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BLD 434 FS 10 Final Exam part 4
autoimmunity, hypersensitivity, vaccinations
95
Immunology
Undergraduate 4
12/09/2010

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Term
HSV
24.2/3
Definition
Herpes Simplex
HSV1 - oral
HSV2 - genital (more serious)
Term
HHV3
24.2
Definition
Varicella-zoster virus (VZV)
chicken pox
shingles
Term
HHV 4
24.2
Definition
Epstein barr virus (EBV)
Infectious mononucleosis
Term
HHV
24.2
Definition
Cytomegalovirus (CMV)
Term
testing for HSV1/2
24.4
Definition
-EIA or latex agglutination for viral Ag
-culture in shell vial, immunofluorescent staining
-PCR, can distinguish between the 2
Term
EBV
24.5
Definition
-infects epithelial cells of the oropharynx and B lymph (via CD21)
-undergo polyclonal activation, proliferate, secrete Ab
Term
Heterophile AB
24.6
Definition
-used to diagnose I.M. (mono)
-detected with extract of bovine RBC Ag, only 80% of true + will show
Term
Confirmatory testing of EBV
24.7
Definition
-IgM Ab to a viral capsid Ag (IgM anti-VCA)
-Ab to EBV nuclear ag (anti-EBNA) appears during convalescence
Term
Population at greatest risk for CMV infection
24.8
Definition
-severe in immunocompromised and newborns
-10% of infected babies exhibit symptoms of CNS/multiple organ infection
5% will die
50% long term consequences: deafness, blindness, retardation
Term
Problems with CMV testing
24.9
Definition
-no rapid detection
-false neg in immunocompromised/infants
-false pos from RF
Term
Preferred methods for CMV testing
24.9
Definition
shell vial with immunofluorescent staining (24-72 hrs)
quantitative PCR-rapid results and stage disease/monitor effectiveness
Term
VZV diseases
24.10
Definition
following resolution of chickenpox, VZV retreats to sensory nerve dorsal ganglion cells and reactivates in 20% of individuals bc of stress
Term
VZV infection detection
29.11
Definition
shell vial with immunofluorescent staining
PCR to identify virus
EIA to detect immunity
Term
Rubella virus
24.12
Definition
causes German measles
can lead to congenital rubella infection, rare but disastrous
Term
Rubella testing
24.13
Definition
post vaccination immunity: >1:8 titer
a 4-fold increase in IgM titer in 5 days indicates a current infection
Term
nontreponemal test
reagin
treponemal test
25.1
Definition
-uses test ag consiting of a soln of cholesterol, lecithin, and cardiolipin to detect reagin ab
-nonspecific ab to cardiolipin
-detect ab specifically to treponemal ag
Term
Lyme disease
25.2
Definition
caused by Borrelia burgdorferi
80% form a bull's eye rash at site of infection after 1 week
if untreated, can spread through body and cause multiple lesions, pain, facial palsy
Term
Screening test for Lyme disease
25.3
Definition
EIA or immunofluorescent assay (IFA)
Western blot is used to confirm
->for IgM 2of3 bands must be present; IgG must have 5of10
Term
Causes of false positives for Lyme disease
25.4
Definition
test lacks sensitivity
syphilis and other treponemal diseases, mono, autoimmune diseases, rocky mountain spotted fever
Term
Syphilis
25.5
Definition
caused by Treponema pallidum ssp. pallidum
transmitted sexually or congenitally
can be easily treated with penicillin if caught early
Term
Stages of syphilis
25.6
Definition
primary-painless lesions with ulcerated center
secondary-25% of untreated infections; generated lymphadenopathy and flu-like sx
latent-no sx
tertiary- 10-30 years later in 30% of cases
Term
3 categories of syphilis testing
25.7
Definition
direct spirochete detection, nontreponemal, treponemal
Term
syphilis; subtypes in nontreponemal tests
25.7
Definition
VDRL- Venereal Disease Research Laboratory->only test approved to test CSF to dx neurosyphilis
RPR-Rapid Plasma Reagin test-> uses plasma instead of serum; like VDRL except with addition of charcoal particles
Term
syphilis; subtypes in treponemal tests
25.7
Definition
EIA-detect IgM or IgG ab to syphilis
FTA-ABS -fluorescent treponemal ab absorption test ->confirmatory test on a slide
TP-PA -T. pallidum particle agglutination ->use gel particles
Term
components of test ag used for nontreponemal tests for syphilis
