Protists Notes

Protists — Host–Pathogen Interactions

Based on lecture slides and transcript

1. Introduction to Protists

  • Protists are single-celled eukaryotic organisms that contain membrane-bound organelles and a nucleus.

  • They are highly diverse organisms and do not fit neatly into the plant, animal or fungal kingdoms.

  • Some protists are free-living, while others are important human pathogens.

  • The lecture focused mainly on protozoan parasites that interact closely with the human immune system.

  • Key examples discussed were:

    • Toxoplasma gondii

    • Plasmodium species

    • Trypanosoma brucei

2. Host Immune Responses Against Protists

Innate Immunity

  • Innate immunity provides the first rapid response against protozoan parasites.

  • It is non-specific and recognises broad pathogen-associated molecular patterns (PAMPs).

  • Important components include:

    • macrophages

    • dendritic cells

    • neutrophils

    • natural killer (NK) cells

    • inflammatory cytokines

Adaptive Immunity

  • Adaptive immunity is slower but highly specific.

  • B cells produce antibodies that help neutralise extracellular parasites or parasite antigens.

  • CD4 helper T cells coordinate immune responses through cytokine production.

  • CD8 cytotoxic T cells kill infected host cells containing intracellular parasites.

  • Adaptive immunity also generates immunological memory.

3. Toxoplasma gondii

General Features

  • Toxoplasma gondii is an intracellular protozoan parasite.

  • It infects many warm-blooded animals.

  • Cats are the definitive host where sexual reproduction occurs.

  • Humans and other mammals are intermediate hosts.

  • Approximately 30% of humans are infected worldwide.

  • Most healthy individuals remain asymptomatic because the immune system controls the infection.

4. Transmission of Toxoplasma gondii

Humans can become infected through:

  • contact with cat faeces containing oocysts

  • contaminated soil, food or water

  • eating undercooked meat containing tissue cysts

  • congenital transmission from mother to fetus

  • organ transplantation

  • unpasteurised milk

5. Lifecycle Stages of T. gondii

Tachyzoites

  • