Fatima Gutierrez M.D.
 Learn
when to Suspect an Immune Deficiency
 Important Aspects of History Taking
 Physical Exam Clues
 Initial Laboratory Work-up
 When to get an Immune Consult
 Overview of Specialized Tests
8
or more new ear infections within one year
2
or more serious sinus infections within 1
year
 Two
or more months on antibiotics with little
effect
2
or more pneumonias within 1 year
 Failure
of an infant to gain weight or grow
normally
 Recurrent,
deep skin or or organ abscesses
 Persistent
thrush in mouth or elsewhere on
skin, after age 1
 Need
2
for IV antibiotics to clear infections
or more deep-seated infections
 Family
history of Primary Immunodeficiency

Sinusitis/Pneumonia




Low Antibody levels




CF
Allergic Rhinitis
Anatomy
Protein-losing
entropathy,
nephropathy
Severe eczema
Burns
2° Immunodeficiency



Malnourishment
Diabetes
Sickle Cell
 Primary
Immunodeficiencies Can Be
Categories by their Defect:

Cellular Immunity (T-Cells)

Humoral Immunity (B-Cell)

Phagocytes

Complement
Immunoglobulins
Plasma
cells
B-lymphocytes
Bone Marrow
Stem Cell
T- cells
 T-Cells
directly Attack Foreign Antigens
 Opportunistic

infections
Candida sp, Pneumocystis jiroveci
 Persistent
Thrush
 Diarrhea/Malabsorption
 Poor Growth/Failure to Thrive
 Unable
to make specific antibodies
 Multiple / Severe Bacterial Infections
 Persistent Upper Respiratory Tract Infections

Streptococcus, Haemophilis
 Usually
seen after 6 months when maternal
antibodies lost
 Growth usually normal unless patient with
chronic infections
 Natural
Killer Cells – directly attack cells
infected with Virus
 Phagocytes – ingest and kill microorganisms
 Chronic Granolomatous Disease –
- Infections caused by catalase + organisms
 LAD
No Pus
 Gingivitis/Periodontitis
 Skin Infections, Liver, GI Tract
 Composed
of 30 proteins
 Function in ordered integrated fashion to defend
against infection and produce inflammation
 C5- C8 deficiency associated with autoimmune
 C1-C4 deficiency



Associated with Rheumatic Disorders
Pyogenic Infections
C5-C9 Complement deficiency

Neiserria Infections
 Basic
Screen – CH50 – measures function of
alternate pathway

Immunodeficiency

Primary

1:500 – 1:100,000 - All




1:500 IgA def
1:100,000 SCID
1:200,000 CGD
Secondary

1:300 - HIV

1:5 “unaware” of their HIV
 History









Infection History
Sex
Consanguinity
History of Miscarriage/ Death in Infants
Primary Immune Deficiency in Family
History of Autoimmune/Connective Tissue d/o
Environment (Smoke, allergies)
Delayed Cord Separation (LAD)
HIV risk factors
 Eczema
, Wiskott Aldrich
or Hyper IgE?
 Wiskott Aldrich
Thrombocytopenia
 Small platelets

 Hyper
IgE -Job Syndrome
Skin infections – Staph
 Sinusitis
 Coarse Facies
 Retain Primary Teeth

Conical Teeth
Look at Mother
Incongentia Pigmenti
 Nuclear


X-Linked
Defect in Cellular Immunity






Factor – kB Essential Modulator
Variable Immunoglubulin levels
Normal B-cell numbers
Recurrent bacterial sinopulmonary and oportunistic
Infections
Ectodermal Dysplasia
Conical Teeth
Treatment Stem Cell Transplant
 Lymphocyte


