1. Potential complication in bone marrow and liver trans- plants and in blood transfusions given to patients with conditions associated with T-cell immunodeficiency 2. Donor T cells recognize host tissue as foreign and activate
host CD4 and CD8 T cells.
3. Clinical findings include bile duct necrosis (jaundice), gastrointestinal mucosa ulceration (bloody diarrhea), and dermatitis.
E. Types of transplants (Table 3-3)
I•
I Chapter 3 Immunopathology 29
TABLE 3-3 Some Types of Transplants
•• Type of
Transplant Comments
• Cornea Best allograft survival rate
Danger of transmission of Creutzfeldt-Jakob disease
• Kidney Better survival with kidney from living donor than from cadaver
• Bone marrow Graft contains pluripotential cells that repopulate host stem cells Host assumes donor ABO group
• Danger of graft-versus-host reaction and cytomegalovirus infection
•
• TABLE 3-4 Autoantibodies in Autoimmune Disease
• Autoantibodies Disease Test Sensitivity (%)
• Anti-acetylcholine receptor Myasthenia gravis 90%
• Anti-basement membrane Goodpasture's syndrome > 90%
•
Antiendomysial and antigliadin Anti-insulin
Celiac disease Type 1 diabetes
95%
50%
• Anti-islet cell 75%
•
Anti-intrinsic factor Anti-parietal cell
Pernicious anemia 60%
90%
• Antimicrosomal
Antithyroglobulin
Hashimoto's thyroiditis 97%
85%
• Antimitochondrial Primary biliary cirrhosis 90-100%
• Antimyeloperoxidase Microscopic polyangiitis 80% (p-ANCA)
• Antiproteinase 3 Wegener's granulomatosis > 90% (c-ANCA) Anti-thyroid-stimulating hormone Graves' disease 85%
• receptor
• c-ANCA, cytoplasmic antineutrophil cytoplasmic antibody; p-ANCA, perinuclear antineutrophilic cytoplasmic antibody.
••
•
• V. Autoimmune Diseases
• Autoimmune dysfunction is associated with a loss of self-
• tolerance resulting in immune reactions directed against host tissue.
• A. Mechanisms of autoimmunity
• 1. Release of normally sequestered antigens (e.g., sperm) 2. Sharing of antigens between host and pathogen 3. Defects in functions of helper or suppressor T cells
•
4. Persistence of autoreactive T and B cells 5. Presence of specific autoantibodies (Table 3-4)
• B. Systemic lupus erythematosus (SLE)
• Connective tissue disease that mainly affects the blood,
• joints, skin, and kidneys
• 1. Occurs predominantly in women of childbearing age
•
30 Pathology
Figure 3-1 Malar rash in sys- temic lupus erythematosus showing the butterfly-wing distribution.
2. Pathogenesis: polyclonal B-cell activation, sustained es- trogen activity, environmental triggers (e.g., sun, procainamide)
3. Clinical findings
a. Hematologic: autoimmune hemolytic anemia, thrombocytopenia, leukopenia
b. Lymphatic: generalized lymphadenopathy, splenomegaly
c. Musculoskeletal: small-joint inflammation (e.g., hands), absence of joint deformity
d. Skin: immunocomplex deposition along basement membrane (liquefactive degeneration), malar butter- fly rash (Figure 3-1)
e. Renal: diffuse proliferative glomerulonephritis (most common glomerulonephritis)
f. Cardiovascular: pericarditis, Libman-Sacks endocar- ditis (sterile vegetations on mitral valve)
g. Respiratory: interstitial fibrosis of lungs, pleural effu- sion with friction rub
h. Pregnancy-related
(1) Complete heart block in newborns, which is caused by anti-SS-A (Ro) antibodies crossing the placenta
(2) Recurrent spontaneous abortions 4. Drug-induced lupus erythematosus
a. Associated drugs: procainamide, hydralazine b. Features that distinguish drug-induced lupus
from SLE
(1) Antihistone antibodies
(2) Low incidence of renal and central nervous system (CNS) involvement
Most common cardiac finding in SLE: fibrinous peri- carditis with effusion
Most common drug associated with drug-induced lupus:
procainamide
Chapter 3 Immunopathology 31 (3) Disappearance of symptoms when the drug is
discontinued 5. Laboratory findings in SLE
a. Positive serum antinuclear antibody (ANA) (almost all cases)
(1) Anti-double-stranded DNA antibodies and anti-Sm antibodies: used to confirm the diag- nosis of SLE because they are highly specific for the disease (i.e., few false-positive results) (2) Anti-Ro antibodies: positive in 25-50% of cases b. Antiphospholipid antibodies (lupus anticoagulant
and/or anticardiolipin antibodies): damage vessel endothelium, producing vessel thrombosis and causing an increased incidence of strokes
Anticardiolipin antibodies may produce a false- positive syphilis serology by cross-reacting with cardiolipin in the rapid plasma reagin (RPR) and Venereal Disease Research Laboratory (VDRL) tests.
c. Lupus erythematosus cell: neutrophil containing phagocytosed altered DNA; not specific for SLE d. Decreased serum complement
e. Immunocomplexes at the dermal-epidermal junc- tion in skin biopsies
C. Systemic sclerosis (scleroderma)
• Excessive production of collagen that primarily targets the skin (scleroderma), gastrointestinal tract, lungs, and kidneys 1. Occurs predominantly in women of childbearing age 2. Pathogenesis
a. Small-vessel endothelial cell damage produces blood vessel fibrosis and ischemic injury.
b. T-cell release of cytokines results in excessive colla- gen synthesis.
3. Clinical findings a. Skin
(1) Skin atrophy and tissue swelling beginning in the fingers and extending proximally;
parchment-like appearance; extensive dystro- phic calcification
(2) Raynaud's phenomenon: sequential color changes (normal to blue to red) caused by digital vessel vasculitis and fibrosis; digital infarcts (Figure 3-2, A)
(3) Tightened facial features (e.g., radial furrowing around the lips) (Figure 3-2, B)
Most common initial sign of systemic sclerosis: Raynaud's phenomenon
32 Pathology
A
Figure 3-2 Systemic sclerosis. The fingers (A) are swollen and tapered; digital infarctions are present in some of the fingertips. The tightening of the skin around the mouth (B) is caused by excess collagen
b. Gastrointestinal
(1) Dysphagia for solids and liquids: no peristalsis in lower two thirds of esophagus (smooth muscle replaced by collagen); lower esophageal sphincter relaxation with reflux
(2) Small bowel: loss of villi (malabsorption), wide- mouthed diverticula
c. Respiratory: interstitial fibrosis of lungs; respiratory failure (most common cause of death)
d. Renal: vasculitis involving arterioles and glomeruli;
infarctions; malignant hypertension 4. CREST syndrome: limited sclerosis
a. Dystrophic calcification, anticentromere antibodies b. Tapered, claw-like fingers (sclerodactyly)
c. Multiple punctate blood vessel dilations (telangiectasia)
5. Laboratory findings in systemic sclerosis a. Serum ANA: positive in 70-90% of cases
b. Antitopoisomerase antibody: anti-Scl-70; positive in 15-40% of cases