SUBJECT:

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PEDIATRICS II
Pediatric Immunology
Celine Ng- Yapjuangco, MD, DPPS, DPSAAI
July 19, 2016

OUTLINE
Introduction
Recognition and Evaluation of Suspected
Immunodeficiency
Primary Defects of Antibody Production
Primary Defects of Cellular Immunity and
Combined Immune Deficiencies
Disorders of the Phagocyte Function
Disorders of the Complement System
Primary Defects of Innate Immunity
Eosinophilic Defects, Leukopenia, Leukocytosis
Quiz
Transers Message

RECOGNITION AND EVALUATION OF SUSPECTED

IMMUNODEFICIENCY
4 or more EAR infections within 1 year
2 or more serious sinus infections within 1 yr
2 or more months on antibiotics with little effect
2 or more pneumonias within 1 year
Failure to thrive
Recurrent deep skin or organ abscess
Persistent thrush in mouth/skin after age 1
Need for IV antibiotics to clear infections
2 or more deep seated infections (meningitis,
osteomyelitis, sepsis, cellulitis)
Family history of immunodeficiency

INTRODUCTION

th

Nelsons Pediatrics 20 ed.

When specific lymphocytes encounter antigens, the

lymphocytes may be activated, leading to immune
responses, or the cells may be inactivated or
eliminated, leading to tolerance
Page 1 of 12

Trans Group: Miranda, Negrillo, Nuez

Edited By:

NERVOUS SYSTEM
with
enterovirus
infection
o RESPIRATORY TRACT INFECTIONS:
Otitis Media, Pneumonia, Bronchitis and
Sinusitis mainly caused by encapsulated
bacteria (S.pneumoniae, H. influenzae)
o GASTROINTESTINAL INFECTIONS:
- Giardia lamblia
- Cryptosporidium spp.
NUMBER: Serum Immunoglobulin (IgA, IgM, IgG), B
cell enummeration
FUNCTION: Isohemagglutinins, Assessment of
antibody function following immunization with a
protein antigen, polysaccharide antigen
Isohemagglutinins: measures IgM function; the presence
and titer of isohemagglutinins, or natural antibodies to type A
and B red blood cell polysaccharide antigens. This test
measures predominantly IgM antibodies. Isohemagglutinins
may be absent normally in the 1st 2 yr of life and are always
absent if the patient is blood type AB.

th

Nelsons Pediatrics 20 ed.

PRIMARY DEFECTS OF ANTIBODY PRODUCTION

Distribution
of PID defects
Phagocyti
Complem
ent 5%
T cell
15%

c
15%

B
cell

B cell
T cell
Comple
ment

Answer: X-linked Agammaglobulinemia or Brutons disease:

B cells are primary cells of the adaptive immune

system
Mediate antibody production; therefore, play a role
in antibody-mediated humoral immunity
Defects relating to B-cell development and/or
maturation result in B-cell disorders.

(from Docs notes) Humoral Immunity: neutralization,

phagocytosis and activation of complement needed for
eliminating extracellular microbes and microbial toxins.
B-cell (antibody-deficiency) disorders are the most common
type of immunodeficiencies, accounting for 65% of all PID
diagnoses

CASE 1
One year and ten months old/M
o Repeated infections of upper and lower respiratory
tract since 6 months of age
o Pedigree analysis suggests: sex-linked recessive
inheritance
o Immunological studies:
panhypogammaglobulinemia, nearly total absence
of circulating B cells, negative isohemagglutinins
o Treatment: Intravenous immunoglobulins,
parenteral antibiotics for pneumonia and purulent
otitis media. He is currently on cotrimoxazole
prophylaxis and periodic intravenous
immunoglobulin infusion

o
o

rare humoral
immunodeficiency characterized by low/absent Ig
levels and B lymphocytes < 2%

Affected patients present after 6 months of age mainly

with increased susceptibility to bacterial infections
Page 2 of 12

PATHOPHYSIOLOGY: BRUTONS TYROSINE KINASE (BTK)

