Immune Deficiency

Front 1

Generally speaking, ____(1)____ tend to produce recurrent bacterial infections, whereas___(2)___produce more viral or fungal infections.

Back 1

Recurrent bacterial infections → think B-cell deficiency
Recurrent viral or fungal infections → think T-cell deficiency

Front 2

Bacterial infxs: NO T-CELLS (1)

Back 2

Sepsis

Front 3

Bacterial infxs: NO B-CELLS (7)

Back 3

Encapsulated organisms: SHiNE SKiS (+Quell)
(S). pneumonia
(H). (i)nfluenza
(N)eisseria meningitidis (M. Gono has no capsule)
(E). coli
(S)almonella
(K). pneumonia
Group B (S)trep

Front 4

Bacterial infxs: NO GRANULOCYTES (4)

Back 4

1. Staph
2. Burkholderia cepacia
3. Serratia
4. Nocardia

Front 5

Bacterial infxs: NO COMPLEMENT (1)

Back 5

Neisseria (=no MAC)

Front 6

Bacterial infxs: Asplenics (7)

Back 6

Encapsulated organisms: SHiNE SKiS (+Quell)
Give 3 vaccines: S. pneumonia + H. influenza + N. meningitidis

Front 7

Viral infxs: NO T-CELLS (3)

Back 7

1. Herpes viruses: CMV, EBV, VZV
2. Chronic infxs w/ Respiratory viruses
3. Chronic infxs w/ GI viruses

Front 8

Viral infxs: NO B-CELLS (2)

Back 8

1. Enterovirus encephalitis
2. Poliovirus (live) vaccine CONTRAINDICATED

Front 9

Viral infxs: NO GRANULOCYTES (!)

Back 9

N/A

Front 10

Viral infxs: NO COMPLEMENT (!)

Back 10

N/A

Front 11

Fungi/Parasites: NO T-CELLS (!)

Back 11

Opportunistic fungal infxs: CANDIDA, PCP

Front 12

Fungi/Parasites: NO B-CELLS (1)

Back 12

GIardiasis 2/2 no IgA

Front 13

Fungi/Parasites: NO GRANULOCYTES (2)

Back 13

1. Candida
2. Aspergillus

Front 14

Fungi/Parasites: NO COMPLEMENT (!)

Back 14

N/A

Front 15

B-cell deficiencies tend to produce______(1)______infections, whereas T-cell deficiencies produce more_____(2)______infections.

Back 15

(1) recurrent bacterial
(2) fungal and viral

Front 16

List the Types of Immune Deficiencies

Back 16

B-cell disorders
T-cell disorders
B-&T-cell disorders
Phagocyte dysfunction

Front 17

B-cell disorders (3)

Back 17

1. Bruton a-gamma-globulinemia
2. Selective IgA Deficiency
3. CVID (Combined Variable Immunodeficiency)

Front 18

T-cell disorders (4)

Back 18

1. DiGeorge syndrome (thymic aplasia)
2. IL-12 receptor deficiency
3. Hyper-IgE syndrome (Job syndrome)
4. Chronic mucocutaneous candidiasis

Front 19

B-&T-cell disorders (4)

Back 19

1. SCID (Severe Combined Immunodeficiency)
2. Ataxia-telangiectasia
3. Hyper-IgM syndrome
4. Wiskott-Aldrich syndrome

Front 20

Phagocyte dysfunction (3)

Back 20

1. Leukocyte adhesion deficiency
2. Chediak-Higashi syndrome
3. Chronic granulomatous disease

Front 21

Case 1: A child with cleft palate, abnormal facies, recurrent viral/fungal infections, congenital heart disease, and tetany has low calcium and PTH. Chest x-ray shows absent thymic shadow. Diagnosis? MOD?

