IMM: Systemic Autoimmune Disease Flashcards
Autoimmune disease results from….?
- Breakdown in regulation.
- Dysregulated inflammatory response.
Central tolerance is a type of self-tolerance.
- What are the mechanisms?
- What are the sites of action?
- Mechanisms?
- Deletion of tissue specific lymphocytes, editing.
- What are the sites of action?
- Thymus, bone marrow.
Describe antigen segregation.
Some organs are immune privileged.
- Brain (BBB), eye, testes, uterus, hamster cheek pouch.
Antigen segregation = physical barriers keep antibodies out of important areas.
- Connective tissue problems is typical of …..
- Typical of systemic autoimmune diseases.
*
5 examples of systemic AI diseases.
- Prototypical = SLE.
- RA.
- Scleroderma.
- Polymyositis/dermatomyositis.
- Sjogren’s syndrome.
Where are antigens found in SLE?
Antigens are within the nucleus.
DEEPSIT for SLE.
- Definition - multisystem, chronic inflammatory disease.
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Etiology - unknown.
- Complex genetic basis.
- Multifactorial.
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Epidemiology
- Predominantly in females (10:1 ratio).
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Pathophysiology
- B cells that are polyclonal, produce many different types of antibodies.
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Signs/Symptoms
- Mild to fatal clinical presentation.
- I
- T
Describe the complement cascade.
Clinical relevance.
Interface between innate and adaptive immune response.
- Augments antibody response.
- Put complement on cell = increased complement dependent cell cytotoxicity.
- Complement deficiency = increased risk of autoimmune diseases.
- Need to clear dead and apoptotic cells so that antibodies don’t come to neutralise them and kill other things.
Describe the classical complement cascade.
Immune complex = antigen bound to antibody.
C1qrs binds onto immune complex. Activates C4 and C2. Becomes a convertase for C3. Lots of C3 can cause phagocytosis and removal).
Marked classical pathway activation consumes C4 and potentially also reduces C3.
C4 activated before C3.
Direct Coomb’s test.
Are the autoantibodies bound directly to the RBC?
Trying to create immune complex (causes agglutination of RBCs - +ve test)
Lupus nephritis.
Glomerular capillary with endothelial cell inside and epithelial cell outside. Immune complexes formed along basement membrane. Abnormal filtration of protein, leading to proteinuria. Rised creatinine. Renal failure.
- 33 yo F.
- Hx:
- 3y of arthralgia and skin rash, presenting with proteinuria.
- Investigations for lupus?
- At dermal-epidermal juction, what is found? Where else is this thing found?
Positive ANA, + anti-dsDNA antibodies
Positive skin biopsy
Swollen joints
Low C4 and C3.
protein creatinine ratio is 90, which is high.
Rash is photosensitive.
At dermal-epidermal juction, what is found? A: Immune complex deposition. Also found in the glomeruli.
Consumption of C4 during disease flare then afterwards.
As dsDNA antibodies go down, complement goes up.
Slide 31.
ARA classification criteria.
Four criteria = cutaneous.
- Malar rash (flash card with pictures) = fixed erythema, flat or raised.
- Discoid rash (flash card with pictures) = sits in disks.
- Has scaling on it.
- Plugging +/- atrophic scarring.
- Photosensitive.
- Turning bright red.
- Oral ulceration.
- Painless oral or nasopharyngeal ulceration.
ARA classification - organs/joints.
Non-erosive arthritis >= 2 peripheral joints
Serositis
Renal
Neuro
