Lecture 11: Differentiation and Functions of CD8+ T cells Flashcards Preview

Immunology 2.0 > Lecture 11: Differentiation and Functions of CD8+ T cells > Flashcards

Flashcards in Lecture 11: Differentiation and Functions of CD8+ T cells Deck (44):

CD4 is on what percentage of T cells



CD8 is on what percentage of T cells



T cells make up ___ % of all the lymphocytes in the blood. While B cells comprise the remaining ___% of blood lymphocytes

  • T cells: 70%
  • B cells: 30%


CD4 cells are  what MHC class restricted 



CD8 cells are what MHC-class restricted

Class-I MHC restricted


Rearrangement of genes of the T cell occurs where in the body

the thymus (this generates a receptor for Ag) 


Functional polarization means that the T cell takes on a particular set of tasks that promote the 

adaptive immune response. These are often called effector or regulatory functions, depending on their nature 


Naive CD8+ cells recognize Ags (signal 1) and proliferate and differentiate in to effector CTLs upon ______ costimulaiton (signal 2) 



activated CTLs contain numerous granules called lysosomes that contain _____ and _____ used by the cells to kill other cells 

perforin and granzymes 


Activated CTLs secrete mostly what cytokine

  • Mostly IFN-gamma (which potently activate macrophages)


similar to activation of Th1 cells, the molecular events in CTL differentiation involve transcription factor 



T-bet regulates transcription of genes encoding for ____, ___, and ____ in CD8 cells

  • Perforin 
  • Granzymes
  • IFN-gamma


  • What is cross presentation

  • Dendritic cells canpresent class II MHC-associated peptides generated in the vesicles to CD4+ helper T cells, which are often required to induce full responses of CD8+ cells 
  • involves the fusion of phagosomes containing the ingested antigens with the ER. Ingested proteins are then translocated from the ER to the cytosol by poorly defined pathways that are likey involved in presentation of proteins degraded in the ER


The full activation of naive CD8+  T cells and their differentiation into functional CTLs and memory cells may require the participation of ______ 

  • CD4+ helper cells 
    • provide second signal for CD8+ T cells
      • secrete cytokines that stimulate differentiation of CD8+ cells
      • express  CD40L which may bind to CD40 on atigen-loaded dednritic cells. This interaction activates the APCs ot make them more efficient at stimulating the differentiation of CD8+ T cells, in part by inducing the expression of costimulators. This process has been termed licensing of APCs
    • There is evidence that CD4+ helper cells are more important for the generation fo CD8+ memory T cells than the differentiation of naive CD8+ T cells into effector CTLs



Mechanism of APC licensing

  • Licensing of the APC occurs when the CD4+ T cell recognizes Ag presented by an MHC class II APC and delivers activating signals through CD80/CD86 and CD40 
  • CD40-CD40L interaction upregulates expression of CD80/CD86 on professional APCs which makes them more efficient at stimulating the differentiation of CD8+ T cells 
  • (does not require CD4+ and CD8+ T cells to be in contact with APC at the same time)


CD4+ helper T cells are required for CD8+ T cell responses when ______ innate immune reactions are evoked by 

  • Relatively weak innate immune responses
  • latent viral infections, organ transplants, and tumors


CD4+ helper t cells provide signal ___ in form of cytokines which enhance activation of CTLs



What cytokines contribute to the differentiation of CD8+ T cells and the maintenance of effector and memory cells of this lineage

  • IL-2
    • promotes proliferation and differentiation of CD8+ T cells into CTLs and memory cells. 
    • CD8+ cells express the beta and gamma chains of the IL-2 receptor and may express high levels of the alpha chain after activation
  • IL-12 & type I IFNs
    • stimulate the differentiation of naive CD8+ T cells into effector CTLs
    • Naive CD8 t cells proliferate in response to TCR and CD28 signals, but require IL-12 or type I IFN for survival and development of optimal effector functions 
  • IL-15
    • important for survival of memory CD8+ cells
    • may be produced by many cell types, including dendritic cells and tissue macrophages
  • IL-21
    • produced by activaed CD4+ T cells
    • plays a role in the induction of CD8+ T cell memory and the prevention of CD8+ T cell exhaustion 


IL-2R shares a common receptor component (the gamma chain) with what other cytokines

