T cells Flashcards
T cell precursors travel from the bone marrow to develop here
Thymus
Immature thymocytes move from the bone marrow to this part of the thymus
Cortex
In the cortex of the thymus, immature thymocytes exist in the presence of these cells
Branched cortical epithelial cells and macrophages
The medulla of the thymus consists of these 4 types of cells
Thymocytes
Medullary epithelial cells
Dendritic cells
Macrophages
Parts of the thymus believed to be sites of cellular destruction and/or commitment of cells to the regulatory T cell lineage
Hassall’s corpuscles
Hassall’s corpuscles are present here
Thymus
Type of cell in the thymus that removes T cells that fail to mature properly
Macrophages
Process where the T cell producing tissue of the thymus begins to be gradually replaced with fatty tissue as we age
Involution of the thymus
Are T cell germline genes rearranged when they leave the bone marrow?
No
Do thymocytes committed to the T cell lineage express CD4 or CD8 when they leave the bone marrow?
No; they are double negative (express neither)
Maturation of T cells occurs here
Thymus
T cell gene rearrangements occurs here
thymus
Are T cells replenished throughout life?
No
Diversity for T cells is likely greater because they aren’t replenished throughout life
Difference between antibody and T cell receptor:
How many antigens can bind simultaneously?
Ab monomers can bind 2; TCRs only bind 1 at a time
Difference between antibody and T cell receptor:
Recognize antigen in what conformation?
Abs recognize native conformation; TCR requires processing and presentation of antigen
Difference between antibody and T cell receptor:
MHC restriction requirement
MHC restriction is not required for Abs; only for TCRs
Difference between antibody and T cell receptor:
Function as effector molecules or effector cell
Ab function as effector molecules, can act from a great distance
TCR is a receptor that activates an effector cell; T cells exert their effect in a local area
This molecule on thymocytes interacts with its ligand on thymic epithelial cells, removing transcription repressors from the DNA in the thymocyte; initiates maturation
Notch-1
Notch-1 is involved in this process
Initiates T cell maturation
T cell chain that rearranges first
Beta chain
T cell beta chain is tested at the cell surface using this alpha chain surrogate
pTɑ
pTɑ is involved in this
Surrogate alpha chain; used to test rearranged Beta chain during gene rearrangement in T cells
The pre-T-cell receptor is expressed in the context of these signaling molecules that are required for T cell activation
CD3 complex
CD4 and CD8 expression of T cells undergoing positive selection
Double positive
T cell positive selection involves this
Recognition of self MHC
T cell selection involving recognition of self MHC
Positive selection
After this process, T cells moves from double positive to single positive
Positive selection (depends on which MHC they interact with)
T cell negative selection involves this
Removal of T cells that recognize self peptide
Transcription factor that turns on the expression of non-thymic self antigens in the thymus
Allows for negative selection of T cells
Autoimmune regulator (AIRE)
Autoimmune regulator (AIRE) is involved in this process
Negative selection of T cells
Turns on the expression of non-thymic self antigens in the thymus
Central tolerance is provided by this process
Negative selection
Negative selection provides this type of tolerance
Central tolerance
(occurs in the thymus)
Negative selection of T cells occurs by these cells
Dendritic cells, macrophages, and other cells in the thymus
Population of self-reactive T cells that recognize self antigens expressed by self MHC
Proliferate, are maintained, and produce the cytokines IL-10 and TGF-beta that suppress the activity of other self-reactive T cells that have bound to the same MHC:peptide complex on the same APC
Regulatory T cells (Tregs)
Regulatory T cells (Tregs) produce these two cytokines that suppress the activity of other self-reactive T cells that have bound to the same MHC:peptide complex on the same APC
IL-10 and TGF-beta
T cells that do not recognize their specific peptide travel to other lymph nodes and eventually re-enter circulation via these
efferent lymphatics
Chemokines secreted by stromal cells and dendritic cells residing in the lymph node cortex, and they attract naive T cells that express the CCR7 receptor
CCL21 and CCL19
CCL21 and CCL19 attract naive T cells that express this receptor to the lymph node
CCR7 receptor
CCL21 and CCL19 are produced by these cells
Stromal cells and dendritic cells residing in the lymph node cortex
