immune tolerance Flashcards
- Why is immune regulation necessary?
Avoid excessive lymphocyte activation and tissue damage during normal protective responses against infections
Prevent inappropriate reactions against self antigens
- Give the steps of cell-mediated immunity
Induction - Cell infected DC collects material
MHC-peptide TCR interaction Effector - Naïve T cell becomes effector Effector cell sees MHC-peptide on infected cell performs function Memory - Effector pool contracts to memory
- What are the 3 signals that are required to activate the T or B cells?
Antigen Recognition
Co-Stimulation - protein interactions on cell surface of APC, T cells and B cells Cytokine Release
- Describe the 3 possible end outcomes of infection
Resolution - No tissue damage, returns to normal. Phagocytosis debris by macrophages
Repair - Healing with scar tissue and regeneration. Fibroblasts and collagen synthesis Chronic Inflammation - Active inflammation and attempts to repair damage ongoing
- What is meant by immunological tolerance?
Tolerance is specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen
- How does B cell selection occur in the bone marrow?
If immature B cells encounter antigen in a form which can crosslink their IgM, apoptosis is triggered
- What are the 2 types of tolerance?
Central - destroy self-reactive T or B cells before they enter circulation
Peripheral - destroy self-reactive T or B cells once they are in circulation
- Which 3 ways does T cell selection occur in the thymus?
Useless- Doesn’t bind to any self-MHC at all; Death by neglect (apoptosis)
Dangerous - Binds to self-MHC too strongly; Apoptosis triggered - negative selection Useful - Binds to self-MHC weakly → Signal to survive - positive selection
- How can a T-cell developing in the thymus encounter MHC bearing peptides expressed in other parts of the body?
- What happens if there is a mutation in AIRE?
Specialised transcription factor - AIRE - allows thymic expression of genes that are expressed in peripheral tissue
so T cell developing in thymus can encounter MHC bearing peptides expressed in other parts of the body
Multi-organ autoimmunity
- What are the 3 pathways that a B cell can go into after maturation?
Antibody Production
Memory Cell Affinity Maturation
- Describe what affinity maturation is
B cells can change specificity after leaving bone marrow
This improves antibody quality Exposure to self-antigens can make them less tolerogenic breaking tolerance
- What is Anergy?
- Explain how Anergy occurs
Anergy is one of three processes that induce tolerance, modifying the immune system to prevent self-destruction
Most cells lack co-stimulatory proteins and MHC class II If naïve T cell sees MHC/peptide ligand without appropriate co-stimulatory protein, it becomes anergic Less likely to be stimulated in the future even if co-stimulation is present
- How does Ignorance lead to peripheral tolerance of T cells?
Antigen present in too low concentration to reach threshold for T cell receptor to become triggered
T cells become anergic or no longer reactive
- At which sites specifically, would ignorance occur in this context?
Immunologically privileged sites- could be compartmentalised by an anatomical barrier or anti inflammatory cytokines released
Where T cells don't come into contact with antigen - because fulminant immune reactions would cause more harm than good and so antigens in these sites do not elicit an immune response e.g - eyes or brain
- Describe Antigen Induced Cell Death in context of peripheral tolerance of T cells?
- Why does this occur?
antigen presenting cell promotes apoptosis in the presence of antigen
T cell binds to APC, encounters a signal eg Fas ligand to undergo apoptosis
mechanism to reduce the amount of self reactive T cells, also occurs at the end of a immune response.
