Regulation of lymphocyte responses Flashcards
Why is regulation of T and B responses important?
Unregulated T and B cell responses lead to autoimmunity, allergy and Hypercytokinemia and Sepsis
What can mediate an Allergy?
Can be mediated by Antibody (IgE) and mast cells – acute anaphylactic shock
Or by T cells – delayed type hypersensitivity
What is an Allergyic reaction?
harmful immune responses to non-infectious antigens that cause tissue damage and disease
What is immunological tolerance?
specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen (tolerogen vs immunogen)
What is a therapeutic potential of immunological tolerance?
Therapeutic potential: Inducing tolerance may be exploited to prevent graft rejection, treat autoimmune and allergic diseases
Name two processes for tolerance?
Central tolerance
Peripheral tolerance
What is Central Tolerance?
Central tolerance – destroy self-reactive T or B cells before they enter the circulation.
What is Peripheral Tolerance?
Peripheral tolerance – destroy or control any self reactive T or B cells which do enter the circulation
Where does central tolerance occur?
Thymus
What mechanism destroys self reactive T or B cells in Central Tolerance?
Positive and negative selection
What happens if an immature B cells in bone marrow encounter antigen in a form which can crosslink their IgM?
apoptosis is triggered
How can a T cell developing in the thymus encounter MHC bearing peptides expressed in other parts of the body?
A specialised transcription factor allows thymic expression of genes that are expressed in peripheral tissues
How does AIRE promote self tolerance?
promotes self tolerance by allowing for the thymic expression of genes from other tissues
What does AIRE stand for and what is it?
AutoImmune REgulator
A specialised transcription factor allows thymic expression of genes that are expressed in peripheral tissues
What do mutations in AIRE result in?
Mutations in AIRE result in multi-organ autoimmunity (Autoimmune Polyendocrinopathy Syndrome type 1)
Name the mechanisms for Peripheral tolerance?
Anergy
Ignorance
Deletion
Regulatiob
RAID
What is Anergy in the context of peripheral tolerance?
Naive T cells need costimulatory signals in order to become activated
Most cells lack costimulatory proteins and MHC class II
If a naive T cell sees it’s MHC/peptide ligand without appropriate costimulatory protein it becomes anergic – i.e. Less likely to be stimulated in future even if co-stimulation is then present
What is ignorance in the context of peripheral tolerance?
Antigen may be present in too low a concentration to reach the threshold for T cell receptor triggering
Name some immunologically privileged sites?
eye, brain
What are immunologically privalages sites?
Certain sites of the human body have immune privilege, meaning they are able to tolerate the introduction of antigens without eliciting an inflammatory immune response.
What is antigen induced cell death?
Activation through the T-cell receptor can result in apoptosis
What is Regulation in the context of Peripheral Tolerance?
A subset of helper T cells known as Treg (T regulatory cells) inhibit other T cells
What transcription factor does Treg express?
FoxP3
What disease is caused by a mutation in FoxP3?
IPEX syndrome
What is the mechanism of action for regulatory t cells?
Secretion of immune suppressive cytokines - IL-10
Inactivation of dendritic cells or responding lymphocytes
Why is regulation critical in pregnancy?
Pregnancy as a parasitic infection
Exposure to new antigen
Expressed in the context of foreign MHCI
What do T Helper cells produce?
Cytokines
Why is IL-10 A master regulator?
Blocks pro-inflammatory cytokine synthesis incl TNF, IL-6, IL-8, IFNγ
Downregulates Macrophages
Viral mimics
Limits the immune response
Produced by Treg
Summarise T and B cell collaboration and the mechanisms governing the generation of antibody classes
T cells are induced to express the B cell stimulatory molecule CD40 ligand on their cell surface that binds to CD40 on the surface of B cells and secrete cytokines.
T cell derived cytokines drive proliferation and differentiation of B cells into antibody secreting plasma cells
T cell derived cytokines direct the immunoglobin class switching
