D2. Parasite immunity

Question 1

Plasmodium

Answer 1

Malaria/ RBC have no MHC = easy target
natural resistance: sickle cell anaemia
Immune suppression: polyclonal B cell activation, strong correlation between Burkitt’s Lymphoma caused by EBV

Question 2

Leishmaniasis

Answer 2

promastigote: flagellum is anterior of nucleus & free from the cell body
Intracellular amastigote: protist cell that don’t have visible external flagella or cilia

Question 3

cutaneous leishmaniasis - healing responses

Answer 3

Healing response:
Leishmania major or Leishmania mexicana
CMI important, Macrophage/dendritic cell: IL-12 activates macrophages to kill intramacrophage parasite, IFNy from NK cells, Th1 cell activate macrophages, Activated macrophages - produce microbicidal products e.g. Superoxide, NO, enzymes - for parasites

Question 4

cutaneous leishmaniasis - non healing responses

Answer 4

No activation of macrophages, Th2 dependent, IL-4 drives Th2 response (macrophages off ), Th2 cells produce IL4/IL-13, IL-4/IL-13 inhibit a Th1 response by inhibiting IL-12 production or preventing IL-12Rβ2 expression.
IL-4/IL-13 inhibit IFNy production & activity

Question 5

Toxoplasma gondii

Answer 5

CMI response most important: humoral response may also have effect
Parasite can live in any cell!
CD8+ T cells producing IFNy main mediators of resistance
In AIDs patients dormant tissue cysts in the brain reactive resulting in encephalitis
IgA may play role in protecting gut mucosa
IgG coated parasites are killed inside macrophages following phagolysosome fusion

Question 6

Trypanosoma brucei

Answer 6

Adaptive immune: B cells: IgM directed against the variant surface glycoprotein
Can kill parasite but it changes its surface coat antigen - antigenic variation
Th1 response - production IFNy acts on macrophages: Reactive O2 intermediates & reactive N intermediates
IFNy –> Macrophages: produce toxic products (NO)

Question 7

which parasite shows best example of antigen variation

Answer 7

Tyrapansoma brucei

Question 8

Antigenic variation

Answer 8

Each peak parasitaemia associated w/ a variant antigen type VAT
Each VAT is associated w/ parasites expressing a variant surface glycoprotein VSG
Parasites can express >1000 VSG’s
Switches occur spontaneously every 100 divisions
Each new variant induces IgM which mediates parasite killing
every VAT (>1000 antigens)

Question 9

Trypanosoma cruzi

Answer 9

Chagas disease
Acute phase involving macrophage infection: 5-10% mortality
Chronic phase: muscle cells infected: cardiopathy/ gastrointestinal disturbances
Infects macrophages inside muscles
Parasites live in macrophages/ muscle cells
CMI important - need IFNy to stimulate macrophages
Cytotoxic T cells kill infected muscle cells

Autoimmunity in Chagas disease
Is pathology caused by autoimmunity induced by the parasite?
Severe clinical disease associated CD8+ T cells
Indeterminate clinical form associated w/ high freq of CD4+CD25+ regulatory T cells & NKT regulatory cells

Question 10

Autoimmunity

Answer 10

Autoimmunity: Antigens on parasite – so like ones of own body = immune response attack own body
Treg cells stop autoimmunity

Question 11

Gut nematodes

Answer 11

MULTICELLULAR 
Need to expel parasite from gut 
Increased mucus production 
Increased peristalsis 
Immunity cell-mediated: Th2 response  - need IL-4 production e.g. Trichuris 
Too big more macrophage/ neutrophil 
Unable to destroy through gran