Immunopathology III

Question 1

describe the bacteria present in a T-cell defect

Answer 1

sepsis due to numerous organisms

Question 2

describe the bacteria present in a B-cell defect

Answer 2

Streptococci, Staphylococci, Haemophilus

Question 3

describe the bacteria present in a granulocyte defect

Answer 3

Staphylococci, Pseudomonas

Question 4

describe the bacteria present in a complement defect

Answer 4

Neisserial infections, pyogenic infections

Question 5

describe the viruses present in a T-cell defect

Answer 5

CMV, EBV, Varicella, respiratory and intestinal viruses

Question 6

describe the viruses present in a B-cell defect

Answer 6

enteroviral encephalitis

Question 7

describe the fungi and parasites present in a T-cell defect

Answer 7

Candida, Pneumocystis jiroveci

Question 8

describe the fungi and parasites present in a B-cell defect

Answer 8

severe intestinal giardiasis

Question 9

describe the basic mechanism and features of DiGeorge syndrome

Answer 9

present at birth

• basic mechanisms: lack of thymic development with subsequent deficient T cell maturation
• features: viral, fungal and protozoal infxns

Question 10

describe the basic mechanism and features of X-linked agammaglobulinemia

Answer 10

present at ~ 6 months

• basic mechanism: BTK mutation with failure of B-cell maturation; no Ig production
• features: pyogenic bacteria; enteroviruses; giardia

Question 11

describe the basic mechanism and features of hyper IgM syndrome

Answer 11

present at 1-4 years

• basic mechanism: mutations in gene encoding CD40L required for T-cell interaction with B-cells and macrophages
• features: pyogenic bacteria; normal or elevated levels of IgM but no IgG, IgE, IgA

Question 12

describe the basic mechanism and features of IgA deficiency

Answer 12

can be asymptomatic

• basic mechanism: impaired differentiation of naive B lymphocytes to IgA-producing cells
• features: sinopulmonary infxns, diarrhea and autoimmune diseases; anaphylactic reactions when transfused with blood containing normal IgA

Question 13

describe the basic mechanism and features of X-linked SCID

Answer 13

presents ~6 months

• basic mechanism: gene mutations coding for γ chain of cytokine receptors (esp. for IL-7)
• features: bacterial, viral, fungal & protozoal infxns

Question 14

describe the basic mechanism and features of autosomal SCID

Answer 14

presents ~6 months

• basic mechanisms: ~50% due to ADA (adenine deaminase) mutation, toxic metabolites accumulate
• features: bacterial, viral, fungal and protozoal infxns

Question 15

describe the basic mechanism and features of common variable immunodeficiency

Answer 15

presents ~2nd or 3rd decade

• basic mechanism: defective Ig production; cause usually unknown
• features: similar to XLA; also autoimmune disease

Question 16

describe the basic mechanism and features of Wiskott-Aldrich syndrome

Answer 16

early onset

• basic mechanism: mutation of proteins linking membrane receptors, such as antigen receptors, to cytoskeletal elements
• features: thrombocytopenia, eczema, recurrent infxns; depletion of T-cells in blood and paracortical area of lymph nodes

Question 17

describe the pathogenesis of HIV

Answer 17

• HIV entry into cells
  
  • gp120 binds to CD4 molecule
    
    • CD4 T cells
    • macrophages
    • dendritic cells
  • gp120 binds to chemokine receptor (CCR5/CXCR4)
  • gp41 penetrates membrane
  • fusion with entry of viral core into cells
  • reverse transcription of viral genome, forming cDNA

Question 18

describe the early/acute phase of HIV

Answer 18

• infection of blood and mucosal lymphoid cells
• transportation to lymph nodes and spleen
  
  • integration of cDNA into genome of dividing T cells
  • viral proliferation
• viremia
• immune response
• nonspecific clinical signs and symptoms; self-limited
• infects many tissues but main targets are immune system and CNS

Question 19

describe the chronic phase of HIV

Answer 19

• clinically latent period
• progressive infection of lymphoid tissue
  
  • immune activation results in increased HIV replication
• progressive destruction of CD4 T cells
  
  • lysis during HIV replication
  • attack by cytotoxic CD8 T cells
  • activation and apoptosis of uninfected CD4 T cells

Question 20

describe the role of the macrophage in the pathogenesis of HIV

Answer 20

• monocytes/macrophages function as HIV reservoirs and replication sites
  
  • HIV can replicate without macrophage division
• circulating monocytes spread HIV
• macrophages major source of HIV in late stages as CD4+ T cell decimated