Autoimmunity Flashcards
(30 cards)
1
Q
type II autoimmunity
A
analogous to type II hypersensitivities in that they are mediated by antibodies that are specific for determinants of cell surfaces structures/extracellular matrix
2
Q
type III autoimmunity
A
are analogous to type III hypersensitivities because they are mediated primarily by IgG and result in immune complex disease
3
Q
type IV autoimmunity
A
analogous to type IV hypersensitivities because they are mediated by T cells. The T cells are specific for self determinants
4
Q
T/F the eyes and testes are functionally separated from the rest of the body in respect to release of antigens and unless there is injury to that site T cells are never presented with these antigens and they are never available for thymic selection
A
true
5
Q
Autoimmune hemolytic anemia (II)
A
- results from priming of an acquired antibody response to surface determinants of RBCs
- response mediated by IgG and some IgM
- activates classical complement cascade and MAC
- lead to phagocytosis/destruction of RBC’s
- symptom: anemia
- Dx- direct coombs test
- treat: corticosteroids
6
Q
Autoimmune idiopathic thrombocytopenic purpura (II)
A
- results in low platelet counts and damaged RBCs (called microangioplastic hemolytic anemia)
- caused by IgG that binds to and inhibits the function of an enzyme that cleaves von Wildebrand factor
- results in platelet aggregation and depletion from the system (abnormal platelet adhesion can cause damage to the RBCs)
- also affects the liver, kidneys, and brain
- purpura present due to reduced ability to clot
- dx: observation of microangioplastic hemolytic anemia
- treat: plasma exchange with plasma from healthy donors
7
Q
Goodpasture’s syndrome (II)
A
- caused by an IgG response to type-IV collagen
- inflammation mediated by the classical complement cascade (and then the alternative pathway) and phagocytes causes tissue damage
- PROGRESSIVE KIDNEY DYSFUNCTION culminating in glomerulonephritis
- loss of appetite, fatigue, weakness, decreased kidney fun
- dx: measurement of glomerular basement membrane-specific antibodies (anti-GBM)
- treat: plasma exchange and with anti-inflammatory drugs
8
Q
Schleroderma (II)
A
- an IgG-mediated autoimmune disease that results in damage to the vascular endothelium of arteriole and smooth muscle cells that results in replacement of damaged tissue with collagen
- symptoms are mediated by ANA (anti-nuclear Abs), ATA (anti-topoisomerase Abs), and ACA (anti-centromere Abs), all IgGs
- skin hardening and damage to liver kidney and brain
- treat: drugs that promote blood flow to extremities
9
Q
Acute rheumatic fever (II)
A
- molecular mimicry
- A normal IgG response to group A Streptococcus pyogenes (GAS) infection cross reacts with normal host tissue
- damage to the heart is mediated by cross-reactive IgG
- results in myocarditis from scarring of the heart
- chest pain, shortness of breath, fever, joint pain
10
Q
Pemphigus vulgaris (II)
A
- chronic painful skin blistering
- is mediated by IgG specific for desmoglein 1 and 3, and it results in loss of cohesion in keratinocytes.
- dx: : immunofluorescent staining to identify IgG4 Ab bound to tissue from a punch biopsy
- treat: corticosteroids and other anti-inflammatories; ritiximab (CD20-specific mAb)
11
Q
Grave’s disease (II)
A
- thyroid stimulating hormone receptor (TSH receptor)-specific IgG antibodies cause over-production of thyroid hormone because the antibodies serve as receptor agonists
- bulging eye syndrome (with a characteristic stare) is hallmark; also: enlarged thyroid, heat intolerance, nervousness, irritability, weight loss, and moist skin
- pregnant mother will pass her IgG on to her child and the child will need plasmaphoresis (plasma exchange)
12
Q
Myasthenia Gravis (II)
A
- an IgG response to acetylcholine receptors on muscle cells that antagonizes normal signaling at the neuromuscular junction
- cause endocytosis and destruction of receptors
- typically begin with facial muscles, and especially muscles of the eyes and eyelids. These patients often present with diplopia (double vision) and ptosis (sagging eyelids). Over time, the condition progresses to generalized muscle weakness
- treat: anti-inflammatory drugs and pyridostigmine
13
Q
Subacute Bacterial Endocarditis (III)
A
- condition mediated by IgG that is made in response the the normal flora organism Streptococcus viridans that have colonized damaged heart valves
- colonizes heart valves that have already been damaged (e.g. rheumatic fever, congenital condition
- IgG specific for determinants of this bug bind to the bacteria, promoting recognition of the immune complex by phagocytes as well as initiation of the classical complement cascade
- causes further damage to heart valves and myocardium
- is considered an immune complex “hypersensitivity” or immune complex autoimmune disease because the inflammation results from recognition of immune complexes
14
Q
Mixed essential cryoglobulinemia (III)
A
- characterized by production of cryoglobulins (immunoglobulins that become insoluble at reduced temperatures; sometimes they are only composed of light chains (Bence-Jones proteins))
- similar to rheumatoid factor in that they have specificity for the Fc regions of antibodies and can cause immune complex disease
- hep B
- Meltzer’s Triad(purpura, arthralgia and myalgia)
15
Q
Systemic lupus erythematosus (III)
A
- autoimmune disease that is mediated by autoantibodies (IgG) that are specific for several self macromolecules, including dsDNA, histones, and ribosomes
- inflammatory response leads to tissue damage and release of auto antigens
- immune complexes are formed in the extracellular spaces and in the circulation
- vasculitis, kidney damage progressing to glomerulonephritis, and even neurological dysfunction due to vasculitis in the brain
- fever, malaise, joint pain, myalgias, and fatigue (kidney dysfunction in advanced cases)
- anti-inflammatory drugs
- wolf-face/butterfly rash
- blood in ruin, high titers anti-histone Abs, high titer anti-ribosome Abs, positive direct Coomb’s(will have anemia), and reduced compliment C1 levels
16
Q
Antiphospholipid syndrome (APS or APLS)
A
- mediated by autoantibodies (IgG) that are specific for host phospholipids-anti-cardiolipin or anti-b2-glycoprotein-I antibodies
- These antibodies cause thrombosis in both arteries and veins
- catastrophic antiphospholipid syndrome, can result in rapid organ failure and death
- also notable for the difficulties it can cause during pregnancy. The autoantibodies can cause miscarriages or stillbirths, preterm delivery, and preeclampsia.
