UNIT 3: Autoimmune Diseases Flashcards
Class I associated
Ankylosing spondylitis
Myasthenia gravis
Class II associated [7]
Hashimoto’s disease
Graves’ disease
Type 1 diabetes
Addison’s disease
Rheumatoid arthritis
Sjögren’s syndrome
Multiple sclerosis
B27
Ankylosing spondylitis
B8
Myasthenia gravis
DR2
Multiple sclerosis
DR3
Graves’ disease
Addison’s disease
Sjögren’s syndrome
DR4
Rheumatoid arthritis
DR5
Hashimoto’s disease
DQ2+DQ8
Type 1 diabetes
DQ6
Type 1 diabetes
DQ8
Type 1 diabetes
RA, several others
PTPN22
Abnormal tyrosine phosphatase regulation of T cell selection and activation
PTPN22
Crohn disease
NOD2
Defective resistance or abnormal responses to intestinal microbes
NOD2
IBD, inflammatory bowel disease
psoriasis, PS
AS
IL23R
Component of IL-23 receptor; role in generation and maintenance of Th17 cells
IL23R
T1D, RA
CTLA4
Inhibitory receptor of T cells, effector of regulatory T cells
CTLA4
MS, type 1 diabetes, others
CD25 (IL-2Rα)
Abnormalities in effector and/or regulatory T cells?
CD25 (IL-2Rα)
SLE
C2, C4 (Complement proteins)
FCGRIIB (FCγRIIb)
Defects in clearance of immune complexes or in B cell tolerance?
C2, C4 (Complement proteins)
Defective feedback inhibition of B cells
FCGRIIB (FCγRIIb)
Autoimmune polyendocrine syndrome (APS-1)
AIRE
Reduced expression of peripheral tissue antigens in the thymus, leading to defective elimination of self- reactive T cells
AIRE
Autosomal dominant immune dysregulation syndrome
CTLA4
Impaired regulatory T cell function leading to loss of B and T cell
CTLA4
Immune dysregulation, X-linked Polyendocrinopathy and enteropathy (IPEX)
FOXP3
Deficiency of regulatory T cells
FOXP3
Autoimmune lymphoproliferative syndrome (ALPS)
FAS
Defective apoptosis of self-reactive T and B cells in the periphery
FAS
IL23R
Ankylosing spondylitis
PTPN22
RA
CTLA4
RA
T1D
CD25 (IL-2Rα)
T1D
MS
C2, C4
SLE
FCGRIIB (FCγRIIb)
SLE
Presence of [?] autoantibodies and/or autoreactive lymphocytes in vivo
high titer
Autoantibody binding and/or T‐cell reactivity to [?] in vitro
autoantigen
[?] with autoreactive serum and/or autoreactive lymphocytes
Transfer of disease
Immunopathology consistent with
autoimmune‐mediated processes
Beneficial effect of
immunosuppressive interventions
Exclusion of [?] of disease
other possible causes
association
MHC
[?] mirroring the human disease
Animal model
Similarities of Organ-Specific and Organ-Nonspecific Disorders
Circulating autoantibodies react with [?]
Increased [?] in serum often found.
Antibodies may appear in each of the main [?] classes.
Disease process not always [?]; exacerbations and remissions occur.
[?] of diagnostic value
normal body constituents
immunoglobulin concentration
immunoglobulin
progressive
Autoantibody tests
Antibodies and lesions are organ-specific
Organ-specific
Antibodies and lesions nonspecific
Non-organ specific
Clinical and serologic overlap
Organ-specific
Overlap of SLE, RA, and other connective tissue disorders
Non-organ specific
Antigens only available to lymphoid system in low concentrations
Organ-specific
Antigens in high concentrations
Non-organ specific
Antigens evoke organ-specific antibodies in normal animals with complete Freund’s adjuvant
Organ-specific
No antibodies produced in animals with comparable stimulation
Non-organ specific
Familial tendency to develop organ
Specific autoimmunity
Organ-specific
Familial tendency to develop connective tissue disease.
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Non-organ specific
Questionable abnormalities in immunoglobulin synthesis in relatives
Non-organ specific