L7-Exam 2 Flashcards
The ___ is an absolute requirement for the maturation and differentiation of mature T cells
Thymus
Children born without a thymus (DiGeorge’s Syndrome) do not have ______
mature T cells
T cell differentiation occurs throughout life , but will tapper off subsequent to ___ as the thymus decreases in size (known as: thymic involution)
puberty
The___ is the site of education of a T cell and is the primary lymphoid organ for development of T cells; it is analogous to the bone marrow as the primary organs for development of B cells
The thymus
What three things occurs to a T cell when it is in the thymus?
1) Acquires T cell antigen receptor (TCR) - antigen specificity
2) Learns tolerance of self
3) Learns self-HLA restriction (recognition of foreign peptide only in association with self HLA molecules)
True or False: A common lymphoid progenitor stem cell leaves the bone marrow, without any T cell features. It could not be distinguished from a pro-B cell.
True
True or False: when T lymphocytes are in the bone marrow, they contain chemokine receptors on their surface
True
The precursor stem cells enter the thymus at the cortical-medullary junction and then migrate to the cortex. At this time, they are called ______ cells.
Double Negative Cells
True or False: Double negative cells expressed both CD4+ and CD8+
False - double negative cells express neither CD4+ nor CD8+
The decision whether to be an alpha-beta or gamma-delta T cell occurs at the ___ stage
Double Negative
Shortly after becoming DN cells, the cells begin expressing the genes for ___ and ___
RAG-1 and RAG-2
What is the function of RAG-1 and RAG-2?
Responsible for randomly rearranging genes that encode the delta/gamma and alpha/beta chains of the T cell antigen receptor (TCR)
The DN cells that become delta-gamma T cells express what three proteins on their cell surface?
CD3+
TCR gamma
TCR delta
True or False: The DN cells that become γδ T cells leave the thymus and migrate to epithelial sites around the body
True
If a DN cell does not become a delta-gamma T cell, it will be come a ____, which expresses what four proteins on its cell surface?
Pre-aßT cell (pre-T cell)
1. CD3+
2. Pre-Ta
3. TCRß
4. Zeta
True or False: γδ T cells continue to differentiate within the thymic cortex
False -Pre-aßT cell (pre-T cell) continue to differentiate within the thymic cortex
The functioning of the pre-T cell receptor results in ___ signals that stop further re-arrangement of the __ chain and initiates rearrangement of the __ chain
intracellular; beta; alpha
What five proteins do double positive cells of the thymus cortex express on their surface?
1) CD3+
2) CD4+
3) CD8+
4) TCRa
5) TCRβ
As maturing double positive thymocytes filter through the thymic cortex, they must pass through a mesh of stromal cells, known as:
1)
2)
1) thymic epithelial cells
2) interdigitating thymic dendritic cells
Double positive CD4+ and CD8+ thymocytes undergo selection, which is mediated by interactions with HLA molecules on ___ cells and CD4 and CD8 molecules on ___
stromal cells; thymocytes
_____ are among the few cells the express both class of HLA molecules (class I and II) constitutively
Thymic epithelium
During ___ selection, thymocytes must bind with a certain critical affinity to HLA molecules on the thymic epithelium.
positive
Once a cell completes positive selection, the cells are now educated to self HLA molecules, meaning they will only responds to….?
And the are considered to be ___-restricted
Self HLA + processed antigen (self or foreign)
HLA-restricted
____ selection occurs during transition from thymic cortex to thymic medulla, when encounter interdigitating dendritic cells at CM junction and later when they interact with medullary epithelial cells
Negative selection
Since T cells that survive positive selection are potentially able to respond to peptides derived from both self and foreign molecules loaded into the MHC, allowing those cells to leave the thymus and enter the circulation could result in ___
autoimmunity
If developing T cells responds to MHC + self peptide at the stage of negative selection, the cells die via ______
central tolerance mechanisms
The process of negative selection weeds out self-reactive cells via ___ or by inducing ___. The surviving cells are said to be ____
apoptosis; inducing T cell anergy
self-tolerant
____ immature thymocytes must bind HLA Class I and II on thymic epithelial cells with “just the right affinity.” If they don’t, they undergo apoptosis and die
CD4+/CD8+
Tolerance learned during ontogeny is called ____
central tolerance
Antigens present in the thymus are almost always ___ antigens
self
True or False: In Central T Lymphocyte tolerance, strong recognition to antigens results in apoptosis
True
Central T Lymphocyte Tolerance involves immature, ____ T cells
Double positive
True or False: The cells that survive both positive and negative selection become either CD8+ or CD4+
True
What are four features of cells that have survived positive and negative selection?
