Immunology of Autoimmune Disease Flashcards
Autoimmune conditions are more common in men. True or False
False they are more common in women
A breakdown of self tolerance (loss of immune regulation results in what 2 possibilities
Autoimmune phenomena
Autoimmune disease
What is a monogenic disorder
Single gene defect which causes an autoimmune disease and is rare
Give an example of a single gene defects associated with autoimmune disease
IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy and X linked inheritance syndrome
What are some of the symptoms of IPEX syndrome
Very early onset of Diabetes Type 1 Severe malabsorption Eczema Autoimmune thyroid disease Autoimmune haemolytic anaemia Severe infections
What is the pathogenesis
Mutation in FOXP3 gene - essential for development of regulatory T cells
What cells are essential in protection against autoimmunity
Regulatory T cells
What do most autoimmune diseases result from
complex genetic interplay
What is the generalised susceptible allele in autoimmune diseases
HLA
Why is HLA important
It is what is used to control T cells
What happens if a person does not carry a specific HLA allele
Their risk of developing the a specific autoimmune disease is much higher
How odes the body recognise foreign antigens in terms of T cells
The foreign body is chewed up by antigen presenting cell and then it is expressed on the cell surface as peptide and it is enclosed in the HLA molecule and this is the only thing that a T cell can see
How many variants of each HLA molecule does each individual possess
2
How can we maximise the net ability to bind peptides
Individual HLA molecules exhibit significant diversity
What are some factors that contribute to autoimmune disease
HLA: association but not a prerequisite for disease
Importance of immune regulation in maintaining tolerance
Infection: cross-reactivity between antigens expressed by pathogen and self
What do hypersensitivity reactions result in
Immune response that results in bystander damage tot he self
Usually exaggeration of normal immune mechanisms
Pathophysiological basis for many autoimmune diseases
What is the classification tool that is used to classify hypersensitivity reactions
Gel and Coomb’s
How do Type 3 sensitivity reactions arise?
You get antibody binding to antigen which circulated in the system and form these immune complexes - these get deposited in small blood vessels and clog them up which causes complaint activation
Often in the Bowmen’s Capsule
What is an example of a Type 3 hypersensitivity reaction
SLE
Disorganisation of the B cells
Describe the pathophysiology of SLE
Antibodies produced against contents of cell nuclei
—Anti-DNA antibodies
-Anti-nuclear antibodies
—Antibodies to extractable nuclear antigens
Immune complexes form
—deposited in small vessels in skin, joints, kidneys
—Result in complement activation
—Inflammation
—Recruitment of other cells
What are some of the clinical features of SLE
CNS - Seizure Skin - Butterfly rash, Discoid lupus Heart - Endocarditis, Myocarditis Arthritis Lymphadenopathy Pleuritis Pericarditis Glomerulonephritis
What investigations should be done for suspected SLE
FBC
inflammatory markers
Renal function
ANA
Autoimmune diseases are associated with a high level of Anti-nuclear antibodies. True or False
True
The speckled antibody is more specific for what 2 diseases
SLE and Sjogrens
What is the speckled antibody associated with
Antiboddies to extractable nuclear antigens e.g Ro and La
What is the anti-centromere antibody very specific for
Limited scleroderma
What is the nuclear ANA associated with
scleroderma
If an ANA test is positive, what is useful to establish
Which nuclear component is being recognised
What are extractable nuclear antigens
Some nuclear antigens which are soluble and that can be extracted from the nucleus
The Rheumatological Association criteria for the classification of SLE requires 4 of what 11 aspects
Serositis
Oral ulcers
Arthritis
Photosensitivity
Blood disorders Renal involvement Antinuclear antibodies Immunologica phenomena Neurologic disorder
Malar Rash
Discoid Rash
SOAP BRAIN MD
What is used to decrease inflammation
Corticosteroids
What is used to decrease production of antibody
Immunosuppressive agents - anti-proliferative agents such as:
Azathioprine
Mycophenolate
Cyclosphosphamide
What type of hypersensitivity reaction is rheumatoid arthritis
Type 4
What occurs during a type 4 hypersensitivity
Infiltration of synovium by CD4+ T cells to produce cytokines
Secondary involvement of activated B cells and antibody
The treatment of rheumatoid arthritis interrupts what
The cytokine networks
eg. anti-TNF antibodies: Infliximab
What other treatments do anti-TNF agents work for
RA
Crohns
Psoriatic arthritis
Ankylosing spondylitis
What serological tests for Rheumatoid arthritis
Rheumatoid factor - antibody directed against the common (Fc) region of IgG
The absence of RhF is insufficiently sensitive to rule out the diagnosis of rheumatoid arthritis. True or False
True
What is a more specific test for Rheumatoid Arthritis
Anti-CCP antibody
