Ch. 12 Immunodeficiencies

Question 1

X-linked SCID

Answer 1

• about 50% of SCID
• mutation in gamma chain of cytokine receptor (2,4,7,9,15)
• IL-7 main growth factor for lymphocytes
• mainly affects T-cells - lack of tcell and cell mediated immunity and humoral b/c no helper T-cells
  
  • may have increased number of B-cells but they aren’t activated by CD4 so don’t produce Ig
• NK also cant’ respond to IL-15

Question 2

Autosomal SCID

Answer 2

1. mutation in adenosine deaminase that breaks down purines
   
   • purines build up in DNA synthesizing cells - maturing T/B
   • greater affect on T
2. mutation in kinase in gamma chain cytokine receptor again
3. mutation in RAG that codes for VDJ recombination

Question 3

DiGeorge

Answer 3

• Lack a thymus and parathyroid
• T-cells can’t mature
• improve with age

Question 4

X-linked Agammaglobulinemia

Answer 4

• Bcells don’t mature past pre-B cell

- no humoral immunity

Question 5

SCID treatment

Answer 5

• standard for all is bone marrow transplant

- specific for B-cell disorders - immunoglobulin replacement therapy

Question 6

X-linked hyper-IgM syndrome

Answer 6

• mutation in CD40L on T-cells
  
  • can’t activate B-cells to isotype switch or affinity mat
  • can’t activate macrophages
• can’t switch isotypes so all IgM antibodies

Question 7

Common Variable Immunodeficiency

Answer 7

• don’t have a good antibody response to infections
• low circulating IgA, IgG, IgM
• susceptible to infections, lymphomas, and autoimmune diseases

Question 8

Bare lymphocyte syndrome

Answer 8

Failure to express MHC- II

- decrease in CD4+ helper cells b/c no MHC-II to stimulate their production in thymus

Question 9

Innate Immunity deficiencies

Answer 9

• Chronic Granulomatous disease
• Leukocyte adhesion deficiency
• Complement protein deficiency
• Chediak-Higashi syndrome
  
  • lysosomal disorder - NK and Macrophage problem

Question 10

Wiskott-Aldrich Syndrome

Answer 10

• Eczema, low platelets, immunodeficiency
• X-linked mutation of adapter molecule that links in cytoskeleton and hematopoietc cells
• small platelets and leukocytes that can’t migrate correctly

Question 11

Ataxia-telangiesctasia

Answer 11

• Ataxia (gait abnormalities), vascular malformation (telangiectasia), immunodeficiencies
• mutation in protein for DNA repair - lymphocyte maturation deficiecy
• Mutation in ATM which is involved in DNA repair

Question 12

HIV viral infection

Answer 12

• HIV uses envelope protein gp120 to bind to:
  
  • CD4 molecules on T-cells
  • chemokine CXCR4 on T-cells
  • chemokine CCR5 on dendritic cells and macrophages
• Dendritic cells pick up HIV and then present it to T-cells in lymph organ effectively infecting the CD4 cells
• Viral protease releases RNA from envelope
• reverse transcriptase, integrase,
• viral genes transcribed and viral products made in response to cytokines
• leads to initial viremia and body defends with normal immune response - really just spreads infection
• CD4 numbers decrease as progesses to AIDs