Immune DO Flashcards
Common Organisms for B cell deficiency
Recurrent bacterial: streptococci, staphylococci, Haemophilus, Campylobacter;
Viral:enteroviruses;
Uncommon: giardia, cryptosporidia
Common Organisms for T cell deficiency
Opportunistic organisms: CMV, EBV, varicella, Candida,
Pneumocystis jiroveci, mycobacteriwa
Common Organisms for Complement deficiency
Pneumococci, Neisseria
Common Organisms for neutrophil deficiency
Bacteria: Staphylococci, Pseudomonas, Serratia, Klebsiella, Salmonella;
Fungi: Candida, Aspergillus
Age onset
B-Cell
T-Cell
Complement
Neutrophil
5-7 months of age or later childhood to adult
Usually 2-6 months of age
Any age
Early onset
Types of infections wth
B-Cell deficiency
Most are recurrent sinopulmonary infections and recurrent
enteroviral meningitis
Types of infections wth
T Cell deficiency
Mucocutaneous candidiasis; pulmonary and GI infections
Types of infections wth
Complement deficiency
Meningitis, arthritis, septicemia, recurrent sinopulmonary
infections
Types of infections wth
Neutrophil deficiency
Skin abscesses, impetigo, cellulitis, suppurative adenitis,
gingivitis, oral ulcers, osteomyelitis, internal organ abscesses
Other findings with:
B-Cell deficiency
Autoimmunity, lymphoreticular malignancy
Other findings with:
T-Cell deficiency
Chronic diarrhea and failure-to-thrive;
postvaccination dissemination - varicella, BCG;
hypocalcemia in infancy;
graft-versushost from transplacental maternal engraftment or nonirradiated blood
Other findings with:
Complement deficiency
Autoimmune disorders, vasculitis, glomerulonephritis,
angioedema
Other findings with:
Neutrophil deficiency
Prolonged attachment of umbilical cord, poor wound healing, decreased signs of infection
Best initial test
B-Cell deficiency
Screen with IgA→if low, measure IgG and IgM (quantitative
immunoglobulins
Best initial test
T-Cell deficiency
Lymphocyte count (low)
Best initial test complement deficiency
Screen is total hemolytic complement (CH50)—will be
depressed if any component is consumed
Best initial test neutrophil deficiency
Neutrophil count
Best cost-effective test for T-cell function –
Candida skin test
Complemend deficiency
all are autosomal except for _______
properdin deficiency (X-linked
Neutrophil respiratory burst after phorbol ester stimulation;
most reliable now uses_________
rhodamine fluorescence (replaced the NBT test
Specific test
B-Cell deficiency
Enumerate B-cells with flow cytometry (monoclonal antibodies to B-cell-specific CD antigens): B cell absent or
present and number
Specific tests:
T cell deficiency
Flow cytometry using monoclonal antibodies recognizing
T-cell CD antigens (phytahemmaglutinin,
concanavalin A, pokeweed mitogen
profound defect in B-cell development
which leads to an absence of circulating B cells and thus leads to severe hypogammaglobulinemia
with small-to-absent tonsils and no palpable lymph nodes
X-linked (Bruton) agammaglobulinemia
> 500 known mutations of the _______ which is necessary for pre-B-cell expansion and maturation; long arm of X-chromosome
Btk gene (Bruton tyrosine kinase),
Findings for X-linked (Bruton) agammaglobulinemia
boys with pyogenic sinopulmonary infections
X-linked (Bruton) agammaglobulinemia Tx
appropriate use of antibiotics + regular monthly IVIG
The only 2 B-cell defects for which stem cell transplantation is recommended are
________ and ______
CD40 ligand defect (extremely rare; one of the known mutations on the X-chromosome for
hyper IGM syndrome) and X-linked lymphoproliferative disease
Common Variable Immunodeficiency (CVID) is _____________
hypogammaglobulinemia with phenotypically
normal B-cells;
What is the problem with CVID
Common Variable Immunodeficiency (CVID) is hypogammaglobulinemia with phenotypically
normal B-cells;
CVID
clinical presentation + serum IG and antibody deficiencies as profound or less than in XLA; normal sized lymphoid tissue; later autoimmune disease and malignancy __________
(lymphoma
Whast is the Tx of CVID
therapy consists of the one IG preparation available that contains no IgA.
__________ is the most common immunodeficiency. It is caused by the absence or near absence of serum and secretory IgA with phenotypically normal B-cells
Selective IgA deficiency
Selective IgA deficiency
Clinical findings: same bacteria as others with most infections in respiratory, GI and urogenital tracts;_________ is common
giardiasis
serum antibodies to IgA can cause severe _______ if any blood product with IgA is administered (NOT a transfusion reaction)
anaphylactic reactions
Tx of IgA Def
Treatment: IVIG is not indicated (95−99% is IgG) because if usual IVIG (containing IgA) product is given, patients are at risk for severe reaction. Additionally, because it is specifically an IgA deficiency, the IVIG product with the IgA removed cannot be used. Treat the infections (generally milder).