Back 21

DiGeorge syndrome (=CATCH-22) → 22q11 deletion syndrome → abnormal development of 3rd + 4th branchial/pharyngeal pouches

Front 22

Presentation-Mnemonic: DiGeorge syndrome

Back 22

CATCH-22
C-Cleft palate
A-Abnormal facies
T-Thymic aplasia → T-cell def. → recurrent viral/fungal infxs; abscent thymic shadow on CXR
C-Cardiac defects (congenital heart disease)
H-HypoCalcemia/HypoPTH → 2/2 Parathyroid aplasia → causing HypoCa Tetany
22-Chrom. 22q11 deletion → abnormal devlop. of 3rd + 4th branchial/pharyngeal pouches

Front 23

22q11 deletion syndromes (2)

Back 23

1. DiGeorge syndrome
2. Velo-cardio-facial synrome

Front 24

Major Defects: DiGeorge syndrome

Back 24

1. Thymic aplasia → T-cell def. → recurrent viral/fungal infxs
2. Parathyroid aplasia → HypoPTH → HypoCa → Tetany
3. Face/Cardiac defects → Cleft palate, Abnormal facies, Congenital heart disease

Front 25

Major Defects: Velo-cardio-facial synrome

Back 25

1. Palate defects
2. Cardiac defects
3. Facial defects

Front 26

MOD: 22q11 deletion syndromes

Back 26

Chrom. 22q11 deletion → abnormal development of THIRD and FOURTH BRANCHIAL/PHARYNGEAL POUCHES

Front 27

Case 2: Patient with recurrent disseminated mycobacterial infections. Diagnosis? MOD-cells and cytokines implicated?

Back 27

IL-12 RECEPTOR DEFICIENCY → ↓ Th1 activation → ↓ IFN-γ
Recall: Th1 → cell-mediated immune response → involved in delayed type 4 HSN rxns → deficiency in Th1 activation → result in poor delayed/cell-mediated type 4 HSN → such as granulomatous diseases, ie. mycobacterium

Front 28

DDx: Type of Immune Response/Cells Involved: Th1 vs. Th2

Back 28

Th1 → cell-mediated immune response → (+) macrophages and (+) CD8+ Tc → Delayed type 4 HSN rxns

Th2 → humoral (Ab+) mediated immune response → by (+) B-cells → (+) Isotype-Class switching

Front 29

Th1 vs. Th2

Back 29

Th1
1. cell-mediated immune response
2. (+) macrophages and (+) CD8+ Tc
3. Delayed type 4 HSN rxns

Th2
1. Humoral (Ab+) mediated immune response
2. (+) B-cells
3. (+) Isotype-Class switching

Front 30

What is the common clinical manifestation in a patient with interleukin-12 receptor deficiency? What cells and cytokines are implicated?

Back 30

Disseminated mycobacterial infections; decreased activation of Th1 helper T cells (from decreased interferon-γ)

Front 31

Case 3: 25 yo presents with recurrent sinopulmonary infxs. Diagnosis? MOD? Pt is at increased risk of which two noninfectious conditions

Back 31

1. Common variable immunodeficiency (CVID) → defect in B-cell maturation (many causes) to plasma cells and memory B cells (specialized B-cells) → Normal # B-cells but ↓ # plasma cells + ↓ Ig's → recurrent sinopulmonary infxs + autoimmune disease + lymphoma
2. Acquired in 20s-30s (onset)

Front 32

Common variable immunodeficiency (CVID) is caused by a defect in___(B-/T-/Plasma)___ cell maturation to ___________ & ___________ ; patients present with _________ infections. It is acquired between ____and____years of age and increases the risk of which two noninfectious conditions?

Back 32

1. Defect in B-cell maturation (many causes) to plasma cells and memory B cells (specialized B-cells): Normal # B-cells but ↓ # plasma cells + ↓ Ig's
2. Present with SINO-PULMONARY infections
3. between 20-30 years of age
4. Autoimmune dzs + Lymphoma

Front 33

Which immune deficiency disease presents with normal numbers of circulating B-cells but a decreased number of plasma cells?

Back 33

Common variable immunodeficiency (CVID)
-MOD: Defect in B-cell maturation (many causes) to plasma cells and memory B cells (specialized B-cells)
-Labs: Normal # B-cells but ↓ # plasma cells + ↓ Ig's

Front 34

Case 4: BOY presents with recurrent bacterial infections after 6 months. Diagnosis? MOD?

