Autoimmunity and immunologically mediated disease Flashcards
What are the differences between innate and adaptive immune system?
a) type of response
b) lag time
c) components
d) memory
e) life forms
Innate = non-specific, immediate maximal response, cell mediated and humeral components , no immunological memory
found in newly all forms of life
Adaptive = pathogen and antigen specific response, lag time between exposure and maximal response
cell mediated and humeral components
exposure leads to memory
Found only in jawed vertebrates
What is self tolerance?
Inherent property that allows response against foreign antigens without attacking self
Which immune system is related to self tolerance?
Adaptive
How is tolerance monitored?
Checkpoints
What occurs if tolerance is not monitored and goes wrong?
Autoimmunity
What are the 2 mechanisms of tolerance?
Central and peripheral
What is central tolerance?
Induced during development of T cells in thymus
What is peripheral tolerance?
Control of auto-reactive cells through non-thymus dependent processes
How does central tolerance develop?
In the thymus, autoimmune regulator element (AIRE) is expressed whilst the T cells develop.
This expresses a variety of peripheral tissue antigens.
Recognition of self antigens by immune lymphocyte leads to negative signal causing death or inactivation
Where is peripheral tolerance most commonly found?
In immune privileged sites (eye/brain)
Naturally less subject to the immune response
How can tolerance be achieved in the periphery?
Anergy - T cell receptors can be engaged without co-stimulation
Regulation - Treg cells can suppress other effector functions and enforce tolerance
Failure to develop tolerance means T cells and antibodies are directed against self-antigens what is the result of this?
Tissue damage and altered physiological function.
Tissue damage causes released of more self-antigen = more reaction
Why does autoimmune disease tend to be active for a very long time?
Autoantigens are very difficult to clear
Why are older adults more at risk of autoimmunity?
Smaller thymus with fewer functional lymphocytes
What are the consequences of autoimmunity over time?
Increased incidence of infection
Higher levels of autoimmunity (increased T cells for self antigens)
What can cause autoimmune disease?
Genetic factors
Infection and environment
How can genetics effect autoimmunity?
Affect availability and clearance of auto antigen
Affect expression of co-stimualtory molecules
Why is it suggested that genetic and environmental factors are reacquired to cause autoimmunity?
Many people with genetic factors predisposing them never get the disease
How can autoimmune disease be classified? Why is this imprecise?
By nature of immune response e.g. antibody mediated (type II, III), T cell mediated (type IV)
Imprecise because the immune response is interlinked - problems with antibody production linked to T cells
What is a type II autoimmune response?
Antibody against cell surface antigens
What is a type III autoimmune response?
Antibody complex against circulating antigen
Name a type III autoimmune disease?
Rheumatoid arthritis
Name a type II autoimmune disease?
Autoimmune haemolytic anaemia, pemphigus vulgaris
What is a type IV autoimmune response?
T-cell mediated
Name a type IV autoimmune disease?
Type I diabetes (insulin dependent)
Other than by nature of immune response how can autoimmunity be classified? What are the problems with this?
Organ specific or systemic
e.g. type I DM is organ specific, Rheumatoid arthritis is systemic
Not all autoimmune disease can be classified this way e.g. autoimmune haemolytic anaemia can occur in isolation or in association with SLE (lupus)
Autoimmune diseases of the endocrine system can affect glands in what 4 ways?
Destruction
Cellular infiltration
Uncontrolled stimualtion
Blockade of stimulation
What is Addisons disease?
Autoimmune disease caused by adrenal insufficiency
What are the consequences of Addisons disease?
Fatigue, depression, collapse, increased pigmentation of skin folds and buccal mucosa, other endocrine diseases accompany
What causes T1DM?
Immunological destruction of pancreatic islets of Langerhans by T cells
How can T1DM affect dentists?
Cause candida, dry mouth, dialysis, severe periodontitis may upset glycemic control
How can autoimmune disease affect the thyroid?
Thyroid disease e.g. hypothyroidism, hyperthyroidism
What are the symptoms of hypothyroidism?
weight gain, hypothermia, dry skin, anaemia
How can hypothyroidism affect dental care?
Analgesics and GA can cause coma
What are the symptoms of hyperthyroidism?
Weight loss, anorexia, diarrhoea, sweating, exopthalamus (protruding eyes)
Carbimazole is used to treat hyperthyroidism, what are the effects of this?
Can cause agranulocytosis which can cause oral and oropharyngeal ulceration
Are typhoid disease, T1DM and Addisons disease endocrine or non-endocrine disease?
Endocrine
What is coeliac disease?
Sensitivity to gluten causing activation if immunological mechanisms leading to small intestinal damage (enteropathy)
How does coeliac disease effect the small intestine?
Loss of villi
Crypt hyperplasia
Chronic inflammatory infiltrate
What are the clinical features of coeliac disease?
Low energy, diarrhoea, oedema, anaemia
How is coeliac disease managed?
Strict gluten free diet
Name 3 autoimmune haematological disease
Autoimmune haemolytic anaemia
Autoimmune neutropenia
Autoimmune thrombocytopenia purpura
What is associated with autoimmune neutropenia?
Oral ulceration
How can the skin be affected by autoimmune disease?
Bullous pemphigoid, pemphigus vulgaris
Goodpastures syndrome is an autoimmune disease of the kidney, what kind of reaction is this?
Type II hypersensitivity
What is the risk of autoimmune kidney disease?
Can progress to chronic renal failure = bleeding tendencies, impaired drug excretion, hypertension, anaemia
What is the difference in symptoms between organ and non-specific organ autoimmune disease?
Symptoms are more widespread and non-specific
Name some extra-articular manifestations of rheumatoid arthritis?
Nodules, GI problems, Sjogrens syndrome
Name 2 systemic autoimmune diseases?
Rheumatoid arthritis
SLE (lupus)
How can SLE effect dental treatment?
Anaemia, bleeding, predisposition to thrombosis, drug reactions e.g. tetracylines
How does Sjogrens syndrome present, what is it associated with?
Dry eyes, dry mouth, associated with arthritis
How should non-organ specific autoimmune disease be treated?
Anti-inflammatories
Steroids
Immunosuppressants
Monoclonal antibodies
What are the side-effects of immunosuppressants?
Poor wound healing
Increased risk of infection
oral candidiasis
