Lec 1 Final Flashcards
(49 cards)
What is immunologic tolerance?
The unresponsiveness of the immune system to an antigen (tolerogen)
Why is immunologic tolerance particularly important when dealing with self-antigens?
It protects against autoimmunity (autoimmune diseases).
What are the types of immunologic tolerance?
1- Central tolerance
2- Peripheral tolerance
How are self-antigens presented to the immune system?
1- locally in the primary lymphoid organs
2- Imported after their capture from the periphery.
When is peripheral tolerance used?
Peripheral tolerance is used when the self-antigen is not presented in the primary lymphoid organ or when the self-antigen is expressed only in adult life.
What happens to self-reactive lymphocytes in peripheral tolerance?
1- apoptosis (programmed cell death)
2- anergic (unresponsive)
3- actively suppressed by regulatory T (Treg) cells.
How does sequestration of self-antigens in immune-privileged areas prevent immune responses?
By keeping self-antigens away from the immune system
Where does negative selection occur in the thymus?
1- Double-positive (DP) T cells ➡️ Cortex
2- Single-positive (SP) T cells ➡️ Medulla.
What happens if a thymocyte’s T cell receptor (TCR) recognizes a self-antigen-HLA complex on an antigen-presenting cell with STRONG SIGNAL
It leads to clonal deletion.
What happens if a thymocyte’s T cell receptor (TCR) recognizes a self-antigen-HLA complex on an antigen-presenting cell with WEAKER SIGNAL
formation of regulatory T (Treg) cells, which are released to the periphery and mediate peripheral tolerance.
What are the pathways of programmed cell death (apoptosis) ?
The intrinsic (mitochondrial) pathway - The extrinsic (death receptor) pathway
The intrinsic (mitochondrial) pathway is related to . . . ?
Central tolerance
The extrinsic (death receptor) pathway is related to . . . ?
Peripheral tolerance
The intrinsic (mitochondrial) pathway is regulated by . . . ?
Bcl-2 family proteins, such as Bim
Explain the process of the intrinsic (mitochondrial) pathway
Bcl-2 family proteins, such as Bim will oligomerize and insert into the outer mitochondrial membrane, leading to the leakage of mitochondrial cytochrome c. This activates caspase-9, which then causes fragmentation of cellular DNA and cell death.
Explain the process of the the extrinsic (death receptor) pathway
It involves the binding of the Fas ligand (FasL) to the Fas (CD95) receptor, which activates caspase-8 and eventually leads to apoptosis.
What is co-stimulation in T cell activation?
Co-stimulation involves the binding of CD28 on T cells to B7-1 (CD80) and B7-2 (CD86) on antigen-presenting cells (APCs).
How does anergy occur?
1- blockage of TCR-induced signal transduction
2- Ubiquitination
3- Activation of inhibitor receptors of the CD28 family, including CTLA-4 and PD-1.
How does CTLA-4 function in T cell tolerance?
1- competing with CD28
2- endocytosis of the corresponding B7 molecule.
How does PD-1 function in T cell tolerance?
By phosphatase activity that inactivates immune receptors.
What are Treg cells?
Treg cells are CD4+ T cells that suppress immune responses.
What are the characteristic features of Treg cells?
1- Express high levels of the IL-2 receptor α chain (CD25)
2- FoxP3 transcription factor.
Name the divisions of Treg cells based on their mode of formation?
1- Thymic Treg (tTreg) cells
2- Peripheral Treg (pTreg) cells.
peripheral Treg (pTreg) cells known as … ?
Known as adaptive or inducible Tregs
