Exam 6: Chapter 8 Flashcards
What type of cell is needed to activate a CD8+ T cell?
An activated dendritic cell (and sometimes an activated CD4+ T cell)
What makes up the synapse attachment between CD8+ cells and their target cells?
The inner TCR:peptide/MHC, a secretory channel, an integrin binding area, and an outer region of bigger interacting molecules
What are the different types of effector T cells?
TH1, TH17, TH2, TFH, and Treg cells
What happens if ONLY the specific signal for T cell activation is present?
The T cell will be rendered anergic
What is the Fas ligand?
A ligand present on CD8+ T cells that binds to Fas receptors on target cells and signals for apoptosis to occur
What are the different pathways via which dendritic cells present antigens to T cells?
Receptor-mediated endocytosis, macropinocytosis, viral infection, cross-presentation, transfer from infected cell to resident cell
How do T cells know to home to secondary lymphoid organs?
- T cells have adhesion molecules on their surfaces
- The HEV has specialized adhesion molecules that interact with T cells
- T cells are also attracted by chemokines
What happens if a naïve T cell fails to find its antigen?
It will leave via the efferent lymphatic vessel
What are the two types of cells that take up antigens and process them for T cells?
Dendritic cells and macrophages
What is the function of TFH cells?
To activate B cell maturation
What happens if ONLY the co-stimulatory signal for T cell activation is present?
There is no effect on the cell
Where do dendritic cells reside within the secondary lymphoid organs?
The T cell area
How does a T cell know when it has bound a specific peptide/MHC complex?
- T cells sense the interaction of peptide/MHC via a TLR
- The TCR sends a signal to the cell; typically via protein phosphorylation of tyrosine residues
- Tyrosine phosphorylation changes the function of proteins or recruits more proteins to the TCR to be phosphorylated
- Protein phosphorylation leads to the activation of other signaling pathways
What is the function of Treg cells?
To suppress the other effector T cells
Where do antigens concentrate, thus making T cell recognition easier?
In the draining lymph node
What is the importance of the Ras-Map kinase pathway?
It leads to the activation of transcription factor AP-1. Co-stimulation through CD28 maintains Lck activation and helps in the activation of AP-1
What are macrophages?
Resident cells that remain in the infected tissue
Why is the pathway that activates Protein Kinase C important?
This pathway leads to the activation of transcription factor NFkB
What is the role of granulysin?
To break down the target cell membrane
Where do macrophages reside within the secondary lymphoid organs?
Both the T and B cell areas
What causes the delay in the adaptive immune response?
The time it takes to activate and differentiate effector T cells
How do T cells enter the lymph node?
Via the high endothelial venule
What are the key kinases associated with the TCR complex?
Lck and Zap-70
How does the synapse form?
A CD8+ T cell and a target cell collide and undergo nonspecific adhesion. Specific recognition then redistributes cytoplasmic and cytoskeleton components of the cell. Lytic granules are localized and released into the synapse between the two cells
What is the function of TH2 cells?
Activate the response against parasites
What are the two components of the AP-1 transcription factor?
Fos and Jun
How do lymphocytes enter the lymph node?
The lymphocyte begins a rolling interaction. LFA-1 activated by chemokines then binds tightly to ICAM-1, and the lymphocyte enters the lymph node via diapedesis
What signaling molecule tells a naïve T cell to leave the lymph node?
Sphingosine-1-phosphate
What are the properties of activated macrophages?
- Increased fusion of phagosomes with the lysosome
- Increased production of microbicidal molecules
- Increased expression of B7 and MHC class II
What is the role of VLA-4?
To allow T cells to interact with endothelial cells in inflamed, infected tissues
What co-stimulatory receptor is expressed by T cells?
CD28
What is the function of TH1 cells?
Activate macrophages
What two signals are required to activate a T cell?
- Interaction between TCR/co-receptor and peptide/MHC
2. A co-stimulatory signal sent only by APCs
What does interferon gamma do?
- Inhibits viral replication
- Increases MHC class I expression
- Activates macrophages at the site of infection to remove dead cells
What is CTLA-4?
A second receptor that binds co-stimulatory molecules but serves to turn off T cell activation
Why is it good to have T cell activation regulated by CTLA-4?
- Ensures a polyclonal T cell response
2. Keeps T cell response from overreacting and damaging healthy cells/tissues
How do lytic granules kill infected cells?
