immunology Flashcards
immune system recognizes what
“self” from “non-self”
what organisms are seen as “non-self” by immune system
- viruses
- bacteria
- parasites
- foreign substances, including allergens
they are attacked by immune system
name autoimmune diseases- major ones
- autoimmune thyroiditis, hashimoto’s
- SLE
- RA
what happens in autoimmune diseases
immune system sees “self” as “nonself”
what is the immune response to non-self, what kind of symptoms occur
fever, hypotension, body aches, generalized not feeling well, fatigue
anaphylaxis can occur (IgE and mast cell mediated)
what happens to genes with immunodeficiencies
can be single gene defect or multiple gene defect
what is anti-nuclear antibody, ANA
antibodies against nuclear components that act as antigens
produced by immune system when it fails to adequately distinguish ‘self’ and ‘non-se;f’
target substances found in nucleus of cell, causes organ and tissue damage
when is ANA used
as initial test to evaluate for autoimmune diseases
if positive more testing is needed
for what s/s is ANA ordered
vague s/s that are associated with systemic autoimmune disorder
Low-grade fever
Persistent fatigue, weakness
Arthritis-like pain in one or morejoints
Red rash (ex: a butterfly rash in lupus)
Skin sensitivity to light
Hair loss
Muscle pain
Numbness or tingling in the hands or feet
Inflammation and damage to organs and tissues
what suggests autoimmune disorder
positive ANA and s/s of autoimmune disease
however, further eval is required
can you see increase in ANA before s/s present
yes
how is ANA reported
as a titer and pattern
relationship of ANA in SLE
95% of ppl with SLE test have positive ANA results
negative ANA makes SLE unlikely
conditions with positive ANA, along with percentages
- SLE, 95%
- Sjogren’s, 40-70%
- scleroderma (systemic sclerosis), 60-90%
- raynauds syndrome
- arthritis
- dermatomyositis or polymyositis
- mixed connective tissue disease
- drug induced lupus (antihistone antibody)
what are the different ANA patterns
- homogenous (diffuse)
- speckled
- nucleolar
- centromere pattern (peripheral)
not always one definitive pattern
ANA homogenous (diffuse) pattern is seen with what diseases
SLE, mixed connective tissue disease, drug induced lupus
what causes drug induced lupus
anticonvulsants, hydralazine, procainamide, isoniazid
what diseases are seen with ANA pattern- speckled
SLE, Sjogren’s, scleroderma, polymyositis, RA, mixed connective tissue disease
what diseases are seen with ANA pattern nucleolar
associated with scleroderma and polymyositis
what diseases are seen with ANA pattern, centromere (peripheral)
scleroderma and CREST
is there a need for serial ANAs
no, ANA is not used to rack or monitor clinical course of disease
ANA false positives occur when
in about 3-5% of healthy adults
may reach as high as 10-37% in adults over 65 y/o bc ANA frequency increases with age
more common in women than men
Which of the following is true of the ANA test?
a. It is a test for the titer and pattern of nuclear antigens in the patients blood.
b. The technique uses fluorescence to detect antibodies to nuclear components.
c. When positive it is diagnostic of SLE and further testing is unnecessary.
d. It is a good general screening test used for routine comprehensive examination of outpatients.
: b. ANA is a test for antibodies to nuclear components, not nuclear antigen.
It is ordered for patients with symptoms and when positive, further testing is in order. It is not a good general screening test for asymptomatic people.
When positive it is not diagnostic of SLE but can tell us there is an autoimmune disease is likely present
what is C reactive protein, CRP
general marker for infection and inflammation
is CRP specific
no, not enough to diagnose a particular disease
must be used in combo or cluster of dx testing
CRP used for what
to detect or monitor significant inflammation in various conditions
infection, autoimmune disease, response to treatment, CVD death risk predictor
what organ is CRP manufactured in
liver
how does CRP participate in activation of immune system
by coating antigens for targeting by complement system
so when immune system is activated and is overactive you see elevated CRP
other things that cause CRP to elevate
Plaques, psoriasis, plaques in brain, plaques in blood vessels, anything that will cause systemic inflammation will cause CRP to elevate
later stages in pregnancy
use of PO contraceptives or hormone replacement therapy (estrogen)
obesity
high sensitivity CRP ranges
Low risk: less than 1.0 mg/L
Average risk: 1.0 to 3.0 mg/L
High risk: above 3.0 mg/L
Which is true of CRP?
a. It is a specific test for atheromatous cardiovascular disease.
b. It is a protein manufactured in the bone marrow.
c. CRP participates in the activation of the immune system.
d. Is elevated when the WBC count is elevated.
Correct answer : c.
