8. Regulation of lymphocyte responses Flashcards
Importance of immune regulation
Avoid excessive lymphocyte activation and tissue damage during normal protective responses against infections
Prevent inappropriate reactions against self-antigens (“tolerance”)
What is autoimmunity?
Immune response against self (auto-) antigen
Systemic or organ specific
Imbalance between immune activation and control
What are the underlying causative factors of autoimmune disease?
Susceptible genes
Environmental influences
Immune-mediated inflammatory diseases
Chronic diseases with prominent inflammation, often caused by failure of tolerance or regulation
e.g. RA, IBD, MS
What may immune-mediated inflammatory diseases result from?
Immune responses against self-antigens (autoimmunity) or microbial antigens
May be caused by T cells and antibodies
What is allergy?
Harmful immune responses to non-infectious antigens that cause tissue damage and disease
What can allergy be mediated by?
Antibody (IgE) and mast cells (acute anaphylactic shock) T cells (delayed type hypersensitivity)
What is hypercytokinemia and sepsis?
When there is too much immune response
Too much cytokines in the blood
Sepsis: bacteria has crossed the mucosa and entered the blood stream
What is a cardinal feature of all immune responses and what is the mechanism for this?
Self-limitation
Manifested by decline in immune response
Removal of antigen means 1st signal for lymphocyte activation is eliminated
Describe the 3 signal model that licences a response
Antigen recognition
Co-stimulation
Cytokine release
What are the 2 general principles of regulating the immune response?
Responses against pathogens decline as infection is eliminated: driven by apoptosis of lymphocytes
Active control mechanisms limit responses to persistent antigens (self-antigens, tumours)
Define Immunological Tolerance.
Specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to the antigen
What is self tolerance and what does breakdown result in?
All individuals are tolerant of their own antigens
Breakdown= Autoimmunity
Therapeutic potential of immunological tolerance
Inducing tolerance may be exploited to prevent graft rejection, treat autoimmune and allergic diseases
What is tolerance?
State of immune functional unresponsiveness
What are the 2 types of tolerance?
Central tolerance: destroy self-reactive B and T cells before they enter circulation
Peripheral tolerance: destroy/ control self-reactive B and T cells which do enter circulation
What happens to Lymphocytes that recognise self-antigens before maturation in the generative organs?
They’re eliminated (deletion) or made harmless
What gene allows thymic expression of all the body’s gene products and what does this allow?
AIRE: autoimmune regulator
Allows T cell developing in thymus to encounter MHC bearing peptides expressed in other parts of body
promotes self-tolerance
What does this AIRE encode?
Specialised transcription factor
Allows thymic expression of all the body’s gene products
What do mutations in AIRE result in?
Multi-organ autoimmunity
Self reactive T cells are released because they haven’t seen proteins from other tissue
What are the 4 mechanisms of peripheral tolerance?
Anergy
Deletion
Ignorance
Regulation
Describe Anergy
T cell sees antigen on DC, but no co-stimulation
Shuts down the T cell and makes it unresponsiveness
(like increasing the activation energy by denying it of co-stimulation)
Describe Deletion
DC can induce cell death, removing T cell from circulation
Describe Ignorance
In some immunologically privileged sites there aren’t any APCs for the T cells to bind with
No antigen
No co-stimulation
No activation of T cell
