Autoimmunity Flashcards
Paul Erlich (1900s) introduced the phenomenon he called “__________” or “_________”
“horror autotoxicus” or “fear of self-poisoning”
The immune system could attack the very host it was intended to protect
“horror autotoxicus” or “fear of self-poisoning”
___________ are targeted toward self-antigens resulting to organ and tissue damage
immune response
Can be caused by T-cell–mediated immune
responses or autoantibodies that are directed
against host antigens
autoimmune diseases
The ability of the immune system to accept
self-antigens and not initiate a response against
them
self tolerance
A state of immune unresponsiveness that is directed against a specific antigen, in this case, a self-antigen
immunologic tolerance
2 levels of immune tolerance
central tolerance
peripheral tolerance
Occurs in the central or primary lymphoid organs,
the thymus, and the bone marrow; Negative and
Positive Selection during T cell maturation; Receptor editing in B cells
central tolerance
Can result from anergy (a specific state of
unresponsiveness to the antigens) caused by the
absence of a costimulatory signal from an
antigen-presenting cell (APC) or binding of inhibitory receptors such as CTLA-4 (a molecule that prevents T-cell activation)
peripheral tolerance
A molecule that prevents T-cell activation
CTLA-4
More prevalent among family members and among monozygotic (genetically identical) twins than dizygotic (non-identical) twins or siblings
genetics
Women are 2.7 times more likely to acquire an
autoimmune disease than men; about 78% of
patients with autoimmune diseases are females; the stimulatory effects of female hormones may place women at a greater risk for developing autoimmune disease
hormonal influence
female hormones affected in autoimmune disease
Estrogen
Androgen
Prolactin
“Immunologic tolerance” some self-antigens may
be cryptic, or hidden within the tissues of the host. T and B lymphocytes are shielded from these
sequestered antigens and are not educated to
become tolerant to them
TISSUE TRAUMA AND RELEASE OF CRYPTIC ANTIGENS
TISSUE TRAUMA AND RELEASE OF CRYPTIC ANTIGENS
Tissue damage could be caused by factors such as:
infections
contact with environmental toxins
physical injury from exposure to ultraviolet (UV) radiation
Bacteria, viruses, and other infectious pathogens
may be able to trigger autoimmune responses
microbial infections
many bacterial or viral agents
contain antigens that closely resemble the structure or amino acid sequence of self-antigens
molecular mimicry
the microorganism can induce a local inflammatory response that recruits leukocytes and stimulates APCs to release cytokines that nonspecifically activate T cells; some of the T cells that are activated may have specificity for self-antigens
bystander effect
proteins that are produced by various microbes that have the ability to bind to both class II MHC molecules and TCRs, regardless of their antigen specificity
superantigens
can cause polyclonal activation of B cells
Epstein-Barr virus (EBV) and cytomegalovirus (CMV)
_______ refers to modifications in gene expression that are not caused by changes in the original DNA sequence.
epigenetics
can induce epigenetic changes by increasing or decreasing methylation of cytosine bases, modifying histones, and causing abnormal regulation by microRNAs; underexpression of certain genes in the immune system may result in
homeostatic imbalances and a breakdown of
self-tolerance, leading to autoimmunity
Triggered by exposure to environmental
toxins, ingestion of harmful foods or drugs,
or the aging process
Exposure to environmental factors can lead
to changes at the protein level; post-translational modifications and may involve biochemical processes such as:
acetylation
lipidation
citrullination
glycosylation
may cause break in immunologic tolerance,
autoreactive T cells recognize and proliferate in
response to self-antigens and B cells develop into
plasma cells that secrete autoantibodies
complex interactions between genetic and environmental factors
Chronic
Peak age of onset: 20-40 years old
W:M – 9:1, 5 yr
Survival rate – 90%
SLE
Complex interactions between environmental
factors, genetic susceptibility, and abnormalities
within the immune system; genetic defects in genes coding for HLA-A1, B8, and DR3
SLE
increases the chance of developing lupus; polymorphisms in genes, genes coding for various cytokines, and genes involved in signaling of innate immune responses - result in uncontrolled autoreactivity of T and B cells, which leads to the production of numerous autoantibodies
