midterm - AUTOIMMUNITY AND TUMOR IMMUNOLOGY Flashcards
are conditions in which damage to organs or tissues results
from the presence of AUTOANTIBODY or
AUTOREACTIVE CELLS.
AUTOIMMUNITY
AUTOIMMUNITY results from the presence or the damage to organs and tissues caused by
autoantibody or autoreactive cells
the conflict in ____ causes the autoimmunity. The reason behind why we were able to get an autoantibody or autoreactive cells
conflict in self tolerance
the ability of the immune system to
recognize self-produced antigens as a non-threat while
recognizing foreign antigen as a threat.
self tolerance
2 stage or 2 parts of self tolerance
central and peripheral tolerance
where do central tolerance happens/occurs?
in the bone marrow, upon the maturation of b and t cells
a self tolerance that happens in the bone
marrow it aids in line with the thymus where the T cells and B cells are manufactured,
central tolerance
on this particular self tolerance it was able to
removed or destroyed the so-called self-reactive B cells or T cells that we have.
central tolerance
the back up of central tolerance just in case some of the self reacting lymphocytes pass through the central tolerance
peripheral tolerance
a self tolerance that happens in a secondary lymphoid organs
PERIPHERAL TOLERANCE
a self tolerance that ensure that those
self-reacting lymphocyte that has been able to
pass through against the central tolerance will be destroyed
peripheral tolerance
the cell in charge of peripheral tolerance
T regulatory cells
t regulatory cells help in suppressing immune response to self antigens maintaining the balance between __ and ___ in the secondary lymphoid organs
T helper 1 and T helper 2
TH1 and TH2
it is the primary mediators of autoimmune disorders, especially which type of it?
t helper cells especially the TH 1 cells
Definitely the role
of ___ is very critical in
maintaining this balance and eliminating
harmful autoimmune response.
T regulatory cells
a shutdown in central tolerance will cause ___ effect resulting to a problem with t regulatory cells causing autoimmune disorders
ladder effect
is thought to be caused by the loss or
breakdown of self-tolerance.
autoimmunity
Several other mechanisms are thought to contribute to
autoimmunity, this includes:
o Released of sequestered antigens, molecular
o mimicry, and polyclonal B-cell activation.
o Inheritance of MHC genes
2 classification of auto immune diseases
organ specific and sytemic
hashimoto’s thryroiditis is a type of auto immune diseases that affects the ____
thyroid
grave’s disease is a type of auto immune diseases that affects the ____
thyroid
pernicious anemia cells is a type of auto immune diseases that affects the ____
gastric parietal
addison’s disease is a type of auto immune diseases that affects the ____
adrenal glands
type 1 diabetes mellitus is a type of auto immune diseases that affects the ____
pancreas
MG or myasthenia gravis is a type of auto immune diseases that affects the ____
nerve muscle synapses
MS or multiple slcerosis is a type of auto immune diseases that affects the ____
myelin sheath or nerves
autoimmune hemolytic anemia is a type of auto immune diseases that affects the ____
red blood cells
idiopathic thrombocytopenic purpura is a type of auto immune diseases that affects the ____
platelets
goodpasture’s syndrome is a type of auto immune diseases that affects the ____
kidney and lungs
rheumatoid arthritis is a type of auto immune diseases that affects the ____
joints, lungs and skin
scleroderma is a type of auto immune diseases that affects the ____
skin, gut, lungs, kidney
sle is a type of auto immune diseases that affects the ____
skin, joints, kidney, brain, heart, and lungs
In myasthenia gravis, there’s a problem with the neuro muscle synapses which is responsible for the nerve impulses for moving muscles which is primarily the ___
acethylcoline
why do systemic auto immune disease are called systemic?
it affects multiple organs not only one
among the mentioned auto immune disease, which are the systemic?
goodpasteur syndrom
rheumatoid arthritis
sle
The peak age of onset is usually between ___ and ___ of age in SLE
20 and 40 years.
____ are much more likely affected.
women
the margin between women and men in terms of the number affected by the SLE
10 to 1.1
Systemic lupus erythematosus
The immune response is directed against a broad range of target antigens, as the typical patient has an average of three circulating autoantibodies.
what are they?
HLA-DR2 and HLA-DR3
class II MHC
SLE is Associated with Complement deficiencies.
what are the complements missing?
