Immunology 8 Flashcards
Describe the importance of immune regulation
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
Describe what is meant by autoimmunity
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 is meant by systemic disease
Every immune cell activated
Describe the features of autoimmune disease
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
Describe immune-mediated inflammatory disease
Chronic diseases with prominent inflammation, often caused by failure of tolerance or regulation
RA, IBD, MS, 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
Describe allergy
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
Describe hypercyokinemia and sepsis
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
Describe a cardinal feature of all immune responses
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
Describe the characteristics of an immune response to a blood infection
The immune response is not localised
Describe the general principles of controlling immune responses
Responses against pathogens decline as the infection is eliminated
Apoptosis of lymphocytes that lose their survival signals (antigen, etc)
Memory cells are the survivors
Active control mechanisms may function to limit responses to persistent antigens (self antigens, possibly tumors and some chronic infections)
Often grouped under “tolerance”
In the absence of antigen, what is there also an absence of
Co-stimulation and APC
Where may active control mechanisms be located
Central or periphery
Define immunological tolerance
specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen (tolerogen vs immunogen)
What is the consequence of 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 type of process is tolerance
Active
What is hypercytokinemia
A cytokine storm, very dangerous, especially in the lungs, it can restrict the airways.
Describe central tolerance
Central tolerance – destroy self-reactive T or B cells before they enter the circulation
Occurs in the bone marrow and thymus
Describe peripheral tolerance
Peripheral tolerance – destroy or control any self reactive T or B cells which do enter the circulation
What causes B cells to be deleted in central tolerance
B cells that recognise self antigen undergo apoptosis.
However, some B cells undergo receptor editing and change their specificity
What causes T cells to be deleted in central tolerance
Failure to recognise self MHC (no positive selection) causes cells to die through apoptosis
Recognises self peptide plus self MHC at high affinity; cells die through apoptosis or become Tregs.
Describe how apoptosis is induced in self-reactive B cells
If immature B cells in bone marrow encounter antigen in a form which can crosslink their IgM (BCR), apoptosis is triggered
Describe the principles behind T cell selection in the thymus
Need to select for T cell receptors which are capable of binding self MHC
If binding to self MHC is too weak, may not be enough to allow signalling when binding to MHC with foreign peptides bound in groove
If binding to self MHC is too strong, may allow signalling irrespective of whether self or foreign peptide is bound in groove Is T cell useless? Doesn’t bind to any self-MHC at all Death by neglect (apoptosis) Is T cell dangerous? Binds self MHC too strongly Apoptosis triggered – negative selection Is T cell useful? Binds self MHC weakly Signal to survive – positive selection
Describe the autoimmune regulator (AIRE)
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
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)
Describe anergy
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 (CD80,CD28) it becomes anergic – i.e. Less likely to be stimulated in future even if co-stimulation is then present
