Blood borne parasites of humans and animals

Question 1

What are the common parasites that live in the blood?

Answer 1

Trypanosomes (African): Trypanosomiasis (sleeping sickness), Nagana disease in cattle
Plasmodia: Malaria
Babesia: Babesiosis (human, cattle, dogs, rodents, birds)
Theileria: East coast fever (cattle)

Question 2

Trypanosomes (T. brucei) life cycle

Answer 2

1. tsetse fly has blood meal
2. injected metacylic trypomastigotes transform into bloodstream trypomastigotes, which are carried to other sites
3. trypomastigotes multiply by binary fission in various body fluids, e.g. blood, lymph
4. trypomastigotes in blood ingested by another tsetse fly
5. trypomastigotes transform into procyclic trypomastigotes in tsetse fly’s midgut; procyclic trypomastigotes multiply by binary fission
6. procyclic tm leave midgut and transform into epimastigotes
7. multiply in salivary gland, transform into metacyclic trypomastigotes
8. tsetse fly takes another blood meal and cycle repeats

Question 3

How do antibodies kill parasites?

Answer 3

Neutralise essential antigens?
Activate complement (MAC) – lyse targets
Act as opsonin’s (facilitate phagocytosis)

Question 4

Immune response to trypanosoma brucei

Answer 4

IgM is effective at killing trypanosomes; doesn’t act as an opsonin
IgM activates complement (MAC)
IgG is more effective at clearing trypanosomes:
a) Higher concentrations in blood
b) Also acts as an opsonin
c) Also activates complement
Phagocytes (macrophages/neutrophils) express Fcgamma receptors

Question 5

Immune response to helminths

Answer 5

IgE predominant antibody
Eosinophils/mast cells; Fcepsilon(3)

Question 6

Trypanosoma brucei

Answer 6

Parasite surface mostly covered by just 1 protein - variable surface glycoprotein (VSG); densely packed; protects more important proteins; IgG less effective against glycoproteins

Question 7

Immune response to T. brucei

Answer 7

For a while the replication rate exceeds the ability of the immune system to destroy parasites
Soon the host produce enough antibodies to kill parasites faster than the parasite can replicate

Question 8

How do parasites escape antibody-mediated killing?

Answer 8

Antigenic drift or shift
T brucei have multiple copies of same gene producing VSG; switches expression to a different VSG gene (epigenetics)
Antibodies to a previous VSG do not
recognise the “new VSG” and the parasite
can grow unchecked until new antibodies
are produced

Question 9

What are Plasmodia parasites?

Answer 9

Single cell apicomplexan (eukaryotic)
Human – P. falciparum and P. vivax
Animals – apes, reptiles, rodents and birds
Mostly host-specific (not zoonotic)

Question 10

Plasmodia life cycle

Answer 10

1. Sporozytes injected when mosquito bites human
2. Human liver stage
3. Merozoites enter human blood cell cycle
4. sexual stage: male/female gametocytes form
5. mosquito stages; mosquito consumes parasite in feeding; gametes form
6. late mosquito stage; oocyst; released as sporozoites again

Question 11

Sporozoites

Answer 11

Do not live for any appreciable time in the blood
Short period to invade hepatocytes (Liver) (minutes)
Circumsporozoite protein (CSP) main surface antigen
Anti-CSP antibodies block invasion

Question 12

The liver stage

Answer 12

Sporozoites infect hepatocytes where they multiply rapidly and develop into merozoites
Intracellular environment protects them against antibodies
Generate cytotoxic T cells that kill infected liver cells
Vaccine R21/matrix-M
Target is circumsporozoite protein (CSP) which is expressed on sporozoites and liver stages

Question 13

Asexual blood stage

Answer 13

1. immature trophozoite in rbc
2. mature trophozoite
3. schizont
4. ruptured schizont; merozoites released from liver and infect more rbc

Question 14

Plasmodia binding

Answer 14

Binding – specific proteins on both the parasite and the rbc, forms a complex
Essential process required for parasite growth – so a key target for vaccines (RH5 in P. falciparum)

Question 15

Plasmodia invasion

Answer 15

Parasite may take several attempts to bind to erythrocytes
Once tightly bound to the erythrocyte surface the merozoite re-orientates so that the apical end is prominent and begins “invasion”
Rhoptry and micronemes – secretory
organelles involved in the invasion process
Invasion is an active process that involves calcium fluxes and active actin-myosin “motors”

Question 16

Asexual blood stages

Answer 16

Parasites have to modify their environment (erythrocyte) - they undergo differentiation and asexual division
-Can produce up to 24 daughter merozoites in 48 hrs
-Surface proteins (PfEMP-1):
Aggregates form knobs that bind to endothelial cells
Binding to endothelial cells (sequestration)
a) May prevent parasitized erythrocytes moving through spleen (areas of high immune surveillance)
b) May be a cause of cerebral malaria
Schizonts are full of merozoites which are released upon schizont rupture and go on to infect new erythrocytes
Factors released during schizont rupture may cause the cytokine storm – and lead to pathology

Question 17

Blood - Plasmodia sexual stage

Answer 17

Male and female (micro and macro gametocytes) survive in host erythrocytes for several days but die if not taken up by mosquitoes
The antigens involved in plasmodium sex are present in mosquitoes, not in the host

Question 17

Asexual blood stages - immunity

Answer 17

IgG main response controlling numbers
Antibodies clear infected rbc (by complement and phagocytosis)
Antibodies can also neutralise (block invasion of new erythrocytes by merozoites)
Plasmodia also use antigenic variation to avoid destruction - most Plasmodium antigens are highly polymorphic
Natural immunity appears to be due to producing antibodies to all the local strains of the parasite

Question 18

Plasmodia in the mosquito

Answer 18

Gamete and Zygote antigens do not
show much antigenic variation
Little selection pressure
Therefore – good Vaccine Target
Transmission blocking vaccines
Mosquito takes up antibodies at the same time as the parasite