EXAM #1: HOST DEFENSE Flashcards
What is the “cytopathic effect” associated with viruses?
Virus induced lysis of host cells
How does the skin prevent viral infection?
Keratinization prevents viral entry into the body
How does the alimentary tract prevent viral infection? What type of virus is better suited to gain entry via the alimentary tract?
1) Acid and proteolytic enzymes break down viruses
2) Bile destroys ENVELOPED viruses
*Thus, naked viruses do a little better
How does the respiratory tract prevent viral infection?
1) Mucus traps virus and via the mucocilliary escalator it is destroyed the stomach acid
2) Nasal turbinates impede viral entry
What are the major components of the innate immune system that defend against viral infection?
1) TYPE I interferon*
2) NK Cells
3) Macrophages
*(a/B vs. gamma that is TYPE II)
Describe the role of interferon in preventing viral infection. What is the difference between the sources of alpha and beta interferon?
1) Virus stimulates a/B interferon (TYPE I)
2) Interferons SURROUND infected cells
3) This inhibits viral replication/infection in ADJACENT cells
*Note that a is produced by leukocytes, B is produced by fibroblasts, BUT they both act on the same IFN receptor
List four actions of interferon a/b.
1) Prevent viral replication in surrounding cells
2) Increase MHC I expression*
3) Activate dendritic cells and macrophages
4) Activate NK cells to kill virus infected cells
*Increases the CD8 T-cell response
What is the MOA of interferon to inhibit viral replication? Draw the specific pathway.
1) a/B IFN binds IFN receptor
2) mRNA is degraded and eIF2 is inactivated
3) END RESULT: inhibition or protein synthesis, interrupting viral replication
What immune cell-type is the first line of defense against virus infected cells?
NK cells
Describe how NK cells are activated.
- Virus infected cells downregulate MHC I to prevent CTL killing
- NK cells are a back-up: they are RELEASED from INACTIVE STATE absence of MHC I proteins
*NK cell activity is also activated by IFN a/b (TYPE I)
What is the mechanism by which NK cells kill virus infected cells?
ADCC–antibody dependent cell mediated cytotoxicity
- IgG/NK cell Fc receptors bind, triggering ADCC i.e. killing of the target cell
What mediates the anti-viral effects of macrophages?
TNF-alpha and NO
What is the downside of the macrophage response to viral infection?
Some viruses can hijack macrophages i.e. infect macrophages to facilitate viral spread
*CMV, Ebola, HIV, measles, and rubella
When is humoral immunity most important in viral infection?
EARLY
When is cell mediated immunity most important in viral infection?
Once infection is ESTABLISHED (CTLs)
How do antibodies function in viral infection?
1) Prevent binding to target cell
2) Opsonization
3) Activate complement
4) Facilitate ADCC by NK cells
5) Downregulate expression of viral genes
What is needed for a CTL to kill a virus infected cell?
Virus bound the MHC Class I
How does the B and T cell memory response differ?
T cells= quiescent until reactivated
B cells= production of antibody for decades post-infection
What are the predominate innate immunity mechanisms against intracellular bacteria?
1) Macrophages release IL-12; IL-12 activates NK cells
2) NK cells release IFN-g (TYPE II IFN), which further activates macrophages
- IFN-g ramps up macrophage production of NO
What are the adaptive immune system responses to intracellular bacteria?
1) DTH-like reaction i.e. T-cells are activated and produce IFN-g ramping up macrophages
2) Some bacteria may persist, so the body responds by walling it off in a granuloma
What cytokine drives Th1 mediated responses?
IL-12
What cytokine drives Th2 immunity?
IL-4
How can intracellular bacteria be targeted by CTLs?
- Bacteria escapes from phagosomes into cytosol
- Processing and expression on MHC Class I activates CLTs
From an immunological standpoint, what is the difference between Tuberculoid and Lepromatous leprosy? Which form will show hypergammaglobulinemia?
Tuberculoid= Th1 mediated
Lepromatous= Th2 mediated
- Hypergammaglobulinemia
What type of T-cell response drives granuloma formation, Th1 or Th2?
Th1 and IL-12 production