Clinical features of XLA

Kinase acts downstream of the preBCR and the BCR signaling complex
for B cell activation and maturation
Mutations result in a block of B cell
development in the bone marrow at
the pro-B to pre- B stage

Clinical symptoms initiate between the age of 6

and 12 months
Recurrent
bacterial
respiratory
and/or
gastrointestinal infections are the hallmark of
this disorder
Such infections are mainly caused by encapsulated
bacteria, namely Streptococcus pneumoniae, Haemophilus
influenzae, Staphylococcus aureus, and others. The most
frequent type of upper respiratory tract infection in large
cohorts of XLA patients is otitis media (70%), followed by
sinusitis (almost 60%). Pneumonia episodes are frequent
features of the clinical history leading to the diagnosis of XLA
(almost 60% of affected patients). The intrinsic B cell defect
that underlies XLA does not influence host defense against
viral infections, with certain exceptions. Affected patients are
particularly susceptible to enterovirus, namely poliovirus,
echovirus, and coxsackievirus.
Infections of the gastrointestinal tract are frequent in XLA
patients. Giardia lamblia is frequently isolated from stool
samples and eradication is frequently unsuccessful resulting in
chronic diarrhea and malabsorption. Campylobacter and
Helicobacter may also present with similar findings
butaccompanied by cutaneous manifestations.
DIAGNOSIS AND TREATMENT
Immunoglobulin replacement therapy
Dose: 400 mg/kg per dose every 3 to 4
weeks
It contains only IgG, secreted antibody
IgA is not replaceable
Frequent antibiotics for repeated infections
Gene therapy; complication is leukemia
The typical laboratory findings of XLA consist
of low to undetectable immunoglobulin
serum levels and the almost complete
absence of peripheral B cells (2% of
lymphocytes)
What is the clinical outcome of patients?
Invasive infections are rarely part of the clinical history
of XLA once early diagnosis is established and
appropriate treatment is initiated
Lung complications are becoming the main cause of
morbidity and mortality, and CLD is now considered
the major cause of death
Inability of immunoglobulin substitution to reach the
mucosal surface where it is expected to play a crucial
protective role, and the absence of the IgA at the mucosal
surfaces

Page 3 of 12

Autosomal Recessive Agammaglobulinemia

Pre-B cells express the pre-BCR, a receptor complex
formed by the heavy chain, VpreB, []5/14.1, Ig,
and Ig that initiates downstream signaling necessary
for B cell differentiation through kinases such as Btk
Mutations in the gene encoding for any of these
components lead to the absence of a functional preBCR complex, arresting B cell development in the
bone marrow at the pro-B to pre-B stage
CASE 2
14/F; A.I.
o Admitted for recurrent respiratory infections
o Born from first pregnancy via SVD, birth weight
3550g, Apgar 9,9
o Past Medical History: pre-school: mild upper
respiratory infections about 10 times a year,
bronchitis 3 times a year, tonsilitis twice a year,
otitis media once a year. Age of 11 chronic
cough. Age 12: hospitalized for pneumonia and
was treated with cefotaxime, clarithromycin. At
the same year, she was hospitalized again for
pneumonia and sinusitis. She was treated with
ceftriaxone and clarithromycin
o On admission: nasal obstruction, unpleasant smell
from mouth and intermittent abdominal pain
o Laboratories: Elevated CRP 2.8 mg/dl complete
blood count showed normal results. Other tests
liver and kidney functions were normal, no
electrolyte abnormalities. Urinalysis revealed no
infection. Abdominal ultrasound was normal. Chest
X-ray: bronchitis.
o Serum Immunoglobulin: significant decreased
levels of all isotypes in two repeated tests;
Antibodies titers after diphtheria and tetanus
immunization were low. The isohemagglutinins
were undetectable.
o Treatment: IVIG

Pathogenesis of CVID- B cell defects

Failure to produce post-germinal center B cells

due to various alterations during B cell
differentiation, leading to loss of plasma cells in
tissues and bone marrow
The severity of the block in forming isotype
switched B cells is reflected in increased
susceptibility to infections, reduced vaccination
responses, higher prevalence of secondary
complications
Clinical presentation

