Autoimmunity Lab
•
•
•
•

-
Discuss rheumatoid factor and immune complexes – relate them to the pathogenesis of
autoimmune disease.
Outline the use of anti-nuclear antibody staining.
Discuss the pathogenesis of autoimmune disease caused by anti-receptor antibodies.
Describe the principles of indirect immunofluorescence and how it is used in the diagnosis
of autoimmune disease.
Autoimmune disease criteria include; presence of autoimmune response, immunisation
produces disease, passive transfer by Ab or lymphocytes, responds to immunosuppression
Pathogenesis of RA; inflamed synovial membrane
pannus cell types T lymphocytes & macrophages
minor cells fibroblasts, plasma cells, endothelium dendritic cells
synovial fluid major cells include neutrophils
also presence of cartilage thining
RF contributes to inflammation
Diagnosis of RA; anti-citrullinated antibodies strongly correlate to disease severity
Importance of ACPAs in RA
Lab tests t detect RF/ ACPAs; enzyme linked immunosorbent assay (ELISA), Nephelometry
(RF)
Good lab test includes reliability (repeatability, precision), accuracy (trueness), specificity
and sensitivity
RF; autoantibody, antibody against Fc portion of IgG, these form immune complexes that
add to the process of disease
Anti-Nuclear Antibodies (ANA); positive in patients with SLE and mixed connective tissue
disease
ANAs
-
useful auto-antibody tests that detect autoimmune conditions, it’s a group of antibodies
that are able to bind to locations in the nucleus
binding sites include; homogenous, centromere, peripheral (nuclear envelope), speckled
(proteins) and nucleolus
the ANA’s are detected through immunoflourescence and ELIZA
diseases that can be identified include SLE, RA, Scleroderma etc.
Sjogren’s syndrome is identified using ‘Schirmer’s Test’, this looks at the dry eye condition, it
tests tear production in patients
Anti receptor antibodies are diagnostic for myasthenia gravis and graves disease
AID’s caused by anti-receptor antibodies
- Myadthenia gravis -> anti-acetylcholine receptor
- Grave’s disease ->anti-TSH receptor
- Type B insulin resistance syndrome -> anti-insulin receptor
- Anti-NMDA autoimmune encephalitis -> anti-NMDA (glutamate) receptor
(controls synaptic plasticity & function of memory)
Immune complex mediated
- Systemic lupus rythromatosis
- Rheumatoid arthritis
- Vasculitis
Antibody mediated
-
Thyrotoxicosis
Pernicious anaemia
Myasthenia gravis
Immune thrombocytopenia
Cell mediated
-
Hashimoto’s Thyrodiditis
Diabetes mellitus
Multiple sclerosis
Sjogrens syndrome
MY RESEARCH TEAM TASK – MULTIPLE SCLEROSIS
MULTIPLE SCLEROSIS
-
It’s a demyelinating disorder characterised by white mater lesions that are separated in
space. Immune system attacks myelin covering nerves this damage disrupts communication
between the brain and the body. Nerves may deteriorate- loss of motor control.
1. Outline the pathogenesis
- Caused by combination of environmental and genetic factors result in a loss of tolerance to
self proteins ‘myelin antigens’
- Genetic risk is associated to HLA-DR variants, DR2 allele increases the risk of developing
MS significantly
- Polymorphisms in genes encoding receptors for cytokines IL-2 and IL-7, control the
activation and regulation of T-cell mediated immune responses
- Immune mediated myelin destruction has a role in MS
- CD4+T cells with increase in Th17 and Th1 CD4+ cells critical role in injury to myelin
- Demyelination is most evident with some axonal loss
- Toxic effects of lymphocytes, macrophages and secreted molecules have been implicated in
initiating the process of axonal injury, leads to neuronal death
2. Describe the type of laboratory tests used in diagnosis
Laboratory test used in diagnosis
-
Tests used include MRI, Cerebrospinal fluid analysis, visual evoked potentials
MRI is the best diagnostic test for MS
Detects areas of the brain/spinal cord that CAT scans may miss
MRI involves injections of contrast dye material that allow us to see the abnormalities found
in the brain in the scan images
3. Explain the principles of how the tests work
-
-
-
Test produces clear images of the human body in this case the brain
It uses large magnetic radio waves and a computer to produce theses images
Unlike conventional x-ray examinations and computed tomography (CT) scans, MRI does
not depend on ionizing radiation. Radio waves redirect the axes of spinning protons, which
are the nuclei of hydrogen atoms.
The magnetic field is produced by passing an electric current through wire coils in most
MRI units. Other coils, located in the machine and in some cases, placed around the part of
the body being imaged, send and receive radio waves, producing signals that are detected
by the coils.
A computer then processes the signals and generates a series of images, each of which
the contrast dye allows for certain tissues and blood vessels to be seen in more detail and
clarity this is usually gadolinium, may be given to you intravenously
The MRI is a cylinder with both sides being open, the patient lies on a motorised bed that
moves inside the scanner
The MRI scan is studied by a radiologist and specialist
4. Discuss any Limitations or issues with the test









There are issues between lesion location and the clinical presentation
Can vary in sensitivity and specificity in diagnosis this depends on the number of
location findings
The strong magnetic field is not harmful, only an issue if patients have implanted
medical devices that contain metal may malfunction or cause problems during MRI
exam include inner ear implants, artificial joints, defibrillator or pacemaker, particular
types of heart valves, vascular stents, brain aneurysm clips
Not recommended for pregnant women
Doesn’t have the ability to find all cancers (breast- microcalcifications)
Cannot always distinguish between benign and malignant
Difficult procedure for those who have claustrophobia
Sometimes patients may develop allergic reaction to the contrasting agent, this is can be
prevented
Expensive procedure