HLA-A1
B8
DR3
Antibodies to double-stranded DNA (dsDNA),
histones, and other nuclear components, as well as
autoantibodies to lymphocytes, erythrocytes,
platelet, phospholipids, ribosomal components, and endothelium
SLE
_______ are present in 70% of patients with lupus and are highly specific for the disease
Antibodies to dsDNA
________ and _________ have been found in immune complexes that are deposited in organs such as the kidneys and skin
Anti-dsDNA and complement proteins
_______ are attracted to the sites of inflammation and release cytokines that perpetuate the response, resulting in tissue damage
Leukocytes
Antibodies to RBCs
hemolytic anemia
Antibodies to platelets
thrombocytopenia
inflammation of the blood vessels and vascular
damage in lupus, which may be responsible for
the vasculitis and neuropsychiatric symptoms
Antibodies to endothelial cells
associated with increased miscarriage, stillbirth, and preterm delivery in pregnant women with lupus
Phospholipid antibodies
occurs in up to 8% of babies born to pregnant women with SLE, is associated with antibodies to the nuclear antigens, SS-A/Ro and SS-B/La
neonatal lupus
neonatal lupus antigens
SS-A/Ro
SS-B/La
SLE
fatigue, weight loss, malaise, fever, and anorexia are often the first to appear
Nonspecific symptoms
SLE
______ and ______ in 90% of patients
(arthritis is symmetric and involves the small joints of the hands, wrists, and knees)
Polyarthralgias or arthritis
________ may appear on any area of the
body exposed to UV light in 80% of patients
(butterfly rash across the nose and cheeks)
Erythematous rash
drug-induced lupus
procainamide, hydralazine, chlorpromazine, isoniazid, quinidine, anticonvulsants such as methyldopa, and possibly oral contraceptives
Acute cutaneous lupus, chronic cutaneous lupus,
oral ulcers, non-scarring alopecia (thinning or
fragility of the hair), synovitis, serositis, renal
involvement, neurological symptoms, hemolytic
anemia, leukopenia, and thrombocytopenia
clinical criteria
Elevated antinuclear antibody titer, elevated
anti-dsDNA titer, presence of antibody to the Sm
nuclear antigen, presence of antiphospholipid
antibody, low complement levels, and positive direct Coombs’ test in the absence of hemolytic anemia
immunologic criteria
A patient must satisfy at least __ of the 17 criteria,
including at least one clinical criterion and one
immunologic criterion, to be classified as having
SLE
4
SLE
For mild symptoms, a high dose of _______ or
other anti-inflammatory drug may bring relief
aspirin
SLE
For skin manifestations, antimalarials such as
__________ or ________ and _________ are often prescribed
hydroxychloroquine
chloroquine
topical steroids
The antimalarial drugs are thought to inhibit
signaling of _____, __, and __
TLR 7, 8, and 9
used for acute fulminant (severe and sudden) lupus, lupus nephritis, or central nervous system (CNS) complications because these suppress the immune response and lower antibody titers
Systemic corticosteroids
laboratory diagnosis of SLE
Complete blood count (CBC), platelet count, and
urinalysis, quantification of complement
proteins (C3) and the detection of specific
autoantibodies
Autoantibodies that are directed against antigens in the nuclei of mammalian cells
ANTI-NUCLEAR ANTIBODIES (ANAs)
Produce a peripheral or a homogeneous staining
pattern on indirect immunofluorescence (IIF)
DOUBLE-STRANDED DNA (dsDNA) ANTIBODIES
ANTIHISTONE ANTIBODIES
_______ are nucleoproteins that are essential components of chromatin
histones
ANTIHISTONE ANTIBODIES
five major classes of histones:
H1, H2A, H2B, H3, and H4
ANTIHISTONE ANTIBODIES:
Antibodies to ____ and ___ can be detected in
almost all patients with drug-induced lupus
H2A and H2B
Also found in RA, Felty’s syndrome, Sjögren’s
syndrome, systemic sclerosis, and primary biliary
cirrhosis, but the levels are usually lower
antihistone antibodies
antihistone antibodies pattern in IIF assay
homogeneous pattern
Stimulated by DNA-histone complexes;
nucleosomes, or deoxyribonucleoprotein (DNP)
nucleosome antibodies
Directed only against the complexes and not against DNA or the individual histones
nucleosome antibodies
Found in about 85% of patients with SLE and their
levels correlate with disease severity
nucleosome antibodies
nucleosome antibodies pattern in IIF assay
homogeneous
