Primary Immunodeficiencies Flashcards
1
Q
What cells make up the innate immune system?
A
Neutrophils, macropahges, eosinophils, NK cells, dendritic cells
2
Q
Big picture: what do B / T cell deficiencies cause?
A
- B cell deficiency → bacterial infections
* T cell deficiency → viral / fungal infections
3
Q
Timeline of diff types of immunodeficiencies
A
- First 3-6 months of life: Immune deficiencies that affect neutrophils and T cells present early in life.
- 6-18 months: B cells normally show up here, so absence causes problems b/c mother’s IgG usually wanes after first 6 months.
- Later: Complement deficiencies may cause problems w/ Neisseria infection.
4
Q
B cell deficiencies
Labs
Treatment
A
- Predispose to bacterial infections (especially encapsulated)
- Recurrent sinopulmonary infections or sepsis.
- Labs: Functional Abs – specific IgG, IgA, IgM to polysaccharide antigens, such as pneumo, diphtheria, or tetanus.
- Quantitative Ig
- CBC w/ differential
- HIV test
- Tx w/ IVIG when IgG levels are less than 800. If Px is IgA-deficient, IVIG and any other transfusions must not contain IgA due to risk of anaphylaxis. AB prophylaxis w/ TMP/sulfa.
5
Q
T cell deficiencies
Predisposition
Associated Syndromes / Diseases
A
Predispose to viral / fungal infections (opportunistic)
Associated w/ DiGeorge Syndrome, Wiskott Aldrich Syndrome, SCID, eczema, and seborrheic dermatitis.
6
Q
Neutrophil deficiencies Associated Disease Clues on physical exam Lab tests Treatment
A
- Predispose to recurrent abscesses and catalase+ organisms, such as Staph aureus, Serratia, and Aspergillus.
- Associated w/ Chronic Granulomatous Disease
- Physical exam: scars from old abscesses, gingivitis, early tooth loss
- Lab tests: CBC, flow cytometry, PMN function test w/ nitroblue tetrazolium (oxidative burst test; tests ability to generate superoxide)
- Superoxide causes blue precipitate in cells, indicating you do NOT have oxidative deficiency.
- Dihydrorhodamine test is more accurate than this.
- Bone marrow transplant may be curative
7
Q
Complement deficiencies
Predisposition
Clues / Clinical Manifestations
Management
A
- Predispose to Recurrent Neisseria infections (meningitides and gonorrhoeae)
- Infection w/o sexual sxs is a clue to complement deficiency, primarily of the terminal complement components.
- May have septic arthritis or skin pustules from disseminated gonococcal infection.
- PMNs seen in CSF w/ intracellular gram neg diplococci
- Total complement test (CH50) and C3 / C4 test
- Px must be educated to seek medical attention promptly w/ fever or other sxs. Do blood cultures and start empiric AB’s in these cases.
- Px should get meningococcal vaccine
- STD education / prevention
8
Q
SCID Stands for Age of presentation Pathology Management Treatment
A
- Severe Combined Immunodeficiency Disorder
- Infections occur in first year of life. Failure to thrive.
- T and B cells are decreased, absent, or don’t function. Fatal w/o immune reconstitution in 1st year of life.
- Management – Protective isolation, antimicrobial prophylaxis, IVIG, no live vaccines (such as rotavirus vaccine), irradiated CMV neg blood products.
- Tx w/ stem cell transplant, gene therapy, PEG-ADA, and thymic transplant.
- PEG-ADA: polyethylene glycol-conjugated adenosine deaminase
9
Q
Clues to diagnosis of SCID
A
- CD3 is T cell marker, CD19 is B cell marker. Both are usually low. Detect w/ flow cytometry.
- T cell count less than 300 makes you think of typical SCID
- T cell Receptor Excision Circles (TRECs), which indicate rearrangement of T cell receptor, are reduced in all forms of SCID. Mutation may occur at many diff steps.
- TRECs are Biomarker of thymic function. Detected by PCR
10
Q
DiGeorge Syndrome Deletion Clinical triad Phenotype Pathophysiology Diagnosis Treatment
A
- 22q11.2 micro deletion (most common micro deletion)
- Clinical triad – conotruncal cardiac anomaly (Tetralogy of Fallot), hypoplastic thymus, and hypocalcemia
- Hypoplastic thymus → low T cells → low cell-mediated immune response. Requires immune reconstitution.
