Immune Tolerance/Auto-immunity Flashcards
Define tolerance.
The elimination or control of latent auto-reactivity (the control of the destructive power of the immune system).
Define auto-immunity.
A failure of tolerance.
Define deletion or negative selection.
Destroy auto-reactive cells at their source.
Define regulation.
Inactivate or suppress auto-reactive cells.
Define co-stimulation.
2 signals required for lymphocyte activation.
What are privileged sites?
Locations hidden from immune system under normal circumstances.
What do active tissue-defense mechanisms do?
Destroy invading auto-reactive T-cells.
What are the 2 types of tolerance?
Central Tolerance: Destruction of auto-reactive cells at the source (negative selection or deletion)
Peripheral Tolerance: Inactivation, elimination, or control of auto-reactive cells after development
Where is the Central tolerance located? Peripheral tolerance?
Primary lymphoid organs (thymus and Bone marrow); Periphery
T-cells develop from which cell types and where?
From hematopoietic stem cells in the bone marrow.
Where do the stem cells become T-cell precursors/rearrange their TCR genes and what are they called here?
In the thymus, called thymocytes.
What percent of thymocytes survive to become T cells? Where do they die?
Only 1% survive, the other 99% die in the thymus.
Why do thymocytes die?
Either their T-cell receptors are not useful (they do not recognize anything) or are harmful (auto-reactive).
What are the limitations of Central tolerance?
- Self antigens must be expressed in the thymus or bone marrow (so what about tissue-specific antigens and pregnancy/puberty antigens?)
- Somatic mutation of Ig genes could also generate auto-reactive antibodies.
Where would a tissue graft never be rejected and why?
Brain, eye or testis since these are “privileged sites” where immune responses are either impaired or suppressed.
What are special characteristics of these sites?
Anatomical (fluid drainage); Cytokine expression (i.e. immunosuppression by TGF-beta); expression of Fas Ligand (causes apoptosis of invading T-cells)
In co-stimulation, what does signal 1 refer to? Signal 2?
Signal 1: Antigen receptor signal
Signal 2: Costimulation signal
Which signal is linked to infection?
Signal 2
What happens when you have signal 1 and not signal 2?
Causes lymphocyte non-responsiveness (anergy) and/or apoptosis of T-cell.
Where does Signal 2 come from in B-cells? In T-cells?
B cells – Helper T-cells
T cells – specialized antigen presenting cells (i.e. macrophages, dendritic cells, B cells)
In Signal 1, what is involved with the T cell and the Antigen presenting cell?
T cell: CD4, TCR and CD3
Antigen Presenting Cell: MHC class II + peptide
In Signal 2, what is involved with the T cell and the Antigen presenting cell?
T cell: CD28, CD40L
Antigen Presenting Cell: B7, CD40
How is B7 up-regulated into the T cell? Why is it important?
Pathogen recognition process causes B7 up-regulation; it signals macrophages to produce more MHC and helps with binding.
What are the only cell types that can provide co-stimulation to T-cells?
Dendritic cells, B-cells and macrophages.
