W13.2 Flashcards
1
Q
Cellular Immunity
A
???
2
Q
T cell f(x) only (ImmunoDef)
A
- DiGeorge Syndrome (DGS)
- Purine Nucleoside Phosphorylase deficiency (PNP)
3
Q
Combined T and B f(x) only (ImmunoDef)
A
- Severe Combined ImmunoDeficiency (SCID)
- Wiskott-Aldrich Syndrome (WAS)
- Ataxia Telengiactasia
4
Q
Varied (ImmunoDef)
A
- Defect can be at many different stages of T-cell development
- Different molecular defects can result in a similar clinical picture (as in SCID)
- Primary defect in cell-mediated immunity may impact humoral immunity
- More difficult to manage than humoral defects
5
Q
ID and GVHD (ImmunoDef)
A
- When cellular ID is treated w bone marrow transplant, higher risk of GVHD
- A severe defect in the T-cell system means donor lymphocytes have higher chance to survive, proliferate, and attack the recipient’s tissues as foreign.
- GvH disease can occur in any individual with a severe defect in cell-mediated immunity (e.g., in bone marrow transplant recipients) and can be fatal.
- GvH disease also occurs in patients who have received a bone marrow transplant for ID.
6
Q
DGS (ImmunoDef)
A
- DiGeorge anomaly is a developmental abnormality of the third and fourth pharyngeal pouches that affects thymic development.
- All organs derived from these embryonic structures can be affected.
- Signs: cardiac anomalies, abnormal facial, thymic hypoplasia, Cleft palate, Hypocalcemia/hypopara thyroidism, Developmentmental retardation
- Quantitative T cell defect: insufficient mature T cells are made, but those that are present are functionally normal.
7
Q
PNP (ImmunoDef)
A
Purine nucleoside phosphorylase (PNP) deficiency
- Rare autosomal recessive trait
- Manifestations: Infants, recurrent or chronic pulmonary infections § oral or cutaneous candidiasis, Diarrhea, skin infections, urinary tract infections, failure to thrive
- PNP enzyme loss shifts purine metabolism to higher levels of phosphorylated nucleotides
- This accumulation is toxic to lymphocytes
- For incompletely understood reasons, affects T cells rather than B cells
8
Q
SCID / Bubble Boy disease (ImmunoDef)
A
- Most serious ID: Early in infancy, infection by nearly any type of organism
- Both B and T cell function is deficient
- Heterogeneous in origin:
- common gamma chain deficiency or X-linked SCID: the most common
- JAK3
- ADA, others
- Bone marrow stem cell transplant therapy
9
Q
X - linked/ common gamma chain SCID (ImmunoDef)
A
- Common gamma chain (IL2RG) deficiency: common chain to receptors for IL-2, 4, 7, 9, 15, and 21
- Gene located on the X chromosomeà Boys only
- Survival and growth signals are missingà T do not mature or survive
- B cells don’t f(x) (may be there though)
10
Q
JAK3 SCID (ImmunoDef)
A
- JAK3 gene is required for processing an interleukin binding signal from the cell membrane to the nucleus.
- This may result in either a T-B+NK+ or a T-B+NK- phenotype, depending on the presence of any additional defect in the JAK3 gene.
- In such cases, no antibody production or lymphocyte proliferative response follows an antigen or mitogen challenge.
11
Q
ADA and other SCIDs (ImmunoDef)
A
Adenosine DeAminase (ADA) gene
- Both B and T cells are killed
- Purine pathway (similar to PNP)
12
Q
WAS (ImmunoDef)
A
- Wiskott-Aldrich syndrome (WAS): rare, X-linked
- Clinical triad: opportunistic infections, eczema + thrombocytopenia
- Usually lethal in childhood: infection, hemorrhage, or malignancy
- Abnormalities exist in both the cellular and humoral arms of the immune system, related to a general defect in antigen processing.
13
Q
WAS pathophysiology (ImmunoDef)
A
- Molecular defect: integral membrane protein CD43 (WASP)
- Defective actin polymerization affects signal transduction in immune cells
- Both T and B cell ImmuneDef
14
Q
WAS lab parameters (ImmunoDef)
A
- Low naturally blood group antigens Abs (isohemagglutinins).
- High levels of serum alpha-fetoprotein
- Low platelet number and size, prolonged bleeding time, bone marrow changes with a normal or somewhat increased number of megakaryocytes
- IgG2, IgA, and IgE are often low or absent
- Decreased circulating T cells
15
Q
AT (ImmunoDef)
A
- Ataxia-telangiectasia (AT)
- Rare, autosomal recessive syndrome
- Cerebellar ataxia
- Telangiectasias, especially on the earlobes and conjunctiva (blood vessels in the sclera of the eyes may be dilated)
- Gene: ATM (Ataxia Telengiectasia Mutated)
- ATM repairs double-strand breaks in DNA
