Lecture 2: General AID Flashcards
Describe autoimmune disease
the failure of an organism to tolerate its own cells and tissues, resulting in an aberrant immune response by lymphocytes and/or antibodies’ causing pathological changes and dysfunction of the tissue that is the target of the self-directed immune response.
How to treat AID
treatment for autoimmune diseases generally focuses on reducing immune system activity.
Autoimmune symptoms
fatigue
achy muscles
swelling and redness
low-grade fever
trouble concentrating
numbness and tingling in the hands and feet
hair loss
skin rashes
What does a POSITIVE ANA (anti-nuclear antibodies) test mean VS POSITIVE ENA test
antinuclear antibody test (ANA). A positive test means you may have one of these diseases, but it won’t confirm exactly which one you have or if you have one for sure
ENA’s - specific autoantibodies (in nucleus) produced by certain AID
Drugs (and assosciated function) to treat AID
- Nonsteroidal anti-inflammatory drugs (NSAIDs) which help ease symptoms like pain, swelling and stiffness.
2.Disease-modifying anti-rheumatic drugs (DMARDs) (holt disease progress),
- Biologics The major category within biologics is tumor necrosis factor (TNF) blockers, which counteract high levels of inflammatory proteins.
4.Corticosteroids suppress the immune system and fight inflammation, eg methohexitone)
5.IVIg (intravenous immunoglobulin) a blood product made up of antibodies which immunomodulatory effects on immune system help get the immune system back on track without suppressing its normal function),
6.Plasmapheresis (a process that removes plasma — the part of the blood that carries antibodies — from a patient’s blood. Because it removes good antibodies along with the bad, however, it leaves the immune system less able to fight off sickness and infection
7.Surgery in rare cases, to deal with certain complications of autoimmune disease such as joint damage injuvenile idiopathic arthritisor bowel obstruction inCrohn’s disease.
Classification of AID and examples
Based on the location of the autoimmune attack: Systemic (SLE attacked kidney and skin) or organ-specific (diabetes affects pancreas, hashimoto impacts thyroid)
Define Connective Tissue
Connective tissue isthe tissue that connects, separates and supports all other types of tissues in the body.
Majorfunctionsofconnectve tissue
binding and supporting
Protecting
Insulating
storing reserve fuel
transporting substances within the body
BAPIST
Types of connective tissue (CABDHB)
dense regular connective tissue which is found in tendons and ligaments
cartilage
adipose tissue
haemopoietic tissue (bone marrow, lymphoid tissue)
blood
bone
Define connective tissue disease and examples
Connective tissue disease isany disease that affects the parts of the body that connect the structures of the body together.
Systemic lupus erythematosus
Sjögren’s syndrome
Sharp syndrome
Connective Tissue Disease markers and the markers antigens
anti-nuclear antibodies (ANA) are important serological markers for CTD
Target antigens include, for example, nucleic acids, cell nuclear proteins and ribonuclear proteins.
Describe Sjogrens Syndrome
Sjogren’s syndrome is an autoimmune disorder that destroys the glands that produce tears and saliva, causing excessive dry eyes and dry mouth.
Diagnostic parameteres of sjogrens syndrome
- Positive serum for anti-SSA/Ro and or anti-SSB/La or positive RF and ANA titre above 1:320
- Labial salivary gland biopsy with focal lymphocytic sialadenitis with focus score = or above 1 focus/4mm2
3.Keratoconjunctivitis sicca with occular staining above 3
What is Myositis and MOST common symptoms
muscle inflammation
caused by lymphocytes that infiltrate healthy muscle fibers as well as foreign invaders.
after a period of inflammation, muscle fibers are destroyed, which affects the functionality of muscle tissue and leads to fatigue and immobility.
Weakness, swelling, and pain are the most common myositis symptoms
Digram of myositis pathogenesis
Lecture slide
Describe the inflammatory myopathy forms
Polymyositis
-inflammatory cells
-Invasion of fibres by inflamm cells
In Polymyositis, inflam cells invade previously healthy muscle cells which become rounded and vary in size
Inclusion body myositis
-inclusion bodies
-vacuoles
In Inclusion body myositis muscle fibres have vacuoles and inclusion bodies (clumps of cellular material) and inflam cells are between fibres
Dermamyositis
-Shrinkage of fibres near border of fascicles
- inflam cells around fascicles and between fibres
- cut off inflam cells around blood vessel
in DM, inflam cells are concentrated arounf blood vessels at the borders of fascicles and fibres in this region shrink. Inflam cells form a cuff around blood vessels.
What is dermatomyositis and who does it affect
an uncommon inflammatory disease marked by muscle weakness and a distinctive skin rash
affects adult and children
In adults, dermatomyositis usually occurs in the late 40s to early 60s.
