111 Questions
What is the primary function of the thymus?
Maturation of T-cells
What happens to the thymus with age?
It atrophies and fills with fibrous tissue
Which of the following is NOT a factor influencing T-cell development?
Spleen
What is the primary role of thymopoietins in T-cell development?
Promotion of T-cell maturation
Which substance is primarily produced by the thymus to support T-cell development?
Thymotaxin
What is the main role of thymotaxin in T-cell development?
Regulating the migration of T-cells
What is required for major histocompatibility complex-restricted antigen presentation?
Interaction of the TCR with antigenic peptide and MHC molecule
How does the TCR differ from the BCR in terms of antigen recognition?
TCR recognizes a linear peptide bound to MHC molecules, while BCR recognizes free antigen
Which subset of T cells reacts to MHC-I?
CD8 T lymphocytes
Which cells express MHC-II?
Professional APCs (pAPCs)
What is the main function of CD4 T cells?
Regulate adaptive immune responses
Where does the process of T cell development start?
Bone marrow
What is the role of T lymphocytes in immune responses?
Recognizing self and non-self
In the context of TCRs and BCRs, what is a major difference between them?
TCRs recognize antigens through MHC-II, while BCRs recognize antigens through MHC-I
Which cells respond to MHC-restricted antigen presentation and require CD4 coreceptors?
T-helper cells
What is the process involved in positive selection of T lymphocytes?
Promotion of self-tolerance in developing T lymphocytes
What is the main function of effector T lymphocyte subset TH1?
Cell-mediated immunity against intracellular pathogens
Which antigen-presenting cells are involved in the development and activation of T-cytotoxic cells?
Dendritic cells
What is the outcome of negative selection in T lymphocytes?
Activation of autoreactive T lymphocytes
Which type of T lymphocytes are characterized by γ:δ TCRs?
Innate-like lymphocytes
What is the function of TH2 effector T lymphocyte subset?
Induction of allergic responses
What is the process that leads to central tolerance in T lymphocytes?
Elimination of autoreactive T lymphocytes
Which cytokines are responsible for the differentiation of CTLs (cytotoxic T-lymphocytes)?
IL-12 and IFN-γ
What is the role of peripheral tolerance in the immune system?
Suppression of immune responses against pathogens
Where do mature T cells traffic from after exiting the thymus in search of their specific antigen?
Lymph node
Where do lymphocyte progenitor cells arise?
Bone marrow
Where do lymphocytes develop into mature naïve T lymphocytes?
Thymus
At which point do T cell progenitors enter the thymus?
Corticomedullary Junction
What type of epithelial cells produce a variety of polypeptides that influence the phenotypic maturation of progenitor cells from the bone marrow and the modulation of the functions of mature T cells?
Medullary thymic stromal cells
Which factor is responsible for engaging thymocyte interleukin 7 receptors and stimulating thymocyte development?
IL-7
What type of animals demonstrate the importance of the thymus in T cell development?
Athymic animals
Which region of the thymus do thymocytes migrate towards upon entering?
Cortex
What happens to T cell progenitors upon interaction with cortical thymic stromal cells (cTECs)?
They receive signals to proliferate and commit to the T cell lineage
Which signaling pathway stimulates Notch1 on the surface of thymocytes?
Direct signaling provided by Notch1 ligand on cTECs
T lymphocytes play a major role in the defense against which of the following?
Viruses and intracellular protozoa
What is the role of T cells in immune surveillance?
Recognition and killing of tumor cells
What is the main component of the antigen receptor complexes in T lymphocytes?
Both antigen binding and signaling parts
How many distinct specificities can each clone of T cell receptors potentially have?
~10^16 distinct specificities
What mediates the effector functions in T cell receptors?
Constant (C) regions of secreted Ig
What type of antigens do B cell receptors (BCRs) recognize?
Free antigens
Apart from the antigen binding part, what triggers a signaling cascade in a B cell receptor complex?
Proteins (Igα and Igß) associated with membrane Ig
What is the function of secreted antibodies as part of the BCR complex?
Ag specificity
What forms of antigens are mainly recognized by antibodies (immunoglobulins)?
Macromolecules (proteins, polysaccharides, lipids, nucleic acids), small chemicals
What is responsible for antigen specificity in the BCR complex?
Antigen binding part only
What type of antigens do T cell receptors (TCRs) recognize?
