Immune Tolerance Flashcards
Consequences of excessive immune system?
Allergies. Autoimmune disease.
Consequences of deficient immune system?
Infection. Cancer.
Major allergy immune system cell?
Mast cell.
What causes acute anaphylactic shock?
IgE and Mast cells.
What causes delayed type hypersensitivity?
T cells.
2 types of allergy?
Acute anaphylactic shock. Delayed type hypersensitivity.
Types of failure of immune regulation?
Autoimmunity. Allergy. Hypercytokinemia and sepsis.
What is Hypercytokinemia and sepsis?
Too much immune response.
What do you call a t cell after it has binded to mhc complex on antigen presenting cell?
Effector.
What converts a naive t cell to an effector t cell?
Antigen recognition. Co-stimulation. Cytokine release.
What occurs as the pathogen is eliminated?
Apoptosis of lymphocytes that lose their survival signals (antigen). Formation of memory cells.
What cells are involved in resolution and repair after infection is cleared?
Macrophages and fibroblasts.
What are the two types of tolerance in immunity?
Central and peripheral tolerance.
When does central tolerance occur?
Before immune cell enters bloodstream.
When does peripheral tolerance occur?
Once immune cell is in bloodstream.
What is central tolerance?
Lymphocytes that recognise self antigens are deleted (apoptosis) or made harmless before they enter bloodstream.
What is peripheral tolerance?
Destroy or control any self reactive T or B cells which do enter the circulation.
What can lead to apoptosis of t cell in thymus?
If the t cell doesn’t bind or binds too strongly to self mhc.
What is negative selection in t cell central tolerance?
T cell binds to self mhc too strongly.
What is positive selection in t cell central tolerance?
T cell binds to self mhc weakly.
What is death by neglect in t cell central tolerance?
T cell doesn’t bind to self mhc.
How can a T cell in the thymus encounter MHC bearing peptides in other parts of the body?
Autoimmune regulator gene (AIRE Gene).
What is the Autoimmune regulator?
Transcription factor that expresses genes from other tissues. This allows T cells to test for self antigens.
Mutations in autoimmune regulator gene causes what?
Multi organ auto immunity.
What are the three pathways for naive b cells?
Plasma cells. Memory cells. Affinity maturation.
Why is peripheral tolerance important in relation to b cells?
B cells undergo affinity maturation. B cells can turn from non self to self even after leaving maturation in bone marrow.
What is anergy (deactivation of t cell)?
Type of peripheral tolerance. T cell binding to mhc but antigen presenting cell doesn’t have co stimulation proteins. Engagement of inhibitory receptors on T cell. T cell less likely to be stimulated in the future even if co stimulatory proteins are present.
What is ignorance?
Type of peripheral tolerance. Antigen is present in too low of a concentration to trigger T cell response.
What is antigen induced cell death?
Activation of t cell receptor leads to apoptosis. Binding of fas ligand to fas receptor causes apoptosis of t cell.
What cytokines to T regulatory cells release?
TGF-Beta (
Transforming growth factor),IL-10,IL-35.
How do Treg cells regulate immune response?
Inactivate dendritic cells so naive T cells aren’t activated. Inhibition of T cell effector functions.
Treg CD phenotype?
CD4 and CD25 present.
How do Treg cells regulate immune response if lymphocytes bind to self antigen?
T lymphocytes are activated by binding to self antigen on MHC in thymus or peripheral tissues. Activated lymphocytes release IL2. IL2 binds to IL2 receptor on Treg cells and foxp3 is expressed. Release of anti inflammatory cytokines such as IL-10. Inhibition of T cell activation or effector functions.
Role of chemokines?
Cell migration.
Role of cytokines?
Level of immune response. Cytokines shape transcription factor pathways. Transcription factor pathways result in different t helper cell types.
What is foxp3?
Transcription factor that controls production of IL-10 in Treg cells.
Mutation in foxp3 leads to?
IPEX syndrome.
IL-10 function?
Anti-inflammatory cytokine. Blocks pro-inflammatory cytokines such as TNF, IL-6, IL-8 and IFN gamma. Downregulates macrophages.
Natural regulatory t cells development?
Recognition of self antigen during maturation in thymus. Reside in peripheral tissues to prevent harmful reactions against self.
Inducible regulatory T cells development?
Develop from mature CD4 T cells that are exposed to antigen in the periphery.
How do T follicular cells activate B cell?
T follicular helper cell binds to MHC II peptide presented by B cell. Release of IL-21 from tfh activates B cell along with the costimulatory proteins.
What can T helper cells do to B cells?
Drive immunoglobulin class switch.
Complement protein c3b role?
Opsonisation.