associated with uridine-rich RNA
extractable nuclear antigens (ENA)
Found in only 20% to 40% of patients with SLE,
depending on the race of the population
antibody to Sm antigen
anti-Sm antibody pattern in IIF
coarse speckled pattern of nuclear fluorescence
anti-RNP antibody pattern in IIF
coarse speckled pattern
anti-RNP antibody meaning
anti-ribonucleoproteins antibody
Detected in 20% to 30% of patients with SLE, but
are also found at a high titer in individuals with
mixed connective tissue disease and in lower levels
in patients with other autoimmune rheumatic
diseases such as systemic sclerosis, Sjögren’s
syndrome, and RA
anti-RNP antibody
Appears in approximately 24% to 60% of patients
with SLE and has been closely associated with the
presence of nephritis, vasculitis,
lymphadenopathy, photosensitivity, and
hematologic manifestations such as leukopenia
ANTI-SS-A/Ro
Found in only 9% to 35% of patients with SLE and
all of these have anti–SS-A/Ro; most often found in
patients who have cutaneous manifestations of
SLE, especially photosensitivity dermatitis
ANTIBODIES TO SS-B/La
Can cross the placenta and have been associated
with neonatal lupus
ANTIBODIES TO BOTH SS-A/Ro and SS-B/La
a prominent structure within the
nucleus where transcription and processing of
ribosomal RNA and assembly of the ribosomes
takes place
nucleolus
Common in systemic sclerosis (also known as
scleroderma)
ANTIBODY TO FIBRILLARIN
ANTIBODY TO FIBRILLARIN pattern in IIF
clumpy nucleolar fluorescence
Associated with scleroderma
ANTIBODIES TO RNA POLYMERASE
ANTIBODIES TO RNA POLYMERASE pattern in IIF
speckled nucleolar pattern
Also known as PM/Scl
ANTIBODIES TO PM-1 ANTIGEN
Found in polymyositis and systemic sclerosis;
homogeneous staining of the nucleolus
ANTIBODIES TO PM-1 ANTIGEN
Bind to proteins in the middle region of a
chromosome where the sister chromatids are joined; directed against three centromere antigens of molecular weights 16kDa, 80kDa, and 120kDa
ANTICENTROMERE ANTIBODIES
3 centromere antigens molecular weights:
16kDa
80kDa
120kDa
Found in 50% to 80% of patients with the CREST
syndrome
ANTICENTROMERE ANTIBODIES
CREST syndrome:
Calcinosis, Raynaud’s
phenomenon, Esophageal dysmotility,
Sclerodactyly, Telangiectasia
anticentromere antibodies pattern
discrete speckled staining in the nuclei
of the cells
methods of ANA detection
IIF, immunoperoxidase staining,
enzyme-linked immunosorbent assay (ELISA),
microsphere multiplex immunoassays (MIA),
radioimmunoassay (RIA), immunodiffusion,
immunoblotting (Western blot), dot blot,
immunoelectrophoresis, and microarray
Heterogeneous group of antibodies that bind to
phospholipids alone or phospholipids complexed
with protein
ANTIPHOSPHOLIPID ANTIBODIES
Associated with deep-vein and arterial thrombosis
and with recurrent pregnancy loss
antiphospholipid antibodies
Found in up to 60% of patients with lupus
antiphospholipid antibodies
Can be identified by their ability to cause
false-positive results in nontreponemal tests for
syphilis, the lupus anticoagulant assay, and
immunoassays for antibodies to cardiolipin or other phospholipids
antiphospholipid antibodies
APTT may be prolonged, but it is not corrected by
mixing with normal plasma; factor assays may also
need to be performed to rule out any factor
deficiencies or factor-specific inhibitors
antiphospholipid antibodies
Affects about 0.5% to 1.0% of the adult
population; age: 25 and 55; W:M – 3:1
rheumatoid arthritis
Can be characterized as a chronic, symmetric, and
erosive arthritis of the peripheral joints that can also affect multiple organs such as the heart and the lungs
rheumatoid arthritis
HLA-DRB1 alleles or PTPN22 gene
polymorphisms
rheumatoid arthritis
Strongest environmental risk factor of RA
cigarette smoking
Caused by an inflammatory process that results in
the destruction of bone and cartilage
rheumatoid arthritis
Lesions show an increase in cells lining the synovial membrane and formation of a pannus, a sheet of inflammatory granulation tissue that grows into the joint space and invades the cartilage
rheumatoid arthritis
RHEUMATOID ARTHRITIS:
Balance between proinflammatory and
anti-inflammatory cytokines _______
IL-1, IL-6, IL-17, and TNF-α
these enzymes degrade important structural proteins in the cartilage
metalloproteinases
Normally, there is a good balance between
bone production and destruction. However, in
RA, the osteoclasts become overly activated in
the inflammatory environment of the joints.
