L28. Self vs. Non-Self Discrimination Flashcards
What is tolerance?
The mechanism of the body to ensure that the immune system is not self reactive (makes sure it doesn’t attack itself)
What are the two main types of tolerance? Where do they occur?
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Central Tolerance: occurs during the development of these lymphocytes
- Thymus for T cells
- Bone marrow for B cells
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Peripheral Tolerance: occurs to circulating/regional lymphocytes that already exhibit specificity for antigens
- Secondary lymphoid tissue (nodes)
- Peripheral tissues
What are the four main mechanisms used to induce tolerance? Define them
Deletion: induction of apoptosis
Anergy: switching off the cell and its processes and reactions
Ignorance: the cell never interacts with its antigen therefore is never activated
Regulation: the actions of the cell are dampened down such that they don’t have any major effect (Treg)
Which is more efficient, B cell or T cell tolerance?
T cell tolerance is much more efficient
What processes (anergy, regulation, deletion, ignorance) are involved in B cell central tolerance?
What mechanisms are involved in peripheral B cell tolerance?
Central: Anergy and Deletion
Peripheral: Ignorance and Anergy
During B cell development (Central), the developing B cells (IgM expressing) are exposed to different antigens.
Draw and describe the outcomes of the following situations
What 2 signals are required for B cells to successfully respond and survive?
- Interaction of the Ig with its specific antigen
- Co-activation signals from CD4 T helper cells via the CD40L and cytokine signalling
What are the steps that occur after B cell activation?
Draw the two possible outcomes: with and without T cell help
Without T cell help: there is low affinity activation leading to a short lived plasma cell that secretes some antibodies. This dies shortly after.
With T cell help: there is high affinity activation in the germinal centre leading to isotype switching and affinity maturation forming long lived plasma cells and memory B cells
Where does T cell development occur?
In the Thymus
Immature in the cortex eventually maturing as they pass the junction and towards the medulla
What are the stages of T cell development?
DN = double negative
DP = double positive
T cells require some small level of self reactivity. What is meant by this?
What is the implication of this on the antigen affinity?
This is because T cells need to have the ability to recognise MHC molecules for presentation and interaction with them
The affinity of T cells to their specific antigens is quite low compared to the affinity of by B cells
What are the main 2 mechanisms involved in central tolerance of T cells?
Deletion
Regulation (Tregs selection)
In which cell stage (of the development of T cells) undergoes selection?
Describe the two processes
The double positive thermocyte stage
1. Positive Selection
MHC recognition capacity is selected for. Those that do not succesfully recognise MHC molecules undergo death by neglect.
2. Negative Selection
T cells that are found to react to self peptides (presented on the MHC) are removed by apoptosis
What is the goldilocks theory?
This states that immature T cell receptors that make the cut into mature T cells have a finite affinity for their antigen.
The affinity to self is limited by negative selection and is promoted by positive selection
How do developing T cells of the thymus get exposed to all the self peptides of the body for negative selection to occur comprehensively?
A transcription factor called Autoimmune Regulator of Expression is expressed in thymic epithelial cells of the medulla (at the corticomedullary junction)
This leads to the ectopic expression of peripheral proteins (and antigens) in the thymic medulla