CCL21 and CCL19 are involved in this process
T cell homing to the lymph node
The initial interaction associated with the homing of T cells to the lymph node is between these
Mucin-like vascular addressins (CD43 and GlyCAM-1) expressed on the high endothelial venule
Bind L-selectin expressed by naive T cells
Molecule on naive T cells which binds with mucin-like vascular addressins (CD43 and GlyCAM-1) expressed on the high endothelial venule in the process of homing mature, unactivated T cells to the lymph node
L-selectin
L-selectin is expressed on these cells
Mature, naive T cells
L-selectin is involved in this process
Homing mature, unactivated T cells to the lymph node
Molecule on the cell surface of T cells that is activated by chemokines bound to extracellular matrix and binds tightly to ICAM-1, leading to diapedesis (lymphocyte leaves blood and enters lymph node)
LFA-1
LFA-1 on lymphocytes binds tightly to this on the high endothelial venule
ICAM-1
ICAM-1 on the high endothelial venule binds tightly to this on lymphocytes
LFA-1
LFA-1 is activated (allowing it to tightly bind to ICAM-1) by this interaction
CCR7:chemokine interaction at the high endothelial venule
Involved in lymphocyte diapedesis
CD2 on T cell binds to this on the dendritic cell
Mediates the initial interactions between T cells and dendritic cells
LFA-3
LFA-1 on T cell binds to these on the dendritic cell
Mediates the initial interactions between T cells and dendritic cells
ICAM-1 and ICAM-2
ICAM-3 on T cell binds to this on the dendritic cell
Mediates the initial interactions between T cells and dendritic cells
DC-SIGN
LFA-3 on dendritic cell binds to this on the T cell
Mediates the initial interactions between T cells and dendritic cells
CD2
ICAM-1 on dendritic cell binds to this on the T cell
Mediates the initial interactions between T cells and dendritic cells
LFA-1
ICAM-2 on dendritic cell binds to this on the T cell
Mediates the initial interactions between T cells and dendritic cells
LFA-1
DC-SIGN on dendritic cell binds to this on the T cell
Mediates the initial interactions between T cells and dendritic cells
ICAM-3
CD2 is present on these cells
T cells
involved in T cell movement within the lymph node
ICAM-3 is present on these cells
T cells
involved in T cell movement within the lymph node
ICAM-2 and ICAM-1 are present on these cells are involved in T cell movement within the lymph node
Dendritic cells
LFA-3 is present on these cells
Dendritic cells
involved in T cell movement within the lymph node
When a T cell recognizes its specific peptide, the TCR and CD4 bind to the MHC and a signal is transduced that changes and increases affinity of these two molecules, prolonging cell to cell contact
changes LFA-1, resulting in an increasing affinity for ICAM-1
One of the first steps associated with the formation of the immunological synapse
When the naive T cell encounters the appropriate peptide:MHC complex, the TCR and CD4 bind to the MHC and a signal is transduced that changes LFA-1, resulting in an increased affinity for ICAM-1 that prolongs cell to cell contact
The gathering of receptors on the surface of an APC and T cell that work in a coordinated effort to prolong their interaction and strengthen the signals associated with activation of the T cell by the APC
Immunological synapse
Second signal required for T cell activation
B7 co-stimulatory molecule (on APC) interaction with CD28 (on T cell)
Expressed on activated T cells
Binds B7 with higher affinity than CD28, but it functions as an antagonist that dampens activation and limits proliferation of activated T cells
CTLA4
CTLA4 binds this
B7 costimulatory molecules
CTLA4 functions in this
Functions as an antagonist that dampens activation and limits proliferation of activated T cells
Costimulatory molecules on APC that interact with CD28 on T cells
Provide second signal required for T cell activation
B7 costimulatory molecules (B7.1 and B7.2), also known as CD80 and CD86
Second signal required for B cell activation
Binding of CD40 on B cells with CD40L on T cells
CD40 on B cells binding with CD40L on T cells provides this signal
Second signal required for B cell activation
All accessory proteins to the TCR
CD3 complex (2 epsilon chains, 1 delta chain, and 1 gamma chain)
2 zeta chains
Cytoplasmic protein tyrosine kinase that plays a critical role in the events involved in initiating T-cell responses by the antigen receptor
Zap-70
Zap-70 is specific to what type of cells
T cells
The TCR signaling chains all contain these which are phosphorylated by kinases
Immunoreceptor tyrosine-based activation motifs (ITAMs)
Does CD4 or CD8 have only one transmembrane portion?
