Ch. 12 Autoimmunity Flashcards
What is autoimmunity?
The breakdown of tolerance
Causes of autoimmunity?
Often drug, virus, or bacteria
Describe Type II hypersensitivity
Organ-specific
Describe Type III hypersensitivity
System
Is system lupus erythematosus a Type II or III hypersensitivity disorder?
Both!
What is the first theory of autoimmune disease development?
Normal self-antigens are altered by drug, pathogen, or mutation and are no longer seen as “self”
What is the second theory of autoimmunity?
Ab against foreign Ag cross-react with a similar self-Ag
What is the third theory of autoimmunity
Clonal deletion theory: defective regulation of lymphocytes. Autoreactive lymphocytes not killed off properly
List 2 autoimmune blood diseases
- Chronic Autoimmune Hemolytic Anemia
- Autoimmune Thrombocytopenic Purpura
Describe Autoimmune Thryoiditis
Hypothyroidism due to autoantibodies destroying thyroid tissue
Describe Grave’s Disease
Characterized by proptosis (bulging eyes) due to edema. Autoantibodies against TSH receptor site mimic TSH and result in hyperthyroidism
Describe Diabetes mellitus (type 1)
Autoimmune destruction of pancreatic beta cells in islets, so they can’t produce insulin -> insulin deficiency
What causes goiter? How does it manifest?
Iodine deficiency. Enlarged thyroid and widened neck
Describe multiple sclerosis
Autoantibodies against myelin sheath on axons. Leads to a lower conduction velocity. May have viral cause. Affects motion, leads to excessive urination, speech impairment, cervical spinal cord problems. Slurred speech, bent neck.
Describe Myasthenia Gravis
Autoantibodies against acetylcholine receptor, thus impairing neuromuscular transmission. Attacks neuromuscular junction at post-synaptic membrane. Symptoms are drooping eye muscles (ptosis), fatigued voluntary muscles, and double vision.
Describe Rheumatic Fever
Affects brain, heart, joints, skin, or subcutaneous tissues. Beta-hemolytic Group A streptococcal infection is the cause. Pharyngitis manifests
Briefly describe Rheumatoid Arthritis
Autoantibodies against gamma globulins cause inflammatory and sometimes deforming collagen disease. Affects joints, lungs heart, kidneys, and skin. Mostly joints though.
Describe SLE
Autoantibodies against a LOT of different things, including DNA and RNA
Describe ulcerative colitis
Severe diarrhea. Systemic complications can include arthritis, kidney and liver disease, and inflammation of the eyes, skin, and mouth
Crohn’s disease and ulcerative colitis are part of ______?
IBD. Absolutely not part of IBS.
How do you treat UC?
Anti-inflammatory drugs, immunosuppression, or colectomy (surgical removal of colon) if needed
List primary disorders characterized by hyperglycemia
Type I and Type II (diabetes??)
List secondary disorders characterized by hyperglycemia
Chronic pancreatitis, hormonal tumors, corticosteroid drugs…etc
Diabetes mellitus is chronic disorder of what types of metabolism?
Carb, fat, and protein
Which cells in which location synthesize and store insulin in granules?
Beta cells in the pancreatic islets
Which molecule is a strong trigger for insulin release?
Glucose
Rise in blood glucose causes immediate release of ____
Insulin
If stimulus persists, active ___ synthesis occurs to lower blood glucose
Insulin
Insulin enables __ and __ to move across cell membranes
Insulin
Amino acids
Insulin reduces serum glucose level by promoting its influx into ____ and ____, where it’s transformed into ___
Liver
Skeletal/cardiac muscles
Glycogen
Insulin stimulates _____…
Glucose conversion into triglycerides in fat cells and synthesis of proteins from amino acids. Plus glucose influx
Describe the steps of glucose uptake
- Insulin binds insulin receptor
- GLUTS (glucose transport units) move from Golgi to cell membrane and phosphorylate glucose
- Glucose translocates into cell
Diabetes is number ___ out of 10 leading causes of deaths in USA
7
Describe Type I Diabetes (age of onset, weight…etc)
Onset less than 20 years old
Normal weight
Reduced blood insulin
Ketoacidosis common
Autoimmune
Insulin deficiency
10-20% of diabetes mellitus cases
Describe Type II Diabetes (age of onset, weight…etc)
Onset greater than 40 years old
Obesity
Normal or increased blood insulin
Ketoacidosis rare
Insulin resistance
Relative insulin deficiency
80-90% of DM cases
Three mechanisms responsible for beta islet cell destruction in Type I DM?
- Genetics
- Autoimmunity
- Environment
Type I DM demographics?
Most common in Northern European descent
Familial
40% twin concordance rate
Is Type I DM congenital or acquired? Why?
Not congenital. May have beta cell destruction years before disease onset
What % of beta cells are destroyed before Type I DM disease manifests?
90% destruction
What % of Type I DM patients have islet cell antibodies after 1 year post-diagnosis?
70-80%
What environmental factors could trigger Type I DM?
Viruses such as coxsackie virus B, mumps, measles, rubella, and mononucleosis. They may exhibit molecular mimicry, meaning viral protein may have similar aa sequence with beta cell protein and trigger autoimmunity
Rheumatoid arthritis is a Type ____ autoimmune disease
III
Rheumatoid arthritis causes chronic inflammation of which connective tissues?
Synovial membrane, articular cartilage, fibrous joint capsule, ligaments and tendons
General systemic symptoms of rheumatoid arthritis?
Fever, fatigue, weakness, anorexia, weight loss, stiffness (flu-like)
Specific rheumatoid arthritis symptoms?
Rash, enlarged lymph nodes, enlarged spleen, widespread joint swelling
Rheumatoid arthritis features ____% insidious onset (slow but grave effect)
85%
Rheumatoid arthritis feature ___% acute onset
15%
Describe pathophysiology of rheumatoid arthritis
Immune complexes activate complement, increase vasodilation, attracts WBCs -> synovial inflammation
Macrophages ingest immune complexes and release enzymes that degrade synovial tissues + articular cartilage
Describe damaging effects on synovial membrane during rheumatoid arthritis
-Venules get blocked with fibrin, platelets, and inflammatory cells
-Compromised circulation leads to acidosis/hypoxia
-Erosion of articular cartilage and inflammation of ligaments + tendons