25.8
Definition
cholesterol, lecithin, cardiolipin
Term
test approved to dx tertiary neurosyphilis
25.9
Definition
VDRL
Term
syphilis test that loses sensitivity during tertiary phase
25.10
Definition
TP-PA
Term
primary diseases caused by group a strep, secondary sequelae, pathophysiology of 2o diseases
26.1
Definition
strep pharyngitis and strep pyoderma (skin infection);
sequelae can result in rheumatic fever and post strep glomerulonephtitis;
rheumatic fever includes joint pain, carditis, heart murmers. post-strep glomerulonephritis includes destruction of kidney glomerulus by deposition of immune complexes and C' lysis following strep
Term
strep testing
26.2
Definition
ASO- negative in 80% of cases
anti-DNase B assay is more sensitive than ASO and will be positive for S. pyoderma
streptozyme test is a slide agglutination screening test but has large amount of false pos and false neg
It is recommended to perform at least 2 tests
Term
usefulness of IVIg and other ab preparations in therapeutic tx of humans
26.3
Definition
concentrated preparations of ab are used in human medicine
RhoGAM and IVIg, concentrated human IgG pooled from multiple donors
monoclonal ab therapies are used to target and kill tumor cells or as immunosuppresants
Term
hybridoma creation for production of monoclonal ab
26.4
Definition
1-inject animal with ag so they will make ab towards ag
2-isolate b cells and fuse to an immortalized hybridoma
3-grow fused cells in chemical selection media so that only cells that have fused B cell and myeloma can survive
4-clone the surviving hybridoma cells and select for a clone that produces high affinity ab against the ag
5-isolate the pure monoclonal ab from this hybridoma cell line
Term
Identify cause of serum sickness and tx associated with it
26.6
Definition
occurs from tx where ab preparations are produced in other species and induce an ab response against foreign ab.
ab:ab immune complexes precipitate, deposit in tissue, fix C' that causes tissue destruction
Term
Type I hypersensitivity
27.1
Definition
IgE, mast cells, eosinophiles and basophiles are designed to fight parasite infections.
IgE triggers a violent fluid laden peristalisis to flush out a parasite from mucosal tissue
Without a parasite the response is activated for harmless environmental ag
Term
Type II hypersensitivity
27.1
Definition
happens when certain drugs bind to cell surface, create a novel ag, B cells respond, and IgG ab is produced
IgG coats cells and causes direct C' lysis and/or uptake by phagocytosis
Term
Type III hypersensitivity
27.1
Definition
Locally injected ag in immune individual with IgG ab forms an immune-complex and activates C'
C5a binds to C5a receptor on mast cell. Binding of immune complex to FcgammaRIII on mast cell induces degranulation.
Local inflammation, increased fluid and protein release, phagocytosis and blood vessel occlusion occurs
Term
Type IV hypersensitivity
27.1
Definition
delayed response (1-3 days) because it is a T cell response and not an ab response like the others
Term
"wheal and flare" vs (delayed-type hypersensitivity"
27.2
Definition
wheal and flare shows within 15min and tests for type I responses
DTH shows within 48hrs and is testing for type IV responses
Term
histamine
27.3
Definition
seen in a type I hypersensitivity
Term
granulocytes: mast cells
27.4
Definition
preformed IgE is bound irreversibly to FCepsilonRI
This cross linking by ag leads to mast cell degranulation and activation
enzymes and toxic mediators are released within seconds
cytokines, chemokines, and lipid mediators are synthesized and secreted following activation
Term
granulocytes: basophils
27.4
Definition
activated in tissue and can migrate to lymphoid tissues, secrete IL-4 and IL-13, and use surface CD40L to activate B cells for IgE and IgG4 production
Their granule contents are similar to mast cells but are more closely related to eosinophiles
Term
granulocytes: eosinophiles
27.4
Definition
accumulate in chronic allergic responses
IL-5 from Th2 cells is an eosinophile growth factor that stimulates increased bone marrow production.
