Primary Immunodeficiencies/Transplants Flashcards
What defect is present in a Type I leukocyte adhesion defect?
Defect in biosynthesis of beta2 chain shared by LFA-1 and Mac-1 integrins
What defect is present in Type II leukocyte adhesion defect?
Absence of sialyl-Lewis X, ligand for E-and P-selectins
What is Chediak Higashi syndrome? What is the gene assoc. with this disorder?
Autosomal recessive condition characterized by defective fusion of phagosomes and lysosomes resulting in defective phagocytes
LYST - encodes a large cytosolic protein which is believed to regulate lysosomal trafficking
What is chronic granulomatous disease?
X-linked inherited defects in genes encoding components of phagocyte oxidase, the phagolysosomal enzyme that generates superoxide - defect in bacterial killing
What is the most common complement protein deficiency? Why do many patients have no clinical manifestations?
C2
No clinical manifestations b/c alternative complement pathway is adequate
What does deficiency in C3 complement protein increase susceptibility to?
Serious and recurrent pyogenic infections
What do deficiencies in C5-C9 complement proteins increase susceptibility to?
Gonococcal and meningococcal infections
What disease is the result of defects in lymphocyte maturation?
SCID - severe combined immunodeficiency
Why do some SCID peds patients develop a rash shortly after birth?
Maternal T cells are transferred across placenta and attack the fetus
What is the most common genetic form of SCID? What is the genetic defect?
X-linked
Genetic defect is mutation in common gamma chain subunit of cytokine receptors, affecting IL-7 which is required for survival of lymphoid progenitors.
About 20% of patients unfortunately develop _______ after receiving viral vector gene therapy for SCID.
T cell lymphoblastic leukemia
What disease is characterized by failure of B cell precursors to develop into mature B cells?
X-linked agammaglobulinemia
What mutation is involved in X-linked agammaglobulinemia?
Mutation in cytoplasmic tyrosine kinase, called Bruton tyrosine kinase (Btk) that is needed for the pre-B cell receptor that delivers signals to nucleus and promotes maturation
Why does X-linked agammaglobulinemia not become apparent until child is about 6 months of age?
This is when the maternal Ig’s are depleted
What are clinical symptoms of X-linked agammaglobulinemia?
Recurrent respiratory tract infections
What disease is a T cell deficiency that results from failure of development of the 3rd and 4th pharyngeal pouches?
DiGeorge syndrome
What clinical manifestations are seen with DiGeorge syndrome?
Tetany - from lack of parathyroids, congenital defects of heart and great vessels, loss of T-cell mediated immunity (from lack of thymus)
What disease encompasses a heterogenous group of disorders in which the common feature is hypogammaglobulinemia, generally affecting all the antibody classes but sometimes only IgG (leading to Ab deficiency)?
Common variable immunodeficiency
What do patients with common variable immunodeficiency commonly present with?
Recurrent sinopulmonary pyogenic infections, about 20% of patients have recurrent herpes infections
What defines a diseases as primary immunodeficiency?
Genetically inherited (vs. HIV/AIDS which is the result of infection and is thus secondary)
Rejection is a process in which _____ and _____ produced against graft antigens react against and destroy tissue grafts
T lymphocytes and Abs
The major antigenic differences between a donor and recipient that result in rejection of transplants are differences in _____ alleles
HLA
In the _____pathway of allorecognition, T cells of the transplant recipient recognize allogeneic (donor) MHC molecules on the surface of APCs in the graft.
direct
It is believed that _______ carried in the donor organs are the most important APCs for initiating the antigraft response, because they not only express high levels of class I and II MHC molecules but also are endowed with costimulatory molecules
dendritic cells
