CHP7: T cells Adaptive Immunity Flashcards
What is T cell priming?
Interaction between naive T cell receptor and MHC peptide complex resulting in signaling cascade leading to T cell activation or inactivation
Which major three cells are able to present antigen to T cells? Must have which MHC class?
1) Dendritic
2) Macrophages
3) B cells
MHC II class
Where are immature dendritic cells found?
Peripheral tissues
Dendritic cells that contain antigen and migrates to secondary tissues will develop into?
Mature dendritic cells
What is a key physical difference between a dendritic cells and a mature dendritic cell?
Cellular projection cells that help activate naive T cells
Immature dendritic cells specialize in?
antigen uptake and processing
Mature dendritic cells specialize in?
Antigen presentation
Interaction between ______ receptor on dendritic cells and chemokine _______ prepares the cells to present antigen to naive T cells.
CCR7; CCL21
Where is CCL21 chemokine released in?
Secondary lymphoid tissues
How do dendritic cells recognize pathogens?
Receptors such as TLR’s and Mannose who recognize PAMPs
Mature dendritic cells express the coreceptor?
B7
Why is the coreceptor B7 necessary on a dendritic cell?
Co-stimulates naive T cells, B7 is only produced if foreign antigen has been recognized
Who secretes chemokine CCL18?
Dendritic cells
What is the function of chemokine CCL18?
Homing of naive T cells to increase dendritic and T cell interaction
Homing of immature dendritic cells to the secondary lymphoid to increase antigen presentation
OVERALL: increase antigen presentation between T cells and dendritic cells by homing in T cells and immature dendritic cells
Which cell performs both phagocytosis and T cell activation?
Dendritic cells
Which cell mainly specializes in phagocytosis and remains at the site of infection?
Macrophages
Why do B cells not play a major role in T cell activation? (although they are able to)
B cell activity is limited to specific antigen recognized by immunoglobulin
B cell immunoglobulin receptor binds antigen and takes it up via?
Receptor mediated endocytosis
What occurs after a B cell takes up an antigen via endocytosis?
1) Vesicle containing receptor antigen complex fuses with a lysosome and degrades antigen
2) Lysosome with antigen peptides fuses with inactivated MHC II
3) HLA-DM vesicle fuses with MHC complex vesicle with antigen peptides and aids in the removal of clip allowing for antigen peptides to load unto MHC class II
4) Presentation of MHC class II onto cell surface
How do T cells migrate to secondary lymphoid tissues?
Cell signaling via chemokines and adhesion molecules allowing cells to attach more easily
Which T cell chemokine receptor is able to bind to CCL19 and CCL21?
CCR7
Which chemokines establish a gradient by binding to endothelial cells? What is the purpose of this?
CCL21 and CCL19; to home in T cells (migration) for antigen presentation and activation
What are the four steps that describe T cell migration into secondary lymphoid tissues?
1) Rolling adhesion
2) Tight binding – interaction with molecules located on epithelial cells causing T cells to slow down
3) Diapedesis – T cell squeezing through endothelial cell junctions entering the secondary lymphoid tissue
4) Migration of T cell
Which molecules do T cells interact with to slow down and cause tight binidng?
ICAM-1 and ICAM-2
T cells that are not activated by interaction with MHC peptide complex will?
Exit secondary lymphoid tissues and reenter lymphatic system through efferent lymphoid vessels
Which lipid molecules mediates the movement of inactivated T cells into lymphatic system?
Sphingosine-1-phosphate
Which two interactions are required for T cell activation?
1) T cell receptor with MHC-peptide complex
2) Interaction between CD28 on T cell and B7
Expression of B7 molecules on the surface of professional APC’s only occur when?
infection is present
Which receptors on dendritic cells are responsible for inducing B7 expression?
PAMP receptors – once antigen is recognize these receptors will signal the nucleus to produce B7
Once activated T cells express _______, an inhibitory receptor instead of _______.
CTLA4; CD28
What is an internal mechanism that helps control the proliferation of activated T cells?
Hint: think of receptors located on T cells
Adhesion between CTLA4 and B7 is 20 times stronger than B7 and CD28
B7 is found on ___________ cells and binds to CD28 or CTLA4 which is found on ______ cells?
Dendritic cells; T cells
Which proteins in the T cell receptor take over the role of signaling to cytoplasm after immunological synapse formation?
CD3 proteins
Which molecule mediates the interaction with cytoplasmic protein tyrosine kinases?
Phosphorylated ITAMs (Immunoreceptor tyrosine based activation motifs)
What are the four steps of signaling transduction at the T cell receptor complex?
1) Coreceptor interaction with MHC, causing coreceptor to interact with kinase Lck
2) Lck phosphorylates ITAMS in the CD3 complex
3) recruitment of ZAP-70 and phosphorylation becoming active
4) ZAP-70 induces signaling that lead to changes in gene expression by activating phospholipase C-Y
Which molecule is responsible for activating PLC- gamma? What does it do?
ZAP-70, phosphorylates PLC gamma
What is the function of a lipase?
cleave lipids
PLC- gamma is a molecule that cleaves lipids from molecule?
