A medical student is presented with a case involving recurrent infections in a child. To determine the likely cause, the student must use an ABCD approach: (1) note the types of infections; (2) identify the deficient immune component based on infection patterns; (3) classify the condition into one of the main immunodeficiency groups; and (4) differentiate it from similar conditions. Key facts to remember include distinguishing features of specific immunodeficiencies like SCID versus DiGeorge syndrome, inheritance patterns of conditions like Chediak-Higashi, and organisms associated with different immune defects.

1. Approaching & Contrasting
Immunodeficiencies
Gazi Rashid, M4

2. 1. List as many immunodeficiencies as you can
•Deficiency of T-Cells
•Deficiency of Humoral
•Deficiency of Both
•Defect in Phagocytosis
• Chediak-Higashi
• Chronic Granulomatous Disease
• Leukocyte Adhesion Deficiency
• DiGeorge Syndrome
• Hyper IgE syndrome (Job Syndrome)
• CVID
• Ataxia-Telangiectasia
• Hyper-IgM syndrome
• Bruton’s Agammaglobulinemia
• SCID
• Wiscott-Aldrich

3. The 4 Groups
• Deficiency of phagocytosis
• Chediak Higashi
• Chronic Granulomatous Disease
• Leukocyte Adhesion Difficulty
• Cellular Deficiency
• DiGeorge Syndrome
• Hyper-IgE Syndrome
• Deficiency of Humoral
• Common Variable
Immunodeficiency
• Selective IgA
• Bruton X-Linked
• Deficiency of Cellular & Humoral
• Severe Combined
Immunodeficiency
• Hyper-IgM syndrome
• Ataxia-Telangiectasias
• Wiscott-Aldrich

8. Objectives
1) Go over ABCD approach to immunodeficiencies
2) Review 4 very generic rules for roles of the immune system
3) Use rules & practice ABCD approach in 4 Qs
4) Take away 5 key facts to differentiate immunodeficiencies

9. • A: A ______ infection occurs in a pt…
• B: Because of a problem with ____... (rules)
• C: Collectively, this dz could be …. (groups)
• DEF: Differentiate with Everything else & FHx (facts)
Approach

10. 4 Generic Rules
•Problem with T cells  fungal, viral infections (local Candida)
•Problem with Phagocytosis  skin inf, abscesses
(bloodstream Candida)
•Problem with B cells bacterial (Sinus, OM, PNA) infections
• Deficiency of IgA  mucus membranes (sinus, GI) infections

16. Q1
A 2-year-old has a history of
recurrent Pseudomonas otitis
media and oral Candida infections.
Laboratory analysis reveals no
electrolyte abnormalities.
Examination of his serum shows
decreased levels of IgG and CT
scan reveals the absence of a
thymus. The child likely has:

17. Q1
• An infection of…
• Pseudomonas, OM  bacteria
• Candida, mucosal  fungal
• Because of problems with…
• Humoral immunity
• Cellular immunity
• Collectively due to…
• Something that affects B & T cells
• Differentiate with…
• Lack of thymus
• No electrolyte abnormalities
A 2-year-old has a history of
recurrent Pseudomonas otitis
media and oral Candida infections.
Laboratory analysis reveals no
electrolyte abnormalities.
Examination of his serum shows
decreased levels of IgG and CT
scan reveals the absence of a
thymus. The child likely has:

18. Q1 - IgA
A 2-year-old has a history of recurrent
Pseudomonas otitis media and oral
Candida infections. Laboratory analysis
reveals no electrolyte abnormalities.
Examination of his serum shows
decreased levels of IgG and CT scan
reveals the absence of a thymus. The
child likely has:
A) Severe Combined
Immunodeficiency
B) Bruton X-linked
agammaglobulinemia
C) DiGeorge Syndrome
D) Selective IgA deficiency
E) Common Variable
Immunodeficiency
(Both)
B cell)
(T cell)
(B cell)
(B cell)

20. Q1
• SCID vs. DiGeorge Syndrome

21. Q2
A 7-year-old boy presents to his
pediatrician for a routine visit. He states
that he has been in good health with the
exception of repeated staphylococcal skin
infections. On exam, the pediatrician
observes the findings demonstrated in
Figure A, as well as numbness. The
pediatrician subsequently order a
peripheral blood smear which is
demonstrated in Figure B. Which of the
following is the most likely mode of
inheritance of this patient's condition?

22. Q2
A 7-year-old boy presents to his
pediatrician for a routine visit. He states
that he has been in good health with the
exception of repeated staphylococcal skin
infections. On exam, the pediatrician
observes the findings demonstrated in
Figure A, as well as numbness. The
pediatrician subsequently order a
peripheral blood smear which is
demonstrated in Figure B. Which of the
following is the most likely mode of
inheritance of this patient's condition?
• An infection of
• The skin, Staph
• No other
• Because of deficiencies in
• Phagocytosis
• Collectively this could be
• Chediak-Higashi
• CGD
• LAD
• Differentiate with
• Numbness, albinism, blood smear

23. Q2
A) Autosomal dominant
B) X-Linked recessive
C) X-Linked dominant
D) Autosomal recessive
E) Mitochondrial
A 7-year-old boy presents to his
pediatrician for a routine visit. He states
that he has been in good health with the
exception of repeated staphylococcal skin
infections. On exam, the pediatrician
observes the findings demonstrated in
Figure A, as well as numbness. The
pediatrician subsequently order a
peripheral blood smear which is
demonstrated in Figure B. Which of the
following is the most likely mode of
inheritance of this patient's condition?