By releasing enzymes that induce apoptosis
How are T cells able to “sample” the peptide/MHC complexes on the antigen-presenting cells?
T cell adhesion molecules interact with complementary molecules on dendritic cells and macrophages
What signal mediates cytokine responses?
STAT
What upregulates B7 expression?
The danger signal
How are co-stimulatory signals regulated?
They are only expressed when induced by infection
What is the function of CD8+ T cells?
To kill cells infected with viruses and intracellular pathogens that antibodies cannot access
Which type of T cell is harder to activate and why?
CD8+ cells, because these cells differentiate into cytotoxic T cells that can kill other cells
What is cognate interaction?
The idea that TFH dependent help only occurs when B and T cells recognize the same antigen, but not necessarily the same epitope of that antigen
What are ITAMs?
Conserved sequences with two tyrosine residues that are present in the CD3 complex and are phosphorylated by kinases
Do the TCR and the associated CD3 complex have the ability to phosphorylate?
No, kinases must be recruited
Why are so many phosphorylation events required for T-cell activation?
T cells use the duration of the TCR-peptide/MHC interaction to determine if the interaction is a specific one; longer interactions allow for more events to occur and for full signaling to activate
What is adjuvant?
A mixture of bacterial products found in vaccines that activate the expression of MHC class II and co-stimulatory molecules
Which kinase phosphorylates the ITAMs?
Lck
How is sphingosine-1-phosphate turned off?
By activated T cells
Why are transcription factors NFAT, NFkB, and AP-1 important?
All three are necessary to form effector T cells
Why is the co-stimulatory signal necessary for T cell activation?
It ensures that only APCs can activate T cells
What are dendritic cells?
Cells that are highly migratory, present in the periphery, and act as sensors for infection
What are regulatory T cells?
Antigen specific T cells that act to suppress auto-immune reactions
Why is it important that CD8+ cells kill via apoptosis and NOT necrosis?
Death by necrosis would lead to the leakage of pathogens into the extracellular space
How do dendritic cells become mature and activated?
By taking up antigens and processing them for presentation
What are granzymes?
Proteases that initiate apoptosis
How is the TH1 response regulated?
- TH2 cytokines inhibit the TH1 response
2. TH1 T cells must maintain contact with TCR:peptide/MHC in order to produce interferon gamma
What is the function of TH17 cells?
Enhance neutrophil response
What is the importance of the pathway that induces Ca2+ from outside of the cell into the cell?
The increase of Ca2+ inside the cell activates the transcription factor NFAT
What is the role of CD45RA and CD45RO?
To dephosphorylate an inhibitory site on Lck
How do TFH cells activate B cells?
TFH cells recognize peptide/MHC presented by B cells, form a synapse, and secrete cytokines that activate B cell differentiation
What are the two functions of chemokines that attract T cells?
- To mark the HEV and attract T cells
2. To send a signal to the T cell that activates the ability of integrins to bind ICAMS
What two signals are required for macrophage activation?
CD40 ligand and Interferon gamma
What type of receptors are involved in the activation of dendritic cells?
Toll-like receptors
What co-stimulatory molecule is expressed by APCs?
B7
Where do adaptive immune responses occur?
In secondary lymphoid organs
What mediates the interaction between T cells and endothelial cells?
Interactions between selectins on the T cells and mucin-like vascular addressins on the endothelial cells
What is the role of perforin?
To make holes in the target cell membrane
How do NFAT, NFkB, and AP-1 induce proliferation of activated T cells?
By inducing the expression of IL-2, a cytokine which stimulates T cells to proliferate
What are the properties of effector T cells?
- Detach from the APCs
- Effector functions are induced by specific TCR:peptide/MHC interaction
- Do not require co-stimulation
- Increase expression of adhesion molecules that will allow them to interact with target cells
What happens if a pathogen can resist activated macrophages?
The immune system walls off these infected cells and forms a granuloma
What two immunosuppressant drugs target NFAT activation?
Cyclosporin A and FK506
What happens after Lck phosphorylates the ITAMs?
The phosphorylated ITAMs serve as bonding sites for Zap-70. Lck also phosphorylates Zap-70, increasing its kinase activity
Why are lytic granules precisely localized?
To prevent the killing of bystander cells