Answer: COMMON VARIABLE IMMUNODEFICIENCY

o Diagnostic Criteria

To verify loss of specific antibody response, re-vaccination

may be needed, with determination of antibody titers 4-6
weeks later

Pneumonia: S. pneumoniae, H. influenzae,

Mycoplasma sp
Other severe bacterial infections: sepsis,
meningitis, osteomyelitis with the same
organisms are less common
Other common presentation are
gastrointestinal infections leading to transient
or persistent diarrhea with G. lamblia

Page 4 of 12

TREATMENT OF CVID
IVIg: reduces the incidence of severe
bacterial infections
Antibiotics
COMPLICATIONS IN CVID

o
o

Autoimmune diseases and cancers are common

complications

CASE 3
6/M
o Third child of unrelated parents, no family history
suggestive X-linked immunodeficiency.
o (+) viral and bacterial vaccines without
complications
o Apparently well until the age of 6 months, when he
had pneumonia requiring hospitalization.
o During the age of 6 months to 1.5 years : 7 times
hospitalization for pneumonia (3 episodes), septic
arthritis (1 episode), urinary tract infection (1
episode), and febrile convulsion (2 episodes)
o Age of 1.5 years (+) pyogenic infection suspicious
of Pneumocystis carinii
o Growth and developmental assessment revealed
mild retardation
o Immunological investigation showed low serum
IgG and IgA accompanied by increased IgM

Mutation detection for CD40L gene showed

deficient results
Treatment: IVIG (400 mg/kg every 3 weeks), GSCF
(7g/kg/day for one month) and antibiotic
(cotrimoxazole ) were started .
The patient responded to the therapy with a
resolution of his infection and rising count of
neutrophils

Answer: CLASS SWITCH RECOMBINATION DEFECTS/ HYPER

IGM SYNDROME
o Rare primary immunodeficiencies with an
estimated frequency of around 1 in 500,000 births
o Elevated or normal serum IgM levels and low or
null serum levels of the switched isotypes (IgG, IgA,
and IgE)
o recurrent bacterial infections predominantly in the
respiratory tract
o Chronic infections of the digestive tract can result
in malabsorption and failure to thrive
o Complications: lymphadenopathy, autoimmunity,
cancer
o PATHOPHYSIOLOGY OF CSR-Defect/ Hyper IgM
Defective production of IgG, IgA, and IgE, and
normal IgM production, resulting from an
abnormal Class switch recombination, a
process is essential for antibody maturation.
Nave B cells exit from the bone marrow and
encounter antigens that they specifically
recognize through IgM isotype BCR and,
through an interaction with the follicular helper
T cells, proliferate vigorously and give rise to a
germinal center
This complex involve interaction through CD40L
and CD40 which leads to activation of several
pathways
This result in B cells undergo the two major
events (CSR and SHM) for antibody maturation
X-LINKED CD40 LIGAND DEFICIENCY
most common CSR-D; approx 50% of patients
harmful mutations in CD40L gene on the X
chromosome
DIAGNOSIS: male child with susceptibility to infection
by opportunistic pathogens, neutropenia
DEFINITIVE DIAGNOSIS: molecular confirmation of
mutations in CD40L gene
TREATMENT: IVIg, prophylaxis for P. jirovecii
infection, G-CSF for neutropenia, careful monitoring
of liver and biliary tract function; Stem cell transplant
only curative treatment
Prognosis is poor; main cause is severe infections
(early) and liver damage (late)
Defects in the CD40L/CD40 interaction prevent the
formation of germinal center in secondary lymphoid
organs and impair CSR and SHM
Page 5 of 12

ISOTYPE OR LIGHT CHAIN DEFICIENCIES

Characterized by aberrant serum Ig expression, but
do not always result in clinical symptoms

Frequency varies from extremely rare to most

common primary immunodeficiency (selective IgA
deficiency).

