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.
- What do T regulatory cells do?
Block T cell activation
Inhibit effect of matured T cells
- Describe the function of IL-10
Key anti-inflammatory cytokine
Pleiotropic - Multi-functional Blocks pro-inflammatory cytokine synthesis including TNF, IL-6, IL-8, IFN-gamma Downregulates macrophage functions
- What might be the reason for T-regulatory cells being present in only mammals?
Critical in pregnancies for mammals
Foetus gets half MHC from mum and other half from dad These may be seen as foreign antigens So immunological tolerance is necessary
- Describe the 2 different types of T-regulatory cells
- Natural T-regulatory cells (nTreg)Development in thymus and requires recognition of self antigen during T cell maturationReside in peripheral tissues to prevent harmful reactions against self
- Inducible regulatory T cells (iTreg)
- What is the function of chemokines?
Chemokines drive movement around the body, sends things to the correct place
chemoattractants and draw immune cells to an area
Chemokine receptor profiles change with activation state of the cells
- What is the function of chemokines?
Chemokines drive movement around the body
Act like address labels sending stuff to the right place Chemokine receptor profiles change with activation state of the cells
- Explain the process in which T cells boost the B cell response
CD4 T cells release a certain type of cytokine
This cytokine is detected by the B cell The antibody that the B cell will produce will now have its constant region altered which determines its class This way, the class of antibody produced is dependent on the cytokine triggered