they produce several toxic products
Term
Produce IL-4 and is currently thought to be the trigger of Th2 responses by naive CD4 t cells
27.5
Definition
basophiles
Term
Total serum IgE testing
27.6
Definition
an elevated total serum IgE suggests type I hypersensitivity
D: not sensitive and does not identify offending allergen(s)
A: cheap and can suggest further testing
Term
Skin testing
27.6
Definition
graded for "wheal" reaction
D: danger of causing a systemic reaction, tramatic to patient, only tests limited individual ag
A: a positive test is clinically significant
Term
Current lab testing for hypersensitivity
27.6
Definition
large automated analyzers that test total IgE or individual ag. Solid phase carb-based assays are used to provide high test ag dose for increased sensitivity
D: lower specificity hat skin test
A: can be used when patient is on an antihistimine
Term
hypersensitivity tests on the horizon
27.6
Definition
miccroarray panels. glass platform based where purified ag is dotted onto glass slide in a predetermined pattern, pt sera is added, anti IgE fluorochrome is added and the fluorescent dots are read via automation
Bead array in which a mixture of beads of different sizes are coated with individual ag, mixed with pt serum, labeled with detectable anti-IgE fluorochrome and ran through a flowcytometer
A: less serum sample and cheaper
Term
two common causes of type II hypersensitivity
27.7
Definition
certain drugs and blood transfusions
Term
serum sickness
celiac disease
poison ivy
allergic asthma
food allergy
27.8
Definition
type III
type IV
type IV
type I
type I
Term
hypersensitivity responses can cause autoimmune disorders
28.1
Definition
type II (MOST COMMON)
type III-systemic autoimmunity
type IV
Term
Grave's Disease
28.2
Definition
due to ab to thyroid stimulating hormone receptor. ab acts as a ligand and stimulates excessive T3 and T4 secretion. thyroid is enlarged as a soft goiter
Dx is assays for T3/T4 (increase) and TSH (decrease) performed in chemistry, thyroid ab
Term
Hasimoto's Disease
28.2
Definition
destruction of thyroid gland leading to hypotrophism. thyroid is infiltrated with lymphocytes, Mo, and plasma cells and germinal centers actually form in the gland->hard rubbery goiter.
Tc destruction of thyroid epithelial cells is thought to be cause
Dx: detection of anti-thyroglobulin or anti-thyroid peroxidase ab by EIA
Term
Addison's Disease
28.2
Definition
auto-ab destroys adrenal cortex (type II)
pts have insufficient cortisol production, salt cravings and increased blood K+
Dx: chem tests for decreased cortisol response to ACTH injection
Term
Type I Diabetes
28.2
Definition
autoimmune Tc destroys pancreatic Beta cells that normally secrete insulin (type IV)
Dx: fasting hyperglycemia
screening for pre-disease includes combination testing for anti-GAD, anti-IA-2, and insulin auto ab
Term
Multiple sclerosis
28.3
Definition
inflammatory autoimmune disease of CNS
autoantigends include myelin basic protein and myelin oligodendrocyte glycoprotein (MBP and MOG) and are targeted by ab and Th1/Tc cells
Term
Myasthenia gravis
28.4
Definition
neuromuscular disorder with fatigue and skeletal muscle weakness
due to ab to acetylcholine receptor (ACH-R). ACH is released from motor neuron ending and binds to ACH-R on muscle fiber to initiate action potential. Ab blocks binding to ACH-R and increases receptor uptake by the muscle cell (decrease available receptor)
Dx: detection of anti-ACH-R ab by precipitation of radioimmunoassay (RIA)
Term
Goodpature's syndrome
28.5
Definition
auto ab to type IV collagen (kidney glomeruli and lung alveoli). can lead to rapid renal failure with necrosis and pulmonary hemorrhage, shortness of breath, cough and weakness.
