  is  meant  by  the  term  “Helper  lineage  commitment”.  
TH  1  cannot  become  TH2  or  TH17  
2. Describe  what  is  meant  by  the  term  “helper  lineage  plasticity”.  
TH1  can  become  TH2  or  TH17  under  different  cytokine  conditions  

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 3. What  blocks  a  differentiated  Th  cell  from  becoming  a  different  type  of  Th  
cell?  
Cytokines  
Slide  19:  
1. Which  type  of  Th  cell  is  produced  when  lots  of  IL-­‐2  is  present?  
Th17  
2. Which  type  of  Th  cell  is  produced  when  minimal  IL-­‐2  is  present?  
Treg  
3. What  are  the  protective  roles  of  the  following  four  Th  cell  types:  
a. Th1:  
Intracellular  pathogens  
b. Th2:  
Parasitic  worms  
c. Th17:  
Extracellular  bacteria  
d. Treg:  

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Counter-­‐  regulation  

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4. What  are  the  harmful  roles  of  the  following  four  Th  cell  types  :  

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a. Th1:  
Systemic  pathology  

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b. Th2:  
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Allergy  and  asthma  
c. Th17:  
Autoimmunity  inflammation  cancer  
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d. Treg:  
Slide  20-­‐21:  
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1. Which  type  of  Th  cell  is  similar  to  a  CD8  T  cell?  
vi y re

TH1  
2. What  3  cell  types  do  CD4  Th1  cells  activate  (i.e.  what  is  their  effector  
function?  
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Macrophage  activation  
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Complement  binfinf  and  opsonizing  antibodies  

Neutrophil  activation  
Slide  22:  
1. What  does  Th1  macrophage  activation  result  in?  
is

Fuse  lysosomes  with  endosomes  to  kill  intracellular  pathogens  

Th

2. Which  cytokines  do  Th1  cells  release  to  cause  this  ^  ?  

IFN  gamma  
3. Which  protein  do  Th1  cells  produce  to  recruit  more  macrophages  to  the  site  
of  an  infection?  
sh

Macrophage  chemoattractant  protein  

Slide  23:  
1. Describe  how  getting  the  wrong  CD4  cell  differentiation  can  lead  to  
formation  of  granulomas.TCR  recognition  of  MHC2:  Ag  results  in  
upregulation  of  CD40L  and  production  of  IFN  gamma.    Lack  of  TH1  or  IFN  
gamma  can  result  in  uncontrolled  microbial  infections  

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Slide  24:  
1. Which  B  cell  isotypte(s)  do  Th1  cells  elicit?  
IgG3  or  IgG2a  
2. Which  cytokine  secreted  by  Th1  cells  is  responsible  for  this  ^  ?  
IFN  gamma  
Slide  25:  
1. Strong  or  systemic  infections  induce  which  cytokine  to  be  produced?  Which  
type  of  Th  response  does  this  elicit?  
IFNg      
TH1  
2. Weak  or  localized  infections  induce  which  cytokine  to  be  produced?  Which  
type  of  Th  response  does  this  elicit?  
IL-­‐4  
TH2  
Slide  26:  

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1. What  are  the  4  effector  functions  of  Th2  responses?  

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Production  of  neutralizing  IgG  antibodies  

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Production  of  IgE  
Suppression  of  macrophage  activation  

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Eosinophil  activation  
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Slide  27:  
1. Which  cytokine  do  Th2  cells  produce  causing  activation  of  eosinophils?  
IL-­‐5  
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Slide  28:  
1. Which  cytokine  do  Th2  cells  produce  causing  suppression  of  macrophages?  
aC s

IL-­‐10  
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2. What  does  this  ^  cytokine  lead  to  expression  of  and  how  does  this  protein  
actually  suppress  macrophage  activation?  
SOCS1  expression  
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Slide  29:  
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1. Which  B  cell  isotype(s)  do  Th2  cells  elicit?  

IgE  or  IgG2b  
2. Which  cytokine  do  Th2  cells  produce  to  cause  this  isotype  switch?  
IL-­‐4  
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Slide  30:  
Th

1. Which  cytokine  causes  Th17  CD4  cell  differentiation  and  which  transcription  
factor  is  induced  to  cause  the  cell  to  become  a  Th17  cell?  
IL17/  IFN  gamma      
2. Are  Th17  cells  inflammatory  or  inhibitory?  
sh

Both  
3. What  cytokine  causes  a  Th17  cell  to  become  inflammatory,  and  when  would  
we  want  this  type  of  response?  
IL  23  
4. What  cytokine  causes  a  Th17  cell  to  become  inhibitory,  and  when  would  we  
want  this  type  of  response?    

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Slide  31:  
1. What  cytokine  are  mucosal  APCs  very  good  at  producing  and  what  is  the  
result  (i.e.  which  Th  cell  type  does  this  induce)?  
IL  17    
Th17  cells  
Slide  32:  
1. What  is  the  effector  function(s)  of  inflammatory  Th17  cells?  
TH17  express  homing  receptor  for  epithelial  and  mucosal  surfaces  
Produce  chemokines  for  attracting  innate  immune  cells  and  effector  T  cells  
Probably  responsible  for  many  autoimmune  reactions  
Slide  33:  
1. Which  B  cell  isotype(s)  do  Th17  cells  elicit?  
IgG1  and  IgG3  
2. Which  cytokine  do  Th17  cells  produce  to  cause  this  isotype  switch?  

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IL-­‐21  

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Slide  35:  

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1. Where  do  Tfh  cells  reside  in  the  body?  
Follicles  

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2. Which  chemokine  receptor  do  Tfh  cells,  causing  them  to  migrate  to  the  
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follicle,  up  regulate?  
CXCR5  
Slide  36:  
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1. What  is  the  function  of  Tfh  cells?  

Migrate  to  follicles  to  Induce  isotype  switching  
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2. Can  any  other  cell  types  perform  this  ^  function?  

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Yes  
Slide  37:  
1. What  is  the  role  of  Treg  CD4  T  cells?  
ed d

Suppress  other  T  cell  responses  

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2. What  inhibitory  cytokine  do  Treg  cells  produce?  

Il-­‐35  and  IL-­‐10  
3. Other  than  producing  inhibitory  cytokines,  how  else  can  Tregs  inhibit  T  cell  
responses?  
is

Metabolic  disruption,  cytolysis,  target  dendritic  cells  

Th

4. What  molecule  do  Tregs  induce  DCs  to  produce,  inhibiting  T  cell  activation?  
Effector  T  cell  
 
 
sh

 
 
 
 
 
 

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