PIP2
The cleaving of PIP2 by PLC-gamma results in?
DAG and IP3
IP3 activates a _______________ __________ involved in T cell activation
Transcription factor
IP3 is a second messenger that activates opening of ________ channels in the ____________ membrane
calcium; ER
The increase of Ca2+ (calcium) into the cytosol activates which phosphatase?
Calcereurin
Calcineurin is a phosphatase that removes phosphates from the transcription factor?
NFAT
The dephosphorylation of NFAT allows it translocate into the ________ and activate ________ involved in T cell activation
Nucleus; genes
Which molecule phosphorylates DAG?
PLC-gamma
DAG activates which protein kinase?
PKC-theta
PKC-theta activates transcription factor?
NFkB
How does PKC-theta activate transcription factor NFkB?
By adding a phosphate group to IkB causing it to degrade and no longer be attached to NFkB allowing it to enter the nucleus and activate genes for T cell expansion and differentiation
Which molecule is responsible for the activation protein Ras?
DAG
Describe the order of molecules activated after DAG activates protein RAG
1) activated Map kinase cascade
2) MAP activates FOS, a component of transcription factor AP-1
IL-2 production requires the costimulatory signal via ______
Hint: receptor found on T cells bind to B7
CD28
Why is costimulatory signal via CD28 important for IL-2 production?
1) increases half life of IL-2 mRNA by stabilizing the molecules
2) enhances IL-2 mRNA transcription
Which molecules prevents CD28 from acting as a costimulatory signal an immunological synapse, so IL-2 mRNA is not stabilized?
CTLA4
Low affinity IL-2 receptors have two protein subunits which are?
Beta and gamma
Activated T cells synthesize a third subunit (alpha) that interacts with beta and gamma subunits to form a?
High affinity IL-2 receptor
Which subunit is added to IL-2 receptor to increase its affinity?
Alpha
The increase of IL-2 affinity ensures that only __________ T cells will bind and respond to ______ that is produced and that clonal expansion driven by IL-2 is restricted to those ________ T cells.
activated; IL-2; activated
T/F: IL-2 production stimulates T cell proliferation
True
Why is costimulatory signal of Cd28 and B7 important?
Prevents activation of T cells that recognize self antigen
The inability of T cells to activate in the absence of B7 is an example of (+/-) selection in the periphery and prevents autoimmune response
Negative
What molecules are necessary for the interaction between APC’s and T cells?
1) MHC peptide complex with T cell receptor
2) coreceptor binding to MHC class
3) Interaction/ binding of B7 with CTLA4 or CD28
How do polarizing cytokines mediate T cell function? What are the steps?
1) binding of cytokine to cytokine receptor
2) causes JAK kinase activation
3) JAK kinase phosphorylates STAT proteins
4) STAT proteins relocate to nucleus and act as transcription factors to induce gene expression
TH1 helper T cells activate?
Macrophages
TH2 helper T cells activate?
B cells and granulocytes
TFH helper T cell activate?
B cells for immunoglobulin production
TH17 helper T cells activate?
Neutrophils
Cytotoxic T cells primarily work to?
Destroy infected cells
T/F: Memory cells typically remain close to where they are first produced to monitor for the return of the antigen
True
_____ and ______ activate CD4 T cells to differentiate into ________ helper T cells
IL-12 and IFN-gamma
TH1 helper T cells produce ______ to activate macrophages and promote differentiation of more TH1 helper T cells
IFN-gamma
IFN- gamma is important to fight (intra/extra) cellular infections?
Intracellular
______ activates TH2 helper T cells to help activate _______ cells
IL-4; B cells
TH2 helper T cells activate B cells to express immunoglobulins that then activate ______ in response to multicellular parasites
Granulocytes
TH2, TFH, and TH17 primarily assist in the activation of cells to fight (intra/extra)cellular pathogens
Extracellular
TFH secrete cytokines _____ and _____ to promote B cell activation and isotype switching
IL-4 and IL-21
T/F: Effector T cells require a costimulatory signal to become activated
False; they undergo changes that no longer require costimulatory signals
How do cytotoxic T cells destroy target cells?
They contain lytic granules that contain cytotoxins, these cytotoxins are secreted at a specific cell and destruction
How do cytotoxic cells prevent necrosis?
Creates pores on target cells to induce apotosis
or
expresses protein FAS ligand that binds to FAS on target cell resulting in the recruitment of apoptotic proteins to the plasma membrane
What two signals do macrophages require from TH1 helper T cells for activation?
1) IFN-gamma secretion from TH1 helper T cell
2) binding of CD40 ligand and CD40 receptor on macrophage
Activated macrophages increase expression of _______ and ______ receptors
Cd40 and TNF-alpha
What is the function of TNF-alpha?
Enhance macrophage activity
T/F: TH1 helper T cell mus remain in contact with macrophages to continue expression of IFN-gamma and CD40L
True
Cytokine ______ is released by ______ helper T cell and activates granulocytes
IL-5; TH2
Helper T cell TH2 secretes _______ cytokine which activates B cells to switch and express the immunoglobulin isotype _____.
IL-4; IgE
