Term
| What are some clinical features of immunodeficiency? |
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Definition
1) Thrush, chronic diarrhea and failure to thrive
2) Recurrent infections
3) Pneumonitis that does not clear
4) Rashes and ezcema
5) Hepatosplenomegaly, lymphadenopathy, Lymphopenia
6) ALC<3400 (may be normal); IgM<20(may be normal or elevated in SCID), IgA<5, <10% lymphocyte proliferation to mitogens |
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Term
| What diagnostic features of immunodeficiency can be detected in terms of Lymphopenia? |
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Definition
ALC<3400 (may be normal)
IgM<20(may be normal or elevated in SCID)
IgA<5
<10% lymphocyte proliferation to mitogens |
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Term
| What is the overall prevalence of immunodeficiency diseases? |
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Definition
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Term
A 1-year-old male patient presents with otitis and pneumonia. as well as absent adneoids and tonsils.
Why might you suspect a a defect in BTK (Bruton's tyrosine kinase) and what disease is associated?
How should you treat? |
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Definition
This is a young patient without appropriate levels of Ig . The age and gender makes this is likely to be X-linked Agammaglobulinema (XLA) and not CIVD, which results is a block in B cell maturation.
1) BTK is important for maturation past pre-B
Once mother stops providing IgG, child gets sick with otitis, sinusitis, pneumonia and diarrhea.
2) Treat with IVIG and sometimes daily prophylactic antibiotics for infections. |
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Term
A patient presents with liver disease and cryptosporidum infection. You notice normal levels of B cells with an abnormally high level of IgM in the serum. You fear the only treatment option is a bone marrow Tx.
What diagnosis have you made? |
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Definition
A Hyper IgM Syndrome called "CD40L deficiency" (X-linked HIGM)
1) CD40L interacts with CD40 on B cells to enable isotope switching and B cell proliferation (also important for macrophage activation and release of GM-CSF).
2) Without CD40L, Ig molecules get stuck as IgM, and cannot become IgA, IgG or IgE.
3) you end up with opportunistic infections, bacterial infections, autoimmunity and cancer.
You can treat CD40 deficiencies with IVIG and antibiotics, but CD40L deficiency requires a transplant. |
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Term
| What is HIGM3? How can you treat? |
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Definition
CD 40 Deficiency of T-cells
Similar manifestation as HIGM1 (CD40L deficiency), with susceptibility to bacterial and opportunistic infections because B cells cannot "class switch"
UNLIKE HIGM1, you can treat HIGM3 with prophylactic antibiotics and IVIG. |
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Term
| What is "Job's Syndrome"? What gene would you analyze with PCR to diagnose? |
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Definition
A Hyper-IgE syndrome (AD-HIES) that presents with baby teeth, bone fragility, hyperextensibility and vascular anomalies
1) STAT 3 mutation
2) Elevated IgE with decreased specific antibody production |
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Term
| How do AD-HIES and AR-HIES differ? |
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Definition
Both are hyper IgE syndromes
AD-HIES involves a STAT 3 mutation leading to bone fractures, delayed shedding of primary teeth and bacterial infections
AR-HIES involves a mutation in either
DOCK 8 (reduced B and T cells with cutaneous viral and staph infections, cancer, atopy and anaphylaxis)
or
TYK2 (Normal T and B cells, and susceptibility to mycobacteria and salmonella) |
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Term
True or False:
In HIES, mutations in DOCK8 lead to reduced B and T cells, while mutations in TYK2 lead to normal B and T cells |
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Definition
| True! Both are Hyper IgE syndromes |
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Term
| What is "Common Variable Immunodeficiency"? (CVID) |
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Definition
B-cell immunodeficiency in older individuals
Reduced levels of one or more Ig and impaired Ab production because of defects in B cell maturation and activation as well as T-cell defects.
1) Recurrent respiratory tract infections
2) Prone to autoimmune and lymphomas
3) TACI/ICOS mutations
4) Treat with IVIG
4) Risk for cancer and bronchiectasis |
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Term
| What is "Selective IgA Deficiency"? |
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Definition
B-cell immunodeficiency
Most common primary immunodeficiency (1:700)
2/3 people are asymptomatic
1) Recurrent infections, autoimmunity, allergy
2) B cells fail to switch to IgA for some unknown reason
3) Treat with prophylactic antibiotics and monitor for development of CVID. |
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Term
| A patient has a defect in NADPH oxidase complex (gp91 phox most common). How did you diagnose? Why are you concerned? |
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Definition
CGD (HSC transplant is cure)
(-) Dihydrorhodamine oxidation assay
Neutrophils and Macrophages can't kill microbes, because they can't generate HOCl!
Granulomatous inflammation from Staph, Serratia, Burkolderia, Nocardia, Candida and Aspergillus Infections.
Treat with prophylaxis with Bactrim (bacteria) and Itraconazole (fungal)
** Can also perform bone marrow Tx** |
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Term
| What is a "Leukocyte Adhesion Deficiency"? How do you treat? |
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Definition
Autosomal Recessive Phagocytic Immunodeficiency
LAD involves impaired leukocyte trafficking with impaired wound healing, periodontitis, absense of pus formation.
LAD 1: Mutation in ITGB2 encoding CD18/b2-integrin (adhesion to endothelial cell)- prophylactic antibiotics
LAD 2: Mutation in GDP-fucose transporter...lack of E selectin ligand...impaired rolling- Fucose supplementation |
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Term
| Why might you see a patient who has an infection without any pus formation and impaired wound healing? |
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Definition
| LAD 1 (ITGB2/CD18) or LAD 2 (GDP-fucose transporter) |
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Term
| A patient presents with partial albinism and giant lysosomes. What is going on? |
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Definition
Chediak Higashi (secretory granule disorder)
Defect in LYST, impaired lysosomal trafficking in leukocytes, causing susceptibility to bacterial infections.
Need a Tx! (often occurs because of inbreeding) |
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Term
| Which B cell defects (immunodeficiency) present early and late? |
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Definition
Early- XLA (Phagocyte disease such as Chediak Higashi, CGD and LAD also presents early)
Late- CVID |
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Term
| What is X_linked hyper-IgM syndrome |
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Definition
Mutations in CD40L prevent
1) T-cell-dependent B cell isotype switching
2) T cell-dependent macrophage activation in cell-mediated immunity |
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Term
| What is caused by defects in C2 and C4? |
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Definition
| Immune complex-mediated diseases resembling lupus (classical pathway) |
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