MHC-linked antigens
Which cytokine is key in the early development of T lymphocytes?
IL-7
What is the primary role of the CD3 molecule in T cell development?
Assisting in signal transduction
Which type of TCR is found on the majority of T lymphocytes?
α:β TCRs
What is the outcome if a functional γ:δ TCR is produced before a functional β-chain?
Formation of δ:γ TCR-expressing T cells
What signals double-negative thymocytes to stop rearrangements of the β-chain gene and undergo proliferation?
Formation of pre-TCR complex
What is the composition of the CD8 molecule?
An α-chain and a β-chain
What is the function of terminal deoxyribonucleotidyl transferase (TdT) in T cell development?
Promotion of gene rearrangement
What is the role of RAG-1 and RAG-2 in T cell development?
Supporting gene rearrangement
What happens if a functional α:β TCR is produced first during thymic development?
Continuation of gene rearrangements
What is the lifespan of double-positive (DP) thymocytes?
3-4 days
Which enzyme joins a D segment to a J segment during TCR rearrangement?
TdT
What type of antigens do γ:δ TCR-expressing T cells recognize?
CD1:glycolipid antigens
What is the role of the CD3 molecule in T cell development?
It provides phosphorylation sites for signal transduction
What triggers a signaling cascade in a B cell receptor complex?
Antigen binding part
What is the outcome if a functional γ:δ TCR is produced before a functional β-chain?
Development of γ:δ TCR-expressing T cells without undergoing any selection process
What type of epithelial cells produce a variety of polypeptides that influence the phenotypic maturation of progenitor cells from the bone marrow and the modulation of the functions of mature T cells?
Thymic epithelial cells
Which type of T cell reacts to MHC-I?
CD8+ T cell
What happens to thymocytes that express a functional β-chain first?
They undergo positive selection
Which molecule is expressed by double-negative (DN) thymocytes at an early stage of their development?
CD2
What is the key cytokine in the early development of T lymphocytes?
IL-7
Which type of TCR is found on the majority of T lymphocytes?
α:β TCRs
What type of antigens does the γ:δ TCR recognize?
CD1:glycolipid antigens
Which genes are only expressed by thymocytes during the rearrangement of the T cell receptor genes?
RAG-1 and RAG-2
What do six subunits, collectively referred to as CD3, provide for the TCR?
Assistance in signal transduction
What does the expression of the pre-TCR signal double-negative thymocytes to do?
Start rearrangement of the β-chain genes
What happens if a functional γ:δ receptor is produced before a functional β-chain in thymocytes?
The cell commits to the γ:δ lineage
What happens if a functional α:β TCR is produced first in thymocytes?
The cell commits to the α:β lineage and continues thymic development
Which enzyme is involved in the rearrangement of the TCR?
Recombination-activating genes 1 & 2 (RAG1/RAG2)
Which co-receptor molecule becomes part of the TCR complex?
CD8
What is the primary tyrosine kinase responsible for the phosphorylation of CD3 ζ-chains?
Lymphocyte-specific protein tyrosine kinase
Where does positive selection of thymocytes occur?
Thymic cortex
Which antigen-presenting cells are involved in the process of positive selection?
cTECs
What is the outcome of positive selection in terms of cell lineage commitment?
CD4+ or CD8+ cell lineage commitment
Where do thymocytes that have been positively selected move on to?
Thymic medulla
Which cells present tissue-restricted peptides in the context of both MHC class I and MHC class II?
cTECs
What is the function of mTECs in thymocyte development?
Negative selection
What is the primary role of CD4 co-receptor molecules in TCR interaction?
Signal TCR to bind self-MHC:self-peptide with moderate affinity
What happens to thymocytes that remain CD4+CD8+?
Undergo negative selection and die if the TCR fails to interact with either MHC class I or MHC class II.
What is the role of signal 3 in T lymphocyte activation?
Differentiation into T lymphocyte subsets
Which part of the TCR complex transduces antigen recognition into an intracellular messaging response?
CD3
What is the T lymphocyte receptor for costimulatory molecules?
CD28
What type of immune responses are TH1 cells involved in?
Adaptive immune responses to intracellular pathogens
In the presence of which cytokines are TH2 cells generated?
IL-4
What is the consequence of T lymphocytes failing to receive co-stimulation during antigen presentation?
