MIDTERM - immunodeficiencies and immunoproliferative disorders Flashcards
Deficiencies of the immune system is also known as
immunodeficiencies
Deficiencies of the immune system include disorders of _
phagocytic cells.
B lymphocytes,
a combination of T and B lymphocytes,
the complement system application of
disinfectant.
The mechanisms of immunodeficiencies it could
be ____
acquired or congenital
____ result in a decreased ability
to phagocytize and kill bacteria.
Phagocytic cell deficiencies
is a genetic disease characterized by ineffective
killing of bacteria by neutrophils.
Chronic Granulomatous Disease (CGD)
characterized by inability of
phagocytes to make the NADH oxidase
Chronic Granulomatous Disease (CGD)
the important enzyme in generating the hydrogen peroxide
NADH oxidase
It is used
to kill the ingested bacteria.
Hydrogen peroxide
The effect of ___ is in line with the
decrease production of the hydrogen
peroxide
CDG
CGD is caused by a defect in __, which results in decreased hydrogen peroxide
production.
cytochrome b
___ is necessary for
producing the toxic superoxides that are critical in bacterial killing.
Hydrogen peroxide
Diagnosis of CDG
nitroblue tetrazolium (NBT) reductase test
is used to detect impaired
neutrophil phagocytosis.
nitroblue tetrazolium
(NBT) reductase test
mechanism of nitroblue tetrazolium reductase test
The neutrophils of CGD patients fail to reduce the Nitroblue tetrazolium dye
Symptoms of chronic granulomatous disease (CGD)
suffer from recurrent infections caused by catalase-positive bacteria, yeast, and fungi.
Treatment for CGD includes
use of GM-CSF or G
CSF and IFN-y.
is inherited as an autosomal
recessive trait and is one of the most common
inherited disorders.
MPO DEFICIENCY
MPO stands for
myeloperoxidase
deficiency”
have decreased or absent in
the primary granules of the
neutrophils
MPO deficiency
In mpo deficiency
The __ in the primary granules of
neutrophils is decreased or absent, and
although phagocytosis takes place
normally, bacterial killing is INEFFICIENT.
MPO
In MPO deficiency, which one is more impaired than bacterial killing
fungal killing
healthy patients with MPO
deficiency do not have an increased
frequency of infection, DIABETIC PATIENTS
who have this disorder may have an
increase in ___. infections.
Candida spp
is another inherited disorder in which
the AEROBIC SYSTEM of neutrophils is impaired.
Glucose-6-Phospate Dehydrogenase (G6PD)
deficiency
This deficiency results in a SUBSTANTIAL decrease in the amount of hydrogen peroxide produced during phagocytosis, and thus decreased bacterial killing efficiency
Glucose-6-Phospate Dehydrogenase (G6PD)
deficiency
___ is considered as an inherited
disorders their mechanism is impaired
aerobic system of the neutrophils.
G6PD
is a rare,
autosomal recessive trait characterized by a
decrease or absence of specific complement
component receptors on neutrophils, monocytes
and lymphocytes.
CR3 (iC3b receptor) Deficiency
CR3 (iC3b receptor) are
responsible for ___
adherence-related functions
CR3 (iC3b receptor) Deficiency result in
defective margination and
diapedesis of neutrophils,
impaired chemotaxis,
ineffective phagocytosis.
this disorder will make T lymphocytes
adhere poorly to target cells
CR3 (iC3b receptor) Deficiency
effect of cr3 deficiency
Clinically, there is
an increased frequency of bacterial infections,
a decreased inflammatory response, and
neutrophilia.
is inherited as an
autosomal recessive trait. Neutrophils fail to
develop specific granules during myelopoiesis,
and as a result, patients who have this disorder
experience severe recurrent bacterial infections
Specific Granule Deficiency
One of the most common examples of
this would be the Chediak-Higashi
syndrome.
Specific Granule Deficiency
under the specific granule deficiency
is an inherited
disorder that is characterized by the abnormal
fusion of primary granules in neutrophils
Chédiak-Higashi syndrome
During phagocytosis, degranulation is
impaired, and little or no MPO is
released into the phagosome.
Chédiak-Higashi syndrome
Patients who have ____have recurrent bacterial
infections and are also characterized by
ALBINISM AND EXTREME PHOTOSENSITIVITY
Chédiak-Higashi
syndrome
conditions under lazy leukocyte syndrome
job syndrome
tuftsin deficiency
actin dysfunction
also known as
hyperimmunoglobulin E
Job syndrome
is
characterized by poor chemotaxis and
recurrent skin infections and abscesses
or nana.
job syndrome
___ is a chemotaxin that also improve phagocyte
motility, engulfment and oxidative
metabolism
Tuftsin
A deficiency of the
cytoskeletal protein actin
Actin dysfunction
Actin dysfunction.
