10. Autoimmunity II Flashcards
Insulin Dependent Diabetes Mellitus (Type I)
• Antigen:
– Pancreatic ____-cells; insulin
• Pathogenesis:
– ____ infiltrate>insulitis; autoAb are present but not ____
• Strong association with MHC ____ genes
• Infectious component:
– ____, rubella, ____ virus (____)
* Minor form where insulin is the target, but mostly b-cells * MHCII > may serve as a receptor for infectious org's (mumps/rubella/cox) > not \_\_\_\_ > leads to break in tolerance > autoreactive T cells (cell-mediated response) * May carry autoAb, but do not \_\_\_\_ * Result of gradual destruction of b cells (takes \_\_\_\_) > threshold is met > not enough b-cells > not enough insulin > overt diabetes (\_\_\_\_ onset)
beta T-cell destructive class II mumps coxsackie antigenic mimicry
all or none
contribute
years
sudden
• Histopathology:
– Lymphocytic infiltrate within the ____
* MT: biopsy of normal pancrease > islet of langerhans * MB: early stages of \_\_\_\_ diabetes > dark staining > T cells > interacting with \_\_\_\_ and induce apoptosis
islets of langerhans
type I
b-cells
Insulin Dependent Diabetes Mellitus (Type I)
• Clinical symptoms:
– Insulin deficiency leads to accumulation of ____ and fatty acids;
– ____, polydypsia, wt. loss, fatigue, visual disturbances
• Clinical complications: – \_\_\_\_ failure – Susceptibility to early and accelerated \_\_\_\_ – Susceptibility to severe periodontitis – Impaired wound healing – \_\_\_\_ – Neuropathy – Oral complications: • Increased frequency and severity of \_\_\_\_ disease • Delayed healing • \_\_\_\_ enlargement (diabetic sialadenosis) • Oral candidiasis
* Predominantly \_\_\_\_ * No glucose (no insulin) > polyuria (bc of hypoosmolality due to glucose) > \_\_\_\_, drink a lot > loss of electrolytes > leads to \_\_\_\_ * Switch from burning glucose to burning FA/protein; no carbohydrates; loss of calories bc glucose cannot be utilized > exhibit \_\_\_\_ * Mobilize fat/protein > acidosis (keto-acids) > in order to equilibrate, labored breathing, deep breathing, smell acetone due to \_\_\_\_ bodies * Right: shows clinical manfiestations of diabetes; but Type I are highlighted in blue * Clinical manifestations apply to uncontrolled diabetic typically * Parotid enalrgement > diabetic sialynosis
gluose polyuria renal atherosclerosis retinopathy periodontal parotid
metabolic
dehydrated
polyphagia
ketone
Sjogren Syndrome
• Etiology/Antigen: – \_\_\_\_ ? (EBV, Hep C) – Cytoskeletal protein- \_\_\_\_ – 0.5% prevalence (\_\_\_\_ f/m) – Primary (\_\_\_\_ alone) vs secondary (occurs with other autoimmune disease such as \_\_\_\_ and SLE)
• Pathogenesis:
– T-cells (____) infiltration and fibrosis of ____ and salivary glands
– AutoAb-present , but do not appear to significantly ____ to disease nor are they diagnostically useful
l
• Combo of genetic predisposition; ____ may contribute (accounting for 9:1); T cells/cytokine/macro-driven, glandular epi destroyed and turned into ____ tissue
• Left: salivary gland; which are ____
• TR: dense infiltrate of inflam cells > CD4/CD8, cytos, macro’s > converted to ____ tissue (deposition of collagen, nonfunctional glandular elements)
virus alpha-fodrin 9:1 sicca syndrome RA
CD4 lacrimal contribute estrogen fibrotic mixed fibrotic
Sjogren Syndrome
• Clinical symptoms:
– Afflicts ____ women (50-60)
– Sicca syndrome:
• xerostomia: difficulty swallowing ____ food, decrease taste
– cracks and fissures, ____ of buccal mucosa