local bone erosion
TNF-α, in conjunction with other cytokines and
a molecule called ___________, induces the differentiation of osteoclasts and inhibits
bone formation
RANKL (receptor activator of nuclear factor kappa-B ligand)
second major type of antibody associated
with RA
Antibodies to cyclic citrullinated proteins (anticyclic
citrullinated peptide antibody [anti-CCP or
ACPA])
modifies the amino acid arginine by replacing an NH2 group with a neutral oxygen
Citrulline
RA
malaise, fatigue, fever, weight loss, and transient joint pain that begin in the small joints of the hands and feet (joints are typically affected in a symmetric fashion); usually present in
the morning
Nonspecific symptoms
Can progress to the larger joints, often affecting the knees, hips, elbows, shoulders, and cervical spine
RA
(T/F)
Inflammation if left untreated, may lead to
permanent joint dysfunction and deformity
true
RA
Extra-articular manifestations include the:
formation of subcutaneous nodules, pericarditis,
lymphadenopathy, splenomegaly, interstitial lung
disease, or vasculitis
RA
Some have nodules over the:
bones, myocardium, pericardium, heart valves, pleura, lungs, spleen, and larynx
RA
Most common cause of death is _______ due to the acceleration of arteriosclerosis by proinflammatory cytokines released during the disease process
cardiovascular disease
tretament for RA
Disease-modifying anti-rheumatic drugs
(DMARDs)
methotrexate
act by inhibiting adenosine metabolism and T-cell activation
methotrexate
RA (TREATMENT):
monoclonal antibodies to TNF-α
infliximab, adalimumab, certolizumab, golimumab
RA (TREATMENT)
TNF-α receptors fused to an IgG molecule
etanercept
_____ is the antibody that is most often tested to aid in making the initial diagnosis (is an autoantibody, usually of the IgM class, that reacts with the Fc portion of IgG; 70% to 90% of patients with RA test positive for RF)
Rheumatoid Factor (RF)
RF can be found in patients with other
connective tissue diseases such as _________, and
_________, as well as in people with some _______
SLE
Sjögren’s syndrome
scleroderma
mixed connective tissue disease
chronic infections
Manual agglutination tests using ______ or _____ particles coated with IgG have been used for many years to detect RF
charcoal or latex
RF detection
ELISA, chemiluminescence immunoassay, and nephelometric methods
RA
Laboratory testing for antibody to:
cyclic citrullinated peptides (anti-CCP) – ELISA
A rare autoimmune disease involving inflammation
of the small to medium-sized blood vessels, or
vasculitis
GRANULOMATOSIS WITH POLYANGIITIS
GRANULOMATOSIS WITH POLYANGIITIS aka _______
WEGENER’S GRANULOMATOSIS
Usually begins with a localized inflammation of
the upper and lower respiratory tract.
GRANULOMATOSIS WITH POLYANGIITIS
General symptoms of granulomatosis with polyangiitis
fever, malaise, arthralgias, anorexia, and weight loss.