In children, it most often appears between 5 and 15 years of age.
What is polymyositis and who does it affect
an inflammatory disease that causes muscle weakness primarily affecting the shoulders, upper arms, pelvis and thighs
can occur at any time of life, although it is uncommon under the age of 18 years and generally occurs between the ages of 30 and 60 years
Women are more commonly affected by the condition than men.
Symptoms of dermatomyositis and polymyositis
Eyelid rash
Shawl Sign
Shoulder/peliv girdle
ground glass opacity in lungs
GI vasculopathy
pharngeal weakness
polymyositis is the same BUT NO RASH
What is inclusion body myositis and when does it develop?
aprogressive muscle disorder characterized by muscle inflammation, weakness, and atrophy(wasting)
develops in adulthood, usually after age 50
Diagnose myositis
Antinuclear antibodies (ANA) IFA methods are present in 80% of patients with polymyositis and dermatomyositis, but are not specific for either condition.
Detection of ENA - anti-SS-A (anti-Ro), anti-SS-B (anti-La), anti-Smith, or anti-ribonucleoprotein (anti-RNP) antibodies strongly suggests the diagnosis of myositis associated with overlap syndromes such as Mixed or undiffereniated connective tissue disease
ENA - Anti-Jo-1 antibodies are directed against anti-histidyl-tRNA synthetase. Anti-Jo-1 antibodies are strongly associated with arthritis, and mechanic’s hands.
What areas of the body does SLE affect
Symptoms
what age does it develop
affects many parts of the body (most commonly the skin, muscles and joints) causing inflammation and tissue damage
symptoms include fatigue, fever, muscle aches and facial rash
there is no cure for lupus so the aim of treatment is to relieve symptoms and protect body systems and organs.
Any age, typically 20-45
SLE diagnostic findings
Almost all are ANA positive (one of diagnostic criteria)
70-98% of patients will be positive for dsDNA antibodies
ENA – positive Ro, La, Sm most common
what does ANA target?
Why are ANA important?
found in healthy people?
react with various nuclear and cytoplasmic components of normal human cells
Found in healthy people
their detection is important in the diagnosis of some connective tissue diseases (CTD)—eg, SLE, Sjögren’s syndrome, scleroderma, polymyositis
Gold standard test for ANA and description
The gold standard is the indirect immunofluorescence test with human epithelial cells (HEp-2)
high sensitivity and specificity
ANA IFA patterns and what diseases they suggest
- Homogenous, in which the entire nucleus fluoresces
= SLE and discoid lupus erythematosus (DLE) - Rim, in which the nuclear perimeter fluoresces
=CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome and SLE - Speckled, in which the nucleus fluoresces in a speckled pattern,
=Sjögren’s syndrome, SLE, and scleroderma
4.Nucleolar, in which the nucleolus fluoresces, =scleroderma
5.Cytoplasmic, in which fluorescence occurs outside the nucleus,
=poly/dermatomyositis, primary biliary cirrhosis, or autoimmune hepatitis.
Correlate the ANA pattern to diseases associated and antigen used for the disease
- Homogenous
SLE -dsDNA
DLE - Histones - Rim
CREST, SLE = centromere - Speckled
Sjögren’s syndrome - SSa/Ro or SSB/La
SLE -Sm
Scleroderma = Scl-70 - Nucleoar
Scleroderma = PM/Scl - Centromere
CREST = anti-centromere
Additional purpose of ANA and example
Besides confirming a diagnosis of CTD in patients with suggestive clinical features, ANA testing serves 2 additional purposes:
- to help determine a patient’s prognosis
2.monitor CTD activity
Patients with Sjögren’s syndrome who test positive for anti-Ro/SS-A antibodies have aggressive, extra-glandular disease that can cause purpura, leukopenia, and thrombocytopenia
Diagnostic features of SLE
Diagnostic Factors:
4 or more
Skin = malar rash, discoid rash, photosensitivity
Mucosa = ulcers (mouth, nose)
Serosa = serositis (pleuritis, pericarditis)
Joints = Arthritis (2 or more locations)
Kidneys = renal disorders (urine protein)
Brain = seizures, psychosis
Blood = hematolologic disorders (anemia, thrombocytopenia, leukopenia)
Antibodies = ANA, Anti-Sm, Anti-dsDNA
Examples of AID (7) and what factors cause them
1.Rheumatoid Arthritis (RA):
- Genetics: There is a genetic predisposition to RA, with certain HLA genes (e.g., HLA-DRB1) being associated with increased risk.
- Environmental Factors: Smoking is a well-established environmental risk factor for RA. Infections, such as the Epstein-Barr virus, have also been linked to the development of RA.