– dry and fissured tongue with atrophy of papillae
– ____ gland enlargement
• xerophthalmia
– Keratoconjunctivitis sicca (dry eyes): ____ vision, burning and ____
* Lose taste > sicca syndrome > atrophy of tongue > fissured; also appears on buccal * R: enlarged parotid > dense inflam infiltrate (T cells)
older solid dryness parotid blurred itching
• ____ biopsy: often used for diagnosis—____
salivary glands
• Tx: supportive, artificial ____ and saliva
• Risk (5-15%) of low grade ____ lymphoma
Lip biopsy: lymphocytic ____ and mucous gland ____
• L: presence of infiltrate ○ \_\_\_\_ cells is positive diagnosis • Supportive therapy to treat
tears non-hodgkin B-cell infiltrate atrophy 25-50
Connective Tissue Diseases (Collagen diseases) • Pathogenesis: – \_\_\_\_, complement, PMN and platelets – Injury to components of \_\_\_\_ wall (collagen, elastin and proteoglycans) – \_\_\_\_ and obstruction – \_\_\_\_ necrosis of arteries and \_\_\_\_
• Examples: – \_\_\_\_ – Rheumatoid arthritis – \_\_\_\_ – Polyarteritis nodosa
* Autoimmune diseases involving a wide array of tissue * Scleroderma - read the textbook * Pathogenic mechanism similar to type \_\_\_\_ hypersensitivity * Basic lesion associated with vasculitis (BV); but also bc \_\_\_\_ are also activated and aggregate and cause microthrombi
immune complexes blood vessel vasculitis fibrinoid arterioles
SLE
scleroderma
III
platelets
Systemic lupus erythematosus (SLE)
• AutoAb to several antigens: – \_\_\_\_, ssDNA,\_\_\_\_, RNA, \_\_\_\_ (ANA) – Specific cells: •\_\_\_\_ • Erythrocytes • \_\_\_\_
– Other antigens:
• ____, thyroglobulin, ____ components, phospholipids (alter clotting time)
• Antibody to nuclear antigens is a hallmark > \_\_\_\_ (ANA) > made to dsDNA, ssDNA, smith antigen, RNA, histones ○ No single patient presents with all of these, the \_\_\_\_ will present with all of them ○ Most common is to \_\_\_\_ antigen ○ Trigger immune complexes (type \_\_\_\_ like rxn) • Table - detection of ANA is a diagnostic criteria in diagnosing, but it is no \_\_\_\_ to this disease (other disorders have it is, SS (systemic sclerosis), polymyositis) • Depending on where the antigen is in the \_\_\_\_ is a different pattern of fluorescence ○ Most common: \_\_\_\_ fluorescence • Complex, not only have ANA, but also have other auto-ab's > lympho's, erythro's, platelets > type II rxn (\_\_\_\_, not hypersensitivity) • RF - rhematoid factors - inflam of joints, similar to \_\_\_\_ but not identical • Ab to thyroglobulin - \_\_\_\_ disorder (not identical, complication of lupus) • Ab to phospholipids - attack clotting factors - patients have problems with \_\_\_\_
dsDNA Sm histones lymphocytes platelets RFs coagulant
anti-nuclear autoantibodies population Sm III exclusive nucleus rimmed autoimmunity RA hasimoto-like coagulation
SLE etiology and pathogeneisis
• Etiology
– infection, hormone (____), drugs, stress, impaired ability to repair ____ breaks
– Genetic factors: ____ association, ____ association
– UV light (Photosensitivity)
– Defective ____ tolerance
• Pathogenesis:
– ____ formation (ANA-DNA complexes
– ____ auto Ab
– Thrombosis (anti-phospholipid Ab)
