Immunology Flashcards
Chediak-Higashi Syndrome
Abnormal intracellular protein transport
- Affects PMNs, lymphocytes, platelets, melanocytes
- Presence of giant granules in neutrophils interferes
with cell’s ability to traverse between endothelial
cells into tissue
- Lysosomes are unable to fuse with phagosomes
no delivery of proteolytic enzymes
Clinical Manifestations:
- Partial oculocutaneous albinism, Photophobia, Rotary nystagmus
- Silvery Hair
- Progressive peripheral neuropathy (teens)
- Mild bleeding diathesis (impaired platelet aggregation)
Recurrent infections:
- Gingivitis/peridontitis
- Skin infections
- Mucous membrane infections
- Respiratory infections
- Entercolitis
- Gram +/- bacteria and fungi
Treatment:
- High dose ascorbic acid for infants and some
children
- Interferon?
- BMT (does not correct or prevent peripheral
neuropathy)
T-cell Defects
T Cell Defects– “WASHeD” - Wiskott-Aldrich -Ataxia-Telangiectasia -Severe Combined Immunodeficiency (SCID) - Hyper IgM, HIV - e - DiGeorge
ATAXIA TELANGIECTASIA
Defect: Inability to repair damaged DNA Clinical Manifestation: Triad - Ataxia, telangiectasias and Immune deficiency Increased risk for Malignancy Genetics: AR Labs: B-cells normal , low IgA and IgE
Tx IVIG and antibiotics
Wisckott Aldrich Syndrome
Triad:
1Small platelets (Thrombocytopenia)
2. Eczema
3. Immune Deficiency
Labs: Decreased T cell numbers (CD3+, CD4+, CD8+) and function; low IgM Prenatal Dx: -chorionic villous sampling - amniocentesis
Treatment:
- IVIG
- BMT
Severe Combined Immune Deficiency
Genetics:
X-linked (MC)
AR = ADA deficiency
Defect: profoundly defective or absent Tcell
and B-cell function; small thymus,
lymphocyte-depleted spleen
Clinical Manifestations:
- Most severe of all the recognized
immune-deficiencies
- Usually presents within first 6 months of life
- May develop severe bacterial-GN sepsis, fungalcandidal,
aspergillus, P. jiroveci, or viral infections-CMV,
disseminated varicella
- FTT, persistent candidiasis, diarrhea,
pneumonia, eczema, seborrhea
*DO NOT GIVE LIVE VACCINES
Tx: BMT
X-linked Hyper-IgM Syndrome
Genetics: X-linked recessive
Defect: Inability to produce antibody specific antibodies
(IgG,IgA, IgE)
* T-cell disorder!!-T-cells unable to signal B cells to undergo isotype switching
Clinical Findings:
Recurrent pyogenic sinopulmonary
infections beginning in 1st or 2nd year of life
- Lymphoid hyperplasia (as opposed to XLA)
- Infections with Pneumocystis carinii, Cryptosporidium
- Extensive verruca vulgaris lesions
- Increased risk of malignancy
Associations:
- Autoimmune disorders (very high)
- Hemolytic anemia
- Thrombocytopenia
- Transient, persistent, or cyclic neutropenia
Labs:
- Elevated IgM
- Low IgG and IgA
- Normal number of B lymphocytes
Treatment:
- HLA-identical BMT at an early age
- IVIG qMonth
- GCSF with cases of severe neutropenia
DiGeorge Syndrome
Associated anomalies:
- C: Cardiac (conotruncal: TOF, truncus arteriosus,
interrupted aorta)
- A: Abnormal facies (short filtrum, low set ears,
hypertelorism, antimongoloid slant)
- T: Thymic hypoplasia-(cellular immune
deficiency: abnormal number and function of T-cells)
-C: Cleft palate
- H: Hypoparathyroidism with Hypocalcemia
- Tetany
- 22: Chromosome 22
B-cell Defect Initial Workup
-Immunoglobulins (IgA, IgG, IgM)
- Antibody titers to tetanus, diphtheria, H.
influenza and S. pneumoniae
B-Cell Defects
- X-Linked Agammaglobulinemia (XLA)
- Common Variable Immunodeficiency
- Selective IgA deficiency
- Transient Hypogammaglobulinemia
- IgG subclass deficiency
- X-Linked Lymphoproliferative disease
X-linked Agammaglobulinemia
Genetics: X-linked Recessive
Clinical Manifestation:
- Boys with recurrent sinopulmonary infections between 6-9
months of life
- Infections with pyogenic organisms (S. pneumo, hemophilus),
Mycoplasma infections, chronic Giardia
- Viruses handled normally except:
Hepatitis, Enteroviruses (meningoencephalitis)
*Hypoplasia of lymphoid tissue
Laboratory Findings:
- Intermittent neutropenia
- Immunoglobulins <5% of normal (IgG, IgE, IgA,
IgM)
- No B/plasma cells on flow cytometry
- Low or absent antibodies to immunization antigens
Treatment:
- Aggressive antibiotics for infections
- IVIG
Common Variable Immunodeficiency
Genetics: unknown– AD with variable expressivity; may have a
common genetic basis with selective IgA deficiency
- Defect: B-cells cannot become plasma cells
- AKA “acquired” hypogammaglobulinemia
Clinical Manifestations:
-Recurrent sinopulmonary infections
usually in older children (approx 10 yo)
- Bacterial infections; Giardia infections common
- Lymphoid tissue present (vs. XLA); Splenomegaly in 25%
Associations:
- GI symptoms/spruelike syndrome/diarrhea/ malabsorption
- Others: thymoma, alopecia areata, hemolytic anemia, gastric
atrophy, pernicious anemia
- High incidence of autoimmune diseases and malignancies
Laboratory Findings:
- Low immunoglobulins
- Normal number of circulating B lymphs on
flow cytometry
Treatment:
- Antibotics
- IVIG qmonth