A deficiency of the
cytoskeletal protein actin, can result in
___ and ___.
decreased bacterial motility and
chemotaxis
may be
inherited or acquired and account for MORE THAN HALF of all immunodeficiencies.
B-lymphocyte Immunodeficiencies
➢ Second factor
B-lymphocyte Immunodeficiencies
A deficiency of a minor immunoglobulin,
such as ___, causes little if any increase
in the incidence of bacterial infections
IgD
because 75% to 85% of total
immunoglobulin is IgG, an individual
deficient in IgG would be significantly
affected.
true or false
true
is a sex-linked
disorder that primarily affects MEN. It is usually
recognized early in life when antibodies fail to
develop.
Bruton’s Agammaglobulinemia
in Bruton’s Agammaglobulinemia,
___cells may be found in the bone
marrow, but they do not mature
Pre-B cells
in bruton’s agammaglobulinemia
what globulin
levels are markedly decreased.
Gamma globulin
how to treat bruton’s agammaglobulinemia
This disorder may be treated with gamma
globulin preparations.
is
an acquired disorder in which one or two
immunoglobulin classes are deficient.
Common Variable Hypogammaglobulinemia
Total immunoglobulin levels are normal, because a decrease in one immunoglobulin is often
compensated by an increase in the production of
another.
Common Variable Hypogammaglobulinemia
___ deficiency is one of the
most common of Common Variable Hypogammaglobulinemia.
Selective IgA deficiency
is cause by the normal immaturity of the neonate’s immune system.
Neonatal Hypogammaglobulinemia
Neonatal Hypogammaglobulinemia
It corrects itself between the ages of ____ as infant’s immune
system matures.
6 and 12 months
composing only 7% of all immunodeficiencies.
These disorders may be acquired or inherited.
T-lymphocyte Immunodeficiencies
results when the thymus
gland develops abnormally during
embryogenesis.
DiGeorge syndrome
Abnormalities of other
endoderm-derived tissues are also seen
DiGeorge syndrome
DiGeorge syndrome
T lymphocytes are usually ___, but may be normal
decreased
DiGeorge syndrome
Most patients have high ___ratio.
CD4-CD8
In DiGeorge syndrome, the antibody responses are normal, which response is considered impaired?
cell mediated immune response
is an autosomal recessive
disorder. Patients are arrhythmic and are
especially susceptible to viral and fungal
infections, which can be fatal in these patients.
Nezelof syndrome
an autosomal recessive, condition presents in infancy with recurrent or chronic pulmonary infections, oral or cutaneous candidiasis, diarrhea, skin infections,
urinary tract infections, and failure to thrive.
Purine Nucleoside Deficiency
Purine Nucleoside Deficiency
Affects an enzyme involved in the
metabolism of ___
purines
Produces a moderate to severe defect
in cell-mediated immunity with
normal or only mildly impaired humoral
immunity.
Purine Nucleoside Deficiency
Purine Nucleoside Deficiency
Cells progressively decreases because
of the accumulation of ___, a toxic purine metabolite
deoxyguanosine triphosphate
are the most serious of
the all immunodeficiencies that we have,
because both cell-mediated and humoral immune responses are affected.
Combined B- and T-lymphocyte
Immunodeficiencies
are characterized by defects in Class I MHC antigen expression, Class II MHC antigen expression, or a combination of both.
Bare-Lymphocyte Syndromes
in Bare-Lymphocyte Syndromes,
CD4-positive T lymphocytes are ___in number,
and B- and T-cell activation is ___.
decreased ; reduced
may be inherited as autosomal recessive or X-linked traits.
All are characterized by markedly decreased numbers
of both T and B lymphocytes.
Severe Combined Immunodeficiency Disease
is
caused by the human immunodeficiency virus 1 (HIV-1)
or the human immunodeficiency virus 2 (HIV-2).
Acquired Immunodeficiency Syndrome (AIDS)
in patients with AIDS, the primary target cells are
The CD4-positive T lymphocytes; approximately 5% of B lymphocytes are also infected.
_ is an X-linked recessive
disorder.
Wiskott-Aldrich Syndrome
One of the clinical features involved with the Wiskott-Aldrich
Syndrome is the: __, __ , and ___
Triad of immunodeficiency,
eczema,
thrombocytopenia
Deficiency of the naturally occurring antibodies to blood
group antigens
Wiskott-Aldrich Syndrome - WAS.
Wiskott-Aldrich Syndrome, WAS.
(isohemagglutinins – ___ antibodies
against ABO blood group antigens)
IgM
in WAS or wiskot-aldrich syndrome
Have low levels of __, normal levels of __, and ___, and increased levels of __
IgM; IgA and IgG; IgE
in wiskott-aldrich syndrome, there is as well an Abnormality of the integral membrane protein ___, which
is involved in the regulation of protein glycosylation.
