Immunology: Autoimmunity Flashcards
Why can autoimmunity be described as a hypersensitivity reaction?
In autoimmunity, there is an exagerrated immune response (thus hypersensitivity) but against autoantigens instead of ones from our environmnent
What is immunological tolerance?
What name is given to antigens that induce tolerance?
unresponsiveness to an antigen that is induced by previous exposure to that antigen
antigens that induce toleracne are called tolerogens or tolerogenic agents
What fault in our immunological tolerance generates autoimmunity?
Tolerance of self-antigens (self-tolerance) is fundamental to a normal immune system
Failure of self-tolerance results in an immune response against autologous antigens (antigens of our own cells)
In a healthy individual - what process prevents the release of dysfunctional immune cells that would attack our own cells?
ie what normally prevents auto-immunity
Before they are released - T & B cells are exposed to multiple self-antigens
If they are overly reactive to self antigens then they get destroyed or downregulated
Immunological tolerance can be split into central and peripheral tolerance
What is central tolerance?
Central tolerance is the process of eliminating any T or B lymphocytes that are self-reactive
For T cells - this happens in the cortex of the thymus
For B cells - this happens in the bone marrow
Immunological tolerance can be split into central and peripheral tolerance
Peripheral tolerance involves a number of mechanisms to make sure that any self-reactive cells do not do naughty things if they escape the thymus/bone marrow
What are these mechanisms?
1) extracellular DNA (following apoptosis) is quickly destroyed by compliment etc to avoid an immune response against our own DNA
2) some cells and tissues have protective barriers
3) although tissues express self-antigens - they do not express co-stimulatory molecules
4) regulatory T cells stop autoreactive T cells
5) repeated antigenic stimulation leads to induced apoptosis of T cells
Through a combination of environmental factors, infections and through genetic susceptibility, peripheral tolerance can be overcome
In what ways does this happen?
1) Innapropriate access of self-antigens
* normally protected self-antigens are exposed to immune system
2) Inappropriate/increased expression of co-stimulatory molecules
3) mhc1 & mhc2 problems such that self-antigens are presented incorrectly to the immune system
Define autoimmunity
Through what type(s) of hypersensitivity can autoimmunity damage tissues?
Adaptive immune responses to self antigens
Autoimmune disease occurs when autoreactive T cells or autoantibodies cause tissue damage through hypersensitivity reaction types II, III and IV
What are B1 cells and natural antibodies?
B1 cells are similar to B cells except they do not need T cell stimulation to produce mainly IgM antibodies
B1 cells secrete natural antibodies which can bind to lots of different bacteria, red cells (ABO antigens), cellular components and act as part of INNATE immune system
But B1 cells are also the major source of autoantibodies
Both genetic and environmental factors play a role in autoimmunity development
Which genes are implicated?
What diseases are caused by the B27 HLA association?
HLA, MHC, AIRE genes implicated
B27 HLA association causes ankylosing spondylitis and Reiter disease
What environmental factors can generate autoimmunity?
Infections
- molecular mimicry
- upregulation of co-stimulation
- antigen breakdown and presentation changes
Drugs
- molecular mimicry
- genetic variation in drug metabolism
UV radiation
- trigger for skin inflammation
- modification of self-antigen
What is molecular mimicry?
Which autoimmune disease (involving the heart) involves molecular mimicry and infection?
Structural similarity between self-proteins and microbial antigens which may trigger an autoimmune response
Rheumatic fever - Group A strep antigen and cardiac muscle antigen are v similar
Is autoimmune disease more common in women or men
Most common in females
except ankylosing spondylitis
What are the differences between organ specific and non organ specific autoimmune diseases?
apart from the obvious one
Non-organ specific:
- affect multiple organs
- autoimmune responses against self-molecules which are widely distributed throughout the body
- intracellular molecules involved in transcription and translation
Organ specific:
- one organ
- esp endocrine glands
What autoimmune diseases involve autoimmunity towards:
- hormone receptors
- neurotransmitters
- cell adhesion molecules
Hormone receptors:
- TSH receptors - hyper/hypothyroidism
- Insulin receptors - hyper/hypoglycaemia
Neurotransmitters:
- ACh receptors - Myasthenia gravis
Cell adhesion molecules:
- Epidermal cell adhesion molecules - blistering skin diseases
What diseases are caused by autoimmunity towards these components of the blood:
- Factor VIII
- Beta-2-glycoprotein & other anticoagulant proteins
Plasma proteins:
- Factor VIII - acquired haemophilia
- Beta-2-glycoproteins - antiphospholipid syndrome
Cell surface antigens:
- RBCs (multiple antigens) - haemolytic anaemia
- Platelets - thrombocytopenic purpura
What diseases are caused by autoimmunity against the following intracellular enzymes:
- thyroid peroxidase
- steroid 21-hydroxylase (adrenal cortex)
- glutamate decarboxylase (b-cells of pancreatic islets)
- lysosomal enzymes (phagocytic cells)
- mitochondrial enzymes
Thyroid peroxidase - Hashimotos thyroiditis, hypothyroidism
Steroid 21-hydroxylase - Addison disease
Glutamate decarboxylase - autoimmune diabetes
Lysosomal enzymes - systemic vasculitis
Mitochondrial enzymes - primary biliary cirrhosis (PBC)
Systemic lupus erythematosis (SLE) is an autoimmune condition in which there is self-reactivity towards DNA and histones
Give an overview of how it works?
Genetic factors:
- inheritance of impaired DNA clearance
- inheritance of HLA-DR2 gene
Persisting extracellular DNA following cell death triggers autoimmunity in pre-disposed individual
This leads to formation of DNA-IgG immune complexes which circulate the body and lead to all sorts of problems
What are the principles of treatment of autoimmune disease
Suppression of the damaging immune response
Replacement of the function of the damaged organ