The majority of patients progress to develop a more systemic form of the disease that can affect any organ system
granulomatosis with polyangiitis
Patients can experience coughing, shortness of
breath, chest pain, or hemoptysis (coughing up
blood)
granulomatosis with polyangiitis
GRANULOMATOSIS WITH POLYANGIITIS
(T/F)
majority of patients have renal involvement,
which can range from mild glomerulonephritis with little functional impairment to severe
glomerulonephritis that can rapidly lead to kidney
failure; pain and arthritis of the large joints, which is usually symmetric but not deforming; skin lesions; ocular manifestations that can potentially lead to vision loss
true
________ has been found to have a strong association with GPA in Caucasian patients
HLA-DPB1*0401 allele
________ and ________ are associated with increased risk in Asian and African American populations
HLA-DRB10901 and HLA-DRB1501 alleles
(T/F)
Chronic nasal infection with Staphylococcus aureus
bacteria has been associated with a greater rate of
relapse in patients with WG
true
(T/F)
Chronic nasal infection with Staphylococcus aureus
bacteria has been associated with a greater rate of
relapse in patients with WG
true
GP:
S. aureus may induce molecular mimicry because it contains peptides that bear similarity to the _______
proteinase 3 (PR3) autoantigen
RISK FACTORS of GP
Exposure to silica or to certain drugs such as
hydralazine and penicillamine
GP
Most have antibodies to neutrophil cytoplasmic
antigens; in 80% of these, the antibody is directed
against an enzyme found in the azurophilic granules of neutrophils called _____
PR3
Autoantibodies that are produced against proteins
that are present in the neutrophil granules
ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCAs)
Strongly associated with three syndromes involving vascular inflammation: GPA or WG, microscopic polyangiitis (MPA), and eosinophilic
granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) - collectively known as ANCA-associated vasculitides (AAV)
ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCAs)
eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as ________
Churg-Strauss syndrome
mainly directed against the PR3 antigen
GPA
specific for myeloperoxidase (MPO)
MPA and EGPA
ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES (ANCAs):
Fluorescence observed through IIF, using _______
ethanol-fixed leukocytes
two patterns of fluorescence
Cytoplasmic or c-ANCA
Perinuclear or p-ANCA
appears as a diffuse, granular staining in the cytoplasm of the neutrophils, staining is most intense in the center of the cell between the nuclear lobes and gradually fades at the outer edges of the cytoplasm
cytoplasmic or c-ANCA
fluorescence surrounds the lobes of the nucleus, blending them together so that individual lobes cannot be distinguished
perinuclear or p-ANCA
Diseases in which the immune response is directed
against self-antigens that are mainly found in a
single organ or gland; systemic effects may
sometimes also occur
ORGAN-SPECIFIC AUTOIMMUNE DISEASES
2 types of AUTOIMMUNE THYROID DISEASE (AITDS)
Hashimoto’s thyroiditis and Graves disease
associated with inheritance of HLA antigens DR3, DR4, DR5, and DQ7
hashimoto’s thyroiditis
HLA-DR3 is affected
graves’ disease
________ are expressed on the surface of thyroid epithelial cells, perhaps increasing the autoimmune response. Mutations in the thyroglobulin gene may allow for interaction of
the protein with HLA-DR antigens, resulting in antithyroglobulin antibodies
HLA-DR antigens
hashimoto’s thyroiditis aka _______
chronic lymphocytic thyroiditis
he discovered hashimoto’s thyroiditis in japan (1912)
Dr. Hakaru Hashimoto
HASHIMOTO’S THYROIDITIS
Most common autoimmune disease, 8 in every
1,000; W:M - ________
5-10:1
Enlarged thyroid called a goiter; production of
thyroid-specific autoantibodies and cytotoxic T cells
hashimoto’s thyroiditis
a state of decreased thyroid function due to immune destruction of thyroid gland
hypothyroidism
dry skin, decreased sweating, puffy face with
edematous eyelids, pallor with a yellow tinge, weight gain, fatigue, and dry and brittle hair
hashimoto’s thyroiditis
Characterized by hyperthyroidism, a state of
excessive thyroid function; manifested as
thyrotoxicosis, or an excess of thyroid hormones
graves’ disease
nervousness, insomnia, depression, weight
loss, heat intolerance, sweating, rapid heartbeat, palpitations, breathlessness, fatigue, cardiac
dysrhythmias, and restlessness
graves’ disease
GRAVES’ DISEASE
Another sign present in approximately 35% of
patients is ________, in which hypertrophy of
the eye muscles and increased connective tissue in
the orbit cause the eyeball to bulge out so that the
patient has a large-eyed staring expression.