(3)Selective IgG subclass deficiency is defined as a

deficiency of one or more IgG subclasses but normal total IgG
concentrations. The usual criterion of an IgG subclass
deficiency is a level less than 2 SDs below the mean for age.
Most IgG subclass-deficient subjects are asymptomatic,
particularly those with an IgG4 deficiency. Thus, IgG subclass
deficiency does not define a disease; instead, it denotes a
clinical laboratory finding. A clinically significant IgG subclass
deficiency occurs when the IgG subclass deficiency is
associated with recurrent infection and a significant defect in
antibody responsiveness.
CASE 4
o 1/F
Apparently well with no known history of recurrent
infections and no family history of immunodeficiency
Admitted due to high fever for 4 days, vomiting, poor
activity and poor appetite
PE: lethargic but arousable. Vital signs: temperature
38.2C, pulse rate 155/min, respiratory rate 30/min,
and blood pressure 88/52 mm Hg. (+) tonsills and
palpable lymph nodes.
Labs:
CBC:
leukocytosis
with
neutrophilic
predominance. CRP and ESR were both elevated
Impression was sepsis, hence vancomycin and
meropenem started after septic work-up. On the
third hospital day, blood culture showed S. aureus
which was susceptible to oxacillin. CSF and urine

cultures were negative. Antibiotics were shifted to

oxacillin and gentamicin. There was persistent fever
and crying on neck movement with limitation. Hence
MRI of the cervical spine was done which showed
deep neck infection. Parenteral antibiotics were
administered for 21 days.
Immunologic studies showed normal results except
for decreased immunoglobulin G levels.
Under the initial impression of primary antibody
deficiency she received regular intravenous
immunoglobulins (IVIG) replacement therapy of 400
mg/kg every 4 weeks, starting at the age of 13
months.
There was gradual increase of IgG levels and IVIG was
discontinued at age 20 months and serum
immunoglobulin concentrations remained within the
normal range at follow-up 6 months later
After this episode, she had no recurrence of infection
during 2 years of follow-up
Due to sepsis of unknown origin and the isolation of a
relatively uncommon microbial organism for a patient of this
age
Answer: Transient Hypogammaglobulinemia of Infancy

Infants over 6 months of age whose IgG is

significantly lower (less than 2 standard deviations)
for age and is corrected by 24 months of age but may
persist for a few more years.
Starting at about the sixth month of pregnancy, the fetus
starts to receive maternal IgG antibody through the placenta.
This increases during the last trimester of pregnancy until at
term birth the baby has a level of IgG, equivalent to that of the
mother. The transplacental IgG slowly disappears from the
infants circulation and is essentially all gone by about 6
months of age. The baby, however, starts to make its own IgG
starting at birth and this increases gradually throughout the
first months of life. Between 3 and 6 months all infants have
low levels of IgG as a result of the maternal IgG falling and the
infants IgG just starting to be made. This low level is termed
physiologic hypogammaglobulinemia of infancy and is usually
not clinically significant.

Page 6 of 12

Suspected Diagnosis of THI

Male/Female age ranging 12 - 24 months

serum levels of IgG <2DS
exclusion of other hypogammaglobulinemia conditions

Normalization of IgG values

Definitive Diagnosis of THI

Clinical Manifestations of THI

Infections, especially bacterial infections are of greatest

concern in THI. A finding in THI is the high prevalence of atopic
disease, including asthma. There is almost no mention of
autoimmunity in the published literature on THI, the sole
exception being Moschese et al., who reported two cases of
neutropenia and one of autoimmune hemolytic anemia
MANAGEMENT
Directed toward two goals:
1. Insuring that hypogammaglobulinemia is transient:
repeat immunoglobulin determinations at
approximately 6-month intervals
2. Preventing and treating intercurrent infections or
other problems:
routine infection preventive measures and
treatment of intercurrent infections

