Life history of a T-cell part 1 Flashcards
What are the key hallmarks of adaptive immunity, and how do they contribute to immune responses?
Specificity - TCR
Diversity - microorganisms are very diverse therefore repertoire of lymphocytes has to match
Tolerance - means by which receptors are generated ,eans we can potentially develop receptors that are effective against own antigens
Circulation - lymphocytes in constant circulation between blood and lymphatic system
Division of labour - not all lymphocytes are equal
Memory - after replication for infection certain few stay behind incase reinfection from same pathogen
What are the stages in the life history of a T-cell, from development to memory?
Developing T-cell
Resting naïve peripheral T-cell
Effector TFH or regulatory T cell
Memory T cell
What is the purpose of positive and negative selection in the thymus?
Positive selection - developing T cells can recognize self-MHC molecules
Negative selection - elimination of developing T cells that react strongly to self-antigens, preventing autoimmunity
How does positive selection determine co-receptor specificity (CD4+ vs. CD8+)?
Selection of thymocytes based on their ability to recognize peptides presented by either:
- MHC class II molecules -> CD4⁺ helper T cells
- MHC class I molecules -> CD8⁺ cytotoxic T cells
Why are antigen-specific T-cells rare, and how does the immune system overcome this challenge?
Each T cell expresses a unique T-cell receptor (TCR) that recognizes only a specific antigen-MHC complex, and the diversity of possible antigens is immense
Clonal expansion - activated T cells proliferate rapidly upon encountering their specific antigen
Antigen-specific T cells encounter professional APCs in lymph node, where T cells are abundant - increases the likelihood of interaction
What is the role of conventional dendritic cells (cDCs) in naïve T-cell activation?
Capturing, processing, and presenting antigens on MHC molecules to T cells
Providing essential co-stimulatory signals and cytokines required for T-cell activation and differentiation
How do dendritic cells migrate to secondary lymphoid organs, and what factors regulate this process?
CCR7 (chemokine receptor) directs migration of dendritic cells thorugh lymphatic vessels
Further regulated by PAMPs or inflammatory cytokines that upregulate CCR7 expressions and enhance dendritic cell mobility
What happens to activated or non-activate naïve T cells in peripheral lymphnodes
Naïve T cells
- Exit the lymph node via the cortical sinuses
Activated T cells
- Start to proliferate and lose the ability to exit the lymph node
- Differentiated to effector cells and exit the lymph node
What is the role of the TCR-CD3 complex in T-cell activation?
Transmits signals from the antigen-specific T-cell receptor (TCR) upon recognition of an antigen-MHC complex, with CD3 proteins (containing ITAMs)
Initiates intracellular signalling cascades that lead to T-cell activation, proliferation, and differentiation
What is signal 1 in T-cell activation, and how is it mediated?
Antigen-specific signal mediated by the interaction of the T-cell receptor (TCR) with a peptide-MHC complex on an antigen-presenting cell (APC)
What is signal 2 in T-cell activation, and why is it required for full activation?
Co-stimulatory signal provided by the interaction of co-stimulatory molecules, such as CD28 on T cells with B7 molecules (CD80/CD86) on antigen-presenting cells
It is required for full activation to prevent anergic (non-responsive) states and ensure proper immune responses
What happens when antigen recognition occurs without co-stimulation?
No effect on T cell and no immune response