Autoimmunities Flashcards
Insulin-Dependent Diabetes Mellitus
Type: Type IV T-cell mediated
Cause: This disease is mediated by CTLs that have specificity for some determinant(s) in beta pancreatic cells in the islets of Langerhans.
Result: Beta cells are destroyed and no longer produce insulin. They cannot regenerate, and there is a finite number.
Symptoms: Heaps, but if left untreated, can lead to coma and death.
Tissue sample: You’ll see mass infiltration of lymphocytes (mostly CTLs) into islets of Langerhans
Treatment: Daily insulin replacement
Grave’s Disease
Type: Type II Antibody Mediated
Cause: Thyroid-stimulating hormone receptor-specific IgG antibodies cause over-production of thyroid hormone because these antibodies serve as receptor agonists - they mimic TSH.
Symptoms: bulging eye syndrome, enlarge thyroid, heat intolerance, nervousness, irritability, weight loss, and moist skin
Long-term Issue: Recall that a mother passes her IgG antibodies to her fetus. A pregnant woman with this condition will pass the IgGs to the developing fetus, and the fetus will also suffer from the condition. Upon birth, the child will receive plasma exchange to restore normal thyroid function
Multiple Sclerosis
Type: Type IV T-cell mediated
Cause: Auto-reactive Th1 CD4+ effector cells lose tolerance for determinants of the myelin sheath around nerve cells. The Th1 cells activate macrophages; macrophages produce inflammatory cytokines. The inflammatory response causes demyelination of white matter in the CNS.
Result: poor transmission of nerve impulses Symptoms: progressive muscle weakness, impaired vision, loss of coordination, and spasticity
Diagnosis: test for oligoclonal bands of IgG in the CSF
Treatment: immunosuppressive drugs and IFN-B1
Pemphigus vulgaris
Type: Type II Antibody Mediated
Cause: An IgG-mediated response specific for desmoglein 1 and 3 Result: loss of cohesion in keratinocytes
Symptoms: painful chronic blistering of skin
Diagnosis: punch biopsy of lesion followed by immunofluorescent staining to ID IgG4 bound to tissue
Treatment: corticosteroids and anti-inflammatory drugs
Point mutation that alters the amino acid at position 57 of the HLA-DQ beta chain has a strong association with?
The development of type I diabetes mellitus
What is rheumatoid factor?
It is an immunoglobulin made by 80% of patients who have rheumatoid arthritis. It is IgG, IgM, and IgA that have specificity for Fc regions of human Ab. The patient is making Ab that bind to the patient’s own Ab.
Rheumatoid Arthritis
Type: Type IV T-cell mediated
Cause: Auto-reactive T-cells produce an inflammatory response in the joints, causing damage to the soft tissues (cartilage and ligaments).
Result: loss of function and disfigurement of the joints.
Epidemiology: 1-3% of US population; women:men = 3:1.
Treatment: infliximab and rutiximab (KNOW THIS)
Autoimmune Hemolytic Anemia
Type: Type II Antibody Mediated
Cause: IgG and IgM antibodies acquire a response to surface determinants of RBCs. They bind to RBCs and become ligands for complement component C1q, activating the classical cascade. Activation results in formation of MAC complexes and of deposition of C3b on RBCs. Opsonized RBCs are taken and destroyed by phagocytes that recognize complement and IgG opsonins.
Symptoms: anemia
Diagnosis: direct Coomb’s Assay
Treatment: Corticosteroids
Your 65 y/o patient comes into the office complaining of being tired and having double vision. You note on physical exam that he is suffering from ptosis (drooping eyelids). What is your preliminary diagnosis, and how do you treat it?
Myasthenia gravis, treated with a cholinesterase inhibitors - pyridostigmine.
Myasthenia is not a painful condition - this is a way to distinguish it from the other nerve conditions in this group.
Miller-Fisher Syndrome
This is a less common form of Guillan-Barre that descends from the facial muscles down to the trunk and limb.
The same result occurs without treatment; this disease is no worse than Guillan-Barre.
Very rapid progression.
Causes demyelination.
A Graves disease sufferer is prego. Is the fetus going to be born with Graves?
Sho is.
But ain no big thang - just give it a plasma exchange!
Myasthenia gravis
Type: Type II Antibody Mediated
Cause: IgG-mediated response to acetylcholine receptors on muscle cells interferes with/antagonizes normal signaling at the NMJ. When these antibodies bind the acetylcholine receptors, the receptors are endocytosed and destroyed.
Result: Depletion of acetylcholine receptors at NMJ, making muscles less sensitive to neuronal stimulation.
Symptoms: Initially, ptosis and diplopia (double vision), then progression to generalized muscle weakness
Treatment: anti-inflammatory drugs and cholinesterase inhibitor to prevent degradation of acetylcholine. Does NOT cause demyelination.
For several years, your 8 y/0 patient has experienced progressive muscle weakness and loss of coordination. His leg muscles have become rigid and painful (hypertonia). What immunological effector is responsible for his condition? What disease is this?