PRIMARY DEFECTS OF CELLULAR IMMUNITY AND COMBINED

IMMUNE DEFICIENCIES
T Lymphocytes
o Essential component of adaptive Immunity
o Do not have adequate cellular immune
responses are prone to opportunistic
infections
o T-cell defects accounts for 5%
Through cytolytic activity and release of Th1 cytokines,
they mediate resistance to intracellular pathogens. In addition,
interaction of T cells with B lymphocytes and antigenpresenting cells on the one hand, and release of soluble
mediators is essential in order to mount T-dependent
antibody responses to soluble and particulate antigens, thus
contributing to defense against extracellular pathogens
Pure cellular defects without antibody defect, are less
common and make up approx 5% of the total. The two most
common
disorders
are
DiGeorge
anomaly
and
mucocutaneous candidiasis
Recognizing T cell immunodeficiency
o Organisms: fungal, protozoal, virus, gram
negative bacteria or mycobacteria
o Symptoms manifest in the first few months
of life
o Eczema, recurrent thrush, diarrhea, fatal
reaction to live virus, opportunistic
infections
o Work up
Number: Absolute Lymphocyte
Count, T cell enumeration
Function:
Delayed
Type
Hypersensitivity,
Lymphocyte
Proliferative Assay
CASE 1
The
Case
of
Elizabeth
Bennet:
Severe
Immunodeficiency as a Result of Disrupted
Development of the Thymus
o Dysmorphic facial features
o Truncus arteriosus s/p repair of cardiac
defect (no thymic tissue identified)
1
o Low blood levels of calcium- 6.2 mg dl
(normal 8.510.2 mg dl1)
o Normal karyotype
o fluorescence in situ hybridization (FISH):
deletion of chromosome 22q11.2

Page 7 of 12

Immune Evaluation
o Absolute lymphocyte count: 560 (low)
o CD3+ T cells: low
o B-cell numbers and CD16+/CD56+ NK cells:
normal

DIGEORGE SYNDROME
Conotruncal cardiac anomaly, hypocalcemic tetany,
unusual facies, hypoplastic thymus glands
Chromosome 22q11.2 deletion: most common cause
Velocardiofacial (Shprintzen) syndrome: mild form
that do not carry the syndromic diagnosis
Chromosomal Abnormalities

TBX1 is one of the more than 35 genes located at

chromosome 22q11.2. Deletion of this region in one of the
two chromosomes 22 is the most common cytogenetic
abnormality associated with DiGeorge syndrome. Tbx1 has
a central role in the development of the pharyngeal
apparatus and its derivates, including the thymus, the
parathyroid glands and some tissues of the developing
heart
Clinical Manifestations:
Cardiac anomaly 49-83%
o TOF 20%
o IAA 15%
o Truncus arteriosus 8%
Palatal anomaly 69-100%
Hypocalcemia 17-60%
Speech delay 75%
Renal anomaly 36-37%
Skeletal anomaly 17-19%
Immunodeficiency 60-77%
Diagnosis
Established by FISH
An infant suspected of having DGS should have an
immediate cardiac evaluation, calcium and phosphorus levels,
and parathyroid hormone assays. CBC also should be done
indicate lymphopenia. FISH studies for chromosome 22q11
deletion should be done, if negative a karyotype examination
for other chromosomal abnormalities is recommended.
Treatment
Antibiotic prophylaxis
IVIG