- Phenotype – Ocular hypertelorism, Downturning eyes, Hooded eyelids, Low-set posteriorly rotated ears, Widened area below nasal bridge, Bulbous nose tip, Micrognathia (small jaw), Short philtrum, High arched palate, Submucosal cleft palate/bifid uvula, Tapered fingers
- Pathophysiology – teratogens (accutane, alcohol, maternal diabetes) that inhibit neural crest cell migration at critical times can result in DGS w/ chromosomal defects.
- Diagnosis: Look for microdeletion w/ FISH. Stimulate chromosomes w/ PHA to induce mitosis.
- No live vaccines. Tx w/ thymic transplant.
11
Q
CATCH 22
A
DiGeorge
•C: cardiac abnormalities, such as Tetrology of Fallot
•A: abnormal facies
•T: Thymus aplasia, causes T cell deficiency
•C: cleft palate
•H: hypocalcemia or hypoplastic parathyroid
•22q11 deletion
12
Q
CVID Name Age of presentation Pathophysiology Treatment
A
- Common Variable Immunodeficiency
- Inherited PI that presents after early childhood. Bimodal age of onset: first and third decades of life.
- Pathophys: Normal B and T-cells but inability to make Abs. B cell memory defect (CD27 cells). Low IgG + low IgM or IgA. Poor response to vaccines. Increased incidence of lymphoid malignancy, autoimmune disease, and atopy
- Treatment – IVIG, aggressive AB’s, immunosuppression for autoimmune problems, possibly bone marrow transplant.
13
Q
CVID Autoimmune manifestations
Heme, GI, rheumatologic, endocrine, dermatologic, neurologic
A
- Hematologic: autoimmune cytopenias
- GI: pernicious anemia, celiac, IBD
- Rheumatologic: SLE, RA, JRA (juvenile), vasculitis
- Endocrine: Hashimoto’s, T1DM
- Dermatologic: vitiligo, alopecia
- Neurologic: Guillain-Barre
14
Q
Wiskott Aldrich Syndrome (WAS) Normal function of WAS protein Pathophys Clinical manifestations Treatment
A
- X linked recessive immunodeficiency secondary to dysfunction of actin cytoskeleton
- WAS protein is normally expressed in hematopoietic cells and functions in modulating actin.
- Recurrent infections, thrombocytopenia, increased risk for autoimmunity and malignancy, eczema
- Tx w/ stem cell transplant
15
Q
X-Linked Lymphoproliferative Disorder (XLP)
Pathophysiology
A
- Severe immune dysregulation after EBV infection.
- Caused by mutation in SLAM-associated protein (SAP), which is necessary for NKT cell development and CD8 T cell responses to EBV infection.
- May involve fatal mononucleosis, hemophagocytic lymphohistiocytosis, lymphoma, and aplastic anemia.
16
Q
Chronic Granulomatous Disease (CGD) Cause Genetic Mutation Pxs at risk Increased risk of what type of infections? Clinical manifestations Diagnosis Treatment
A
- Inherited neutrophil defect – Caused by failure of phagocytes to produce H2O2 and superoxide due to problems in NADPH generation from hexose monophosphate shunt.
- Most common genetic mutation is XLR, gp91 deficiency. X-linked, so more common in teenage boys.
- Infection w/ catalase positive bacteria / Microbes that require highly reactive bacteriocidal oxidative metabolites: S. aureus, Klebsiella, Aspergillus, Burkholderia, Serratia
- Recurrent abscesses, pneumonia, osteomyelitis
- Gingivitis, poor wound healing, colitis, gastric / urinary tract obstruction
- Diagnosis: Detect poor oxidative activation w/ dihydrorhodamine test
- Treatment – Antimicrobial prophylaxis, IFg prophylaxis, steroids for inflammation, bone marrow transplant, gene therapy.
17
Q
Tests for T Cell Deficiencies
A
- Quantitative T cell test: skin test (testing for delayed type hypersensitivity). Candida skin test is good b/c most people have been exposed to it.
- Quantitative Ig: T cell dysfunction may inhibit activation of B cells → inability to make Abs.
- Presence / absence of thymic shadow on X ray
18
Q
Treating T cell deficiencies
A
•Tx of choice is bone marrow transplant
•IVIG b/c if T cells are really low, Abs are prob not being made
•Oral fluconasole for candidiasis.
•Prophylactic antimicrobials, including TMP/sulfa for bacteria, fluconazole
for fungi, antivirals for influenza (in season). Monoclonal antibody for RSV.
•Avoid live vaccines
•Irradiate any blood cell infusions to prevent GVHD.
19
Q
Pathognomonic for PJP
A
Hypoxia out of proportion to CXR b/c may not see infiltrates. Usually interstitial infiltrates if they are present.