CD43
Rare autosomal recessive
Ataxia Telangiectasia
is a rare autosomal
recessive/disorder in which it is also considered as a rare
childhood neurological disorder.
Ataxia Telangiectasia
degeneration in the part of the brain causing problms with the motor movements and speech
Ataxia Telangiectasia
Syndrome characterized by cerebellar ataxia and
telangiectasias, especially on the ___ and ___
earlobes and conjunctiva
___ are small, widened blood vessel on the skin
or or so called spider veins.
It can be seen
especially on the earlobes and conjunctiva.
Telangiectasia
spider veins are seen in
It can be seen
especially on the earlobes and conjunctiva.
Abnormal genes produce a combined defect of both
humoral and cellular immunity.
Ataxia Telangiectasia
describe the t cells of patients with ataxia telangectasias
Number of circulating T cells is often decreased
Defect in a gene that is apparently essential to the
recombination process for genes in the immunoglobulin
superfamily
ataxia telangectasias
Myeloproliferative disorder – consists of CML, MMM, PV, ET
CML MEANS
Chronic Myeloid Leukemia
Myeloproliferative disorder – consists of CML, MMM, PV, ET
\
MMM?
Myelofibrosis with Myeloid Metaplasia
pv means
Polycythemia Vera, an increase production of red
blood cells; it is also considered as a myeloproliferative
disorder.
ET means
Essential Thrombocytopenia, a decrease production
of the thrombocytes or platelets.
Classified as leukemia and lymphoma
Lymphoproliferative disorder
__
are malignant cells. They are primarily present in the bone
marrow and in the peripheral blood.
Leukemias
___ –
malignant cells din and it mainly arise in the lymphoid
tissue such as lmph nodes tonsils and splen
Lymphoma
They are considered biologically distinct and not classified
as either leukemia or lymphoma
Plasma Cell Dyscrasias/Disorder:
___is a premalignant condition, which is associated
as a Monoclonal Gammopathy of Undetermined
Significance (MGUS)
MGUS
SMM –
Smoldering Multiple Myeloma
LYMPHOMA is divded into
Hodgkin’s Lymphoma and Non-Hodgkin’s
Lymphoma.
he lymphomas can be divided into Hodgkin’s Lymphoma
and Non-Hodgkin’s Lymphoma.
Among the two, and pinaka
kilala dito would be the ____
kin’s Lymphoma
Highly treatable and often curable lymphoma that occurs both
in young adults and in the elderly.
Hodgkin’s Lymphoma
a lymphoma that is It is characterized by the presence of Reed Sternberg (RS) cells
in affected lymph nodes and lymphoid organs
Hodgkin’s Lymphoma
Though, itong RS cells ay pinagtalunan pa kung san ba
nanggagaling itong RS cells na ito. Through the different
studies, generally, nagmula itong ating RS cells in line with
a__
B cell lineage.
___ are typically large with a bilobed nucleus and two
prominent nucleoli.
RS cells
This gives the cell an owl’s eyes appearance.
Hodgkin’s Lymphoma
rs cells
__ seems to be the greatest risk for the
Non-Hodgkin’s Lymphoma.
Immunosuppression
__
Lymphoma has a wide range of neoplasm.
Non-Hodgkin’s
in non hodkins, Over ___ of the patients are greater than 60 years of age and the
incidence is greater in men compared with the women.
two-thirds
it has an increased risk also
for
some
autoimmune
diseases,
congenital
immunodeficiency disorders, organ transplantation, and
exposure to other infectious agents.
Non-Hodgkin’s Lymphoma
leukemia
AML
(* ALL
* CML
* CLL
AML (Acute Myeloid Leukemia)
* ALL (Acute Lymphocytic/Lymphoblastic Leukemia)
* CML (Chronic Myelogenous Leukemia)
* CLL (Chronic Lymphocytic Leukemia/Lymphoma)
classify leukemia based on
morphology and of course we should consider the
cytochemical staining
FAB Classification
morphology, cytochemical staining, genetic
characteristics, serological markers (CD markers).
WHO criteria
The World Health Organization (WHO) considered __ and ___a single disease with different clinical
presentations. They both reveal that they have the
capacity for the B cell marker.
CLL
and SLL
__ is a common hematopoietic malignancy that involves
the expansion of a clone of B cells that have the appearance
of small mature lymphocytes.
CLL
What are the B cell
marker that are mainly incorporated with the CLL and SLL? T
hey have both CD19, but weakly expression of
CD20.
CLL primarily occurs in patients over __years of age.
