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.
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
4.
5.
6.
7.
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
11.
12.
13.
14.
15.
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)
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?
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?
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?
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
Notas del editor
4 min – Intro
0.5 min – write down the ones you remember (keep a wordbank)
0.5 min – write down and group them based on
0.5 min – this is what you’ll see on FA vs. how we’re going to think about it today there’s a lot, can’t go over everything, simplify
1 min - overview, objectives
1 min – approach
4 min - rules
12 min – 5 Qs
First 2 – do together – 5 min
Next 3 – try apart, review together in 7 min
Go over Q & Approach & Teaching point
ABC – igA deficiency, Bruton, CVID
D, J
WASH
Patterns to help you narrow down possibilities
T-cells & phagocytosis are most helpful, bc B-cells can present pretty broadly
Cellular deficiencies or T-cells tend to produce viral infections and opportunistic infections like seen in HIV/AIDS or organ transplant immune suppression
B cell/humoral deficiencies tend to produce bacterial infections, encapsulated bacteria (IgM antibodies needed to opsonize encapsulated bacteria and allow them to be phagocytized)
Mnemonic: WASH Both of your hands
Honestly, aside from SCID, the rest are weird
For lymphocytes (notably T-cells), this build-up is toxic; the result is a deficiency in T-cells. The result is a great decrease in the number of T-cells and a subsequent decrease in humoral immunity which relies on T-helper cells for activation
Without T-cells, absence of of the thymus (where T-cells mature)
Without B-cells, absence of tonsils (B-cells proliferate) or germinal centers
DiGeorge syndrome is mild-moderate decrease T-cells (whereas SCID is severe loss of T-cells), so in DiGeorge, the decrease in T-cells does NOT lead to hypogammoglobulinemia (remember, Th cells are needed for class switching)
https://step1.medbullets.com/immunology/105007/chediak-higashi-syndrome?expandLeftMenu=true
Answer is (D) Autosomal Recessive
Aanswer is (A) – next few slides have more explanation
Bruton’s is “Brutal” – more severe than CVID Bruton’s is near total lack, so after maternal stuff runs out, pt presents w/ infections
Bruton’s is XLR
Both will have dec Ig and dec lymph tissue, but again, Bruton’s is more severe, so will be lower than CVID
https://www.usmle.org/pdfs/step-1/samples_step1.pdf - q57
Ans - http://www.benwhite.com/medicine/explanations-for-the-2018-official-step-1-practice-questions/
https://www.usmle.org/pdfs/step-1/samples_step1.pdf - q57
Ans - http://www.benwhite.com/medicine/explanations-for-the-2018-official-step-1-practice-questions/
Even in pt w/ CGD, OTHER body rxns still produce enough H2O2 (hydrogen peroxide)
but
Catalase converts that H2O2 harmless water - so in these pt, these bugs are deadly