Immune Response to Microbes

Question 1

Indirect effects of IFN alpha/beta on immunity

Answer 1

• Causes sequestration of lymphocytes in lymph nodes
• Increase cytotoxicity of NK cells, macrophages and CTL
• Promote differentiation of naive Th0 cell to Th1
• Increases Class I MHC expression
• Very important bridges between innate and acquired immunity

Question 2

NK cells

Answer 2

• Incredibly responsive to many cytokines

*Type I IFNs

*IFN-gamma

*IL-2

*IL-15

*Others (IL-12)

• Recognize target cells via KARs and KIRs

*regulate lytic activity

*lysis proceeds (perforin/granzymes; ADCC (NK cells have Fc receptor for IgG)

Question 3

Macrophages

Answer 3

• Act on viruses at 3 levels
  1. Phagocytosis of virus and virally-infected cells
  2. Killing of virally infected cells
  3. Release of antiviral molecules

*IFN alpha

*TNF alpha

*Nitric oxide

Question 4

Specific immune responses to viral infection

Answer 4

• Virus-specific antibodies control viruses when they are EXTRACELLULAR
• Major mechanism for prevention of viral spread b/w cells and tissues
• Importan in restricting viremia (especially IgG)
• IgA at mucosal surfaces: prevents re-infection (remember that viruses often enter via mucosal surfaces)
• Mechanism of antibody action…

Question 5

Antibody roles durin viral infection

Answer 5

• Neutralization of viral infectivity
• Bind to and block viral attachment structure
• Important in re-infection scenarios
• Activation of complement and destruction of enveloped viruses
• Virolysis
• Probably not major clearance mechanism (Complement deficiencies not assoc. w/increased susceptibility to viral infectio)
• Killing of infected cells (INTRACELLULAR virus)

*antibody and complement

*ADCC

Question 6

CD4+ T cells roles during viral infection

Answer 6

• Antiviral antibody production is usually T-dependent (CD4+ Th1 cells)
• Class switching and affinity maturation
• Help in the induction of CD8+ CTL
• Production of cytokines (IL-2, IFN-gamma)
• Recruit and activate macrophages (CD40L and IFN-gamma)

Question 7

CD8+ T cell roles during viral infection

Answer 7

• KILL VIRALLY INFECTED CELLS IN A CLASS I MHC-RESTRICTED, ANTIGEN-SPECIFIC MANNER

*kill via perforin/granzymes

*induction of apoptosis: Fas/FasL

*cytokine production

Question 8

Virchow’s class triad in sepsis

Answer 8

• Changes in coagulation: disseminated intravascular coagulation
• Endothelial cell injury
• Abnormal blood flow
• All 3 are present in sepsis and culminate in:

*reduced blood flow to vital organs: end organ failur/shock

*death

Question 9

Job’s syndrome

Answer 9

• Defective Th17 cells are assoc. w/increased susceptibility to bacterial and fungal infections

Question 10

Innate immune response to intracellular bacteria is mainly mediated by

Answer 10

• Phagocytosis and NK cells
• Initially, phagocytic cells (neutrophils and macrophages ingest and attempt to destroy these pathogens)
• NK cell are induced by intracellular infection

*IL-12 and IL-15 from dendritic cells and macrophages

*NK cells then produce IFN-gamma which acts on macrophages; activation and killing of phagocytosed bacteria

Question 11

Adaptive immune response to intracellular bacteris is mainly mediated by

Answer 11

• THE MAJOR PROTECTIVE IMMUNE RESPONSE AGAINST INTRACELLULAR BACTERIA IS T CELL-MEDIATED IMMUNITY
• NK cells and cytokines only transiently control infection