1) alpha/beta TCR+, CD3+, and CD4+
(or: alpha/beta TCR+, CD3+, and CD8+)
2) self-HLA restricted
3) self-tolerant
4) foreign antigen specific (HLA + foreign peptide specific)
If they survive the positive and negative selection process in the thymus, a mature, naiive T cell will leave the thymus and enter the circulation via the ____ and ____
blood; secondary lymphoid organs
What population of T cells leave the thymus for epithelial sites without undergoing positive and negative selection?
T cells that have the γδ TCR
Stem cells migrating to the thymus express this/these molecules on their surface
A. CD3
B. CD3, CD4, and CD8
C. CD4 and CD8
D. Chemokine receptors
E. Chemokine receptors and CD3
D. Chemokine receptors
True or False: Recirculation increases the change that a lymphocytes will encounter its antigen
True
Specific receptor-ligand interactions between ____ and _____cells occurs that mediate ___ and homing of the lymphocyte
lymphocytes and endothelial cells; recirculation
If, while filtering through a lymph node, a T cell encounter an APC (dendritic cell or B cell) expressing HLA+foreign peptide, it may respond (___) or not responds (___)
respond = activation
not respond = tolerance
T lymphocytes respond only to processed protein antigens derived from what three pathways?
-Endosomal
-Phagosomal
-Cytosolic (exogenous and endogenous)
B cells differentiate into ___ cells, which produce antibodies to deal with ___ antigens
plasma cells; extracellular antigens
Are T cells designed to deal with extracellular or intracellular cellular-associated antigens?
Intracellular antigens (cell-associated antigens)
What are the two possible outcomes due to T cell activation by antigen?
1) Production of cytokines, which signal other cells of immune system to become activated (helper T cells)
2) Killing cell possessing or expressing foreign antigen (cytoxic T cells)
T cells become activated with the immunological synapse is formed between an ___ and a ___ cell
APC (dendritic cell) and a T cell
___: a disulfide linked heterodimer glycoprotein belonging to the Ig superfamily of molecules
TCR (T-Cell Receptor)
True or False: Each member of the Ig Supergene Family is involved in binding or recognition of foreign antigens (HLA, Ig, TCR, etc.)
True
Like Ig receptors in B cells, the TCR is clonally distributed, which means that?
Each T cell clone bears a unique TCR that determines its antigen specificity
The majority of T cells have a ___ heterodimer composed of _ and _ chains and mature in the ___
TCR heterodimer; alpha/beta; thymus
True or False: A smaller population of T cells posses gamma and delta chains (gamma/delta TCR+) and mature without a requirement for the thymus
True
TCR’s have variable region domains in the alpha and beta chains
(_ and _)
Va and Vβ
In the Va and Vβ regions of the TCR, the two polypeptide chains come together to form a ____ site (similar to antibody hypervariable region) - this is where antigen binds
terminal antigen binding
True or False: CD3 is composed of gamma, epsilon and delta chains
True
True or False: CD3+ is a complex found on all mature T lymphocytes
True
___ is a chaperone for TCR and is a critical signaling molecule
CD3+
Which is a member of the Ig superfamily gene: TCR or CD3?
TCR
True or False: TCR has conserved and variable domains AND recognizes antigens and HLA on APC
True
Which molecules contain signaling molecules known as zeta chains (CD247) ?