C1q, C2 and C4
CLINICAL SIGNS OF SLE
joint involvement
skin manifestation
renal complications
joint involvement of SLE results to
polyarthralgia’s or arthritis
most frequently reported
manifestation of SLE
joint involvement
90% with joint involvement with patients with SLE has
polyarthralgia’s or arthritis.
second most common sign or manifestation of SLE
skin manifestation
in skin manifestation of SLE
an erythematous rash may appear on any area of
the body exposed to ____.
ultraviolet light
appearance of the classic butterfly rash across
the nose and cheeks may appear in ____ % of
all SLE patients.
30-40%
the hallmark butterfly rash is responsible for the name lupus,
derived from the Latin term meaning “___”
wolflike
Renal complications may occur in SLE in a form of
glomerulonephritis
IMMUNOLOGIC FINDINGS OF SLE
discovery of LE cells
anti DNA antibody
is a neutrophil that has engulfed
the antibody-coated nucleus of another neutrophil.
LE cells
the autoantibody Anti-ds- DNA is associated wth the disease
homogenous pattern
SLE
anti- ss Dna is associated with the disease
not detected on routine screen
SLE with many other disease
anti histone is associated with the disease
homogenous pattern
drug induced sle, other diseases
anti dnp is associated with the disease
homogenous pattern
sle, drug induced sle
anti sm is associated with the disease
speckled pattern
diagnostic for sle
anti rnp is associated with the disease
speckled pattern
sle, mixed with connective issue disease
anti ss- B (ro) and
anti - SS- B (la) is associated with the disease
finely speckled pattern
sle, sjogren’s syndrome, others
anti-nuclear is associated with the disease
homogenous staining of nucleolus pattern
sle, systemic sclerosis
anti - sci - 70 is associated with the disease
atypical speckled
systemic sclerosis, scleroderma
anti - jo - 1 is associated with the disease
fine cytoplasmic specklin
polymyositis
which autoantibody of sle is not detected on routine screening?
anti - ss - dna
which autoantibody of sle has a homogenous pattern in immunofluorescene
anti histone
anti - dnp
which autoantibody of sle has a speckled pattern in immunofluorescene
anti - sm
anti - rnp
which autoantibody of sle has a finely speckled pattern in immunofluorescene
anti - ss A
anti - SS b
which autoantibody of sle has a homogenous staining of nucleolus pattern in immunofluorescene
anti - nuclear
which autoantibody of sle has a atypical speckled pattern in immunofluorescene
anti-sci- 70
which autoantibody of sle has a fine cytoplasmic speckling pattern in immunofluorescene
anti - jo - 1
what is the screening test for sle
ana or antinuclear antibody
an example of ana test
fluorescent antinuclear antibody
is the most widely used and accepted test, because it detects a wide
range of antibodies and is positive in about 95 percent of
patients with lupus.
Fluorescent antinuclear antibody (FANA) testing
___ are a heterogeneous group of
antibodies that bind to phospholipid alone or are complexed
with protein.
Antiphospholipid antibodies
ANTIPHOSPHOLIPID ANTIBODIES
They have been found in up to ___ percent of patients with lupus.
60%
one of the several types of
antiphospholipid antibodies that will prolonged the APTT and PT
lupus anticoagulant
in RHEUMATOID ARTHRITIS
describe the likeliness of women to men being affected with RHEUMATOID ARTHRITIS
women are 3 times as likely to be affected as men
rheumatoid arthritis Strikes individuals between the ages of ___ and ___
35 and 50
RHEUMATOID ARTHRITIS
usually affects what organs
joints, heart, and lungs
which hla is rheumatoid arthritis associated into
hla-dr4
IMMUNOLOGIC FINDINGS of rheumatoid arthritis
lesions
mass of cells called Pannus
presence of inflammatory agents
rheumatoid factor
The earliest lesions in rheumatoid joints show an increase in cells lining the ___and an infiltration of mononuclear cells, mostly __- and ____
synovium , CD4+ T lymphocytes.
in rheumatoid arthritis
Macrophages and neutrophils are attracted to the area,
and this results in the formation of an organized mass of
cells called a ____, which grows into the joint space
of an individual with Rheumatoid Arthritis and invades the
cartilage
pannus
Presence of Pro-inflammatory agent for rheumatoid arthritis
IL-1, IL-6, IL-8,
TNF-α. (IL-15, IL-18)
Approx. 75% of patients with RA have an antibody that has
been called ____
Rheumatoid factor
Diagnosis for rheumatoid arthritis
Clinical Manifestations, Radiographic Findings,
and Laboratory Testing.