________is thymic and parathyroid hypoplasia to aplasia from dysmorphogenesis of the 3rd and 4th pharyngeal pouches
DiGeorge syndrome
Other structures involved in Di Georg
great vessel anomalies (right-sided aortic arch, interrupted aortic arch), esophageal atresia, bifid uvula, congenital heart disease (conotruncal malformations, septal defects), facial dysmorphism (short philtrum, thin
upper lip, hypertelorism, mandibular hypoplasia, low-set, often notched ears), and cleft palate
What is the CATCH 22 syndrome
Cardiac, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia); partial DiGeorge is more common, with
variable thymic and parathyroid hypoplasia.
About 1/3 with complete DiGeorge have the ____
CHARGE association.
Initial presentation of Di George is?
neonatal hypocalcemic seizures
Tx of Di Georg
complete form correctable with either culture unrelated thymic tissue transplants or bone marrow or peripheral blood transplantation from HLA-identical
sibling
_________ is the absence of all adaptive immune function, and in some, natural killer cells due to diverse mutations. It is the most severe immunodeficiency
known
Severe Combined Immunodeficiency (SCID)
Clinical findings associated with SCID
first 1-3 months of life with recurrent/persistent diarrhea and
opportunistic infections that may lead to death;
Pts with SCID
also at risk for graft-versus-host disease from ________that crossed the placenta in
utero
maternal immunocompetent T-cells
the presence of low but not absent T-cell function and low
but not absent antibodies; patients survive longer but have failure-to-thrive and still die relatively
early in life
Combined immunodeficiency
_________ is an impaired humoral immune response and highly variable concentrations of the IGs with moderately reduced T-cells and variable mitogen responses.
Wiskott-Aldrich Syndrome
Clinical findings of WAS
(1) thrombocytopenia presenting in neonatal period
(2) atopic dermatitis, and
(3) recurrent infections in first year of life
Dx of WAS
most common IG pattern is low IgM,
high IgA and IgE and normal to slightly low IgG and variably reduced T-cells.
WAS
Rare survival beyond adolescence (bleeding, infections and EBV associated malignancies and autoimmune complications) without a _______
bone marrow
transplant
______ is a moderately depressed response to T and B-cell mitogens, moderately reduced CD3 and CD4 T-cells with normal or increased percentages of CD8, T-helper cell and intrinsic B-cell defects, and hypoplastic thymus
Ataxia-telangiectasia
Mutation of AT
AT mutation (ATM) at 11.22-23
AT
(1) ataxia evident with onset of walking and progresses until
age______ when confined to a wheelchair
(2) ______ develop at 3-6 years of age and
(3) recurrent sinopulmonary infections most with
common viruses and occasional fatal _____
10-12 years
oculocutaneous telangiectasias
varicella
___________ is a rare disorder of leukocyte function causing recurrent bacterial and fungal infections and decreased inflammatory responses in the presence of neutrophilia (increased counts
Leukocyte adhesion deficiency
MC infections associated with Leukocyte Adhesion Deficiency
most common organisms are S. aureus, gram-negatives and Candida and Aspergillus
Leukocyte Adhesion Deficiency Dx
paucity of neutrophils in affected tissue but circulating neutrophil count is significantly elevated
Tx of Leukocyte Adhesion Def
early allogenic stem-cell transplantation for severe forms otherwise supportive care
_________is when neutrophils and monocytes phagocytize but cannot kill catalase-positive microorganisms as a result of a defect in production of oxidative metabolites
Chronic granulomatous disease (CGD)
- Autosomal recessive
* Abnormal secretory/storage granules lead to large and irregular seen in neutrophils
Chediak-Higashi Syndrome
Associations of Chediak-Higashi Syndrome
Oculocutaneous albinism from birth, prolonged bleeding time, peripheral neuropathy, recurrent infections
All components are autosomal recessive or co-dominant, except for ______ which is X-linked recessive
properdin deficiency
Decrease in both _____ and ____suggests activation of the alternative pathway; this is most useful in distinguishing nephritis secondary to immune complex deposition
from that due to nephritic factor
C3 and C4
Results of Defect in complement function
recurrent angioedema, autoimmune disease,
chronic nephritis, HUS, recurrent pyogenic infections, disseminated meningococcal or gonococcal infections or a second episode of bacteremia at any age; high
incidence of pneumococcal and meningococcal infections
Major cause of morbidity and mortality after allogenic stem cell transplantation
Graft-Versus-Host Disease (GVHD)
__________ 2-5 weeks post-transplant; erythematous maculopapular rash, persistent anorexia, vomiting and/or diarrhea and abnormal liver enzymes and LFTs;
Acute GVHD:
primary prevention of GVHD is with ________
post-transplant immunosuppressive drugs and corticosteroids
_______develops or persists >3 months after transplant; major cause of non-relapse morbidity and mortality in long-term transplant survivors
Chronic GVHD:
