Autoimmunity Flashcards
What are antigens that induce tolerance called?
Tolerogens
What is tolerance to self-antigens?
AKA self-tolerogens
Fundamental property of normal immune system
How is autoimmune disease normally avoided?
T and B cells bearing self-reactive molecules must be eliminated or downregulated
(peripheral tolerance)
Where are T cells with high affinity to self-antigens eliminated?
The thymus
What organ is important in B cell tolerance?
Bone marrow
What are the ways in which T cells are managed?
Anergy – made functionally unresponsive
Suppression – killled by a regulatory T cell
Deletion (cell death)
How might peripheral tolerance be over come?
Inappropriate access of self-antigens
Inappropriate or increased local expression of co-stimulatory molecules
Alterations in the ways in which self-molecules are presented to the immune system
Why might peripheral tolerance be more likely be overcome?
When inflammation/tissue damage is present due to the increased activity of proteolytic enzymes which can cause intra- and extracellular proteins to be broken down, leading to high concentrations of peptides being presented to responsive T cells
The structures of self-peptides may be altered by viruses, free radicals or ionising radiation, thus bypassing previously established tolerance
What is an autoimmune disease?
When autoreactive T cells or autoantibodies cause tissue damage through hypersensitivity reaction types II, III and IV
Most healthy individuals produce some autoantibodies (very low level and low affinity)
Genetic, environment, infections
How are natural antibodies secreted?
By B1 cells (major source of autoantibodies) - normally IgM
They are produced without T cell help
Natural antibodies bind with low affinity to antigens on a variety of bacteria. This activates complement and helps clear invading bacteria rapidly
How do natural antibodies affect the blood?
Natural antibodies cross-react with the inherited A and B antigens of red cells
Unless they have inherited either A or B antigens, individuals make IgM anti-A and anti-B antibodies, even if they have never been exposed to red cells from another person
Natural antibodies can bind to normal cellular constituents, such as nuclear proteins and DNA
(Develops an negative immune response to blood unless they have inherited A and B antigens)
What is HLA?
The human leukocyte antigen (HLA) system or complex is a group of related proteins that are encoded by the major histocompatibility complex (MHC) gene complex in humans
These cell-surface proteins are responsible for the regulation of the immune system
If there is a defect in this, may allow auto-reactive T cells to leave the thymus
“Human major histocompatibility complex (MHC)”
Describe how genetics affect autoimmunity
Clusters within families
Alleles of MHC (HLA)
AIRE gene
Some rare genetic diseases cause autoimmunity
Common polymorphisms, rather than rare mutations, are implicated in the breakdown of immune tolerance that leads to these diseases
What are some HLA genes associated with autoimmune diseases?
B27 - ankylosing spondylitis, Reiter disease
DR2 - Goodpasture syndrome
DR3 - Sicca syndrome, Addison disease
DR4 - insulin-dependent DM
How can infections lead to autoimmune disease and what are some examples?
The body fights the infection and produce antibodies against item unfortunately, some molecules in the body resemble those of the infection and the body begins to attack itself.
Group A strep protein is similar to antigens found in cardiac muscle –> Rheumatic fever
Coxsackie protein is similar to molecules of pancreatic islet cells –> insulin-dependent DM
Campylobacter similar to myelin proteins –> Guillain-Barre syndrome