CD4
Does CD4 or CD8 have 2 transmembrane portions?
CD8
3 transcription factors released upon activation of the T cell and consequent signaling through the TCR
NFAT, NF-kB, AP-1
Uptake of an antigen by a professional APC induces expression of this costimulatory molecule by the APC
B7
Interactions that keep the T cell and APC in close proximity
LFA-1:ICAM-1
Cell surface molecule expressed by T cells that interacts with B7 (on the APC) to signal survival and move toward complete activation of the T cell
CD28
Surface molecule of T cells that functions in signal transduction by TCR complex
Expressed on all T cells
Zeta chain
2 coreceptors of T cells
CD4 and CD8
Costimulatory receptor of APCs on T cells
CD28
What makes up the IL-2 receptor on naive T cells?
Gamma and beta chain
Subunit that binds to the beta and gamma chains of the IL-2 receptor to increase the affinity of the receptor for IL-2
Alpha subunit
Cytokine produced by T cells that binds to its receptor (also on T cells), and this signals to Ag-specific T cells to proliferate and produce multiple clones
Activated, effector T cells no longer require costimulatory molecules to act on cells they recognize via TCR:MHC interactions
IL-2
IL-2 is produced during this
T cell activation
Leads to T cell proliferation and production of clones
T cell anergy occurs when this happens
Specific signal alone is encountered (TCR:MHC) but no costimulatory signal
This occurs when specific signal is encountered by T cell (TCR:MHC) but no costimulatory signal is present
Anergy
T cell becomes non-responsibe so it does not respond to a potential self Ag
This occurs when a T cell only receives the costimulatory signal from APC, but no TCR:MHC
No effect
Integrin that interacts with the adhesion molecule VCAM-1
VLA-4
VLA-4 interacts with this
Adhesion molecule VCAM-1
Adhesion molecule that is selectively expressed by activated endothelium around inflamed tissue
Interacts with VLA-4
VCAM-1
Interaction between these two molecules is important for recruitment of effector T cells into the site of infection
VLA-4 (integrin on T cells) with VCAM-1 (cell adhesion molecule selectively expressed by activated endothelium around inflamed tissue)
Cytokine receptors signal through this pathway
JAK:STAT
(phosphorylated STAT dimers go to the nucleus and initiate gene expression)
CD4 T cell fate is determined in this location
Lymph node
What tells CD4 T cells which lineage they should commit to in order to deal with that pathogen?
APCs
Defining cytokines of Th1 cells
IFN gamma and IL-12
IFN gamma and IL-12 are defining cytokines of these cells
Th1 cells
Defining cytokines of Th2 cells
IL-4, IL-5, IL-6, IL-13
IL-4, IL-5, IL-6, and IL-13 are defining cytokines of these cells
Th2 cells
Defining cytokines of Th17 cells
IL-17, IL-22
IL-17 and IL-22 are defining cytokines of these cells
Th17 cells
IL-21, IL-4, and IL-13 are defining cytokines of these cells
Tfh cells
Defining cytokines of Tfh cells
IL-21, IL-4, and IL-13
Principal responding cells to Th1 cells
Macrophages
Principal responding cells to Th2 cells
Eosinophils
Principal responding cells to Th17 cells
Neutrophils
Principal responding cells to Tfh cells
B cells
Th1 responses are used for these types of pathogens
Viruses and intracellular bacteria (due to IFN gamma production and macrophage response)
Th2 responses are used for these types of pathogens
Extracellular pathogens
Effector T cells used in immune response toward viruses and intracellular bacteria
Th1
Effector T cells used in immune response toward extracellular pathogens
Th2
Does this describe classically or alternatively activated macrophages:
Microbicidal actions - phagocytosis and killing of bacteria and fungi
Inflammation
Classically activated macrophage (M1)
Does this describe classically or alternatively activated macrophages:
Anti-inflammatory effects, wound repair, fibrosis
Alternatively activated macrophage (M2)
Cytokines which lead to differentiation into classically activated macrophages
Microbial TLR ligands, IFN gamma