  • IL-4, IL-7, IL-9, IL-15, and IL-21


Ligands of Type I cytokine (hemopoietin) receptors 

  • IL-2
  • IL-3
  • IL-4
  • IL-5
  • IL-6
  • IL-7
  • IL-9
  • IL-11
  • IL-12
  • IL-13
  • IL-15
  • IL-21
  • IL-23
  • GM-CSF
  • G-CSF


Ligands of IL-1 receptor family

  • IL-1
  • IL-18
  • IL33


Ligands of Type II cytokine receptors 

  • IFN-alpha/beta
  • IFN-gamma
  • IL-10
  • IL-22


Ligands of seven transmembrane G-protein coupled receptors



Local release of IL-2 can lead to activation of nearby CD8+ T cells in a ____ fashion



IFN-gamma is a ____ composed of subunits of approximately 25kDa



IFN-gamma is released by ___ cells and ___, as well as by activated _____

Th1 cells, CTLs, as well as by activated NK cells 


IL-12 is a key cytokine is produced by activated 

DCs and Macrophages 


IL-12 has a profound effect of inducing naive CD4 T cells to differentiate into ______

Th1 effector cells 


The balance of IL-12 and IL-4 during naive CD4  T cell activation thus determines whether these cells become _____ or ____

Th1 or Th2


IL-12 thus promotes production fo the pro-inlammatory cytokines ____ and ____ by CD4+ and CD8+ T cells 

IFN-gamma and TNF-beta 


IL-12 simulated CD8+ T cells are more effective in controlling tumor and they maintain 

high numbers and function as compared to type I IFNs-stimulated cells 


IL-12 assists in prevention of CD8+ T cells ____



Activated CTLs secrete pro-inflammatory 

TNF-beta, IFN-gamma and cyotoxic Perforin and granzymes 



exhausted CD8+ T cells show reduced production of IFN-gamma and increased expression of ____ 

PD-1 inhibitory receptor 


PD-1 mediated T cell exhaustion may contribute to the chronicity of 

HIV and hepatitis C virus (HCV)


Anti-PD-1 Abs are effective in the 

immuno-therapy of tumors


Perforin and granzymes are secreted by CTLs into the ____ and perform the killing and cannot diffuse to other nearby cells



What are the two mechanisms by which CTLs kill target cells

  • Complexes of perforin and granzymes are released from the CTL by granule exocytosis and enter target cells. The granzymes are delivered into the cytoplasm of the target cells by a perforin-dependent mechanism, and they induce apoptosis 
  • The FasL is expressed on activated CTLs, engages Fas on the surface of target cells, and induces apoptosis 


There are Granzymes A, B, and C, which are serine proteases. But which one is the only one to be required for CTL cytotoxicity in vivo

Granzyme B


Perforin is a membrane-perturbing molecule that is homologous to the ____ complement protein



CTL granules contain a sulfated proteoglycan ____ which serves to assemble a complex containing granzymes and perforin



When in the target cell, granzyme B activates _____ , that triggers apoptosis 



Explain Fas-FasL-mediated apoptosis 

  • Binding of FasL to Fas recruits Procaspase-8 thourhg the FADD adaptor converts it into the active enzyme caspase-8
  • in type-I cells such as thymocytes, caspase-8 can directly cleave caspase-3
  • In type-II cells such as virus-infected hepatocytes, caspase-8 cleaves Bid and the truncated Bid stimulates the release of cytochrome c from mitochondria
    • cytochrome c, together with Apaf-1 (apoptotic peptidase activating factor 1) and ATP then activates caspase-9 which in turn then activates caspase-3 
  • Caspase-3 activates CAD (caspase-activated DNase) via degradation of ICAD (inhibitor of CAD) 
    • Activated CAD causes DNA degradation in nuclei


Viruses can enter the cells by two ways. explain

  • Some virsuses can infect cells directly, leading to replicaiton of virus inside the cell. During this process, some of the viral proteins will be degraded into peptide fragments, which will be presented on MHC class I molecules to CD8+ cells 
  • APCs, such as DCs can also take up viral particles or remnants of virally-infected cells 
    • during processing by professional APCs, viral peptides can be presented on MHC class I molcules via the cross-presentation pathway