- dx-(1) at least one clinical event that could be either thrombosis or a complication of pregnancy, and (2) measurement of either lupus coagulant or anti-cardiolipin or anti B2-glycoprotein-1 antibodies in serum samples collected at least 3 months apart
17
Q
Insulin-dependent diabetes mellitus (IV)
A
- autoimmune disease that is mediated by CTLs that have specificity for some determinant(s) in beta pancreatic cells in the islets of Langerhan’s
- many symptoms, can lead to coma and death when untreated
- treat: insulin therapy (ususally insulin is non-human derived but some individuals cannot tolerate that resulting in immune complex hypersensitivity reactions and must use the more expensive human derived insulin)
18
Q
Rheumatoid arthritis (IV)
A
- mediated by autoreactive T cells
- The inflammatory responses in the joints cause damage to the soft tissues (cartilage and ligaments), causing loss of function and disfigurement of the joints
- dx: rheumatoid factor
- treat: (1) infliximab (anti-TNF-alpha MAb), and (2) rutiximab (anti CD20 MAb, a B cell surface marker)
19
Q
Sjögren’s Syndrome (IV)
A
- is mediated by autoreactive T cells that are specific for determinants expressed in the exocrine glands that produce tears and saliva
- also effects kidneys, blood vessels, brain
- dry eyes, mouth, nose, sometimes skin, and vaginal dryness
- dx: Schirmer test to measure tear production. Measurement of ANA (anti-nuclear antibody) titers and rheumatoid factor (not required for disease)
- treat: artificial tears, punctal plugs, and goggles
20
Q
Multiple sclerosis (IV)
A
- caused by a break down in tolerance to determinants of the myelin sheath around nerve cells
- mediated by autoreactive TH1 CD4+ effector cells that activate macrophages, enticing them to produce inflammatory cytokines
- inflammation leads to poor transmission of nerve impulses
- progressive muscle weakness, impaired vision, loss of coordination and spasticity (muscle hypertonia/stiffness)
- treat: immunosuppressive drugs and IFN-b1
- dx: oligoclonal bands of IgG in the cerebrospinal fluid is found in 85% of patients
- sclerotic plaques
21
Q
T/F autoimmune disease is mediated by MHC inheritance
A
true
22
Q
T/F MHC inheritance follows mendelian genetics
A
true
23
Q
T/F women are much more likely to develop an autoimmune disease?
A
true
24
Q
T/F environmental factors can predispose to autoimmunity
A
true
25
What environmental factors are at play in autoimmunity?
injury, microbial infection
26
immunologically privileged sites (injury environmental factor)
- eyes, testes, and placenta
- none of the antigens that are unique to that tissue were available during thymic negative selection
- when injury occurs the antigens are released and T cells can enter these blood perfused tissues and mount an effector response
- exception=corner bc it is not vascularized
27
molecular mimicry (microbial infection environmental factor)
mimicry occurs when a determinant of a microorganism is similar enough to a host determinant that when the host generates an immune response against the pathogen, the antibodies that have specificity for some of the pathogen's determinants cross-react with host determinants
28
Guillain Barré syndrome (molecular mimicry)
- results from production of an IgG response during infection (often with Campylobacter jejuni infection)
- IgG made for the bacterium cross-reacts with gangliosides, resulting in demyelination
- symmetrical weakness of lower limbs, rapidly ascending to upper limbs and face with difficulty swallowing and breathing (reversible partial paralysis also key)
- treat:plasma exchange and immunosuppressive drug treatment
- sclerotic plaques
29
Granulomatosis with polyangiitis (formerly Wegener’s granulomatosis)
- molecular mimicry condition that is mediated by antibodies generated in response to either viral or bacterial infection that cross-reacts with neutrophil determinants
- ANCAs (IgG anti-neutrophil cytoplasmic antibodies) bind to their determinants on the surface of neutrophils causing them to become “activated"(de facto activated but basically cause them to induce inflammatory reaction)
- 1st symptom is typically rhinitis and conjunctivitis; lung infiltrates, rapidly progressive kidney dysfunction leading to glomerulonephritis, and usually granulomas are found in all affected tissues
- treat: plasma exchange and anti-inflammatories
30
Miller-Fischer Syndrome
-the unusual version of GB that progresses from the top down rather that bottom up.
