L5 protozoan immunology Flashcards
What stages does Typanosoma have in the mammalian host and insect host?
Sleeping sickness
Insect: Procyclic form in midgut, Metacyclic form in Salivary glands
Mammal: Long slender form in blood, Short stumpy form in blood.
What is the mammalian response to Trypanosoma infection
Response is antibody dependent, IgM.
Effective antibody function, in 20 mins, 10^7 parasites cleared from blood.
Causes complement cascade to activate and destroy cells.
Phagocytosis in liver
In a trypanosoma infection why are there peaks and troughs of no. parasites in blood?
Each has a different antigen, parasite is exploiting specificity of immune system and stays ahead of host by changing antigen.
Once one type becomes common it is removed. Immune response is only against the most dominant type. Frequency dependent response.
What is VSG in trypanosoma?
What is the conversion process?
Variant Specific Glycoprotein
10% dry mass of parasite
Each cell has 1 antigenic type at a time, but can change the VSG expressed.
Different gene for each VSG - gene conversion process.
Gene from library of variants (in a transcriptionally silent site) get copied into the genome and the old one is removed.
Why is plasmodium challenging for the immune system?
MALARIA
Plasmodium Lifecycle is in many different organs of host, so must have many parts and the antigens for each stage may not be related.
What is CSP? How would a vaccine work?
CSP - Circum Sporozoites Protein on surface of plasmodium.
Using CSP we have experimentally made very strong immmune response, and an effective immunisation with irradiated sporozoites.
Antibodies can cover sporozoite cell, preventing molecular communication.
Why does malaria persist?
Sporozoite stage is breif, 45mins so limited exposure to immune system. Hosts don’t become immune.
Different strains have CSP variation. in Africa, many different types of malaria parasite.
How does trypanosome and plasmodium antigenic variation differ?
Trypanosome - intergenome. individual trypanosomes can change themselves.
Plasmodium - interstrain. Individual plasmodiums cant change themselves.
What does malaria form in the liver?
Schizont
contains merocytes
exo-erythrocytic stage
Describe the schizont stage of plasmodium
Exposed to host immune system
parasite molecules expressed on host hepatocyte surface. with MHC 1 molecules.
Hepatocytes are short lived, so poor immune response.
What stage comes after the schizont stage of malaria?
What does it do?
Erythrocytic stage, most genetically diverse. Merozoites leave liver and enter RBC: to form gametocytes, or grow into schizonts and release more merozoites.
RBC dont express MHC1 so no antigen presentation. ineffective Tc responses to RBC
What is the dominant molecule on merozoites? Why does this make immunisation difficult?
MSP - Merozoite surface protein
in vitro, antibody binds to MSP and blocks its ability to invade RBC.
However is antigenically diverse, and there is inefficient cross immunity. Strain specific immune responses.
What types of malaria are there?
K1 - 5 alleles of MSP
MAD20 - 14 alleles for MSP
How can immunity to malaria develop?
Need sustained exposure to infection to develop immunity to parasite, over many years will see many types and produce antibodies for each type.
This is why transient travellers get affected more.
Anti malaria immune memory is short lived.