RIA, EIA, or indirect immunofluorescence (IFA) are screening tests for auto ab but western blot is confirmatory test
Term
Autoimmune diseases in developed nations
28.6
Definition
5% of individuals in developed nations have an autoimmune disease and it is on the rise
Term
2 most common rheumatologic diseases
29.1
Definition
rheumatoid arthritis (RA) and systemic lupus erthematosus (SLE, lupus)
Term
why are rheumatological diseases difficult to dx
29.2
Definition
there is an overlap of symptoms from one disease to another and there is no sensitivity/specificity in lab tests
Term
rheumatoid factor
29.3
Definition
RF is IgM, IgG or IgA ab to the Fc portion of IgG (autoimmunoglobulin ab)
most significant in RA
Term
inflammatory infiltrate in RA
29.4
Definition
chronic and episodic inflammation in joints that slowly destroys the joint tissue
caused by massive cell influx combined with immune complex deposition fixing C'
Cd4 and CD8 T cells, B cells, plasma cells, neutrophils and Mo all infiltrate the joint and will eventually digest the cartilage and erode bone
Term
Dx criteria for RA
29.5
Definition
Must have 4 Sx for 6 weeks:morning joint stiffness, swelling of soft tissue around 3+ joints, swelling of fingers/wrists, symmetric arthritis, subcutaneous nodules, xray evidence of joint erosion, positive test for RF and/or anti-CCP
Term
Screening test for isotype IgM RF
29.6
Definition
differs from IgG, IgA bc only IgM RF will cause agglutination
most specific test for RA is anti-CCP -> 98% specific
Term
anti-CCP testing
29.7
Definition
citrulline is a nonstandard amino acid created by deamination of arginine by the enzyme peptidylarginine deaminase
this process is post-translational modification of joint proteins fillagrin, vimentin, fibrin, and others
often paired with RF testing
Term
following RA progression
29.8
Definition
indicators of inflammation: increase in erythrocyte sedimentation rate, increase in C-reactive protein, decrease in C3, C4
Term
treatment for RA
29.9
Definition
anti-TNF=alpha monoclonal ab
Term
FANA, ANA, ENA
29.10
Definition
fluorescent antinuclear ab
antinuclear ab
extractable nuclear ag
Term
Patterns seen in FANA
29.10
Definition
homogenous, speckled, nucleolar, mixed (of multiple patterns)
Term
2 specific ENAs for SLE dx
29.10
Definition
anti-dsDNA and anti-Sm
not sensitive
Term
autoimmune mechanism responsible for lupus
29.11
Definition
caused by auto ab to intracellular components (nucleic acids, nucleoproteins, cyotplasmic proteins)
igG auto ab complex with these components and deposit into tissue
type III hypersensitivity
Term
interpretation of FANA and titer
29.12
Definition
results include both a titer and patter of ab binding
normal titer is =/< 1:80 and a suggestable positive is >/= 1:160
Term
other diseases with a low + titer of FANA
29.13
Definition
5% of healthy population has a low +
70% of elderly population has a low +
low + titers in RA (50%), scleroderma (60-90%), Sjogrens syndrome (80%)
Term
ENA associated with drug-induced lupus
29.14
Definition
histone ENA
Term
why can lupus pts have a false + syphilis test
29.15
Definition
because of auto-cardiolipin
false + would show in a nontreponemal test
Term
Dx of lupus
29.16
Definition
must have 4 Sx at any point:
malar rash (cheeks), discoid rash (circular), photosensitivity, painless oral ulcers, arthritis, serositis (inflammation of pleural sac), renal disorder, anemia, leukopenia, thrombocytopenia, positive FANA, positive anti-dsDNA or anti-Sm or false + of nontreponemal syphilis test
Term
Lab test for lupus progression
29.17
Definition
rise in C-reactive protein, erythocyte sedimentation rate, anti-dsDNA titer, urine protein
