immune tolerance part 1+2 Flashcards
define immune regulation
control of the immune response to prevent inappropriate reactions
give two reasons why immune regulation is required
.avoid excessive lymphocyte activation and tissue damage
. prevents inappropriate reactions against self antigens (tolerance)
what is meant by pathologic
immune response against self antigen
disorders are often classified as …
immune mediated inflammatory diseases
immune mediated inflammatory diseases can either be …. or ….
systemic, organ-specific
give 3 examples of chronic inflammatory diseases
psoriasis, rheumatoid arthiritis, lupus
What are the three phases of cell mediated immunity
induction
effector
memory
describe the steps of cell mediated immunity
1) cell infected dendritic cell (DC) collects material
2) MHC: peptide TCR interaction
3) Naive t cells become effectors
4) effector cells sees MHC: Peptide on infected cells performs function
5) effector pool contracts to memory
what is the cardinal feature of ALL immune responses
self limitation
explain self limitation
.immune response eliminates antigens that initiated the response
hence first signal for lymphocyte activation is eliminated
what licences a cell response
.antigen recognition
. Co-stimulation
. cytokine release
what are the three possible outcomes from an immune response
resolution: .no tissue damage
.phagocytosis of debris by macrophages
repair: . healing with scar tissue and regeneration
. Fibroblasts and collagen synthesise
chronic inflammation: ACTIVE INFLAMMATION AND ATTEMPTS TO REPAIR DAMAGE ONGOING
define tolerance
specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen
Give 2 significant features of tolerance
All individuals HAVE tolerance to self antigens where breakdown of this phenomena is autoimmunity
Theraputic potential which can treat autoimmune disease and prevent graft rejection
when does tolerance occurs
Before T/B cells enter circulation (central) In circulation (peripheral)
define central tolerance
destroys T/B cells before they enter circulation
How does B-cell selection for central tolerance occur
Immature B cell encounters antigen in form which cross links their IgM triggering apoptosis
How does T-cell selection for central tolerance occur
.Need to select for TCR which can bind to self MHC/self peptides
what happens if T cell doesn’t bind to any self-MHC
apoptosis
what happens if T cell binds too strongly to MHC?
apoptosis-NEGATIVE selection (no survival)
what happens if T cell binds too weakly to MHC?
Positive selection. (survival)
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
AIRE promotes self tolerance by allowing the thymic expression of genes from other tissues
Mutations in AIRE result in multi-organ autoimmunity (Autoimmune Polyendocrinopathy Syndrome type 1)
define peripheral tolerance
destroy or control any self reactive T/B cells which do enter circulation
what is AIRE
AutoImmune REgulator (AIRE
what determines B cell antigen specificity?
BCR
what does BCR consist of?
1 heavy chain
1 light chain
what happens to B cells after antigen exposure
.Antibody production
.Memory
.Affinity maturation-process whereby the immune system generates antibodies of higher affinities during a response to antigen.
true or false: B and T cells can change specificity after leaving bone marrow (somatic hypermutation)
False- only B cells can undergo somatic hypermutation
define anergy
lack of response by body’s defence mechanism against foreign substances
describe how peripheral tolerance occurs in T cells
. Naive T cells need Co-stimulatory Signals (CSS) TO BECOME activated
. most cells lack CSS and MHC CLASS II molecules
naive T cell meets MHC/PEPTIDE ligand without appropriate Co-stimulatory protein hence becomes anergic
cells less likely to be stimulated in future even if Co-stimulation is present
describe how ignorance causes peripheral tolerance
.Antigen may be too low of concentration for TCR to be triggered e.g immunological privileged sights such as eye, brain
Explain Antigen Induced Cell Death (AICD)
.Activation of the TCR can result in apoptosis
. in peripheral T cells is often caused by induction of expression of the death ligand: Fas Ligand (CD95,FasL)