L26- Autoimmune Diseases Flashcards
Autoimmune disease previous names
CT diseases
collagen vascular disease
describe central tolerance process
(T cells in thymus and B cells in BM)
1) APC presents self Ag in thymus or BM
2) immature T/B cell binds with high, low, or no affinity
3a, thymus) high affinity, T cell deletion or Treg cell; low affinity, reprogramming
3b, BM) high affinity, B cell deletion; low affinity, reprogramming
describe peripheral tolerance process
- backup mechanism to neutralize self-reactive T and B cells (if they escape central neutralization)
1) APC presents self in periphery – T cell or B cell binds
2a) suppression of T cell via Treg cells
2b) T cell deletion
2c) T cell anergy- failure of response
2d) B cell anergy- failure to respond
Autoimmune mechanisms in general involve the following 3 processes before occurring
1) Loss of Self-Tolerance via genetic predisposition – multifactorial, due to multiple and many mutations = ‘susceptibility genes’
2) tissue injury or 3) infection –> change to self-Ag
______ is the common genetic locus with relation to Autoimmune diseases (bonus- specific gene for ankylosing spondylitis)
HLA locus
HLA-B27 for ankylosing spondylitis (strong association – weaker for other autoimmune diseases)
-note many other loci can be involved
briefly describe the ways infections and injury contribute to the Autoimmune mechanism
- Molecular mimcry (infection): microbes with cross-reactive epitopes with self-Ags
- Up-regulation of immune response (more sensitive and hyperactive) due to inflammation and necrosis (trigger)
- altered display of self-Ag
SLE:
- affects (males/females) more
- (2) and (3) contribute to etiology
- (4) are the affected systems
- (5) is common in terms of associated diseases
1- females, 9:1
2- genetic susceptibility
3- environmental triggers (proposed mechanism has triggers damaging tissue, releasing many DNA Ags)
4- skin, kidneys, serosa, joints, heart
5- overlaps with other autoimmune diseases
SLE involves (1) as the basic mechanism with (2) as the predominant antibodies. SLE is a type (3) hypersensitivity reaction.
1- loss of self-tolerance
2- Abs against nuclear components (Anti-dna), Abs against phospholipids/others
3- type II (Ig targets membrane Ag, direct Ab injury), type III (immune complex deposition)
SLE, skin effects:
- (1) is most common, worsened by (2)
- (3) may be present
1- malar / butterfly rash — non-scarring
2- sun light (photosensitive)
3- features of vasculitis
describe microscopic appearance of SLE in the skin
- inflammatory cell infiltration
- edematous tissue around vacuolar/liquefactive necrosis via basal keratinocyte degeneration
-IgG present on immunofluorescence on stratum basale layer of epidermis (basal keratinocytes) due to abundance of nuclear products (in comparison to surrounding cells)
list the different presentations of SLE in the kidney (hint: I-V)
I- normal LM, deposits on IF
II- (10-20%) mesangioproliferative glomerulonephritis
III- (20-35%) focal proliferative glomerulonephritis
IV- (35-60%) diffuse proliferative glomerulonephritis
V- (10-15%) membranous glomerulonephritis
describe the effects SLE has on joints
- pain, swelling, inflammation, stiffness of joints
- neutrophils and fibrin in synovial fluid
- non-erosive synovitis == articular cartilage intact
- no deformities
describe the effects SLE has on Heart + BVs
Heart:
- pericarditis, myocarditis
- Libman Sacks endocarditis: 1-3 mm aseptic vegetation on any valve on either surface
BVs:
-necrotizing vasculitis of small arteries, arterioles (via complement activation) –> effects any tissue –> complete CNS angiograph
SLE Diagnosis (Igs):
- (1) testing is specific and diagnostic
- (2) testing is useful because it is sensitive, but nonspecific
- (3) are the ‘other’ antibodies that can be tested
1- anti-dsDNA, anti-Smith
2- ANA, anti-nuclear antibodies via indirect IF
3- *anti-phospholipid, anti-platelet, anti-RBC
list the many other tests that are useful in diagnosis and monitoring of SLE (indicate what each is checking for)
- UA and renal function tests: kidney status
- kidney biopsy if necessary
- CBC: hemolysis
- coagulation studies: platelet destruction
- complement levels: reduced in active disease b/c of deposition
describe the SLE diagnostic criteria according to ACR
4 out of 11 of the following:
- malar (cheek) skin rash
- discoid (disc shaped) skin rash
- photosensitive rash
- oral ulcers
- arthritis
- serositis
- renal / neurologic / hematologic / immunologic disorder
- anti-nuclear Ab (ANA)
Anti-phospholipid Abs are found in (1)% of SLE patients. (2) is the main change as a result, which can lead to (3) or (4).