Bone marrow or peripheral blood lymphocyte

transplantation
Children with markedly diminished CD4 T cells should be
given PCP prophylaxis
Hypogammaglobulinemia is severe or is accompanied by
defect in antibody function
Provide mature T cells rather than HSC. These latter cells,
lacking thymic tissue, are unable to mature appropiately. Only
sibling matched transplants are attempted in this setting. It
has an excellent record of success and nearly immediate
appearance of functional T cells.
CASE 2: I CURED MY CANDIDA, JUST NOT YET
12/M
7 years old admitted due to Candida skin infection
Five years later readmitted for facial skin lesions and
eye infection
Recurrent respiratory tract infections and recurrent
mucous membrane lesions treated with topical
antifungal agents and fluconazole OPD
(+) Diabetes Mellitus and Hypothyroidism
CHRONIC MUCOCUTANEOUS CANDIDIASIS
Recurrent infections of the skin, nails, and mucous
membranes caused by Candida, most cases Candida
albicans
Responds to adequate treatment with antifungal
drugs, but candida of mucous membranes, skin and
nails recurs soon after antifungal therapy is
discontinued.
Treatments:
Thymus transplantation
Antifungal Drugs
Mycostatin: used initially. Because Mycostatin is not
absorbed, very safe but usually of limited efficacy in CMC
Oral systemic antifungal drugs: mainstay of CMC therapy.
Most owe antifungal activity to inhibition of synthesis of
ergosterol, main sterol in fungal cell membranes
SEVERE COMBINED IMMUNE DEFICIENCY (SCID)
Results from mutations in any 1 of at least 13 known
genes that encode components of the immune
system crucial for lymphoid cell development
All patients with SCID have very small thymuses
containing no thymocytes
Both the follicular and paracortical areas of the
spleen are depleted of lymphocytes.
Lymph nodes, tonsils, adenoids, and Peyer patches
are absent or extremely underdeveloped
Clinical Manifestations and Treatment
Presents within the 1st few months of life with
recurrent or persistent diarrhea, pneumonia, otitis
media, sepsis, and cutaneous infections
Persistent infections with opportunistic organisms
Page 8 of 12

Inability to reject foreign tissue and risk for severe or

fatal graft-versus- host disease
profound T-cell lymphopenia, absence of lymphocyte
proliferative responses to mitogens, antigens
Serum immunoglobulin concentrations are low or
absent, and no antibodies are formed after
immunizations
Pediatric Emergency and stem cell transplantation or
gene therapy should be done. Death usually occurs
during the 1st year of life and almost invariably
before 2 years of age

WISCOTT- ALDRICH SYNDROME (WAS)

X-linked recessive syndrome
Defective WASP gene
Atopic dermatitis, thrombocytopenic purpura with
normal-appearing
megakaryocytes
but
small
defective platelets, and undue susceptibility to
infection
Impaired
humoral
immune
response
to
polysaccharide antigens
Treatment:
Good supportive care includes
appropriate nutrition, routine IVIG, use of killed
vaccines, aggressive management of eczema and
associated cutaneous infections, platelet transfusion
for serious bleeding episodes
Bone marrow or cord blood transplantation is the
treatment of choice and is usually curative.
DISORDERS OF THE PHAGOCYTE FUNCTION
CHRONIC GRANULOMATOUS DISEASE
2 y/o boy, born of a non-consanguinous marriage
Recurrent raised multiple lesions on face, neck and
flexural areas since 2 months old
Nodules gradually enlarge to form large
granulomatous masses
Recurrent fever, respiratory tract infection and
pyoderma
Given multiple courses of antibiotic and TB drugs with
no resolution
NBT test revealed inability to oxidize NBT into blue
formazan
Recurrent life threatening infection with bacteria and
fungi and chronic inflammation with dysregulated
granuloma formation
Hallmark is recurrent infections in the skin, lungs and
gut
The basic defect lies in NADPH oxidase enzyme,
resulting in:
o failure of neutrophils and monocytes to
produce superoxide (O2-.) when stimulated
upon encountering
bacterial or fungal
pathogens, or a variety of soluble
inflammatory stimuli
o

Diagnosis
Nitroblue tetrazolium (NBT)
Assays that rely on superoxide production
NBT is the oldest and most recognized diagnostic test for
CGD, but it relies qualitative determination of NADPH oxidase.
It is read manually to distinguish reducing (blue-black insoluble
formazan precipitate) from non-reducing (unstained) cells
activity
The direct measurement of superoxide production DHR
ability to distinguish XL from Autosomal forms by flow
cytometry
Carriers give a characteristic mosaic pattern on oxidative
testing