45
CLL is the Chronic Lymphocytic Leukemia. They have
revealed a B cell marker CD19, but weak expression of
CD20. Aside from having a small mature lymphocyte, CLL
is incorporated also in the __ cells
smudge
__ CELLS are remnants of cells that lack any identifiable
cytoplasmic membrane or nuclear structure. S
SMUDGE
Smudge cells, also
called ,
BASKET CELLS
are most often associated with
abnormally fragile lymphocytes in disorders such as chronic
lymphocytic leukemia (CLL).
Smudge cells
A rare, slowly progressive disease characterized by infiltration of
the bone marrow and spleen by leukemic cells, without
involvement of lymph nodes
HAIRY CELL LEUKEMIA
hairy cell leukemia is seen in individuakls over __ years of age
20
They often have irregular “hairy” cytoplasmic projections from
their surfaces.
HAIRY CELL LEUKEMIA
HAIRY CELL LEUKEMIA
The malignant cells strongly express B-cell markers
CD19,
CD20, and CD22.
May weaker expression ito for the CD20.
Includes
Multiple
myeloma
and
Waldenstrom
macroglobulinemia, MGUS and SMM.
PLASMA CELL DYSCARIAS
MGUS means
Monoclonal Gammopathy of Undetermined
Significance
SMM means
Smoldering Multiple Myeloma
These conditions are characterized by the overproduction of a
single immunoglobulin component called a myeloma protein (M
protein), or paraprotein, by a clone of plasma cells.
PLASMA CELL DYSCARIAS
these condition are characterized by a development of a
single immunoglobulin component and it is called as a
myeloma protein or M protein or paraprotein. It is by clone
of the plasma cells.
PLASMA CELL DYSCARIAS
The laboratory evaluation is an important factor in line with
the diagnosis and differentiation of this condition.
PLASMA CELL DYSCARIAS
Diagnosis and monitoring of the plasma cell dyscrasias
depend heavily on detecting and quantitating the __
M protein.
A malignancy of mature plasma cells that accounts for
about 10 percent of all hematologic cancers.
MULTIPLE MYELOMA
MULTIPLE MYELOMA
It is usually diagnosed in persons between ___
of age with a peak age of ____
40 and 70 years ; 67 years.
The American Cancer Society estimates there are about
__ new cases of multiple myeloma diagnosed each
year in the United States, along with about __ deaths
20,000; 11,000
Patients progress from asymptomatic MGUS to SMM to the
symptomatic disease multiple myeloma. ____% of people
with MGUS will progress to Multiple myeloma
20-25
Patients with multiple myeloma typically have excess
___ in the bone marrow, a monoclonal
immunoglobulin component in the plasma and/or urine, and
lytic bone lesions.
plasma cells
Malignant plasma cells phenotypically express
CD38,
CD56, and CD138.
A malignant proliferation of IgM-producing lymphocytes and
corresponds to lymphoplasmacytoid lymphoma as defined
by the WHO.
WALDENSTROM MACROGLOBULINEMIA
WALDENSTROM MACROGLOBULINEMIA
The median age of affected patients is ___
65 years
The etiology of this disease is unknown
WALDENSTROM MACROGLOBULINEMIA
Genetic factors are thought to be involved.
WALDENSTROM MACROGLOBULINEMIA
The monoclonal IgM can accumulate in any tissue, forming
deposits that lead to inflammation and tissue damage.
WALDENSTROM MACROGLOBULINEMIA
The median length of survival for patients with
Waldenström’s macroglobulinemia is longer than with
multiple myeloma—____
5 years versus 3 years.
20-30% of patient the IgM paraprotein behaves as
_____ - precipitate at cold temp. and can occludes
small vessels in the extremities in cold weather.
cryoglobulin
The laboratory is involved in three major ways in evaluating
lymphoproliferative disorders.
1st, it can assess the immunophenotype of
hematopoietic cells in the blood, bone marrow, or
lymphoid tissues by flow cytometry.
Done by
detecting the antigens on the surface of the cells that are characteristic of specific lineage and stage
of differentiation.
2nd, evaluating the amount and characteristics of
immunoglobulins.
3rd, genetic and chromosomal abnormalities
assessment.
Analysis of cell surface marker expression is commonly
used in the diagnosis and classification of leukemias and
lymphomas.
MMUNOTYPING BY FLOW CYTOMETRY
Samples of potentially neoplastic cells are incubated with
antibody preparations specific for relevant antigens.
IMMUNOTYPING BY FLOW CYTOMETRY
n a malignant disorder, the clonal
proliferation of transformed plasma cells leads to
overproduction of a single immunoglobulin.
monoclonal
gammopathy.
s a technique in which serum proteins are separated on the
basis of their size and electrical charge.
SERUM PROTEIN ELECTROPHORESIS
SPE results in four regions:
Albumin, and Alpha, Beta, and
gamma globulins.