CRP is manufactured in the liver. It participates in the activation of the immune system by coating antigens for work by the complement system. Levels correlate with cardiovascular events, and it is thought that atheromas activate the immune system, but CRP is not a specific test for atheromatous disease. Can only be used as a predictor
what is erythrocyte sedimentation rate, ESR
non-specific marker of inflammation
is ESR specific
no, not to any specific disorder
used in combination with other testing
positive ESR indicates what
immune system activation (eg bacteria or autoimmune disease), however can be normal when immune system is activated
often elevated with acute exacerbation of SLE or RA, during high inflammatory times
also elevated with malignancy, thyroid disease, pregnancy, MI
what is ESR useful for
to r/o disease caused by activation of immune system
to confirm immune activation (flair of Chron’s, RA, or SLE)
is ESR ordered for viral or bacterial disease
rarely
ESR is not always elevated with immune system activation
high ESR is seen with what
older pt with polymyalgia rheumatica with diffuse myalgias and low grade fever
classic presentation is shoulder girdle and pelvic girdle pain with diffuse myalgias
w/o treatment can cause blindness and temporal arteritis
Which is true of the ESR test?
a. It is an old test not sensitive or specific and so is not used much.
b. When elevated it is specific for polymyalgia rheumatica.
c. It is a very sensitive test for activation of the immune system.
d. When elevated in a patient with autoimmune disease it can be used to follow the effectiveness of therapy.
Correct answer: C
The ESR is not always elevated in autoimmune disease and so is not a reliable marker of the presence or absence of disease. Though it is usually markedly elevated in patients with polymyalgia rheumatica, this result is not diagnostic (not specific). It is an old test but still useful
what does epstein - barr virus cause
mononucleosis (can be caused by wide spread herpes virus), which is indicated in chronic fatigue syndrome
also causes rare ca- Burkitt’s Lymphoma
EBV test, how is it performed
done with serum that is diluted until antibody is no longer detectable
last detectable dilution is reported as a titer
what is mono spot test
agglutination blood test for antibodies to EBV
When is EBV done
when dx of infectious mononucleosis is questionable
pt will have chronic fatigue but dx of mono is questionable
is EBV test needed when clinical fx fairly clear and monocyte count is elevated
no
what should you order if clinical exam/hx strongly in favor of infectious mononucleosis, other than typical tests
CBC
if lymph and atypical lymph counts are elevated, mono dx pretty sure
which does clinical presentation of mono include
pharyngitis, sore throat, fevers, arthralgias, extreme fatigue, lympahdenopathy
usually pt in teens but has been known to affect adults too
heterophile antibodies seen with what and what are they
EBV
human antibody that reacts with proteins from another species
mono test timing
rapid and easy
tends to be negative in early disease
Usually by the 6 – 10th day of onset the infectious mono antibody will elevate and continues to rise through the 3rd week of illness
May persist for awhile, but then over the next 12 months it will gradually decrease
also tends to be negative with young kids
EBV test results indicative of acute EBV infection
titer high or there is a 4 fold increase in titer over 10 - 14 days
heterophile antibodies also positive in people with
lymphoma
SLE
some GI CAs
Epstein-Barr virus (EBV) antibodies are used to help diagnose infectious mononucleosis (mono) if a person is symptomatic but has a negativemono spot
Viral capsid antigen (VCA)-IgM
VCA-IgG
D early antigen (EA-D)
Epstein Barr nuclear antigen (EBNA)
VCA-IgM
viral capsid antigen
in most patients is detectable with symptom onset; peaks at 2 to 3 weeks; becomes unmeasurable by 4 months.
VCA-IgG
viral capsid antigen
peaks at 2 - 3 months
persists for life
antibodies to early antigens in EBV
d early antigen EA-D
rise in acute stage; become undetectable by 3 to 4 months; may reappear with reactivation of EBV infection.
also can be detectable in some clinically healthy ppl
EBNA , Epstein Barr nuclear antigen
rise in resolution phase, and remain detectable for life.
These antibodies develop after 6 to 8 weeks and can be used to identify past infection, or as evidence to rule out acute EBV infection.
Which is true of the EBV test?
a. A four-fold increase in the IgM antibody is diagnostic of acute infection
b. A low level of IgG antibody is indicative of early acute infection.
c. It is routinely ordered to confirm the diagnosis of infectious mononucleosis.
d. When the IgM antibody is not present, infectious mononucleosis is not the diagnosis.
Correct answer: A. IgM antibodies are the first response of the body’s immune system to the EBV virus. They may not be detected early in the course of the disease, so a repeat test in a week or two is indicated if negative. It is not ordered routinely because some cases of IM are typical of IM on clinical grounds and a lymphocyte count with atypical cells is all the confirmation needed. And EBV test is very expensive
HIV serology
series of highly specific tests used at various stages
initial HIV serology test
usually ELISA (enzyme linked immunosorbent assay) test for antibody to HIV antigen
recommend HIV screening for ppl at risk including
exposed to blood or body fluids from an infected individual or person of unknown HIV status (needle stick, etc)
IV drug users
Homosexual men and bisexual men and women
Multiple sex partners
persons from countries with a large portion of the population infected
HIV serology timing
12 week window when test can be falsely negative those exposed to blood or body fluids of an infected individual are usually treated for 4 weeks and the test is repeated at 3 & 6 months
HIV vs AIDS
A person who is infected with HIV does not have AIDS until the AIDS clinical signs and symptoms are present
Which is true regarding HIV and a needle stick injury of a healthcare worker?
a. When indicated, treatment should begin within 24 hours of the needle stick.
b. Treatment is begun when the ELISA test is positive.
c. Healthcare workers with a recent needle-stick injury should be counseled about the signs and symptoms of AIDS and should be treated when they develop.
d. Treatment is begun when tests for the HIV antigen are positive.
