Regulation of Lymphocytes Flashcards
What is immune regulation?
mmune regulation is control of the immune response to prevent inappropriate reactions
Why is immune regulation important?
- Immune regulation is of paramount importance for protection from infection by pathogenic microorganisms and for survival of the infected mammalian organism.
- Immune regulation is achieved by a complex interactive network of immune cells.
- It is required to:
- To avoid excessive lymphocyte activation and tissue damage during normal protective responses against infections
- To prevent inappropriate reactions against self antigens (“tolerance”)
- Failure of control mechanisms is the underlying cause of immune-mediated inflammatory diseases
Why is autoimmunity a failure?
•Definition: immune response against self (auto-) antigen = pathologic
–Disorders are often classified under “immune-mediated inflammatory diseases”
•General principles:
–Pathogenesis: Susceptibility genes + environmental triggers
–Systemic or organ-specific
What are the features of autoimmune diseases?
•Fundamental problem: imbalance between immune activation and control
–Underlying causative factors: susceptibility genes + environmental influences
–Immune response is inappropriately directed or controlled; effector mechanisms of injury are the same as in normal responses to microbes
•Many immunological diseases are chronic and self-perpetuating
What re immune mediated inflammatory diseases?
•Chronic diseases with prominent inflammation, often caused by failure of tolerance or regulation
–Rheumatoid Arthritis, Irritable Bowel Disease, Multiple Sclerosis, psoriasis, many others
–Affect 2-5% of people, incidence increasing
•May result from immune responses against self antigens (autoimmunity) or microbial antigens (Crohn’s disease?)
•May be caused by T cells and antibodies
•May be systemic or organ-specific
Why is allergy a failure?
- Harmful immune responses to non-infectious antigens that cause tissue damage and disease
- Can be mediated by antibody (IgE) and mast cells – acute anaphylactic shock
- Or by T cells – delayed type hypersensitivity
Why is hypercytokinemia and sepsis a failure?
- Too much immune response
- Often in a positive feedback loop
- Triggered by pathogens entering the wrong compartment (sepsis) or failure to regulate response to correct level
What is the 3 signal model in licensing a response?
3 Signals Required 1. Antigen Recognition 2.Co-stimulation 3.Cytokine Release This licenses the cell to respond
What is self limiting responses?
- Immunity comes with a price tag
- Cardinal feature of all immune responses: SELF-LIMITATION
- Manifested by decline of immune responses
- Principal mechanism: immune response eliminates antigen that initiated the response
- => First signal for lymphocyte activation is eliminated
What is resolution and repair at the end of a response and chronic inflammation?
- Resolution – no tissue damage, returns to normal. Phagocytosis of 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 the definition of immunological tolerance?
specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen (tolerogen vs immunogen)
What is the significance of immunological tolerance?
–All individuals are tolerant of their own antigens (self-tolerance); breakdown of self-tolerance results in autoimmunity
–Therapeutic potential: Inducing tolerance may be exploited to prevent graft rejection, treat autoimmune and allergic diseases
What is central tolerance?
-Central tolerance – destroy self-reactive T or B cells before they enter the circulation
-Lymphocytes that recognise self antigens before maturation in the generative organs are eliminated (deletion) or made harmless.
Central tolerance: B cells
•If immature B cells in bone marrow encounter antigen in a form which can crosslink their IgM, apoptosis is triggered
What is peripheral tolerance?
- Peripheral tolerance – destroy or control any self reactive T or B cells which do enter the circulation
- Some B cells may change their specificity and some T cells develop into regulatory (suppressive) T lymphocytes
How can a T cell developing in the thymus encounter MHC bearing peptides expressed in other parts of the body?
Autoimmune regulator (AIRE
•A specialised transcription factor allows thymic expression of genes that are expressed in peripheral tissues
•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