Laboratory test for rheumatoid arthritis
Agglutination test
what immunoglobulin is associated with the agglutination test of rheumatoid arthritis?
IgG
Agglutination test: detects only the IgG isotypes and is found approx. in ___% of patients, thus, a negative result does not rule out the presence of
the Rheumatoid Arthritis,
75%
conversely, if you tested positive for rheumatoid factor, it will not immediately indicate that you do have rheumatoid arthritis as RF can be found as well in other diseases such as
as Syphilis, SLE,
Chronic Active Hepatitis, TB, Leprosy, Infectious
Mononucleosis, Malaria, and Sjogren’s
Syndrome.
the agglutination test for rheumatoid arthritis will uses the ___
sheep red blood cells coated with IgG
Immunoassays for rheumatoid arthritis
o EIA (Enzyme Immunoassay)
o Nephelometric Methods
Both have greater precision and
sensitivity because they are automated.
the 2 most common disease associated with thyroid
Hashimoto’s thyroiditis and Graves’ Disease
a large iodinated glycoprotein
produced by Colloids particularly the Follicular
cells in the colloids
Thyroglobulin➔
is a precursor of the thyroid
hormones, which is known as the T3
(triiodothyronine) and the T4 (thyroxine).
thyroglobulin
explain how thyroid release hormones
from the hypothalamus, it will secret thyrotropin-releasing hormone. The thyrotropin-releasing hormone acts on the pituitary gland to induce the release of thyroid-stimulating hormone. The thyroid-stimulating hormone will binds to the receptor of the cell membrane of the thyroid gland and causing thyroglobulin to be
broken down into secretable substances, which is the T3 and the T4.
HPT axis (HPTA) is composed of
Hypothalamus, pituitary and
Thyroid gland axis
Production of ___ interferes with this process
and causes under- or overactivity of the thyroid
autoantibodies
Associated with HLA (chain):
o Graves’ disease➔ ____
o Hashimoto’s thyroiditis➔ _____
o Graves’ disease➔ HLA-DR3
o Hashimoto’s thyroiditis➔ HLA-DR5
Also known as chronic autoimmune thyroiditis.
Hashimoto’s Thyroiditis
Hashimoto’s Thyroiditis is Most often seen in ___ women.
middle-aged
in hashimoto’s thyroiditis, Women are ___0 times more likely to develop the
disease.
5 to 10
Hashimoto’s thyroiditis’ patients will develop what signs and symptoms
enlargement of thyroid gland, hypothyroidism, dry skin, decreased sweating, puffy face with edematous eyelids, pallor with a
yellow tinge, weight gain, and dry and brittle hair.
what would be the thyroid antibodies produced by the patients with Hashimoto’s thyroiditis?
anti-thyroglobulin.
a type of thyroid disease wherein there will be an Increase levels of T and B cells (predominantly T cells),
macrophages, and plasma cells.
hashimoto’s thyroiditis
auto antibody produced by the patient with grave’s disease?
(Anti-TSHR)
grave’s disease’s patients will develop what signs and symptoms
hyperthyroidism, increase levels of T3 and T4.
nervousness, insomnia,
depression, weight loss, heat intolerance, sweating, rapid
heartbeat, palpitations, breathlessness, exophthalmos,
fatigue, cardiac dysrhythmias, and restlessness.
what are the 3 major auto antibodies for thyroidism
anti-thyroglobulin, anti-TPO, and anti-TSHR.
for anti- thyroglobulin, we can conduct a test such as
indirect IFA (indirect immunofluorescent assay), Passive hemagglutination, and EIA
a test for anti-thyroglobulin that is using a tanned red blood cells
passive hemagglutination
an anti-thyroglobulin test that is the most commonly used
passive hemagglutination
an anti-thyroglobulin test that is less sensitive than passive hemagglutination but it can detect non-agglutinating antibody
Indirect immunofluorescent testing
an anti-thyroglobulin test that uses methanol-fixed monkey cryostat tissue sections as
substrate.
Indirect immunofluorescent assays
an anti-thyroglobulin test that will create a floccular
or puffy staining pattern
Thyroglobulin antibodies
The antibodies to thyroglobulin can be detected in
___ % of patients with Hashimoto’s thyroiditis.
90%
what are the parallel test for thyroid?
tsh, t4, t3, ft4 and thyroglobulin test.