T cell anergy
What is the primary outcome of incomplete T lymphocyte activation in secondary lymphoid tissue?
Peripheral tolerance
Which molecules deliver the survival signal to T cells in the form of surface co-stimulatory molecules?
CD80 and/or CD86 (B7.1 and B7.2)
Where does activation of mature T lymphocytes also require differentiation signals in the form of cytokines?
Secondary lymphoid tissue
What is the main driving force behind the development of central tolerance in the immune system?
Negative selection
What is the function of thymic regulatory T lymphocytes (tTreg) in the periphery?
Peripheral tolerance
What process leads to the maturation and exit of mature, naïve T lymphocytes from the thymus?
Positive selection
Which signaling molecules are required for T lymphocyte activation per se?
CD3 molecules
What happens to mature, naïve, resting T lymphocytes in the absence of antigen stimulation?
They may live for years
Which process eliminates T lymphocytes encountering large, constant amounts of antigen shortly after exiting the thymus and in specific locations?
Activation-induced cell death
What is responsible for the elimination or rendering of T lymphocytes unresponsive to 'ubiquitous' antigens in the periphery?
Peripheral tolerance
What is the ability of thymocytes specific for selfMHC: self-peptide complexes that receive co-stimulation in the thymic medulla?
They are signaled to die
What happens to thymocytes that have escaped negative selection?
They become mature, naïve T lymphocytes and leave the thymus
What is crucial for antigen presentation with co-stimulation to yield activation, clonal expansion, and differentiation instead of death?
Co-stimulation (CD28 engagement)
Which cytokines are involved in yielding TH17 cells during antigen presentation?
IL-6 and TGF-ß
What are the two forms of TCRs that T lymphocytes can express?
α:β and γ:δ
Which cells are specialized in the killing of infected host cells and transformed cells?
CTLs
In the presence of which cytokines do TH17 cells yield inflammatory TH17 cells or regTH17 cells?
IL-6 and TGF-ß
Which type of TCR-expressing T cells comprise a small population of the T cell pool?
γ:δ TCR-expressing T cells
In which stage of the T cell's life cycle does antigen presentation serve the purpose of reactivation of memory T lymphocytes?
Response to infection
Which type of effector and memory cells are yielded from the activation of CD4+ T lymphocytes?
TH1 and TH2 cells
What is the main outcome of the activation of CD8+ T lymphocytes?
Activation into cytotoxic T lymphocytes (CTLs)
What is the role of IL-23 in antigen presentation for yielding TH17 cells?
Yielding pathological TH17 cells
Study Notes
- T lymphocytes are crucial for adaptive immune responses, including B lymphocyte activation and antibody production.
- This session focuses on T lymphocyte development, early life cycle, and self/non-self discrimination.
- Knowledge gained here is essential for understanding immunodeficiencies and immunopathologies.
- T lymphocytes recognize antigens through T cell receptors (TCRs) and major histocompatibility complexes (MHCs).
- TCRs are complex-restricted and engage MHCs for successful interaction.
- MHC-I and MHC-II molecules are present on different antigen-presenting cells.
- T cells can be CD4 or CD8, with distinct functions, requirements, and cells involved in their development and activation.
- α:β and γ:δ TCRs differ in development and functions of the cells bearing them.
- Bone marrow, thymus, and secondary lymphoid tissue contribute to the life cycle of α:β T lymphocytes.
- Positive and negative selection processes shape the immune response, leading to central and peripheral tolerance.
- Antigen presentation and T cell activation occur through specific mechanisms.
- Incomplete T lymphocyte stimulation results in peripheral tolerance and the development of effector T lymphocyte subsets (TH1, TH2, TH17, CTLs, TFH, and Treg) with unique functions.
- Innate-like lymphocytes (ILLs) such as NK cells, NKT cells, and IELs also play important roles in the immune system.
- The topics covered include T lymphocyte development, structure and function of various immune cells, antigen processing and presentation, and host defense mechanisms.
- Multiple resources, such as books and online content, are available to supplement learning.
- The session aims to help students understand the complex immune system, its components, interactions, and functions.
This workshop focuses on the major histocompatibility complex-restricted antigen presentation and the interactions of the T cell receptor with antigenic peptide and MHC molecule. Learn about the composition and function of the T cell receptor complex.
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