Lecture 2: General AID

Question 1

Describe autoimmune disease

Answer 1

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.

Question 2

How to treat AID

Answer 2

treatment for autoimmune diseases generally focuses on reducing immune system activity.

Question 3

Autoimmune symptoms

Answer 3

fatigue
achy muscles
swelling and redness
low-grade fever
trouble concentrating
numbness and tingling in the hands and feet
hair loss
skin rashes

Question 4

What does a POSITIVE ANA (anti-nuclear antibodies) test mean VS POSITIVE ENA test

Answer 4

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

Question 5

Drugs (and assosciated function) to treat AID

Answer 5

1. Nonsteroidal anti-inflammatory drugs (NSAIDs) which help ease symptoms like pain, swelling and stiffness.

2.Disease-modifying anti-rheumatic drugs (DMARDs) (holt disease progress),

3. 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.

Question 6

Classification of AID and examples

Answer 6

Based on the location of the autoimmune attack: Systemic (SLE attacked kidney and skin) or organ-specific (diabetes affects pancreas, hashimoto impacts thyroid)

Question 7

Define Connective Tissue

Answer 7

Connective tissue isthe tissue that connects, separates and supports all other types of tissues in the body.

Question 8

Majorfunctionsofconnectve tissue

Answer 8

binding and supporting
Protecting
Insulating
storing reserve fuel
transporting substances within the body

BAPIST

Question 9

Types of connective tissue (CABDHB)

Answer 9

dense regular connective tissue which is found in tendons and ligaments
cartilage
adipose tissue
haemopoietic tissue (bone marrow, lymphoid tissue)
blood
bone

Question 10

Define connective tissue disease and examples

Answer 10

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

Question 11

Connective Tissue Disease markers and the markers antigens

Answer 11

anti-nuclear antibodies (ANA) are important serological markers for CTD

Target antigens include, for example, nucleic acids, cell nuclear proteins and ribonuclear proteins.

Question 12

Describe Sjogrens Syndrome

Answer 12

Sjogren’s syndrome is an autoimmune disorder that destroys the glands that produce tears and saliva, causing excessive dry eyes and dry mouth.

Question 13

Diagnostic parameteres of sjogrens syndrome

Answer 13

1. Positive serum for anti-SSA/Ro and or anti-SSB/La or positive RF and ANA titre above 1:320
2. Labial salivary gland biopsy with focal lymphocytic sialadenitis with focus score = or above 1 focus/4mm2

3.Keratoconjunctivitis sicca with occular staining above 3

Question 14

What is Myositis and MOST common symptoms

Answer 14

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

Question 15

Digram of myositis pathogenesis

Answer 15

Lecture slide

Question 16

Describe the inflammatory myopathy forms

Answer 16

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.

Question 17

What is dermatomyositis and who does it affect

Answer 17

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.

Question 18

What is polymyositis and who does it affect

Answer 18

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.

Question 19

Symptoms of dermatomyositis and polymyositis

Answer 19

Eyelid rash
Shawl Sign
Shoulder/peliv girdle
ground glass opacity in lungs
GI vasculopathy
pharngeal weakness

polymyositis is the same BUT NO RASH

Question 20

What is inclusion body myositis and when does it develop?

Answer 20

aprogressive muscle disorder characterized by muscle inflammation, weakness, and atrophy(wasting)

develops in adulthood, usually after age 50

Question 21

Diagnose myositis

Answer 21

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.

Question 22

What areas of the body does SLE affect
Symptoms
what age does it develop

Answer 22

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

Question 23

SLE diagnostic findings

Answer 23

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

Question 24

what does ANA target?
Why are ANA important?
found in healthy people?

Answer 24

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

Question 25

Gold standard test for ANA and description

Answer 25

The gold standard is the indirect immunofluorescence test with human epithelial cells (HEp-2)

high sensitivity and specificity

Question 26

ANA IFA patterns and what diseases they suggest

Answer 26

1. Homogenous, in which the entire nucleus fluoresces
   = SLE and discoid lupus erythematosus (DLE)
2. Rim, in which the nuclear perimeter fluoresces
   =CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome and SLE
3. 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.

Question 27

Correlate the ANA pattern to diseases associated and antigen used for the disease

Answer 27

1. Homogenous
   SLE -dsDNA
   DLE - Histones
2. Rim
   CREST, SLE = centromere
3. Speckled
   Sjögren’s syndrome - SSa/Ro or SSB/La
   SLE -Sm
   Scleroderma = Scl-70
4. Nucleoar
   Scleroderma = PM/Scl
5. Centromere
   CREST = anti-centromere

Question 28

Additional purpose of ANA and example

Answer 28

Besides confirming a diagnosis of CTD in patients with suggestive clinical features, ANA testing serves 2 additional purposes:

1. 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

Question 29

Diagnostic features of SLE

Answer 29

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

Question 30

Examples of AID (7) and what factors cause them

Answer 30

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.

3. 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.
4. 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.
5. 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.
6. 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.
7. 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.

Question 31

Draw diagram of AID and then describe the 5 causes of AID using example and details

Answer 31

1. 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)
2. 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.
3. 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.
4. 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.
5. 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