Absolute Lymphocyte count
Lymphopenia


Screen for B and T cell Deficiencies
Lymphocytosis

Omenn Syndrome, Leukocyte Adhesion Deficiency
 Neutrophil

Count
Leukocyte Adhesion Deficiency - >100,000/mm3
 Platelet

count
Size and Number
Wiskott Aldrich
 WBC
total x %lymphocytes = Absolute
Lymphocyte Count (ALC)
 Normal
absolute lymphocyte count 10th90th percentiles (#/μL) by age



0-3months
6-12months
1-2 years
 Look
3400-7600
3900-9000
3600-8900
at normal values based on Age!!
 IgG,
IgM, IgA, IgE
 IgG in young infants less reliable –largely
maternal
 Lab Variations! Age Adjusted Normals
 Low IgG in Infant

Hypogammaglobulinemia of Infancy
 Undetectable

Primary Immune Deficiency
 High

IgA
Levels IgM + Absence of other Ig
Hyper IgM
 IgE

Atopic Disease or Parasitic Illness, Hyper IgE
Immunoglobulin Development
•IgG nadir for infants is age 3 months to 1 year of life
•Premature infants will lack adequate maternal IgG
•Note in IgG at approximately 6 months of life (maternal vs infant sources)
•IgM production starts immediately after birth
•IgA rate of synthesis is slowest
 THYMUS!
 May
No Thymus
shrink in
response to
stress/surgery/infe
ction
 Thymus continues
to grow until teens
 Largest size
relative to body
weight at birth
 T-cell
Response
 Common Antigens





Candida
Trychophyton
Tetanus
Diphtheria
PPD
 Anergy (no response)
 Immune suppr. Meds- Steroids
 Infants < 6 months / 2yrs
 Malnutrition
 Collagen Vascular Disease
 Fever- Leukocytosis
Reaction
measured at
48 hours
 HIV
– DNA when IgG unreliable
 ELISA



tests IgG
Infants have Maternal IgG
Severe Hypogammaglobulinemias
Liver Disease
 Guidelines
: www.aidsinfo.nih.gov
Measurement of
Specific T, B, NK
and phagocytic
cells
The Case of SCID
NK Cells
TcellsB-Cells
Tests your Body’s Ability to
Make Antibodies – Majority
of Vaccines activate Bcells in the presence of Tcell
Tests for Common Vaccines
Diphtheria
Tetanus
Streptococcus
Normal Response
Diphtheria > 0.1
Tetanus > 0.1
Or…
4 fold increase of baseline 1
month after vaccine given
Streptococcus – Note minimal
response
Serotypes in Prevnar:
4, 6B, 9V, 14, 18C, 19F, 23F
Serotypes in PCV13
Serotypes 1, 3, 4, 5,
6A, 6B, 7F, 9V, 14,
18C, 19A, 19F, 23F
Measures the ability of
lymphocytes to respond to
mitogens and Specific
antigens
Strongly Mitogenic on T-Cells
- PHA (Phytohemagluttin)
- ConA (Concanavalin-A)
Minimal Response
Assay working well
Stimulates T&B cells (Mitogen
- Pokeweed
Antigens:
- Candida
-Tetanus
- Dipthera
*Prior exposure required for
response !! > 2yrs age
 Early
Recognition of Primary Immune
Deficiency – Many Primary Immune
Deficiencies are Lethal!
 Recognize
 Don’t
Lab Value Diversity
forget to look for HIV






Noroski MD, L., Shearer MD, W. Short Screening for
Primary Immunodeficiencies in the Clinical
Immunology Laboratory. Clinical Immunology and
Immunopathology. Vol. 86, No3, March pp. 2237-245,
1998
Fleisher, Shearer, Kotzin, Schroder. Clinical
Immunology – Principles and Practice 2nd Ed. Rich, R.
Schmitz PhD, Folds PhD. Clinical and Laboratory
Assesment of Immunity. Journal of Allergy and
Immunology 2003: 111:S702-11
American Academy of Allergy Asthma and Immunology
– www. aaai.org
Immune Deficiency Foundation – primaryimmune.org
Jeffrey Modell Foundation www. jfmworld.org