Path 16: Pathology Autoimmune Disease

Front 1

Leading causes of death in SLE patients? Mechanism of this pathology?

Back 1

Renal failure (glomerulonephritis) by the buildup of immune complexes (DNA-anti-DNA) in glomeruli. Also, infection and cardiovascular disease.

Front 2

Describe the patterns of renal change in SLE. Which is most common? Key pathological features for each?

Back 2

Class 1 and 2 (don't worry about these), Class 3 Focal Lupus Nephritis (focal necrotizing lesions seen on stain of glomeruli), Class 4 Diffuse Lupus Nephritis is most common and most serious (diffuse increase in cellularity, "wire loop" lesions indicative of subendothelial immune complex deposition, and granular patterns of subendothelial IgG seen with fluorescence), Class 5 (not so important), Class 6 Advanced Sclerosing Lupus Nephritis (sclerotic glomeruli, aka scarring, into a crescent shape that eventually obliterates the structure and function leaving "ghost glomeruli")

Front 3

*High Yield* Histopathological findings of the skin in SLE patients? What biological mechanism underlies these findings?

Back 3

1) Liquefactive degeneration at the basal layer of epidermis 2) Edema at the dermoepidermal junction 3) Mononuclear inflitrates around vessels and skin appendages 4) Mucin between cells in the dermis.

All of these symptoms result from the deposition of immune complexes and complement at the dermoepidermal junction, which can be visualized through immunofluorescence.

Front 4

Histopathological findings of the heart in SLE patients? What biological mechanism underlies these findings?

Back 4

Primarily pericarditis (nonbacterial, verrucous "Libman-Sacks" endocarditis) caused by mononuclear infiltrates, tissue granulation involving fibrin, debris, and histiocytes, and the valve lesions resulting from these processes.

Front 5

Describe the time course (without immunosuppressant treatment) and morphology of the major rejection reaction classes for a kidney transplant. Also, explain the immunological mechanisms for each.

Back 5

Hyperacute rejection (min-hours) involves the action of preformed host antibodies and results in endothelial damage and ischemia of the graft which can be seen as a darkening in color of the anastomosing blood.

Acute (days-weeks)

-Cell mediated relies on the action of inflammatory cells which can be visualized in the interstitium between tubular epithelial cells

-Humoral relies on antibodies, inflammatory cells, and smooth muscle cells and results in rejection vasculitis.

Chronic (months-years) occurs when the arterial lumen is replaced with smooth muscle cells and connective tissue, resulting in graft arteriosclerosis.

Front 6

What causes amyloidosis?

Back 6

Deposition of misfolded protein in extracellular tissues to disrupt normal cell function. Misfolded protein monomers assemble into beta-pleated sheets to form "fibrils"

Front 7

Describe the features of each major type of amyloidosis and their mechanisms. Which is most common?

Back 7

Primary (AL)- most common, amyloid light chain protein is misfolded resulting in monoclonal plasma cell proliferation.

Secondary (AA)- acute response serum proteins, referred to as "amyloid associated", are misfolded yielding their deposition and resulting inflammation.

A-beta (Alzheimer's dz)- misfolding of the amyloid precursor protein yields beta amyloid plaques and fibrils in cerebral blood vessels and lesions

Transthyretin (TTR) or Prealbumin- misfolding of this normal serum protein, otherwise involved in binding thyroxine and retinol, results in a host of disorders known as familial amyloid polyneuropathies, but is also seen deposited in the heart of patients with senile systemic amyloidosis.

Beta-2 microglobulin- a component of MHC class 1, this normal serum protein is often seen misfolded in patients on long term hemodialysis and it deposits in joints, synovium, and on the tendon sheath.

Type 2 diabetes- amyloid deposits in the pancreatic islets of Langerhans often contain amylin, or islet amyloid polypeptide.

Front 8

What are the two major conditions that exhibit primary amyloidosis, and how are they similar/different?

Back 8

Multiple myeloma and plasmacytomas both represent the neoplastic proliferation of monoclonal plasma cells, resulting from a misfolding of kappa or lambda light chain in antibodies, but the difference is that a plasmacytoma is a single, discrete lesion in bone/soft tissue while multiple myeloma is considered a systemic amyloidosis with >5% of all plasma cells.