Immune Deficiencies

Question 1

Chronic granulomatous disease

Answer 1

Phagocyte dysfxn
NADPH oxidase deficiency-decreased ROS and resp. Burst in neutrophils

Still have H2O2 to kill bacteria except in catalase + organisms which destroy H2O2

Susceptible to:   Catalase +
You need PLACESS for your CAT(alase)
Pseudomonas
Listeria
Aspergillus
Candida
E. coli
Staph aureus
Serratia

Test=dihydrorhodaminepositive, nitroblue tetrazolium NEGATIVE means you have disease

Question 2

X linked / Bruton agammaglobinemia

Answer 2

B cell disorder
Defect in BTK tyrosine kinase gene
Can’t make pre B cell to immature B cell

Recurrent bacterial/enteroviral infections in child past 6 months when maternal IgG decreases

No CD19 cells, decreased immature B cells and pro-b, small lymph nodes/tonsils

Question 3

Selective IgA deficiency

Answer 3

Most common primary immune deficiency

Mostly asymptomatic
Some airway/GI (mucosal) infections
Ass’d with autoimmune diseases
Anaphylaxis to IgA containing products

IgA<7 with normal IgM and IgG

Question 4

Leukocyte Adhesion Deficiency

Answer 4

Phagocyte dysfxn
Defect in LFA-1 integrin (CD18) on phagocytes- cant adhere during neutrophil migration

Recurrent bacterial skin/mucosal infections
No Pus
Delayed umbilical cord falling off(omphalitis)
Increased neutrophils in serum (b/c not adhering but being called)

Question 5

Chediak-Higashi

Answer 5

Phagocyte dysfxn
Defect in Lysosomal Trafficking Gene (LYST)
Microtuble defect in phagosome-lysosome fusion

Recurrent PYOGENIC infections with staph and strep
ALBINISM, peripheral neuroppathy, progressive neurodegenertion

Giant granules in neutrophils
Pancytopenia

Question 6

Common variable immune deficiency

Answer 6

Defect in B cell maturation

• Acquired in 20s-30s
• Increased risk autoimmune disease, bronchiectasis, lymphoma, sinopulmonary infections

-Decreased plasma cells and decreased Ig due to failure in B cell maturation

Question 7

Thymic aplasia (DiGeorge syndrome)

Answer 7

• T cell disorder
• 22q11 deletion, failure to develop 3rd and 4th pharyngeal pouches–>absent thymus and parathyroids and cardiac abnormalities
• Clinical: tetany due to hypoCa2+, recurrent viral/fungal infections due to T cell deficiency, tetraology of Fallot/truncus arteriosus
• low T cells, low PTH, low Ca2+, no thymic shadow

Question 8

IL-12 Receptor deficiency

Answer 8

• Autosomal recessive T cell problem
• Normally TH1 activates macophages via IFN-gamma–>macrophage release IL-12 to stimulate maturation of Th1 cells
• Disease: lack of Il-12 receptor causes diminished Th1 (cellular immune) response
• Clinical: disseminated fungal and mycobacterial infections, esp with BCG vaccine administration
• decreased IFN-gamma

Question 9

Autosomal Dominant Hyper-IgE syndrome/Job syndrome

Answer 9

• Deficient Th17 cells due to STAT3 mutation
• Low IFN-gamma impairs recruitment of neutrophils to infection
• FATED: coarse Facies, cold/noninflamed staphylococcal Abscesses, retained primary Teeth, high IgE, dermatologic problems (Eczema)

Question 10

Chronic Mucocutaenous Candidiasis

Answer 10

• T cell dysfxn-no response to candida

- Noninvasive infection of skin/mucous membranes

Question 11

Severe Combined Immunodeficiency (SCID)

Answer 11

• Combined B and T cell disorder
• Defective Il-2R gamma chain (most common) OR adenosine deaminase deficiency (fail to break down dATP)–>imbalanced nucleotide pool–>inhibits B and T cell DNA synthesis–>absent)
• Bubble boy!: failure to thrive, chonic diarrhea, thrush, vira/bacterial/fungal/protozoal infections
• absence of thymic shadow on x-ray, absent germinal centers in lymph nodes, and absent T cells in flow cytometry
• Tx: bone marrow transplant-no worry of rejection

Question 12

Ataxia-telangectasia

Answer 12

• Combined B and T cell disorder
• defect in ATM gene–>failure to repair double strand breaks–>cell cycle arrest
• Triad of symptoms: cerebella defects=Ataxia, spider Angiomas (telangectasia), IgA deficiency
• high Alpha fetoprotein, low IgA, IgG, and IgE
• lymphopenia and cerebellar atrophy

Question 13

Hyper-IgM syndrome

Answer 13

• T cell disorder impacting B cell function
• X-linked recessive
• defective CD40 ligand on Th cells—> can’t bind B cells to cause class switching for Ig production
• Symptoms: severe pyogenic infetions, opportunistic (penumocystis, crypto, CMV early in life)
• high IgM, low to none other Ig (A, E, G)

Question 14

Wiskott-Aldrich

Answer 14

-Combined B and T cell disorder
-defect in WAS gene (X-linked recessive)
-Actin skeleton dysfxnal in T cells
-WATER: Wiskott Aldrich, Thrombocytopenia purpura, Eczema, Recurrent infections esp
1. polysaccharide capsules (Neisseria, H flu, strep) due to low humoral response
2. opportunistic (pneumocystis) due to low T cell response
-increased risk autoimmune disease and cancer
-Low to normal IgG, IgM
-High IgE, IgA
few and small platelets
-Tx: treat with HLA matched bone marroww