Correct Answer: a Early treatment (within 24 hrs. if possible and definitely within 72 hrs.) with anti-retrovirals has been shown to stop replication and in many cases, the HIV is eliminated. Waiting for any of the other options doesn't offer the possibility of eliminating the infection. Check the policy at your place of employment. Employee Health should be a good source of information. Policies change is knowledge about disease changes.
what kind of approach for lyme disease testing
CBC recommends 2 step approach
- ELISA- antibody screening
- Western blot- confirmation
Lyme disease testing ordered for
typical rash of Lyme disease (erythema migrans)
recent onset of polyarthralgia (arthritis like symptoms in joints) after exposure to deer ticks
neurologic or cardiac symptoms
chronic symptoms of the same systems months or years after infection (late disease)
IgG and IgM testing for Lyme disease
Both IgG and IgM tests should be done together in the first 4 weeks,
only the IgG test is necessary after 4 weeks
what indicates current lyme disease
high titer or 4 fold increase in IgM indicates current Lyme disease
elevation in IgM and IgG for lyme disease indicates
recent infection but at later stage than when IgM alone is elevated
remote lyme disease infection
elevation in IgG alone
what to do if IgM is negative and infection is thought to be less than 4 weeks prior
repeat tests in 1-2 weeks
Which is true of Lyme disease testing?
a. The presence of the IgG antibody is indicative of acute infection.
b. A culture for the spirochete in the deer tick is the most common diagnostic test.
c. The tests are most often positive when the maculopapular rash develops.
d. A four-fold increase in the IgM antibody titer is indicative of acute disease.
Correct Answer: d
IgM antibody is the first response of the immune system to the spirochete causing Lyme disease. A high titer or a four-fold increase is indicative of acute disease. It is difficult to grow the spirochete in culture, and the offending tick is usually long gone when the patient presents with symptoms so culture of the deer tick is not a reasonable test. Patients have a target, bulls eye rash - not a macula-papular rash (small spots like measles).
what is macula-papular rash
small spots
like with measles
A patient reports that he found a tick on himself about one month ago. He was left with a red circle rash with a white center. He did not seek treatment. What lab test can be used to diagnosis Lyme disease?
a. CBC
b. culture for spirochete antigen
c. ELISA test for antibody to the spirochete antigend. cerebrospinal fluid analysis for the spirochete
Correct answer: C
The Elisa test if positive can be confirmed by a Western blot test for antibodies to the spirochete. CBC would be inconclusive. Testing the CSF for the presence of the spirochete would be difficult and inconclusive.
what is rubeola antibody
blood test to detect antibodies to rubeola virus
causes measles
IgG testing for rubeola antibody
useful to document previous disease or vaccination
when should IgG testing for rubeola be ordered
before vaccination if reason to believe pt already had measles or has been vaccinated
health care workers and women wishing to becoming pregnant
to test for immunity
positive rubeola antibody means
previous disease or vaccination
unclear rubeola antibody result, do what
vaccinate health care workers and women wanting pregnancy
is testing done to diagnose acute measles
no, clinical signs and symptoms are characteristic
Which is true of rubeola testing?
a. When present in high titer, vaccination is not necessary.b. If antibody titers are not present, pregnant women should be vaccinated because of the risk of harm to the fetus if the mother develops measles.c. It is falsely negative in patients who take systemic steroids.d. The test will be positive after rubella vaccination.
Correct answer: a
When the rubeola titer is elevated, immunity is present and vaccination is not necessary. Measles infection during pregnancy is associated with fetal abnormalities, so maternal immunity before becoming pregnant is very desirable. Steroids do not interfere with the test though they might blunt the response to vaccination. Pregnant women should not receive the vaccine because it is a live virus. The same is true of patients on steroids who might develop infection from the vaccine.
Rubella is a different virus. It causes rubella or German Measles - a different disease.
Which one of the following tests, if positive, is part of the criteria for a diagnosis of SLE?
a. ANAb. CRPc. elevated monocyte countd. elevated ESR
Correct answer: A
A positive ANA usually with a homogeneous pattern is one of the criteria for a diagnosis of SLE (not definitive,but lets us know something autoimmune is occurring). The ESR can be elevated but is not specific, the CRP is usually normal unless there is another cause for its elevation, and the monocytes are not elevated.