Antibody to CA2 produces a ___ appearance.
diffuse or ground-
glass
test we can conduct for anti tpo (thyroid peroxidase)
EIA, Indirect IFA, Particle agglutination assays.
an anti tpo/ thyroid peroxidase test that is the most
commonly used test in detecting this antibody
Enzyme immunoassay (EIA)
an anti tpo/ thyroid peroxidase test that is
Antibodies to __ are
directed against a 105 kD membrane enzyme that
catalyzes tyrosine iodination.
thyroid peroxidase (TPO)
thyroid peroxidase or anti tpo is found in approximately___ percent
of patients with the disease.
90 to 95
___ produce staining of the
cytoplasm and not the nucleus of thyroid cells.
Peroxidase antibodies
These antibodies can be found in approximately
90 percent of patients with Hashimoto’s disease
and 80 percent of patients with Graves’ disease,
so the two cannot be distinguished on the basis of
this test.
anti thyroid peroxidase test
what are the test we can conduct in Anti-TSHR
Bioassays, Binding Assays
The ___, this would be intended for Grave’s
disease.
anti-TSHR
an anti-tshr test that requires tissue culture and thus, it is
very difficult and requires a properly trained
personnel to perform this procedure.
bioassays
an anti-tshr test that is based on the competition
between the radiolabeled TSH and patient
autoantibodies for binding to thyrotropin receptor.
binding assays
Autoimmune diabetes mellitus, now termed
type IA diabetes,
is a chronic autoimmune disease that occurs in a genetically susceptible individual as a result of environmental factors.
Autoimmune diabetes mellitus,
Insufficient insulin production caused by selective
destruction of the beta cells of the pancreas.
Autoimmune diabetes mellitus,
Autoimmune diabetes mellitus, is associated with what mhc hla
HLA-DR3 or HLA-DR4.
type I diabetes mellitus may occur in thewhat mhc region.
HLA-DQ region especially in the coding of the DQβ chain.
type I diabetes mellitus may occur in the HLA-DQ region.
Within the β chain, substitutions for the amino acid 57, ___, are associated with increasing risk for diabetes
aspartic acid
type IA diabetes mellitus
Progressive inflammation of the islets of Langerhans in the
pancreas leads to __and destruction of most beta
cells.
fibrosis
in hyperglycemia, almost or around how many percent are the beta cells being destroyed after the subclinical period of how many years
80% of the beta cells
type I diabetes mellitus
Predominance of T-cells (CD4+ and CD8+), B cells, TH1
cells, plasma cells and macrophage➔ their activities are
responsible for the inflammatory response and eventually
killing/destroying the ___ cells.
beta
this would be the islets cells antigen
anti- ica
is glutamic decarboxylase
Anti-GAD
Production of autoantibodies in type 1 diabetes mellitus
Anti-IA2, Anti-IA-2βA, Anti-Insulin, Anti-GAD and Anti-ICA
Antibodies to islet cells have traditionally been detected by using ___ of human pancreas.
frozen sections
an immunologic manifestation in which there will be an activation of t lymphocytes
sarcoidosis
an immunologic manifestation in which there will be a sensitized t cells
disseminated encephalomyelitis
an immunologic manifestation in which there will be an streptococcal antibodies that cross react with heart tissue
rheumatoid fever
marker for nonseminomatous testicular germ cell liver
afp
screening conducted in high risk populations for liver cancer such as those with liver cirrhosis and chronic hpatitis. in germ cell tumors both ___ and __ are elevated
afp and hCG
higher levels of this markers imply poor prognosis in multiple myeloma
b2 microglobulin
non cancerous conditions of elevated afp
pregnancy and nonneoplastic liver disease
normal sources of AFP
fetal liver, yolk sac, ault liver
elevated ____ can be found in cancer associated with specific wbc malignancies
cd markers
non cancerous conditions we can found an elevated cd markers
wbc increase such as infection
a marker we can found in a cancer associatde with familial medullary thyroid carcinoma
calcitonin and calcium
normal sources of calcitonin and calcium
thyroid
a markr that has a short half life
pth and ca
the marker that will elevate in parathyroid carcinoma
pth and ca
normal sources of pth and ca
parathyroid glands
pth has a short half life, so levels are done intraoperatively to ensure complete ___
parathyroid tumor removal
a marker that will elevate in thyroid cancer
TG