Malaria

Question 1

Hepatocytes infected with sporozoites release Type I Interferon to produce an anti-viral state in the liver. Why is this a protective innate response against malaria? (Select all statements that are true).

–Signals to neighbouring hepatocytes to reduce their chance of infection.
–Induces apoptosis of infected hepatocytes.
–Generates an IgG antibody response to neutralise sporozoites when they enter the liver.
–Upregulates Class I MHC on infected hepatocytes to increase their recognition and killing by Cytotoxic T Lymphocytes.
–Promotes production of nitric oxide by infected hepatocytes to kill sporozoites.

Answer 1

• True
  -False
  -False
  -True
  -False

Type I Interferon is produced by hepatocytes infected with sporozoites. This cytokine signals to neighbouring cells to make them less permissive to infection, and also increases their expression of Class I MHC so that should they become infected they are more likely to be recognised and killed by Cytotoxic T Lymphocytes (CTL). It is CTL that induce apoptosis of infected hepatocytes either through ligation of Fas (a death receptor expressed by the hepatocyte) or via release of perforin and granzyme molecules.

Question 2

Match the cytokine with its function in malaria.

-TNF
-IL-10
-IFN-γ

-Induces fever and promotes parasite killing
-Activates macrophages
-Regulates the immune response to malaria

Answer 2

TNF- fever and parasite killing
IL-10- Regulates immune response
IFN-γ- activates macrophages

IFN-γ is produced by NK cells and helper T cells and promotes the activation of macrophages. This increases their capacity to phagocytose infected red blood cells and upregulates their killing mechanisms (such as production of nitric oxide). Activated macrophages also make a lot of TNF, which at high concentrations is toxic to malaria parasites. TNF is also the hallmark proinflammatory cytokine produced during malaria; it is important for driving inflammation and raising body temperature. IL-10 is produced by helper T cells later in infection, and is important to counterbalance the proinflammatory response. This makes sure that activated macrophages, and the cytokines TNF and IFN-γ, don’t cause excessive tissue damage that could contribute to severe disease (immunopathology).

Question 3

How is an immune response primed to kill an intracellular pathogen, such as a sporozoite?

which antigen processing & presentation parthway is involved?
- what are the methods of killing?

Question 4

How does the innate immune system recognise pathogens, such as the blood-stage malaria parasite?

• what are the key cell type(s) and the molecules involved in recognition?
• which effector molecules do innate cells release and why?

Question 5

What is the 2-way interaction between the innate and adaptive immune response that is required to clear blood-stage malaria parasites?

• how does the innate immune system initiate an adaptive response?
• how does the adaptive immune response help innate cells kill pathogens?

Question 6

What are possible unwanted side-effects of an immune response?

Question 7

Give an example of immunopathology in malaria. How does the immune system self-regulate to prevent immunopathology?

Question 8

How can the immune system can provide protection against reinfection?

Question 9

What are the central characteristics of immune memory?

Question 10

How do pathogens, such as malaria parasites, overcome immune memory?