Approaching & Contrasting Immunodeficiencies

Approaching & Contrasting Immunodeficiencies Gazi Rashid, M4

1. List as many immunodeficiencies as you can • Chediak-Higashi • Chronic Granulomatous Disease • Leukocyte Adhesion Deficiency • DiGeorge Syndrome • Hyper IgE syndrome (Job Syndrome) • Common Variable Imm Def • Ataxia-Telangiectasia • Hyper-IgM syndrome • Bruton’sAgammaglobulinemia • Severe CombindImm De • Wiscott-Aldrich Syndrome • Deficiency of T-Cells • Deficiency of Humoral • Deficiency of Both • Defect in Phagocytosis

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

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

Approach • 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)

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

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:

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:

Q1 - IgA (Both) B cell) (T cell) (B cell)(B cell) 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: • Severe Combined Immunodeficiency B) Bruton X-linked agammaglobulinemia C) DiGeorge Syndrome D) Selective IgA deficiency E) Common Variable Immunodeficiency

Q1 • SCID vs. DiGeorge Syndrome Vs. DiGeorge Syndrome Normal

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?

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

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?

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

XLR - BeWise Fool's GOLD HoldsAsinineHOpe • Bruton'sagammaglobulinemia • Wiskott-Aldrich • Fabry's • G6PD def • Ocular albinism • Lesch-Nyhan • Duchene (DMD, BMD) • Hunter Syndrome • Alport • Hemophilia A, B

Q3 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? • A) Abnormally low B cells • B) Abnormally low T cells • C) Abnormally high B cells • D) Abnormally high T cells • E) Elevated Ig levels

Q3 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? • 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…

Live in Lymph Tissue B cells Produce Ig

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? • Deficient leukocyte production • Failure of leukocytes to migrate between endothelial cells • Failure of leukocytes to roll along the endothelial surface • Inability of leukocytes to ingest microorganisms • Inability of leukocytes to kill intracellular microorganisms

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?

Cats Need PLACES

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

Summarize – 4 Generic Rules • Problem with T cells  fungal, viralinfections (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

Summary - 5 Differentiating Facts • SCID vs. DiGeorge Both lack thymus bc of… • T-cell deficiency; with DiGeorge check Ca2+, Ig levels • Chediak-Higashi – inheritance and problem with? • AR problem with trafficking lysosomes  can’t transport, combine • Inheritance – the 2 XLR, 1 AR? • Know the 2 definitive XLR (Bruton’s, Wiscot-Aldrich: “Be Wise”) • Know the AR (Chediak-Higashi) • Bruton & CVD – which one is worse? • Bruton is more severe defect of B-cells  less Ig & lymphoid tissue, earlier • Know which organisms are catalase + • Cats Need PLACESS

Extra Q • An asymptomatic 32-year-old man comes for a routine health maintenance examination. He has a 10-year history of frequent sinus and pulmonary infections. He had an anaphylactic reaction to a blood transfusion following a motor vehicle collision 3 years ago. His temperature is 37 C (98.6 F). Examination shows mild erythema in the posterior pharynx. The lungs are clear to auscultation. A complete blood count and serum protein electrophoresis are within normal limits. Which of the following is the most likely cause of the frequent infections?A) Colonization with Streptococcus pneumoniaeB) Common variable immunodeficiencyC) HIV infectionD) Selective IgA deficiencyE) X-linked agammaglobulinemia

Approaching & Contrasting Immunodeficiencies