1- 40-50%
2- prolongs coagulation time (in vitro)
3- recurrent thromboemboli (in vivo)
4- recurrent abortions, focal cerebral ischemia (in vivo)
define anti-phospholipid antibody syndrome
presence of anti-phospholipid Ab w/o criteria to meet SLE Dx (presents alone)
Drug-induced SLE:
- (1) list drugs, indicate most common cause
- (2) are frequently measured / present
- (3) Sxs are commonly not present
- (4) doesn’t occur with drug removal
1- procainamide* (most common), hydralazine, isoniazid, D-penicillamine
2- anti-histone Abs
3- renal and CNS (no encephalopathy)
4- improvement of Sxs or eradication of SLE
Systemic Sclerosis = (1):
- (2) definition
- (3) are the affected systems
- (4) are the systemic types
1- scleroderma
2- excessive fibrosis throughout body
3:
- skin (100%), GIT (90%), lungs (50%)
- kidneys, heart, skeletal muscle (less common)
4- diffuse or limited (= CREST syndrome)
Systemic Sclerosis:
- (1) affected age range
- affects (males/females) more
- overlapping features with (3) and (4), where their features may be masked
1- 50-60 y/o
2- females (3:1)
3- SLE
4- RA
describe skin features of Systemic Sclerosis
- skin sclerosis –> fingers affected first –> UEs, neck, face
- Reynaud’s phenomenon: reversible vasospasm with white/ischemic, blue/cyanotic, red/hyperemic areas
-fibrosis and atrophy of muscles – limited ROM, ulcers
describe GIT features in scleroderma
- muscular atrophy and fibrosis –> strictures in GIT (vomiting) or esophagus (dysphagia)
- loss of normal motility and absorption
It is thought that (1) are the main mediators of scleroderma, explain.
- (2) is highly specific humoral abnormality (although non-pathogenic)
- (3) is highly specfic for CREST syndrome
1- fibroblastic activation via CKs from Th cells –> macrophages and mast cells –> fibrogenic CKs –> sclerosis
2- Anti-topoisomerase (anti-Scl 70)
3- Anti-centromere
list the two main microscopic features of scleroderma in the skin
- flattening of epidermis (less troughs and pits)
- focal lesion of inflammatory cells
describe the differences in development and presentation of CREST in comparison to diffuse systemic sclerosis
-limited form – mild and indolent course
Sxs: CREST
Calcinosis (Ca deposition in soft tissues)
Raynaud phenomenon
Esophageal dysmotility
Sclerodactyly (skin thickening => hypomobility, ulceration)
Telangestasia (spider veins)
Graves disease = (1):
- (2) affected age range
- affects (males/females) more
1- diffuse toxic hyperplasia of thyroid
2- 20s-30s
3- females
______ are the Abs for Graves disease
- TRS-Ab, thyrotropin-receptor stimulating Ab
- TPO-Ab, thyroid peroxidase Ab
- TBII-An, thyrotropin binding inhibitor Ig
list symptoms of Graves disease
(hyperthyroidism) heat intolerance increased appetite, weight loss palpitations -- AFib tremor myopathy ophthalmopathy (exophthalmos)
Autoimmune Gastritis = (1):
- Abs against (2)
- (3) decrease leads to (4)
- (5) decrease leads to (6)
1- atrophic gastritis of pernicious anemia
2- gastric parietal cells
3- dec acid secretion
4- poor digestion / absorption
5- Intrinsic Factor
6- B12 deficiency –> macrocytic anemia + neurological symptoms
