Exam 3: Dr. Pinchuk Immunodeficiency Diseases Flashcards
What are the affected genes of SCID?
RAG1 or RAG2
What is the immune defect of SCID?
No gene rearrangements in B cells and T cells
What are the affected genes of omenn syndrome?
RAG1 or RAG2 or Artemis
What is the immune defect of omenn syndrome?
Impaired RAG function
What are the affected genes of bare lymphocyte syndrome?
TAP1 or TAP2
What is the immune defect of bare lymphocyte syndrome?
Low MHC class I expression
What are the affected genes of complete DiGeorge’s syndrome?
No known
What is the immune defect of complete DiGeorge’s syndrome?
Absence of the thymus and T cells
What are the affected genes of autoimmune polyendocrinopathy candidiasis ectodermal dystrophy(APECED)?
Autoimmune reglator (AIRE)
What is the immune defect of APECED?
Reduced T cell tolerance to self antigens
What are the affected genes of IPEX?
FOXP3
What is the immune defect of IPEX?
Lack of regulatory T cells and peripheral tolerance
What are rare primary immunodeficiency diseases caused by?
Exceedingly rare mutant alleles of immune genes without selective benefit for the individuals who carry them
Where are rare primary immunodeficiency diseases found?
In small geographically or culturally isolated populations
What do rare primary immunodeficiency diseases help to do?
Recognize the novel forms of immunodeficiency syndrome
What are the primary immunodeficiency diseases?
Dominant
Recessive
X-linked
What do recessive and dominant mutations in the INF-γ receptor cause?
Diseases of different severity
Describe INF-γ
Major cytokine that activates macrophages
Made by NK, Th1 CD4 and cytotoxic CD8 cells
Important in the defense against intravesicular bacteria
What happens in X-linked agammaglobulinemia (XLA)?
B cells do not develop beyond the pre-B cell stage
What is the defect in XLA?
Bruton’s tyrosine kinase protein that contributes to intracellular signaling from the BCR involved in growth and differentiation of pre-B cells
What does antibody deficiency with B cells lead to?
An inability to clear extracellular bacteria
Describe antibody deficiency with T cell help
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
How can antibody deficiency with T cell help be treated?
Regular injection of gamma globulin
What do defect in phagocytes result in?
Enhanced susceptibility to bacterial infection
What do defects in T cell functions cause?
SCID
What are the different SCID phenotypes that can arise?
X-linked deficiency (common gamma chain syndrome and Wiskott-Aldrich syndrome)
Bare lymphocyte syndrome
Describe common gamma chain syndrome
Protein subunit of several cytokine receptors, IL-2, 4, 7, 9, 15
Cytokine signaling is affected
Describe Wiskott-Aldrich syndrome
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
Describe bar lymphocytes syndrome
Lack of MHC class I-II, MHC class I absence is less severe
Describe ADA or PNP deficiencies
Defects in the enzymes are responsible for burin degradation
Accumulation of nucleotide metabolites are extremely toxic to developing T cells
What does HIV infect?
CD4 T cells, macrophages, and DC
What is favored the HIV life cycle?
CD4
What happens at the end of the HIV life cycle?
New viruses are assembled and leave the cell
What does HLA polymorphism do?
Influences the progression of AIDS
What does KIR polymorphism do?
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
What does the genetic deficiency of the CCR5 co-receptor for HIV confer?
Resistance to infection
What makes it difficult to develop a vaccine against HIV and other retroviruses?
High mutation rates
What are potential targets for anti-HIV drugs?
Viral reverse transcriptase that is responsible for the provirus synthesis
Viral protease that cleaves viral proteins
How long does the resistance to protein inhibitors take?
A few days
How long does the resistance to the reverse transcriptase inhibitor zidovudine take?
Months
What is the use of several antiviral drugs called?
Combination therapy or highly active anti-retroviral therapy
What is the purpose of highly active anti-retroviral therapy?
To destroy the entire population of viruses before any one of them has accumulated enough mutations to resist all the drugs
What are the proteins that are anti-viral drugs on the polymerase gene?
Reverse transcriptase
Protease
Integrase enzymes
What is the mechanism of antiviral drugs?
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
What does HIV infection lead to?
Immunodeficiency and death from opportunistic infections
What infections can HIV lead to?
Parasites
Bacteria
Fungi
Viruses
What malignancies can HIV lead to?
Kaposi’s sarcoma
Non-hodgkin’s lymphoma
Primary lymphoma of the brain