Back 34

Bruton a-gamma-globulinemia → XR (X-linked Recessive) → defect in BTK (tyrosine kinase) → no B-cell maturation from pro-B to mature B-cells → Normal pro-B cells but ↓ # mature B-cells → ↓ Plasma cells = ↓ Ig's of ALL classes → results in OPSONIZATION defect → RECURRENT BACTERIAL INFX after 6 MONTHS = when maternal Ig wear off

Front 35

Bruton's agammaglobulinemia is a(n) ____-recessive disorder caused by a defect in ____ kinase, preventing ____ (B-/T-) cell maturation.

Back 35

Bruton a-gamma-globulinemia → XR (X-linked Recessive) → defect in BTK (tyrosine kinase) → preventing B-cell maturation

Front 36

Patients with Bruton presents with ___________ after ____ months, as a result of ___________ defect.

Back 36

Bruton → p/w RECURRENT BACTERIAL INFECTIONS after 6 months (when maternal Ig wear off) → as a result of OPSONIZATION defect (2/2 Ig deficiency of all classes)

Front 37

Which immune deficiency disease presents with normal numbers of circulating pro-B cells (precursors) but a decreased number of mature B cells + plasma cells + and Ig's?

Back 37

Bruton a-gamma-globulinemia → defect in BTK → no B-cell maturation from pro-B to mature B-cells → Normal pro-B cells but ↓ # mature B-cells = ↓ Plasma cells = ↓ Ig's of ALL classes.

Front 38

An eight-month-old boy presents with recurrent bacterial infections and suspected immunodeficiency. Explain the timing of presentation.

Back 38

Depletion of maternal IgG; boy has Bruton's agammaglobulinemia with ineffective maturation and low B cells and immunoglobulins

Front 39

Case 5: Patient with recurrent candida infections of skin and mucous membranes. Diagnosis? MOD?

Back 39

Chronic muco-cutaneous candidiasis
MOD: T-cell dysfunction

Front 40

Case 6: Boy with retained primary teeth and coarse facies presents with recurrent cold abscesses + chronic dermatitis. Labs show elevated IgE and eosinophilia. Diagnosis? MOD?

Back 40

Hyper-IgE syndrome (aka Job's syndrome)
1. Th1 cells fail to produce IFN-y → inability of PMNs to respond to chemotactic stimuli → cold (noninflamed) staph abscesses
2. Hyper-IgE & Eosinophilia → chronic dermatitis (unusual eczema-like rash)

Front 41

Mnemonic: Job's syndrome (aka Hyper-IgE syndrome)

Back 41

Job's "FATEE" is to have:
coarse FACIES
cold (noninflamed) staph ABSCESSES
retained primary TEETH
hyper-IgE (w/ esosinophilia)
ECZEMA-like rash (2/2 hyper-IgE)

Front 42

Job' syndrome is characterized by ____ (B-cell/T cell/neutrophil) dysfunction due to low levels of ____ (IL-12/CD40L/interferon-γ/BTK).

Back 42

1. Neutrophils
2. Interferon-γ

Front 43

Case 7: Patient goes into anaphylaxis after receiving blood products. Diagnosis? Presentation?

Back 43

Selective IgA deficiency
1. Majority are asxs
2. Can see sinopulmonary/GI infx (IgA protects mucous membranes) or autoimmune disease
3. Classic: Anaphylaxis to IgA-containing blood products

Front 44

The most common primary/selective immunoglobulin (Ig) deficiency is a lack of Ig ____ (M/D/A/G/E) due to poor maturation of ____ (B/T/plasma) cells.

Back 44

1. IgA
2. Plasma cells (no isotype switching specifically for IgA)

Front 45

What lab values do you look for in a patient with selective immunoglobulin A (IgA) deficiency?

Back 45

1. IgA < 7 mg/dL with normal IgG, IgM, and IgG vaccine titers
2. False-positive β-HCG 2/2 presence of heterophile antibody

Front 46

Case 8: Infant initially p/w FTT, chronic diarrhea, and thrush. In the following months, he experiences recurrent viral, bacterial, fungal, and protozoal infections. Workup reveals ABSENCE of (1) thymic shadow (on X-ray), (2) germinal centers (on LN biopsy), and (3) T-cells (on flow cytometry). Diagnosis?