Cytokines which lead to differentiation into alternatively activated macrophages
IL-13 and IL-4
Microbial TLR ligands and IFN gamma promote the differentiation of these types of macrophages
Classically activated macrophages (M1)
IL-13 and IL-4 promote the differentiation of these types of macrophages
Alternatively activated macrophages (M2)
Cytokines secreted by classically activated macrophages which promote inflammation
IL-1, IL-12, IL-23, chemokines
Cytokines secreted by alternatively activated macrophages which promote anti-inflammatory effects, wound repair, and fibrosis
IL-10, TGF-beta
IL-1, IL-12, IL-23, and chemokines are produced by this type of macrophage
Classically activated macrophage (M1)
IL-10 and TGF-beta are produced by this type of macrophage
Alternatively activated macrophage (M2)
Destruction of an intracellular pathogen involves this type of effector T cell
Th1
IL-12 induces this response to intracellular pathogens
Th1 response
Mycobacteria have evolved to survive within these cells by resisting the killing activity of Th1 cells
Macrophages
Mycobacteria have evolved to survive within macrophages by resisting the killing activity of these cells
Th1 cells
Defined by the presence of multi-nucleated giant cells surrounded by T cells, many of which are CD4
Granulomas (e.g. tuberculosis)
Multi-nucleated giant cell made up of multiple fused macrophages contain this
Mycobacteria
Fas ligand or LT produced by activated Th1 cell kills these cells when they are chronically infected, releasing bacteria to be destroyed by healthy cells
Macrophages
Produced by activated Th1 cells
Kills chronically infected macrophages, releasing bacteria to be destroyed by healthy macrophages
Fas ligand or LT
IL-3 + GM-CSF produced by activated Th1 cells induces differentiation of these cells in the bone marrow
Macrophages
Produced by activated Th1 cells
Induces macrophages differentiation in the bone marrow
IL-3 + GM-CSF
Produced by activated Th1 cells
Activates endothelium to induce macrophage adhesion and exit from blood vessel at site of infection
TNF-alpha + LT
Chemokine produced by activated Th1 cells
Causes macrophages to accumulate at site of infection
CXCL2
Function of CXCL2
Causes macrophages to accumulate at site of infection
Produced by activated Th1 cells
Th1 cytokine that can stimulate isotype switching of Ag-specific B cells toward IgG1 Abs that can fix complement and interact with Fc receptors to enhance opsonophagocytosis
IFN-gamma
IFN-gamma produced by Th1 cells can stimulate isotype switching of B cells toward these antibodies
IgG1 (can fix complement and interact with Fc receptors to enhance opsonophagocytosis)
Does immunity towards polysaccharides involve T cells?
No
Must be linked to protein
Conjugate vaccines link these
Polysaccharides to a protein
Allows Ab to be produced directed toward the polysaccharide
In conjugate vaccines, which type of cell is specific for polysaccharide? And which is specific for the protein?
B cell specific Abs for polysaccharide
T cell specific for peptide
Cytotoxin released by CD8 T cells that forms pores in cell membranes of target cells
Perforin
Perforin is released by this cell
CD8 T cell
Cytotoxin released by CD8 T cells that is a serine esterase that enters the cytoplasm of target cells, inducing apoptosis
Granzyme
Granzymes are released by this cell
CD8 T cell
Cytotoxin released by CD8 T cells that is a membrane-perturbing protein that works with other cytotoxins to form pores in target cells
Granulysin
Granulysin is released by this cell
CD8 T cell
Type of effector T cell that activates macrophages
Th1
Type of effector T cell that activates eosinophils and mast cells; alternative macrophage activation
Th2
Type of effector T cell that recruits and activates neutrophils
Th17
Type of effector T cell that promotes antibody production
Tfh
Th1 cells act on these cells
Macrophages
Th2 cells act on these cells
Eosinophils and mast cells
Th17 cells act on these cells
Neutrophils
Tfh cells act on these cells
B cells