Primary Immunodeficiencies/Transplants

Question 1

What defect is present in a Type I leukocyte adhesion defect?

Answer 1

Defect in biosynthesis of beta2 chain shared by LFA-1 and Mac-1 integrins

Question 2

What defect is present in Type II leukocyte adhesion defect?

Answer 2

Absence of sialyl-Lewis X, ligand for E-and P-selectins

Question 3

What is Chediak Higashi syndrome? What is the gene assoc. with this disorder?

Answer 3

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

Question 4

What is chronic granulomatous disease?

Answer 4

X-linked inherited defects in genes encoding components of phagocyte oxidase, the phagolysosomal enzyme that generates superoxide - defect in bacterial killing

Question 5

What is the most common complement protein deficiency? Why do many patients have no clinical manifestations?

Answer 5

C2

No clinical manifestations b/c alternative complement pathway is adequate

Question 6

What does deficiency in C3 complement protein increase susceptibility to?

Answer 6

Serious and recurrent pyogenic infections

Question 7

What do deficiencies in C5-C9 complement proteins increase susceptibility to?

Answer 7

Gonococcal and meningococcal infections

Question 8

What disease is the result of defects in lymphocyte maturation?

Answer 8

SCID - severe combined immunodeficiency

Question 9

Why do some SCID peds patients develop a rash shortly after birth?

Answer 9

Maternal T cells are transferred across placenta and attack the fetus

Question 10

What is the most common genetic form of SCID? What is the genetic defect?

Answer 10

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.

Question 11

About 20% of patients unfortunately develop _______ after receiving viral vector gene therapy for SCID.

Answer 11

T cell lymphoblastic leukemia

Question 12

What disease is characterized by failure of B cell precursors to develop into mature B cells?

Answer 12

X-linked agammaglobulinemia

Question 13

What mutation is involved in X-linked agammaglobulinemia?

Answer 13

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

Question 14

Why does X-linked agammaglobulinemia not become apparent until child is about 6 months of age?

Answer 14

This is when the maternal Ig’s are depleted

Question 15

What are clinical symptoms of X-linked agammaglobulinemia?

Answer 15

Recurrent respiratory tract infections

Question 16

What disease is a T cell deficiency that results from failure of development of the 3rd and 4th pharyngeal pouches?

Answer 16

DiGeorge syndrome

Question 17

What clinical manifestations are seen with DiGeorge syndrome?

Answer 17

Tetany - from lack of parathyroids, congenital defects of heart and great vessels, loss of T-cell mediated immunity (from lack of thymus)

Question 18

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)?

Answer 18

Common variable immunodeficiency

Question 19

What do patients with common variable immunodeficiency commonly present with?

Answer 19

Recurrent sinopulmonary pyogenic infections, about 20% of patients have recurrent herpes infections

Question 20

What defines a diseases as primary immunodeficiency?

Answer 20

Genetically inherited (vs. HIV/AIDS which is the result of infection and is thus secondary)

Question 21

Rejection is a process in which _____ and _____ produced against graft antigens react against and destroy tissue grafts

Answer 21

T lymphocytes and Abs

Question 22

The major antigenic differences between a donor and recipient that result in rejection of transplants are differences in _____ alleles

Answer 22

HLA

Question 23

In the _____pathway of allorecognition, T cells of the transplant recipient recognize allogeneic (donor) MHC molecules on the surface of APCs in the graft.

Answer 23

direct

Question 24

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

Answer 24

dendritic cells

Question 25

In the_____ pathway, recipient T lymphocytes recognize MHC antigens of the graft donor after they have presented to the recipient’s own APCs. This process involves the uptake and processing of MHC molecules from the grafted organ by host APCs. The peptides derived from the donor tissue are presented by the host’s own MHC molecules, like any other foreign peptide.

Answer 25

indirect

Question 26

______ cellular rejection is an inflammatory reaction in the graft triggered by cytokines released by activated CD4+ T cells. The inflammation results in increased vascular permeability and local accumulation of mononuclear cells and graft injury is caused by the activated macrophages.

Answer 26

Acute

Question 27

_____ rejection consists of lymphocytes reacting against alloantigens in the vessel wall that secrete cytokines that induce local inflammation and may stimulate the proliferation of vascular endothelial and smooth muscle cells

Answer 27

Chronic

Question 28

_______ rejection occurs when preformed antidonor antibodies are present in the circulation of the recipient

Answer 28

Hyperacute

Question 29

In what organ transplant are there substantial benefits if all the HLA alleles are matched?

Answer 29

Kidney

Question 30

What immunosuppressive drug is often used with transplants and inhibits phosphate calcineurin, which is required for activation of transcription factor NFAT which stimulates transcription of IL-2?

Answer 30

Tacrolimus - inhibits T cell functions

Question 31

What is one of the most frequent opportunistic infections that arises from immunosuppresion administered to prolong graft survival?

Answer 31

Polyoma virus - latent infection of epithelial cels in lower GU tract