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
Lymphoid invasion, parenchymal destruction by questionable cell mediated hypersensitivity or antibodies
Organ-specific
Lesions caused by deposition of antigen antibody (immune) complexes
Non-organ specific
Tendency to develop cancer in the organ
Organ-specific
Tendency to develop lymphoreticular
neoplasia
Non-organ specific
joints
SLE
RA
lungs
SLE
Granulomatosis with polyangiitis
Multiple cells and organs
SLE
skin
kidneys
brain
heart
SLE
bone; other tissues in some cases
RA
Upper respiratory system
blood vessels
Granulomatosis with polyangiitis
• Antibodies to double-stranded DNA
and other nuclear components, such as Sm (ANAs)
SLE
RA
Granulomatosis with polyangiitis
• Phospholipid antibodies
SLE
• Antibody to RBCs
SLE
• Antibody to platelets
SLE
• Antibody to lymphocytes
SLE
• Antibody to ribosomal components
SLE
• Antibody to endothelium
SLE
• Rheumatoid factor
SLE
RA
Granulomatosis with polyangiitis
• Anti-CCP (cyclic citrullinated proteins)
RA
• Antineutrophil cytoplasmic antibodies (ANCA); c-ANCA pattern
Granulomatosis with polyangiitis
Liver
Autoimmune hepatitis (AIH)
Small intestine and other
organs
Celiac disease
Kidneys
Goodpasture’s syndrome
Poststreptococcal glomerulonephritis
lungs
Goodpasture’s syndrome
Thyroid gland
Graves disease
Hashimoto’s thyroiditis
Myelin sheath
of nerves
Multiple sclerosis
Nerve-muscle synapses
Myasthenia gravis
Stomach
Pernicious anemia
Intrahepatic bile ducts
Primary biliary cirrhosis
Heart
Rheumatic fever
Connective tissue
Scleroderma
Eyes, mouth
Sjogren syndrome
Pancreas
Type 1 diabetes mellitus
Antibody to adrenal cells
Addison’s disease
AIH-1—smooth muscle antibodies
Autoimmune hepatitis
AIH-2—anti-liver kidney microsomal antibody
Autoimmune hepatitis
anti-liver cytosol type 1 antibody (anti-LC-1)
Autoimmune hepatitis
Antitransglutaminase (tTG)
Celiac disease
Antibodies to deamidated gliadin peptides (DGPs)
Celiac disease
Endomysial antibodies
Celiac disease
Antibody to an antigen in the renal and
pulmonary basement membranes
Goodpasture’s syndrome
Thyroid-stimulating hormone receptor antibodies (TRAbs)
Graves disease
Antithyroglobulin
Graves disease
Hashimoto’s thyroiditis
Antithyroid peroxidase (TPO)
Graves disease
Hashimoto’s thyroiditis
Antibodies to myelin basic protein
Multiple sclerosis
Antibodies to acetylcholine receptors (AChR)
Myasthenia gravis
Anti-muscle-specific kinase (MuSK)
Myasthenia gravis
Antibody to the lipoprotein LRP4
Myasthenia gravis
Parietal cell antibody, intrinsic factor
antibody
Pernicious anemia
Streptococcal antibodies that cross-react
with kidney tissue
Poststreptococcal glomerulonephritis
Antimitochondrial antibodies (AMA)
Primary biliary cirrhosis
Streptococcal antibodies that cross-react
with cardiac tissue
Rheumatic fever
Antinuclear antibodies: anti-Scl-70
Scleroderma
anticentromere antibody
Scleroderma
rheumatoid factor
Sjogren
antisalivary duct antibodies
Sjogren
antilacrimal gland antibodies
Sjogren
Anti-insulin
Type 1 diabetes mellitus
IA-2 and anti–IA-2Ba
Type 1 diabetes mellitus
Antibody to glutamic acid phosphatase (GAD)
Type 1 diabetes mellitus
HLA-A1, B8, and DR3
SLE
may cause DNA to form thymine dimers
UV light
described in anti–TNF-treated rheumatic patients
lupus-like autoantibodies
Antibody-forming B lymphocytes are stimulated in a relatively nonspecific manner
polyclonal B cell activation
specific for SLE and are observed at a frequency of 75% to 90% in SLE patients with active disease
Anti-ds DNA Auto Ab
containing complement-activating IgG3
have a particular tropism for basement membranes
readily deposited in the kidney glomeruli
DNA-anti-DNA immune complexes
can also cause cellular destruction by other mechanisms
Autoantibodies to nuclear and nonnuclear antigens
can cause hemolytic anemia
Antibodies to red blood cells (RBCs
and antibodies
to platelets can cause thrombocytopenia by
antibody-mediated cytotoxic (type II) hypersensitivity
can cause inflammation of the blood vessels, and
vascular damage in lupus, responsible for the vasculitis and neuropsychiatric symptoms are seen in some SLE patients
Antibodies to endothelial cells
associated with increased miscarriage, stillbirth, and preterm delivery in pregnant women with lupus
Phospholipid antibodies
Neonatal lupus, which occurs in up to 8% of babies born to pregnant women with
SLE, is associated with antibodies to the nuclear antigens,
SS-A/Ro and SS-B/La
diverse; nonspecific symptoms
SLE
may appear on any area of the body exposed to UV light
erythematous rash
butterfly rash (“malar rash”) across the nose and cheeks
Wolf-like
increased in those who have antibodies to nuclear RNP in their serum
Raynaud’s phenomenon
polyarthralgia or arthritis
Joint involvement
Nephritis
Renal involvement
the most dangerous type of lesion characterized by cell proliferation
diffuse
proliferative glomerulonephritis
pericarditis, tachycardia, ventricular enlargement; pleuritis
cardiac involvement
seizures, mild cognitive dysfunction, psychoses, or depression
neuropsychiatric manifestations
anemia, leukopenia,
thrombocytopenia, or lymphopenia
Hematologic abnormalities
About 20% of episodes of fever are caused by
Infections
leading cause of death in hospitalized patients
Infections
can interfere with host defense against opportunistic infections
Immunosuppression
✓ Complete blood count (CBC) ✓ Platelet count
✓ Urinalysis ✓ Erythrocyte sedimentation rate (ESR) determination ✓ CRP levels
SLE
quantification of complement proteins
and the detection of specific autoantibodies
SLE
is the most commonly measured complement protein
C3
may be low during disease flares as a result of
complement consumption by immune complexes. Thus, complement levels can be helpful not only in the initial diagnosis but also for monitoring patients over time
Serum complement levels
