Chapter 13

Question 1

What is antigenic drift?

Answer 1

• small changes in virus antigens (hemagglutinin=HA)
  
  • due to mutations
  • antibodies cannot bind to new antigen -> primary response again
• HA needed for virus to bind to cell surface and infect the cells

Question 2

What is antigenic shift?

Answer 2

• virus undergoes a major change
  
  • new strain with significantly different antigens
• genetic reassortment: 2 different strains of virus infect the same cell
  
  • new combination of viral antigens -> new strain produced (never encountered before)

Question 3

What is gene conversion?

Answer 3

• process whereby one copy of a gene is replaced by a different version of that gene
  
  • in its antigens
  • cannot be recognised by the same antibodies
• deposition of immune complexes -> inflammation
• used by trypanosome

Question 4

How does a virus reduce presentation of its antigens by MHC class I?

Answer 4

• degradation of MHC class I
• subverting proteasome
• interfering with TAP and tapasin
• retention of MHC in ER
• this favours NK-cell presponse

Question 5

What is the mode of action for herpesviruses?

Answer 5

• invasion of host cells (lytic phase) -> cells die
• termination of lytic phase -> dormant state = latency
• when host is subjected to stress, virus is reactivated

Question 6

How do viruses reduce NK-cell response?

Answer 6

• production of proteins interfering with recognition of missing-self-MHC-class I by NK receptors
• also for recognition of MIC glycoproteins by activating NKG2D

Question 7

What is the role of bacterial superantigens?

Answer 7

• bind to MHC class II on B cells
• bind T cell receptor and CD28
  
  • activation fo CD4 T cells (many kinds)
  • causing rapid immune adaptive immune response
• confusion of innate immunity -> no phagocytosis of bacteria that just crossed the mucosa

Question 8

What is the role of SSLP7?

Answer 8

• protein prevents monomeric IgA from delivering bacteria to phagocytes
• SSLP7 has binding sites for Fc of IgA and C5 (complement protein)
  
  • bound simultaneously to those two -> immune response cannot occur

Question 9

What is the cause and result of IFN-y receptor deficiency?

Answer 9

• caused by mutation (recessive or dominant) in IFNyR1 receptor gene
• dominant: eliminates residues on tails needed for starting cascade
  
  • heterozygous are also affected (receptor is a dimer) -> to a lesser degree
  • 2 alleles are needed for a functional receptor (only 25% of receptors are functional)
• recessive: lack of IFNyR1

Question 10

What is X-linked agammaglobulinemia (XLA)?

Answer 10

• an example of antibody deficiency
• X-linked disease (more common in men)
• B cells do not develop beyond pre-B-cell stage

Question 11

What happens when CD40 ligand is not expressed?

Answer 11

• helper T cells are not functioning properly
• cannot activate B cells
• T cell dependent antigens not targeted
  
  • high levels of IgM (no isotype switching)
• no activation of macrophages by T cells
  
  • no activation of neutrophils

Question 12

What happens complement is not activated?

Answer 12

• complement deficiency (ex: in C3)
• immune complexes accumulate on erythrocytes
  
  • damage to tissue -> inflammation
  • immune-complex disease
• antibody-mediated immunity also impaired

Question 13

What are the consequences of T cell defects?

Answer 13

• mutation in X-chromosome gene encoding common gamma chain
  
  • signalling component of cell-surface receptors for IL-2, -4, -7, -9, -15 cytokines
  • upon binding there is no signal
• MHC class II deficiency
  
  • CD4 T cells fail to develop (no interactions in thymus)
  • homozygous defect in HLA genes
• defect in one of the two proteins forming TAP peptide transporter
  
  • no peptide binding by HLA class I
  • reduced recruitment of CD8 T cells

Question 14

What is HIV?

Answer 14

• human immunodeficiency virus causing acquired immune deficiency syndrome (AIDS)
  
  • RNA virus
  • retrovirus = RNA genome used to synthesise DNA intermediate (backwards = retro)
    
    • by reverse transcriptase into cDNA
    • viral proteins made
• lentivirus = slow in progression

Question 15

Which cells does HIV target?

Answer 15

• CD4-expressing cell: macrophages, T cells, DCs
  
  • CCR5 interaction is also needed for virus to enter the cell, CCR5 acts as a co-receptor
  • viral phenoty can switch to bind CXCR4 on activated T cells (later on in the progression of the disease)
    
    • the latter causes immunodeficiency (AIDS) -> targeting CD4 T cells

Question 16

What is the life cycle of HIV in human cells?

Answer 16

• infected CD4 T cell activated
  
  • synthesis of NFkB -> activates promoters in provirus
  • trascription of viral RNA
• proteins encoded by virus promote replication of viral genome
  
  • Tat protein prevents transcription from shutting off
  • Rev protein controls supplu of viral RNA to cytoplasm and extent of splicing
• virions with viral RNA assembled
  
  • bud from cell

Question 17

Why is HIV resistant to immune response?

Answer 17

• high mutation rate
  
  • new variant glycoproteins is not recognised by antibodies
  • reverse transcriptase has no proofreading -> many mistakes
• drugs usually target reverse transcriptase
  
  • successful in preventing infection of baby from an infected mother
  • combination therapy (anti-retroviral therapy) with viral protease inhibitor
    
    • prevents infection of new cells (but doesn’t help the already infected ones)
• mutations also produce drug-resistant proteins

Question 18

What are the consequences of HIV infection?

Answer 18

• lack of CD4 T cells
  
  • number of cells gradually decreases
  • during clinical latency (low HIV activity), many cells are produced and many killed
• increased susceptibility of infected cells to apoptosis (progression to AIDS)
  
  • infection by opportunistic pathogens
  • in oral and respiratory tract
• killing by CD8 T cells
  
  • recognise viral peptide on MHC class I on CD4 T cells