Autoimmune Disease Flashcards
What is immune tolerance?
State of unresponsiveness of the immune system to substances or tissues which have potential to induce an immune response
What 3 mechanisms achieve self tolerance?
- Central tolerance
- Peripheral tolerance
- Acquired tolerance
Why is immune tolerance important?
Give the immune system the capacity to deal with many diverse pathogens but avoid self-reactivity
In which 2 ways can self-reactive receptors be eliminated?
- Physically
2. Functionally
What mechanism controls the induction and maintenance of lymphocyte tolerance?
Central importance
Why is the induction and maintenance of lymphocyte tolerance of central importance?
- It determines how the immune system discriminates between self and non-self
- It determines how the system responds to different forms of foreign antigens
How is central tolerance achieved with respect to T cells?
Immature T cells are which react with self-antigens are deleted in the thymus by apoptosis
How is central tolerance achieved with respect to B cells?
Undergo apoptosis or receptor-editing to produce a non-self receptor in the bone marrow
What are the 2 stages of positive and negative selection of thymocytes in the bone marrow?
- Positive selection of cells whose receptors bind to MHC molecules
- Positive selection of cells with low-affinity receptors for self-MHC
Name 2 reasons self-reactive B and T cells escape central tolerance?
- Recognize self-antigens not expressed or present in the bone marrow or thymus
- Remain in a state of clonal ignorance
What occurs to self-reactive B and T cells which escape central tolerance?
Enter the peripheral circulation
What does anergic mean?
The cell cannot divide or clone
What 2 things can occur when a B cell encounters a self-antigen in the peripheral system?
- Clonal deletion
2. Cell becomes anergic
What suppresses the reaction of T cells to self antigens?
Regulatory T cells
Name 3 ways which regulatory T cells suppress the action of T cells to self-antigens?
- Direct contact with the target cell
- Production of inhibitory cytokines IL-10 and TGF-b
- Scavenging of IL-2, a key T cell growth factor
How are self-reactive B and T cells activated if they persist in normal subjects?
Environmental triggers
What are the 2 classifications of autoimmune diseases?
- Organ specific
2. Systemic (non-organ specific)
What does the classification of an autoimmune disease depend on?
Whether the response is primarily against antigens localized to particular organs or against widespread antigens
Name 5 examples of organ specific autoimmune diseases
- Type I diabetes
- Goodpasture’s syndrome
- Multiple sclerosis
- Grave’s disease
- Myasthenia gravis
Name 4 examples of systemic autoimmune diseases
- Rheumatoid arthritis
- Systemic Lupus Erythematosus (SLE)
- Discoid Systemic Lupus Erythematosus
- Primary Sjogren’s syndrome
What is Grave’s disease a common cause of?
Hyperthyroidism
What is hyperthyroidism?
Over-production of thyroid hormone which causes enlargement of the thyroid
What are 3 symptoms of hyperthyroidism, excluding enlarged thyroid?
- Exophthalmos
- Heat intolerance
- Anxiety
What is exophthalmos?
Bulging eyes
How does negative feedback of the thyroid cells usually work?
- Pituitary gland produces TSH which binds to thyroid cell receptor
- Stimulates hormone synthesis
- Negative feedback regulates pituitary gland
How does Grave’s disease differ to regular negative feedback of thyroid cells?
Auto-antibody binds to receptor and there is no negative feedback loop (there is no organ which can be signalled to stop producing antibodies as with TSH)
How does myasthenia gravis occur?
Autoantibodies to the acetylcholine receptor block nerve signals to the muscles which become non-functional
How does type I diabetes occur?
Autoantibodies attach beta-cells of the pancreas which produce insulin so plasma glucose rises
Name 2 organ-specific autoimmune disease with manifestations in the mouth
- Pemphigus
2. Pemphigoid
What physical symptoms can pemphigus vulgaris cause?
Blisters develop on skin and lining of the mouth, nose, throat and genitals
What is desmoglein?
A protein which holds cells of skin and mucous membrane together
Why do blisters develop as a cause of pemphigus vulgaris?
Autoantibodies combine with desmogleins so the cells in the skin no longer stick properly and fall apart
What is the major difference between pemphigus and pemphigoid?
Blisters are sub-epidermal rather than intra-epidermal in pemphigoid
What is the difference between SLE and discoid SLE?
Two ends of a spectrum where SLE has severe involvement of kidney, joints, brain and skin and discoid SLE is benign, chronic and purely cutaneous
How can SLE manifest in the oral cavity?
Lesions can affect the oral mucosa and salivary gland including erythematous areas and ulcers on the lips and oral mucosa
What causes SLE?
RBCs and platelet autoantibodies lead to complement-mediated lysis of cells (type II hypersensitivity)
Name 5 physical manifestations of SLE
- Fever
- Arthritis
- Skin rashes
- Pleurisy
- Kidney dysfunction
Who is affected by SLE?
Women between 20-40 years old affecting females at a 10:1 ratio compared to males
What is Sjogren’s syndrome?
An autoimmune disease involving the inflammation salivary and tear glands and some other tissues of the body
Who is affected by Sjogren’s syndrome?
Mostly female patients
What can complicate Sjogren’s syndrome?
Infections of the eyes, breathing passages and mouth
What is molecular mimicry?
Sequence similarities between foreign and self-peptide chains
What is a potential complication of molecular mimicry?
An antibody produced in response to a virus can recognise and attack self-antigens due to similar peptide chains