2.Systemic Lupus Erythematosus (SLE):
- Genetics: SLE tends to run in families, suggesting a genetic component. Specific genetic variations, like variations in certain interferon-related genes (IFN type 1), can increase the risk.
- Hormones: The female hormone estrogen is thought to play a role, as SLE is more common in women. Hormonal changes, such as those during pregnancy, may affect disease activity.
- Multiple Sclerosis (MS):
- Genetics: There is a genetic susceptibility to MS. Specific genes, like the HLA-DRB1 gene, have been associated with increased risk.
- Infections: Viruses such as Epstein-Barr virus (EBV) have been studied for their potential role in triggering or exacerbating MS. - Celiac Disease:
- Genetics: Celiac disease is strongly linked to certain genes, including HLA-DQ2 and HLA-DQ8, which are necessary but not sufficient for the disease to develop.
- Environmental Triggers: Exposure to gluten (a protein found in wheat, barley, and rye) is the primary environmental trigger. It causes an immune response in the gut of susceptible individuals. - Type 1 Diabetes:
- Genetics: There’s a strong genetic component in type 1 diabetes. Specific HLA genes, particularly HLA-DR3 and HLA-DR4, are associated with an increased risk.
- Infections: Some viral infections, such as enteroviruses, have been suggested as potential triggers for type 1 diabetes. As enteroviruses have tropism for pancreatic islet cells causing beta cell damage and therefore lack of insulin production. - Psoriasis:
- Genetics: Psoriasis has a strong genetic component. Variants of specific genes, such as PSORS1, contribute to the risk.
- Environmental Factors: Infections, such as streptococcal infections, have been linked to psoriasis exacerbations. - Inflammatory Bowel Disease (IBD), including Crohn’s Disease and Ulcerative Colitis:
- Genetics: Multiple genes, including NOD2 and ATG16L1, have been associated with IBD.
- Gut Microbiota: Imbalances in the gut microbiota may play a role in triggering IBD, and infections can also exacerbate symptoms. Dysbiosis (unbalanced microbiome) causes the lack of regualtion of the pro and anti inflammatory processes in the gut. This causes increase pro inflammatory actions leading to a pro-inflammatory environment and thus degradation of intestine lining due to ongoing inflammation causing leaky gut and thus IBD.
Draw diagram of AID and then describe the 5 causes of AID using example and details
- Genetics
There is ample evidence for genetic susceptibility (e.g. clustering in families, higher concordance in monozygotic twins, higher prevalence in specific ethnic groups)
Rarely, single gene mutations lead to autoimmunity, thus most autoimmune diseases are polygenic (30+ genes contribute). The genes shown to have a strong association with many autoimmune diseases are within the MHC locus, eg celiac (HLA-DQ2/8), TD1 (HLA-DR3/4), psoriasis (PSORS1) and RA (HLA-DRB1) - Environmental
Environmental agents are able to amplify autoimmunity in genetically susceptible individuals and to break tolerance in genetically resistance individuals thereby increasing the risk of development of AID. Eg, Damage to tissues by microbes, trauma, and UV radiation can also lead to exposure of previously-sequestred autoantigens and alongside exposure to sunlight can also exacerbate SLE, as damaged keratinocytes release nuclear autoantigens. Specific drugs can cause drug induced lupus. - Infections
Infections are suspected of triggering or exacerbating autoimmune diseases. For example, viral infections, such as enteroviruses, have been implicated in the development of Type 1 Diabetes. In the case of MS, there is evidence to suggest that infections, such as the Epstein-Barr virus, may contribute to the onset or progression of the disease. These infections can alter the immune system’s response, leading to autoimmune reactions against the body’s own tissues. Psoriasis, on the other hand, may worsen due to environmental factors, such as infections (e.g., streptococcal infections), which can activate the immune system and trigger the characteristic skin lesions. Several mechanisms have been proposed; direct viral damage, molecular mimicry, bystander activation. - Hormones
Most AIDs are more prevalent in women than men (80% of individuals with AID are women). Hormones can amplify or inhibit the immune response. For example, SLE is more common in women, suggesting a hormonal link. The body’s endocrine system and hormonal balance can play a pivotal role in modulating immune responses and the development of autoimmune disorders. - Diet
Chemical food additives and Pesticides may predispose someone to AID
Iodine – has caused increased prevalence of autoimmune thyroid disuse is associated with increased use of iodised salt. Iodine binds to thyroglobulin, making it a target of the IS resulting in the increased autoantibodies against thyroglobulin and recruitment of inflammation to the thyroid gland
Coeliac disease resulting form gluten sensitivity: Genetically susceptible individuals develop hypersensitivity to wheat gluten when consumed