exophthalmos
treatment for GD
Daily oral thyroid hormone replacement therapy, with levothyroxine (T4)
radioactive iodine therapy
surgery to remove part of the thyroid
GRAVES’ DISEASE
Measurement of circulating TSH levels –
chemiluminescent immunoassays that can detect
fewer than ______
0.1 mU/L
An endocrine disorder characterized by
hyperglycemia (a high level of glucose in the blood); characterized by a complete or nearly complete deficiency in insulin
type 1 DM
Involves selective destruction of the beta cells of the pancreas (located in clusters called the _________ and are responsible for the production and secretion of the hormone, insulin) resulting in
insufficient insulin production, hyperglycemia, and
toxic effects on the body
islets of Langerhans
Long-term effects include cardiovascular complications, renal disease, nerve damage, blindness, and infections of the lower extremities, which can lead to amputation
type 1 DM
Carry the HLA-DR3 or DR4 gene
type 1 DM
treatment for type 1 DM
Daily injectable insulin
Transplantation of pancreatic beta islet cells (for patients who have poor glucose control)
Islet cell transplantation
T1DM
a fasting glucose greater than ______ on more than one occasion (normal value is lower than 100 mg/dL)
126 mg/dL
T1DM
a random plasma glucose level of _______ or more with classic symptoms of diabetes
200 mg/dL
T1DM
an oral glucose tolerance test of ______ or more in a 2-hour sample with a 75g glucose load
200 mg/dL
T1DM
a hemoglobin A1c value (HbA1c) greater than _____
6.5%
a glycated form of hemoglobin that
is made when the RBC protein combines with
glucose in the blood.
HbA1c
The HbA1c plasma level is proportional to the life span of the circulating RBCs (up to _______) and
reflects the average plasma glucose concentration over the previous ________
120 days
2 to 3 months
T1DM
________ and _______ can be done to confirm the diagnosis
Antibodies to glutamic acid decarboxylase (GAD) and insulinoma-antigen 2 antibodies (IA-2A)
An autoimmune disease affecting the small intestine and other organs; associated with a known environmental trigger—dietary gluten
celiac disease
HLA-DQ2 ((90% to 95%) or HLA-DQ8
W:M - 2-3:1
celiac disease
CELIAC DISEASE
diarrhea, abdominal distention, and
failure to thrive, but may also experience
vomiting, irritability, anorexia, and constipation
infants symptoms
CELIAC DISEASE
classic symptoms of diarrhea and abdominal
pain or discomfort, but often have
extraintestinal manifestations that make the
condition difficult to diagnose
Older children, teenagers, and adults
short stature, arthritis or arthralgia, osteoporosis,
neurological symptoms, iron-deficiency anemia, and dermatitis herpetiformis (a skin disorder with itchy blistering)
extraintestinal
Treatment of celiac disease involves placing patients on a _________
gluten-free diet
CELIAC DISEASE
Based on clinical symptoms, serological findings,
duodenal biopsy, and presence of the ______ or
_______
HLA-DQ2 or HLA-DQ8 haplotype
AUTOIMMUNE LIVER DISEASES
Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC)
Formerly known as chronic active hepatitis, is an
immune mediated liver disease that can lead to
end-stage liver failure if left untreated
autoimmune hepatitis (AIH)
Adults usually present with an unexpected onset of vague symptoms, including fatigue, nausea, weight loss, abdominal pain, itching, and maculopapular rashes
autoimmune hepatitis (AIH)
2 types of AIH
AIH-1
AIH-2
accounts for two-thirds of all AIH cases and has a female:male ratio of 4:1
AIH-1
______ has a female:male ratio of 10:1 and is
seen mostly in children
AIH-2
________ and ________ are associated with a higher risk of developing AIH
HLA-DRB1 and HLA-DQB1 alleles
AIH treatment
Standard immunosuppressive treatment of prednisolone (+/–azathioprine)
liver transplant
The most common autoimmune liver disease; W:M -10:1
PRIMARY BILIARY CIRRHOSIS (PBC)
Genetic link with certain HLA-DRB1, HLA-DQA1,
HLA-DPB1, and HLA-DQB1 haplotypes
primary biliary cirrhosis (PBC)
Involves progressive destruction of the intrahepatic bile ducts
primary biliary cirrhosis (PBC)
A condition in which the flow of bile is slowed or