Th1 cells specific for myelin sheath determinant Multiple sclerosis
Autoimmune (Idiopathic) Thrombocytopenic Purpura
Type: Type II Antibody Mediated
Cause: 2 targets:
1) IgG binds to and inhibits the enzyme that cleaves von Wildebrand factor. When vWF is not cleaved, excessive platelet adhesion occurs, partially occluding small blood vessels so that when RBCs travel through, they are damaged (this is called microangioplastic hemolytic anemia); and
2) IgG can be specific for a surface integrin of platelets called Gp2b/3a) In addition, excessive platelet adhesion leads to an overall reduction of platelet number, so patients develop purport.
Symptoms: microangioplastic hemolytic anemia, thrombocytopenia (low platelet count), purpura, damage in kidneys, liver, and brain due to excessive platelet adhesion, and reduced platelet numbers
Diagnosis: observation of microangioplastic hemolytic anemia
Treatment: Plasma exchange with healthy donor
All autoimmune diseases are more likely to happen after ________________
an infection. Other than that, your body should not be able to mount an immune response against self determinants.
Sjogren’s Syndrome
Type: Type IV T-cell mediated
Cause: Auto-reactive T-cells are specific for determinants expressed in the exocrine glands that produce tears and saliva. Other affected tissues can include kidneys, blood vessels, liver, and brain.
Symptoms: dry eyes, mouth, nose, skin, and vag; sometimes tooth decay due to lack of saliva
Epidemiology: 2nd most common rheumatic disease; men:women = 1:9
Diagnosis: Schirmer test to measure tear production and measurement of anti-nuclear antibody titers Anti SSA (Ro) and Anti SSB (La) (KNOW SCHIRMERS)
Treatment: artificial tears, punctal plugs, and goggles.
A 21-yr old female complains that her fingers and knees have been becoming increasingly achy over the past year and half. Blood work reveals an anti-dsDNA titer of 512. What additional clinical findings do you expect?
Reduced kidney function caused by immune complex deposition in the kidney.
Blood in urine; protein as well High titers of anti-histone ABs and anti-ribosome ABs
Positive direct Coomb’s test because many develop autoimmune hemolytic anemia
Reduced complement C1 levels (C1 most commonly measured)
Scleroderma
Type: Type II Antibody Mediated
Cause: IgG-mediated response causes damage to vascular endothelium of arteriole and smooth muscle cells that results in replacement of damaged tissue with collagen, and eventually, skin hardening and thickening.
Result: Skin damage, as well as damage to kidneys, blood vessels, liver, and brain
Diagnosis: presence of anti-nuclear Ab, anti-topoisomerase Ab, and anti-centromere Ab
Treatment: Nothing standard
Mixed Essential Cryoglobulinemia
Type: Type III Antibody Mediated
Cause: Cryoglobulins are immunoglobulins that become insoluble at reduced temperature. They are usually produced by patients that have a B-cell proliferative disorder. They bind to the Fc regions of antibody molecules, causing an immune complex disorder.
Symptoms: Meltzer’s Triad: purpura, arthralgia (joint pain), and myalgia (muscle pain) Be familiar with Bence-Jones proteins, a way to describe the composition of some cryoglobulins that have only a light chain.
Systemic Lupus Erythematosus
Type: Type III Antibody Mediated
Cause: An IgG autoantibody response specific for self macromolecules, including dsDNA, histones, and ribosomes. These autoantibodies bind to surface determinants, initiating inflammatory responses that lead to tissue damage and release of autoantigens. Immune complexes are formed, resulting in an immune complex disease.
Result: progressive disease that leads to vasculitis, kidney damage progressing to glomerulonephritis, and neurological dysfunction.
Symptoms: fever, malaise, joint pain, myalgia, and fatigue. Progressive kidney dysfunction due to the deposition of immune complexes and resulting inflammation.
Treatment: anti-inflammatory drugs
Immunologically Privileged Sites
Eyes, testes, and placenta During development of immune system, no elimination of self-reactive T-cells to determinants of those locations occurred, so if a person is injured, and one such determinant is released into the bloodstream, a response can be generated. The T-cells will then return to that site of injury and carry out a response against the “determinant”.
The difference between an agonist antibody and an antagonist antibody?
Over-production vs. under-production respectively of normal result of ligand binding.
Subacute Bacterial Endocarditis
Type: Type III Antibody-Mediated
Cause: Streptococcus viridans can colonize heart valves if they become damaged. IgG antibodies specific for S. viridans determinants bind to the bacteria, promoting recognition of the immune complex by phagocytes and the initiation of the classical complement cascade.
Result: inflammation due to the immune response causes further damage to heart valves and myocardium.
Your previously healthy patient presents with bulging eyes with little eye movement and complains of numerous symptoms including unexplained weight loss, nervousness, and irritability. On physical exam, you note that her thyroid is enlarged. What clinical finding do you expect in this case?
Anti-TSHR (thyroid-stimulating hormone receptor) Abs
