Immune Pathology III: Autoimmune Diseases Flashcards Preview

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Flashcards in Immune Pathology III: Autoimmune Diseases Deck (25):

What are the three properties of autoimmune disease?

- presence of autoimmune reaction
- evidence that autoimmune response is primary source of injury, not a secondary reaction to some other source of tissue damage
- absence of other well-defined cause of disease


What are four general features of autoimmune diseases?

- failure to recognize self --> immune reaction mounted against self antigens
- tend to be progressive, with sporadic relapses and remissions
- clinical and pathologic features depend on the particular immune response
--> some dominated by neutrophils, some by macrophages or lymphocytes
- clinical, pathologic, and serologic features may overlap with other autoimmune diseases
--> complicates diagnosis, treatment


What is tolerance?

The usual state in which the body's immune system does not react to self stimulus.


What are the three features of the autoimmune disease spectrum?

- may be very organ specific (ex: Hashimoto's thyroiditis)
- may involve several defined organs (ex: lung and kidney in Goodpasture's syndrome)
- may have widespread, protean (changing) targets (ex: SLE)


What are the three results of peripheral tolerance?

- anergy
- suppression
- activation induced cell death


What are the three results of peripheral tolerance?

- clonal anergy
- peripheral suppression (by T cells)
- activation induced cell death - clonal deletion

also mechanism of immunologic tolerance:
antigen sequestration


Molecular mimicry is when the self antigen is molecularly similar to what?

to foreign antigen


What are six ways of escape from tolerance?

- FAILURE of anti-self cells to undergo APOPTOSIS (failure of clonal deletion)
- LOSS OF ANERGY (return to immunoreactivity by previously anergic cells)
- MOLECULAR MIMICRY (self antigen is molecularly similar to foreign antigen)
- POLYCLONAL LYMPHOCYTE ACTIVATION (activation overwhelms or bypasses normal regulatory controls)
- EMERGENCE OF SEQUESTERED ANTIGEN (able to interact with immune system)


Polyclonal lymphocyte activation overwhelms or bypasses what controls?

The normal regulatory controls


Emergence of antigen that was previously sequestered renders the antigen able to do what?

interact with the immune system


Do autoimmune disease cluster in families? What gene?

Yes. This is associated to certan human leukocyte antigen (HLA) types
- HLA-B27: associated with ankylosing spondylitis; induction of autoimmune disease in HLA-B27 transgenic animals


How are microbial agents involved in autoimmunity?

- share cross-reactive epitope with self antigen
- modify self antigen or complex with it --> antigen no longer recognized as self
- produce superantigens
--> cause powerful T and B cell activation and proliferation sufficient to break normal self-tolerance


What are autoantibodies?

Antibodies that target self antigens


What antigens are recognized by autoantibodies?

- cell surface proteins
- components of cell cytoplasm
- nuclear components


How do autoantibodies assist in diagnosis?

- typing of autoantibodies in serum
- may be specific for certain diseases


How do autoantibodies assist in current disease?

levels of autoantibodies correlate with disease severity


What are antinuclear antibodies (ANA)?

Autoantibodies commonly present in patients with autoimmune disease.
They are directed against nuclear antigens.


What types of ANA exist?

Antibodies to
- histones
- non-histone proteins bound to RNA
- nucleolar antigens


What are the limitations associated with ANA?

False-positive ANA is detected in up to 15% of population.
In these people, levels of ANA are low.
In this case, people test positive for ANA, but have no autoimmune disease.


ANAs are characterized by immunofluorescence staining of inflammatory cells. What are the staining patterns?

- homogeneous: non-specific
- rim (peripheral): think SLE
- speckled: think SLE
- nucleolar: think systemic sclerosis (scleroderma)


Contrast clonal anergy with clonal deletion (both mechanisms of immunologic tolerance)

Clonal anergy: (anti-self lymphocytes are rendered non-reactive to antigen stimulation)
- lack of activation of a lymphocyte which it needs in order to be active and an effector of the immune system
- occurs due to lack of costimulation when a lymphocyte reacts with self antigen

Clonal deletion: (anti-self lymphocytes undergo apoptosis)
- removes any lymphocyte (T cell) that reacts with self through apoptosis


How can superantigens break tolerance?

- microbial agents share a cross-reacting epitope with self antigen; modify self antigen or complex with it to change recognition as self
- cause a nonspecific activation of T cells that produces a powerful response


What are two common laboratory tests for SLE?

- testing for antibodies (antinuclear antibody ANA) via immunofluorescence; if rim or speckled, likely SLE
--> antibody to double stranded DNA: ds-DNA antibody
--> antibody Smith antigen: anti-Sm antibody
- renal biopsy (look for glomerular disease)
- direct immunofluorescence of skin (look for immune complexes at dermal-epidermal junction)


What abnormalities of facial skin and renal glomeruli are present in SLE?

- kidney develops glomerulonephritis
--> glomerulus becomes inflamed and the basement membrane becomes defective due to deposits (type III hypersensitivity mechanism)

- face develops butterfly rash
--> red rash on nose, cheeks, forehead
--> deposition of antibody complexes at dermal/epidermal junction


What are three non-genetic factors which may act as triggering events for clinically apparent SLE?

- drugs
- ultraviolet light
- estrogens (sex hormones; pregnancy)
- injury/trauma (including surgery)