Autoimmunity

Question 1

Factors in Autoimmunity

Important

Answer 1

Evironmental and endogenous
- Female hormones, tissue injury, microbes, epigenetic factors like aging, food, drugs can trigger

Leads to genetic susceptibility
- Then to loss of immunologic tolerance, self reactive T cells and B cells activate in response to self antigens

Question 2

Role of Genetic Factors

Answer 2

Complex diseases: multiple genetic variants, MHC haplotype is common risk factor
- Some rare diseases caused by single gene mutation

Question 3

Wrong Place Wrong Time

Special about DNA and MHC?

Answer 3

Autoreactive B + autoreactive T together can cause APC to present to T cell and form autoantibodies
- DNA is sugar, not protein so its not on MHC

Question 4

Super Antigens

Answer 4

Random or large stimulation, kills whatever wherever, not targeted, releases irrelevant or autoimmune antibodies

Question 5

Autoantigen Appearance Factor

Answer 5

Antibodies: recognize 3D epitopes
TCRs: recognize peptides

Some human antigens may look similar to foreign antigens

Question 6

Organ Specific Vs. Systemic Autoimmunity

Answer 6

Organ: chronic inflammatory in specific organ, autoAb specific for Ag of organ, autoAb are species specific

Systemic: widespread, many organs, autoAbs not organ specific or species specific

Question 7

Autoimmune Thryoid Diseases: Basics

what does AITD lead to

Answer 7

Increased or decreased production of thyroid hormones due to disregulation of endocrine feedback loop

Question 8

Thyroid Function & Formation

Answer 8

Thyroid has follicles filled with colloid
- Colloid has thyroglobulin

Thyroglobulin modified into T4 and T3
- Thyroid peroxidase synthesizes T3/T4

Question 9

Hashimoto’s Thyroiditis

Organ specific

Answer 9

Hypothyroidism
Destruction of thyroid glands
Type II and Type IV

Question 10

Graves Disease

Organ specific

Answer 10

Hyperthyroidism
Thyroid stimulates Abs, excessive releaseand overstimulation of heart

Type II

Question 11

Thyroid Issues and The Mechanism Behind It

With symptoms!

Answer 11

Low T3/T4
Hashimoto’s: anti-thyroglobulin, anti-thyroid peroxidase

High T3/T4
Low

Question 12

Type I Diabetes Mellitus

Answer 12

Endocrine disorder, hyperglycemia - Type I destruction of beta cells in pancreas = insulin deficiency

Type IV

Question 13

Celiac Disease

Answer 13

Gluten triggered
AutoAbs form in HLA-DQ2/DQ8 positive people to:
- Gliadin peptides
- Tissue transglutaminase, IgA
- Endomysium (tissue around intestinal muscles

Question 14

Multiple Sclerosis

Answer 14

CNS AI disorder
- Abs against myelin basic membrane
- Demyelination
- T cell disease, Th17 myelin specific CD4 cells

Question 15

Lab Diagnostic of Multiple Sclerosis

Important

Answer 15

Oligoclonal banding
Distinct bands in patients in Ms

Question 16

Myasthenia Gravis

Answer 16

Neuromuscular junction
- Abs to acetylcholine receptors = weak muscles

Question 17

Goodpasture’s Syndrome

Answer 17

Abs to basement membranes of renal glomeruli, can also affect lungs
Type II

Question 18

Systemic Lupus Erythematosus SLE: Basics

Answer 18

Chronic inflammatory disease
- Numerous AutoAbs
- Immune complexes form, trigger C activation and inflammation
- Involves kidneys, renal failure

Type III

Drug induced: stops once drug stops
Discoid: cutaneous but progresses into SLE

Question 19

Anti-Nuclear Abs

Answer 19

Not specific
- Vivo: react with free nuclear material of disrupted cells
- Vitro: react with nuclei of different species

Question 20

ANA Target Classification

Answer 20

• Ab to DNA
• Ab to histones
• Ab to extractable nuclear antigens
• Ab to nucleolar material

Question 21

Homogenous Pattern

anti what, seen in what

Answer 21

Anti: DNA, histones, nucleosomes
Seen in: RA, SLE, others

Question 22

Peripheral/Rim

anti what, seen in what

Answer 22

Anti: dsDNA
Seen in: SLE specific

Question 23

Speckled Pattern

anti what, seen in

Answer 23

Anti: extractable nuclear Ag-SnRNPs
Seen in: SLE, Sjorgren’s syndrome, scleroderma, rheumatic

Question 24

Nucleolar Pattern

Answer 24

Anti: nucleolus
Seen in: SLE, progressive systemic sclerosis

Question 25

Centromere Pattern ## Footnote seen in

Answer 25

**Seen in:** CREST syndrome

Question 26

SLE: Lab Diagnosis

Answer 26

ANA positive - dsDNA Abs + low C3 levels = SLE diagnosis You can also test anti-histone/rim pattern, speckles pattern is SPECIFIC to SLE

Question 27

Using Crithidia Luciliae For IFF

Answer 27

Kinetoplast in C. luciliae high in dsDNA

Question 28

Rheumatoid Arthridis: Basics ## Footnote anti what

Answer 28

**Rehumatoid factor:** autoAb against Fc of IgG **Type III**

Question 29

RA: Diagnostics

Answer 29

**Agglutination test**: cells with IgG - Does not rule out! **IgA/IgG isotype RF:** more specific, nephelometry or EIA **A-CCP Abs:** lead marker for RA, much more specific, detected by ELISA **ANA**

Question 30

Granulomatosis with Polyangiitis (Wegner's Granulomatosis)

Answer 30

Inflammation of blood vessels in respir. tract - Becomes systemic **Abs to:** neutrophil cytoplasmic antigens - Can be type II, III, or IV

Question 31

Sjogren's Syndrome

Answer 31

Moisture glands attacked - Can be secondary to other AI disease **Lab Diagnostics:** nonspecific by ANA, so confirm by doing Ab to Ro and La by ELISA

Question 32

Progressive Systemic Sclerosis/Scleroderma

Answer 32

Ab to ENA, nucleolus, centromere, Scl-70 - Speckled and nucleolar

Question 33

AI Liver Diseases

Answer 33

AI hepatitis: SMA (smooth muscle), ANAs Primary Biliary cirrhosis: mitocondral Abs