fall in CBC, complement, serum albumin
Term
cells responsible for autoimmune diseases
30.1
Definition
ab and CD8+ T cells (Tc) are responsible for autoimmune disease
Term
2 proteins involved in T cell tolerance when defective lead to autoimmune disease
30.2
Definition
homozygous deletions of AIRE and FoxP3
Term
how CTLA-4 can lead to susceptibility to autoimmune disease
30.3
Definition
one allele limits production of soluble CTLA-4 which could be important in Treg function
it is a very weak risk factor (in 50% of normal population, 60% of autoimmune)
Term
Relative risk
30.5
Definition
if you have the associated HLA type, RR is the increased risk you have over the general population to get the disease
Term
role of HLA alleles in development of autoimmunity
30.6
Definition
HLA is a gene that codes for MHC which is on APCs and presents the antigen
HLA presents self ag on our cells
Term
risk factors for autoimmunity: releasse of sequestered ag by tissue damage
30.7
Definition
omtracellular proteins and nucleic acids are released into extracellular fluid and elicit an immune response
Term
risk factors for autoimmunity: inflammation causing ectopic expression of MHC class II on cells that normally do not express it
30.7
Definition
IFN-gamma can cause several cell types to express MHC class II
these cells may express a protein not made in thymus-> no t cell tolerance exists
Term
risk factors for autoimmunity:molecular mimicry- pathogen triggers a TCR/BCR that cross reacts with self ag
30.7
Definition
pathogen looks like one of our proteins
Term
risk factors for autoimmunity: polyclonal B cell activation can trigger ab synthesis to many self ag
30.7
Definition
yeh
Term
risk factors for autoimmunity: inhibitory FcyR polymorphisms lead to inability to inhibit B cell responses even when ab is adequate
30.7
Definition
yeh
Term
risk factors for autoimmunity: environmental
30.7
Definition
can act as hapten to change self proteins into novel ag
can cause chronic damage that releases hidden ag
Term
epitope spreading
30.8
Definition
when first Dx, pt has limited auto ab
as disease progresses, pt develops auto ab against more and more auto ag
Term
hapten
31.1
Definition
small molecules that become immunogenic when complexed to larger molecules
Term
adjuvant
31.1
Definition
a substance administered with an ag to enhance the immune response to the ag
Term
characteristics of good immunogens
31.2
Definition
high molecular weight
high molecular complexity
taxonomically distant from host
inflammatory (possess TLR ligand or inducing cell stress)
Term
4 mechs that allow adjuvants to enhance immune response to vaccination
31.3
Definition
-complex with ag to increase its size
-trap ag in material that is relatively indigestable so it leaks out slowly
-hyperactivate the innate immune cells
-modulate the immune response by favoring th1 vs th2 or vice versa
Term
how ISCOMs are used as an adjuvant
31.4
Definition
peptide is loaded into the cytosol
it is cell mediated immunity with Tc
Term
Viral vaccinations
31.5
Definition
killed/inactivated: whole virus, cannot replicate
live-attenuated: more potent, virus replicates and mimics disease. only for healthy population
subunit: purified surface components or viral capsid/envelope to induce neutralizing ab
Term
Bacterial vaccinations
31.5
Definition
Live attenuated: less pathogenic strain
Subunit, inactivated toxin: destroyed toxicity, retains antigenicity. must be combined with another vaccine to be effective
subunit, purified capsular polysaccharide: ab to polysaccharide (protects bacteria) can induce C' binding and lysis. only induces productive T-independent ab in healthy adult
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