Exam 3: Dr. Pinchuk Immunodeficiency Diseases

Question 1

What are the affected genes of SCID?

Answer 1

RAG1 or RAG2

Question 2

What is the immune defect of SCID?

Answer 2

No gene rearrangements in B cells and T cells

Question 3

What are the affected genes of omenn syndrome?

Answer 3

RAG1 or RAG2 or Artemis

Question 4

What is the immune defect of omenn syndrome?

Answer 4

Impaired RAG function

Question 5

What are the affected genes of bare lymphocyte syndrome?

Answer 5

TAP1 or TAP2

Question 6

What is the immune defect of bare lymphocyte syndrome?

Answer 6

Low MHC class I expression

Question 7

What are the affected genes of complete DiGeorge’s syndrome?

Answer 7

No known

Question 8

What is the immune defect of complete DiGeorge’s syndrome?

Answer 8

Absence of the thymus and T cells

Question 9

What are the affected genes of autoimmune polyendocrinopathy candidiasis ectodermal dystrophy(APECED)?

Answer 9

Autoimmune reglator (AIRE)

Question 10

What is the immune defect of APECED?

Answer 10

Reduced T cell tolerance to self antigens

Question 11

What are the affected genes of IPEX?

Answer 11

FOXP3

Question 12

What is the immune defect of IPEX?

Answer 12

Lack of regulatory T cells and peripheral tolerance

Question 13

What are rare primary immunodeficiency diseases caused by?

Answer 13

Exceedingly rare mutant alleles of immune genes without selective benefit for the individuals who carry them

Question 14

Where are rare primary immunodeficiency diseases found?

Answer 14

In small geographically or culturally isolated populations

Question 15

What do rare primary immunodeficiency diseases help to do?

Answer 15

Recognize the novel forms of immunodeficiency syndrome

Question 16

What are the primary immunodeficiency diseases?

Answer 16

Dominant
Recessive
X-linked

Question 17

What do recessive and dominant mutations in the INF-γ receptor cause?

Answer 17

Diseases of different severity

Question 18

Describe INF-γ

Answer 18

Major cytokine that activates macrophages
Made by NK, Th1 CD4 and cytotoxic CD8 cells
Important in the defense against intravesicular bacteria

Question 19

What happens in X-linked agammaglobulinemia (XLA)?

Answer 19

B cells do not develop beyond the pre-B cell stage

Question 20

What is the defect in XLA?

Answer 20

Bruton’s tyrosine kinase protein that contributes to intracellular signaling from the BCR involved in growth and differentiation of pre-B cells

Question 21

What does antibody deficiency with B cells lead to?

Answer 21

An inability to clear extracellular bacteria

Question 22

Describe antibody deficiency with T cell help

Answer 22

X-linked hyper IgM syndrome
No specific antibody is made against T cell-dependent antigens
IgG, IgA, and IgE are virtually absent, however IgM is extremely high

Question 23

How can antibody deficiency with T cell help be treated?

Answer 23

Regular injection of gamma globulin

Question 24

What do defect in phagocytes result in?

Answer 24

Enhanced susceptibility to bacterial infection

Question 25

What do defects in T cell functions cause?

Answer 25

SCID

Question 26

What are the different SCID phenotypes that can arise?

Answer 26

X-linked deficiency (common gamma chain syndrome and Wiskott-Aldrich syndrome) Bare lymphocyte syndrome

Question 27

Describe common gamma chain syndrome

Answer 27

Protein subunit of several cytokine receptors, IL-2, 4, 7, 9, 15 Cytokine signaling is affected

Question 28

Describe Wiskott-Aldrich syndrome

Answer 28

Involves the impairment of platelets and T cells WASP-protein involved in cytoskeletal reorganization of T cells T cells cannot deliver cytokines and signals to B cells, macrophages, and other target cells

Question 29

Describe bar lymphocytes syndrome

Answer 29

Lack of MHC class I-II, MHC class I absence is less severe

Question 30

Describe ADA or PNP deficiencies

Answer 30

Defects in the enzymes are responsible for burin degradation | Accumulation of nucleotide metabolites are extremely toxic to developing T cells

Question 31

What does HIV infect?

Answer 31

CD4 T cells, macrophages, and DC

Question 32

What is favored the HIV life cycle?

Answer 32

CD4

Question 33

What happens at the end of the HIV life cycle?

Answer 33

New viruses are assembled and leave the cell

Question 34

What does HLA polymorphism do?

Answer 34

Influences the progression of AIDS

Question 35

What does KIR polymorphism do?

Answer 35

Influences the progression of AIDS suggesting that the type of NK cell response at the start of HIV infection affects the relative success of the subsequent adaptive response

Question 36

What does the genetic deficiency of the CCR5 co-receptor for HIV confer?

Answer 36

Resistance to infection

Question 37

What makes it difficult to develop a vaccine against HIV and other retroviruses?

Answer 37

High mutation rates

Question 38

What are potential targets for anti-HIV drugs?

Answer 38

Viral reverse transcriptase that is responsible for the provirus synthesis Viral protease that cleaves viral proteins

Question 39

How long does the resistance to protein inhibitors take?

Answer 39

A few days

Question 40

How long does the resistance to the reverse transcriptase inhibitor zidovudine take?

Answer 40

Months

Question 41

What is the use of several antiviral drugs called?

Answer 41

Combination therapy or highly active anti-retroviral therapy

Question 42

What is the purpose of highly active anti-retroviral therapy?

Answer 42

To destroy the entire population of viruses before any one of them has accumulated enough mutations to resist all the drugs

Question 43

What are the proteins that are anti-viral drugs on the polymerase gene?

Answer 43

Reverse transcriptase Protease Integrase enzymes

Question 44

What is the mechanism of antiviral drugs?

Answer 44

Productive infection of CD4 T cells accounts for more than 99% of virus in plasma Infected cells are short-lived, so HIV must continually infect new cells If virus production is blocked by a drug, the virus is rapidly cleared from the blood CD4 T cell numbers rapidly increase, replacing those lost by infection

Question 45

What does HIV infection lead to?

Answer 45

Immunodeficiency and death from opportunistic infections

Question 46

What infections can HIV lead to?

Answer 46

Parasites Bacteria Fungi Viruses

Question 47

What malignancies can HIV lead to?

Answer 47

Kaposi's sarcoma Non-hodgkin's lymphoma Primary lymphoma of the brain