Autoimmunity Flashcards
autoimmunity:
-immune reactions directed at ____
self-antigens
autoimmunity:
-acute and/or chronic _____ and _____
inflammation;
cell injury
autoimmunity:
severity ranges from _____ to _____
minor;
lethal
autoimmunity:
cures
no cure for most
allergy: _____ antigen and _____ duration
environmental;
limited
allergies ____ with removal of environmental antigen
resolve
autoimmunity: _____ antigen and _____ duration
environmental or endogenous;
chronic
autoimmunity ____ with removal of environmental antigen
does not resolve
autoimmunity is largely limited to type ____ hypersenstivities
II - IV
most affected organs and tissues
- bone marrow
- lining of the joints
- blood vessels
- connective tissues
- endocrine glands
- kidneys
- muscles
- skin
steps to autoimmunity
- “normal” autoimmunity
- multigenic
- hormonal
- environmental triggers (infections, drug-induced, toxins)
- breakdown of tolerance
there are some ____ that predispose people to autoimmune diseases
alleles
uveitis is associated with ____
HLA B27
uveitis:
- inflammation of ____
- etiology:
uvea;
idiopathic, infection, injury, or autoimmune disorders
breakdown of central and peripheral tolerance:
-faulty ____
clonal deletion (auto-reactive lymphocytes allowed to mature and enter circulation)
breakdown of central and peripheral tolerance:
-loss of ____
Treg-cells (hyper-responsive T and B-lymphocytes; prolonged immune reactions)
breakdown of central and peripheral tolerance:
abnormal expression of _____
HLA class II molecules
antigens in autoimmunity:
sequestered antigens
immunoprivileged organs
antigens in autoimmunity:
infectious disease
- molecular mimicry
- original insult
tissue-specific, antibody-mediated, autoimmune diseases (Type II)
- auto-antibodies direct at auto-antigens
- affect normal function of the target organ
- induce tissue damage
- auto-Ab levels increase with age in healthy adults
rheumatic fever
- Type II
- strep infection induces cross-reactive auto-Abs
- molecular mimicry
- protein in wall of strep bacteria looks similar to antigens of tissues in our heart and myocardium - auto-Abs attack our heart
pernicious anemia
- Type II
- auto-Abs block transport molecule in GI tract
myasthenia gravis
- Type II
- auto-Abs block muscle function
- prevent ACh from binding, no muscle contraction, paralysis
graves disease
- Type II
- auto-Abs stimulate thyroid gland to produce more thyroid hormone
- have low levels of TSH and high levels of thyroid hormone
ocular manifestations of myasthenia gravis
- diplopia
- ptosis
- blurred vision
ocular manifestations of graves disease
- proptosis
- periorbital edema
- abnormal EOMs
- exposure keratopathy
- optic nerve compression
autoimmune complex-mediated diseases (Type III)
- auto-Ab:Ag immune complexes deposit throughout body
- infectious initiation (reactive arthritis, poststreptococcal glomerulonephritis)
- undetermined initiation (lupus, rheumatoid arthritis (also type IV))
cell-mediated autoimmunity (Type IV)
- does not involve antibodies
- APC activates Th cell, which activates Tc cell
- Tc cells use perforin and granzymes to attack cells
- Th cell will increase amount of cytokines it produces, including interferon gamma, which increases macrophage activity
cell-mediated autoimmune diseases (type IV)
- rheumatoid arthritis (targets multiple cell types)
- Crohn’s disease (targets epithelial cells of GI tract)
- multiple sclerosis (targets oligodendrocytes in CNS)
- type I diabetes (targets beta cells in pancreas)
organ-specific autoimmune diseases
- directed against a unique antigen in a given organ
- type II hypersensitivity (myasthenia gravis, Hashimoto’s thyroiditis, pernicious anemia)
- type IV hypersensitivity (Crohn’s disease, type I diabetes)
systemic autoimmune diseases
- wide range of antigens
- widespread damage
- general defect in immune regulation
- examples: lupus, MS, scleroderma
- may be types II, II, or IV, or combination
systemic lupus erythematosus epidemiology
- chronic, multisystem inflammatory disease
- type III hypersensitivity
- 90% of cases in women between 20-40
- female:male 10:1
- black:white 8:1
pathogenesis of SLE
- DNA and histones released from cells
- phagocytized by APCs
- activate T-cells
- activate B-cells
- produce antibodies against nuclear antigens
SLE target organs
- joints
- blood vessels
- kidneys
- heart
- skin
- lungs
- brain
SLE auto-antibodies against:
- nucleic acids
- erythrocytes
- lymphocytes
- platelets
- coagulation proteins
- phospholipids
11 common symptoms of SLE
- facial (malar) rash
- discoid rash
- photosensitivity
- oral or nasopharyngeal ulcers
- non-erosive arthritis
- serositis
- renal disorders
- neurologic disorders
- hematologic disorders
- immunologic disorders
- presence of anti-nuclear antibodies (ANA)
ocular manifestations of SLE (present in ____ of patients)
50%;
- secondary Sjogren syndrome
- uveitis (rare)
- episcleritis/scleritis
- neuro-ophthalmic lesions
- retinal vasculopathy (cotton wool spots, most common)
- bulls-eye maculopathy
Sjogren’s syndrome epidemiology
- targets salivary and lacrimal glands
- ~4 million affected in US
- 40-60 years of age
- female:male 9:1
- primary and secondary forms
primary Sjogren’s syndrome
lymphocyte infiltration of salivary and lacrimal glands (cause damage and reduce function)
secondary Sjogren’s syndrome
immune-complex accumulation in salivary and lacrimal glands (causes inflammation and reduced function)
Sjogren’s syndrome pathogenesis
- systemic autoimmune disease: RA and SLE
- lymphocytic infiltrations
- auto-antibodies play a role