Presence of myeloperoxidase is also necessary for

neutrophils to generate superoxide; myeloperoxidase
deficiency can therefore lead to abnormal DHR assay results
OTHER
TESTS:
ferricytochrome,
c
reduction,
chemiluminescece
Labs: mild to mod leucocytosis with immature forms in the
presence of infection with bacteria or nocardia, fungal
typically silent from lab standpoint; ESR and CRP elevated, Igs
are elevated and antibody titers are N, T cells are N
Treatment
Hematopoietic stem cell transplantation (HSCT) is the
only known cure for CGD
LEUKOCYTE ADHESION DEFICIENCY
impaired step in the inflammatory process: the
emigration of leukocytes from the blood vessels to
sites of infection requiring adhesion of leukocytes to
the endothelium
LAD I: structural defects in the integrin molecule,
preventing a firm adhesion to occur.
LAD II: GDP-fucose transporter defect that leads to
absence of the selectin ligand on the leukocyte and a
defective rolling
LAD III or LADI variant is due to defects in the integrin
activation process

Page 9 of 12

Leukocyte Adhesion Deficiency -1

Presents with severe infections, impaired pus
formation and impaired wound healing; delayed
umbilical cord separation more than 30 days;
omphalitis persistent leucocytosis (>15k) in the
absence of overt and active infection; gingivitis with
periodontitis and associated tooth loss and alveolar
bone resorption
Pathogenesis
o Defect in B2 integrins
Diagnosis
o Flow cytometry analysis of LAD 1 blood
samples
Treatment
o early and aggressive treatment with
antibiotics
o BM transplant is the definitive corrective
treatment
Viral infections are not a major problem in LAD
Scars end to acquire a cigarette-paper appearance
Each B2 integrins is a heterodimer composed of an A chain
(CD11a, CD11b or CD11c) non-covalently linked to a common
B2 subunit (CD18)
Leukocyte Adhesion Deficiency 2
Pathogenesis
o Selectins are adhesive molecules that
mediate the initial rolling of neutrophils and
monocytes over the endothelium resulting in
defective leukocyte migration to sites of
infection
Clinical Features
o Increased
infection
susceptibility,
leucocytosis and poor pus formation. Severe
mental retardation, short stature, distinctive
facies and Bombay blood phenotype are part
of the system
Treatment
o Oral fucose reported a significant reduction
in infectious episode and neutrophil baseline
counts
and
improved
psychomotor
capabilities
Again, viral infections are not a major problem in LAD
DISORDERS OF THE COMPLEMENT SYSTEM
Complement System
Serum and cell surface proteins that interact with one
another and other molecules of the immune system
in a regulated manner to generate products able to
eliminate microbes.
Complement Proteins
plasma proteins normally inactive; but are activated
by microbes and antibodies attached to other
antigens
Activation of complement leads to sequential proteolysis of

proteins to generate enzyme complexes with proteolytic

activity, zymogens

PRIMARY DEFECTS OF INNATE IMMUNITY

HYPER IgE SYNDROME
IL-17 deficiency may account for susceptibility to
Candida infection
IL-17 is a cytokine that acts on monocytes to induce
secretion of proinflammatory mediators
Recurrent severe staphylococcal abscesses of the
skin, lungs, and other sites, pneumatoceles,
osteopenia, and unusual facial features
Coarse facial features, including a prominent
forehead, deep-set wide-spaced eyes, a broad nasal
bridge, a wide fleshy nasal tip
Markedly elevated levels of serum IgE
Autosomal Dominant: most common form
EOSINOPHILIA, LEUKOPENIA, LEUKOCYTOSIS
EOSINOPHILIA
The absolute eosinophil count (AEC) is used to
quantify eosinophilia
Calculated as the white blood cell count/L percent
of eosinophils: <450 cells/L
Varies diurnally, with eosinophil numbers higher in
the early morning and diminishing as endogenous
glucocorticoid levels rise.
Diseases such as allergic, infectious, hematologic,
autoimmune, or idiopathic origins are associated with
moderate (AEC 1,500-5,000 cells/L) or severe (AEC
Page 10 of 12