• Lupus etiology different ○ Estrogen - hyper-active on immune response > promote overreaction; \_\_\_\_ develop more than men • Episodic onset - UV light - hyper-photosensitive • Little tolerance to antigens - within cells [???] • \_\_\_\_ susceptibility > how B/T cells see self • An assumption is that normally when cells undergo apoptosis (may be due to UV) > break into apoptotic bodies; may be a defect in \_\_\_\_ of bodies which occurs by local phagocytes > exposure of immune system to contents of bodies > immune response > high antinuclear-antibody titer ○ Epithelial cells exposed to UV, no clearance ○ Kidneys, lungs, joint; complexes travel via bloodstream • Develop lesion - rash on skin - initially develops anywhere where surface is exposed to sun; lesions similar to \_\_\_\_ (if deveop IgM ab's)
estrogen DNA familial HLA peripheral
immune complex
secondary
women
genetic
clearance
raynouds
Clinical Manifestations of SLE
• Skin and Mucocutaneous lesions:
– ____ rash (butterfly rash)
– Photosensitivity
– Erythematous, maculopapular plaques and ulcers
– Oral ulcers
• Arthritis
• ____ (proteinuria, HTN and insufficiency)
• Serositis (pericarditis and pleuritis)
• ____ (anemia, leukopenia, thrombocytopenia and lymphopenia)
• Cardiovascular Manifestations - ____ or symptomatic (tachycardia and/or abnormal ECG)
• CNS (____, pscyhosis): autoAb, cytokines??
• ____ signs: fatigue, fever, myalgia, wt. loss)
* Most common - butterfly rash * \_\_\_\_ - around the heart (immune complexes) * Secondary ab > hematologic outcomes
malar renal hematologic asymptomatic seizures constitutional serositis
SLE: Skin and mucocutaneous lesions
– ____ rash
– Photosensitivity
– ____, maculopapular plaques and ulcers
* Start off on sun exposed surfaces > can develop anywhere as \_\_\_\_ form * Prominent on skin over \_\_\_\_ surfaces
malar
eryhematous
immune complexes
flexor
• Complexes form, in areas of ____ flow and bifurcations > ____ vasculitis (in the skin area, within the subdermal CT), BV destroyed (adverse effects on blood supply), some vessels have ____ necrosis (no EC left)
turbulent
necrotizing
fibrinoid
- Degeneration of basal cell layer > immune complexes form, in and around the cutaneous tissue and up against the epithelium
- Non-diseased that hasn’t been destroyed (left) > ANA (complexes) > ____ band (____ here against the BM, will be destroyed by complement, and attraction of PMN > degeneration of ____ cells)
positive
IgG
basal
SLE: oral ulcers
* Patients quite often early in disease process > develop oral ulcers (\_\_\_\_!) * these lesions will fit into differential diagnosis of other diseases as Rosef \_\_\_\_; this is important bc it early sign of a systemic disorder and speaks to the important role we play as dentists in detecting some morbid systemic diseases.
anywhere
lichen planus
SLE: Renal manifestations
• Critical feature of SLE - may lead to ____, HTN and insufficiency
– ____ glomerular capillary loops
– granular deposits of immunoglobulin and complement
– Urinalysis reveals ____ and ____ casts
* Same rxn with immune-complex mediated hypersens * Can accumulate anywhere, but within BV in areas of \_\_\_\_ flow * Activate complement > C5a/5,6,7 > recruit PMN > activated, in digesting complexes > release lysosomal enzymes > \_\_\_\_ vasculitis * Chemotactic factors, also develop dilated BV, and edema (bc C3a, C5a) * Platelet agg, formation of microthombi > ischemia > tissue necrosis * Glomerular nephrotisi > starts in glomeruluis; positive immunofluorescence (for \_\_\_\_ or complement [\_\_\_\_]) * Protein ends up in urine, RBC and WBC > end up as casts (from the kidney tubules)
proteinuria thickened RBC WBC turbulent necrotizing IgG C3