Back 46

Severe Combined Immunodeficiency (SCID)

Front 47

What are three possible causes of severe combined immunodeficiency?

Back 47

1. Inability to synthesize MHC II antigens
2. Defective IL-2 receptors (MCC, X-linked)
3. Adenosine deaminase deficiency

Front 48

Classic Presentation-Initially: SCID

Back 48

1. FTT
2. Chronic diarrhea
3. Oral thrush

Front 49

Diagnostic Findings: SCID

Back 49

ABSENCE of following:
1. X-ray → NO thymic shadow
2. LN biopsy → NO germinal center
2. Flow cytometry → NO T-cells

Front 50

Classic Presentation-Later On: SCID

Back 50

Recurrent viral, bacterial, fungal, and protozoal infections

Front 51

Case 9: Patient p/w ATAXIA + TELANGIECTASIA. Diagnosis? MOD? Classic Presentation?

Back 51

Ataxia-telangiectasia → defective ATM gene = DNA repair gene → TRIAD: Ataxia + Telangiectasia (Spider angiomas) + IgA deficiency

Front 52

Classic Triad: Ataxia-telangiectasia

Back 52

1. Ataxia
2. Spider angiomas = Telangiectasia
3. IgA deficiency (-reason it's grouped with immunodef. dz)

Front 53

Classic lab finding: Ataxia-telangiectasia

Back 53

↑ AFP

Front 54

Case 10: Child p/w recurrent severe pyogenic infections. Diagnosis? MOD? Lab findings?

Back 54

Hyper-IgM syndrome → defective CD40L on helper T cells → inability of B-cells to class switch → ↑↑ IgM = ↓↓ IgG, IgA, IgE → recurrent + severe sinopulmonary and GI infxs with pyogenic bacteria and opportunistic organisms after 6 months (Ig wean off)

Front 55

Case 11: Infant boy p/w triad purpura + bacterial URTI + eczema. Diagnosis? MOD?

Back 55

Wiskott-Aldrich syndrome (WAS) → mutation in WAS gene on X-chrom (=XR) → T cells unable to reorganize actin cytoskeleton → inability of T-cells to interact with APC or target cells → T-cell don't do their job → uncontrolled recurrent infections

Front 56

Classic lab findings: Wiskott-Aldrich syndrome

Back 56

1. ↓↓ PLT → purpura
2. ↓ IgM →
3. ↑ IgE and IgA → eczema

Front 57

Wiskott-Aldrich syndrome is aka

Back 57

eczema-thrombocytopenia-immunodeficiency syndrome (original name)

Front 58

Case 12: Child w/ pmh of delayed separation of umbilical cord p/w recurrent bacterial infections + absent pus formation + neutrophilia. Diagnosis? MOD?

Back 58

Leukocyte adhesion deficiency (type 1) → Defect in LFA-1 integrin (CD18) protein on PHAGOCYTES

Front 59

Case 13: Patient w/ partial albinism + peripheral neuropathy p/w recurrent pyogenic infections by staph + strep. Workup reveal giant granules in neutrophils. Diagnosis? MOD?

Back 59

Chédiak-Higashi syndrome (AR) → defect in lysosomal trafficking regulator gene (LYST) → microtubule
dysfunction in phagosome-lysosome fusion in PMNs → recurrent pyogenic infections by staphylococci and streptococci

Front 60

Case 14: Patient p/w recurrent infections by catalase (+) organisms. Diagnosis? MOD?

Back 60

Chronic granulomatous disease (CGD) → lack NADPH oxidase → ↓ ROI → absent respiratory burst in neutrophils → inability to kill catalase (+) organisms

Front 61

Mnemonic: Catalase (+) Organisms

Back 61

Pseudomonas, Listeria, Aspergillus, Candida, E. coli, S. aureus, Serratia

"You need PLACESS for your cats:"

Front 62

Diagnosis: Chronic granulomatous disease (CGD)

Back 62

Abnormal di-hydro-rhodamine (DHR) flow cytometry test

Note: Nitroblue tetrazolium dye reduction test no longer used