24. Q4
• Microtubule problems  weird presentations
• – microtubule dysfx (granules, albinism, neuropathy)
Can’t
Move
or Combine
Phagosomes &
Lysosomes
Neurotransmitters
Melanin

26. XLR - Be Wise Fool's GOLD Holds Asinine HOpe
• Bruton's agammaglobulinemia
• Wiskott-Aldrich
• Fabry's
• G6PD def
• Ocular albinism
• Lesch-Nyhan
• Duchene (DMD, BMD)
• Hunter Syndrome
• Alport
• Hemophilia A, B

27. Q3
• A) Abnormally low B cells
• B) Abnormally low T cells
• C) Abnormally high B cells
• D) Abnormally high T cells
• E) Elevated Ig levels
You are seeing a 4-year-old boy in
clinic who is presenting with concern
for a primary immune deficiency. He
has an unremarkable birth history,
but since the age of 6 months he has
had recurrent otitis media, bacterial
pneumonia, as well as two episodes
of sinusitis, and four episodes of
conjunctivitis. He has a maternal
uncle who died H. influenza
pneumonia. If you drew blood work
for diagnostic testing, which of the
following would you expect to find?

28. Q3 - Bruton
• An infection of…
• Bacterial PNA
• Recurrent otitis media
• Sinusitis
• Because of problem with
• Ig deficiency
• B cell deficiency
• Collectively this could be…
• Humoral immunodeficiency
• Differentiate with
• Maternal uncle, FHx…
You are seeing a 4-year-old boy in
clinic who is presenting with concern
for a primary immune deficiency. He
has an unremarkable birth history,
but since the age of 6 months he has
had recurrent otitis media, bacterial
pneumonia, as well as two episodes
of sinusitis, and four episodes of
conjunctivitis. He has a maternal
uncle who died H. influenza
pneumonia. If you drew blood work
for diagnostic testing, which of the
following would you expect to find?

29. B cells

30. Q5
A 5-year-old boy is admitted to the hospital
because of a 1-week history of fever and
increasingly severe abdominal discomfort. At
the age of 7 months, he was treated for
osteomyelitis caused by Aspergillus
fumigatus. He has been to the hospital three
times in the past 4 years for severe
pneumonias and skin abscesses. Abdominal
ultrasound shows an intrahepatic abscess
that, when cultured, grows Staphylococcus
aureus. Further analysis shows failure of the
neutrophils to undergo an oxidative burst
when exposed to S. aureus. This patient has
an increased susceptibility to infection as a
result of which of the following
abnormalities?
A) Deficient leukocyte production
B) Failure of leukocytes to
migrate between endothelial
cells
C) Failure of leukocytes to roll
along the endothelial surface
D) Inability of leukocytes to ingest
microorganisms
E) Inability of leukocytes to kill
intracellular microorganisms

31. Q5
• An infection with
• Aspergillus osteomyelitis
• Pneumonia
• Hepatic, skin abscesses
• Because of problems with
• Cellular immunity
• Humoral immunity
• Phagocytosis
• Collectively
• Could be a lot of things
• Differentiate with
• Failure of oxidative burst test
• Abscesses are common
• Aspergillus & Staph share…
A 5-year-old boy is admitted to the hospital
because of a 1-week history of fever and
increasingly severe abdominal discomfort. At
the age of 7 months, he was treated for
osteomyelitis caused by Aspergillus
fumigatus. He has been to the hospital three
times in the past 4 years for severe
pneumonias and skin abscesses. Abdominal
ultrasound shows an intrahepatic abscess
that, when cultured, grows Staphylococcus
aureus. Further analysis shows failure of the
neutrophils to undergo an oxidative burst
when exposed to S. aureus. This patient has
an increased susceptibility to infection as a
result of which of the following
abnormalities?

32. Cats Need PLACES

34. • Nocardia
• Pseudomonas
• Listeria
• Aspergillus
• Candida*
• E. Coli
• S. aureus
• Serratia*
Cats Need PLACES

35. Summarize – 4 Generic Rules
•Problem with T cells  fungal, viral infections (local Candida)
•Problem with Phagocytosis  skin inf, abscesses
(bloodstream Candida)
•Problem with B cells bacterial (Sinus, OM, PNA) infections
• Deficiency of IgA  mucus membranes (sinus, GI) infections

36. Summary - 5 Differentiating Facts
• SCID vs. DiGeorge
• Both lack thymus, with DiGeorge  check Ca2+, Ig levels
• Chediak-Higashi –
• Problems with microtubules  can’t transport, combine  presentation
• Inheritance
• Know the 2 definitive XLR (Bruton’s, Wiscot-Aldrich: “Be Wise”)
• Know the AR (Chediak-Higashi)
• Bruton & CVD
• Bruton is more severe defect of B-cells  less Ig & lymphoid tissue, earlier
• Know which organisms are catalase +
• Cats Need PLACESS