>5,000 cells/L) eosinophilia in peripheral blood

Prolonged eosinophilia is associated with end-organ
damage, especially involving the heart
Allergic Diseases: patients with allergic asthma commonly
have eosinophils in the blood, sputum, and/or lung tissue.
Hypersensitivity drug reactions can elicit eosinophilia, and
when associated with organ dysfunction (e.g., DRESS [drug
rash with eosinophilia and systemic symptoms]), various skin
diseases have also been associated with eosinophilia, including
atopic dermatitis/eczema, pemphigus, urticaria, and toxic
epidermal necrolysis. Eosinophilic gastrointestinal diseases are
important emerging allergic causes of eosinophilia
Infection: helminthic parasites such as Giardia lamblia and
Enterobius vermicularis

HYPEREOSINOPHILIC SYNDROME
3 diagnostic criteria
o AEC >1,500 cells/L persisting for 6 months
or longer or at least on 2 occasions or with
evidence of tissue eosinophilia;
o absence of another diagnosis to explain the
eosinophilia
o signs and symptoms of organ involvement
Clinical signs and symptoms of hypereosinophilic
syndrome can be heterogeneous because and
involves diverse organ system
NEUTROPENIA
Leukopenia refers to an abnormally low number of
white blood cells (WBCs) in the circulating blood
secondary to a paucity of lymphocytes, granulocytes
or both
Decrease in the absolute number of circulating
segmented neutrophils and bands in the peripheral
blood
The absolute neutrophil count (ANC) is determined by
multiplying the total WBC count by the percentage of
segmented neutrophils plus bands
Acute neutropenia: result of rapid neutrophil use
and/or compromised neutrophil production
Chronic neutropenia: lasts longer than 3 months and
arises from reduced production, increased
destruction or excessive splenic sequestration of
neutrophils
The etiology of neutropenia can be classified as either
an acquired disorder or extrinsic insult, or, more
rarely, an inherited, intrinsic defect

LEUKOCYTOSIS
Elevation in the total leukocyte or white blood cell
(WBC) count that is 2 SD above the mean count for a
particular age
WBC count exceeding 50,000/L is termed a
leukemoid reaction which is most frequently
associated with septicemia and severe bacterial
infections

A proportion of immature neutrophil cells >5%,

termed a left shift, indicates rapid release of cells
from the bone marrow, primarily of band forms
Higher degrees of left shift with more immature
neutrophil precursors are indicative of serious
bacterial infections and may occasionally be
encountered with trauma, burns, surgery, acute
hemolysis, or hemorrhage.
Because of the similarity to some features of leukemia.
Leukemoid reactions are usually neutrophilic, and unlike true
leukemia, show only small proportions of immature myeloid
cells

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d. Delayed separation of umbilical cord

What does leukemoid reaction signify
a. Severe bacterial reaction
b. Allergies
c. Malignancy
d. Immunodeficiency
8. What is the defect in DiGeorge Syndrome that causes
immunodeficiency?
a. Thymus gland aplasia
b. Parathyroid gland aplasia
c. Congenital heart disease
d. None of the above
9. What organism causes eosinophilia?
a. Helminthic parasites
b. Neisserial infection
c. E. coli
d. All of the above
10. In X- linked aggamaglobulinemia, what gene is the
defect?
a. BTK gene
b. XLA gene
c. Both
d. Neither
7.

1.

2.

3.

4.

5.

6.

QUIZ
The most common presenting symptom in CGD
a. Cellulitis
b. Pneumonia
c. Abscess
d. Osteomyelitis
Which among the immune system is affected in a
child presenting with recurrent sinopulmonary
infection?
a. B cell
b. T cell
c. Phagocytic
d. Complement
FALSE about LAD
a. LAD I: defect in integrin molecule
b. LAD II: GDP-fucose transporter defect
c. delayed umbilical cord separation more
than 30 days
d. elevated lymphocyte count
Which among of the immune system is affected in a
child who have recurrent infection at 3 months and
infected with viral and unusual pathogens
a. B cell
b. T cell
c. Phagocytic
d. Complement
Which organism is usually involved in complement
deficiency
a. S. aureus
b. K. pneumonia
c. Candida
d. Neisseria
Which among is not included in the 10 warning signs
of immunodeficiency
a. 2 pneumonias in a year
b. Failure to thrive
c. Family history of immunodeficiency

TRANSERS MESSAGE

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