blocked), inflammation of the portal vein in the liver, and accumulation of scar tissue that can ultimately lead to cirrhosis and liver failure. Individual patients can be asymptomatic or have slowly or rapidly progressing disease
primary biliary cirrhosis (PBC)
include fatigue, pruritus (itchy skin), abdominal
pain, and dry eyes and mouth; in the later stages, symptoms include jaundice, ascites, and greasy
stools
primary biliary cirrhosis (PBC)
PBC treatment
Ursodeoxycholic acid (UDCA)
liver transplant
a bile acid that helps move bile through the liver
Ursodeoxycholic acid (UDCA)
LAB DIAGNOSIS OF PBC
Anti-mitochondrial antibodies (AMAs)
IIF and ELISA, serum alkaline phosphatase level elevated at least 1.5 times the upper limit of normal for 6 months or more and liver biopsy showing nonsuppurative destructive cholangitis and interlobular bile duct injury
anti-microbial antibodies (AMAs)
An autoimmune disorder involving inflammation and destruction of the CNS
multiple sclerosis
MULTIPLE SCLEROSIS
Most closely associated with inheritance of a
particular HLA molecule coding for the beta chain of the DR subregion, namely ________
DRB1*1501
Environmental factors that appear to be associated with MS include _________
reduced exposure to sunlight, vitamin D deficiency, and cigarette smoking
Characterized by the formation of lesions called
plaques in the white matter of the brain and spinal
cord, resulting in the progressive destruction of the myelin sheath of axons
multiple sclerosis
Visual disturbances, weakness or diminished
dexterity in one or more limbs, locomotor
incoordination, dizziness, facial palsy, and numerous
multiple sclerosis
MS
Sensory abnormalities such as tingling or _________that run down the spine or extremities, as well as flashes of light seen on eye movement;
“pins and needles”
MS ratio
W:M - 2:1
treatment for MS
Corticosteroids
IFN-β1a and IFN-β1b
natalizumab
to reduce inflammation
corticosteroids
downregulate MHC molecules on APCs, decreasing production of proinflammatory cytokines, and upregulating anti-inflammatory cytokines
IFN-β1a and IFN-β1b
a humanized monoclonal antibody directed against an adhesion molecule of lymphocytes, preventing them from binding to endothelial cells and crossing the blood–brain barrier
natalizumab
An autoimmune disease that affects the
neuromuscular junction; characterized by weakness and fatigability of skeletal muscles
MYASTHENIA GRAVIS (MG)
Antibody-mediated damage to the acetylcholine
receptors in skeletal muscle or to other proteins in
the neuromuscular junction leads to progressive
muscle weakness
MYASTHENIA GRAVIS (MG)
S/S: ptosis (drooping of the eyelids); diplopia
(double vision); and the inability to retract the
corners of the mouth, often resulting in a snarling
appearance; muscle weakness is most noticeable in the upper limbs; some have difficulty in speaking, chewing, and swallowing and may be unable to maintain support of the trunk, neck, or head
MYASTHENIA GRAVIS (MG)
treatment for MYASTHENIA GRAVIS (MG)
Anticholinesterase agents
acetylcholine
thymectomy
plasmapheresis or intravenous immunoglobulin
monoclonal antibodies or fusion proteins
to prevent destruction of the neurotransmitter
Anticholinesterase agents
should be performed on patients who have a thymoma
thymectomy
targeted to specific components of the immune system involved in the pathogenesis of MG
monoclonal antibodies or fusion proteins
Characterized by the presence of autoantibody to an antigen in the basement membranes in the glomeruli of the kidneys and alveoli of the lungs
GOOD PASTURE’S SYNDROME
GOOD PASTURE’S SYNDROME
Identified by ______ in _______; affects
two age groups—men in their 30s and men and
women in their 60s and 70s
Ernest Goodpasture in 1919
_________ is a rare disorder that is found mainly in Caucasians of European origin
goodpasture’s syndrome
S/S: fatigue and malaise followed by clinical signs of kidney involvement such as edema and hypertension, which can rapidly progress to acute
renal failure if left untreated; 60% to 70% of patients have pulmonary involvement and exhibit symptoms such as cough, shortness of breath, and hemoptysis
goodpasture’s syndrome
treatment for goodpasture’s syndrome
high dose of corticosteroids
immunosuppressive drugs (cyclophosphamide)
plasmapheresis
hemodialysis
kidney transplantation