TCR
Most exogenous exogenous antigens are processed by dendritic cells and presented to:
A. CD4+ T Helper Cells
B. CD8+ T Cytotoxic Cells
A. CD4+ T Helper Cells
True or False: TCR is noncovalent but closely associated with a number of transmembrane polypeptides (signaling and accessory molecules)
True
True or False: CD8+ is T cell specific
False: CD3 is T cell specific
What are the two primary functions of CD3?
1) Chaperone for TCR - transports newly made TCR molecules to cell surface
2) Cellular signaling molecule via transmembrane cytoplasmic domains
____ molecules are tightly associated with zeta chains, which are two identical polypeptides that are not T cell specific and are mostly intracellular
CD3
When antigen is process and presented with HLA molecules, it can be recognized and subsequently bound by the antigen binding site of TCR - known as ____
Signal 1
- This relays a conformational change that, in turn, activates CD3 and zeta molecule associated tyrosine kinases, and sets of a “cascade of intracellular events” leading to activation of T cell
Binding HLA and associated processed peptide to the TCR is stabilized by ____
CD4 and CD8
CD4 facilitates binding of HLA Class ___ molecules to TCR
HLA Class II
___ facilitates binding of HLA Class I molecules to TCR
CD8
___ and ___ are mutually exclusive in mature T lymphocyte
CD4 and CD8
CD4 and CD8 are ___molecules and also function in _____
adhesion; signal transduction
True or False: Binding of accessory molecules can function to either positively or negatively impact T cell activation
TRue
Positive, co-stimulatory interactions (signal 2) include:
1)
2)
- Binding of accessory molecule B7 (CD80) on APC to CD28 on T cell
- CD40 on APC to CD40L on T cell (CD154)
True or False: Positive, co-stimulatory interactions (signal 2) are critical to initial activation of a naiive T cell, but are not required for activation of memory T cells
True
Negative co-stimulatory interactions include:
1.
2.
- Binding of accessory molecules PD-L1 on APC to PD-1 on T cell
- Binding of B7 (CD80) on APC to CTLA-4 on T cell
____ binding strongly inhibits T cells and induces Treg differentiation. Further, it is essential for maintaining peripheral tolerance and limiting immune response.
PDL1/PD-1
Activation of a T Helper cell includes the transcription of ____ and ___ receptor genes
IL-2 and IL-2 receptor
___: an autocrine growth factor for T cells that induces both proliferation (entering the cell cycle) and eventually a differentiation to effector cell function (production of cytokines)
IL-2
IL-2 receptor is also known as ___
CD25
True or False: Memory T cells have fewer activation requirements upon second encounter with antigen and, therefore, are more easily activated than naiive T cells
True
Once activate in subsequent encounters with antigen, memory cells become either ___ or ___ cells
effector or memory cells
What interaction is critical for T cell activation?
Accessory B7 molecule (on the APC) interacts with CD28 on the T cell
When does peripheral tolerance of T cell occur?
In the lymph nodes, when T cells are stimulated (MHC/peptide-TCR) without secondary stimulation (B7-CD28)
When the primary signal (MHC/peptide-TCR binding) happens without the “second signal” (ex: B7-CD28) it can result in functional inactivation of T cell, known as: ______
clonal anergy
True or False: Once T cells become anergic, they can only be activated if they encounter their specific foreign peptide/MHC molecule
False - Once T cells become anergic, they CANNOT be activated, even encounter their specific foreign peptide/MHC molecule
Repeated stimulation of activation T cells can cause the T cell to due by _____
apoptosis (clonal deletion)
____ cells can inhibit activation of T cells by self-peptide/MHC
Regulatory T cells
Secondary signal is needed to stabilize ___ mRNA
IL-2 mRNA
Activation-induced cell death induces expression of ___ and ___, resulting in apoptosis
Fas and Fas ligand
In activation-induced cell death, expression of pro-apoptotic proteins results in ___
apoptosis
What are three examples of Regulatory T cells?
CD4+
CD25+
Fox P3+
True or False: Regulatory T cells suppress/inhibit activation of other T cells, most likely due to production of inhibitory cytokines
True
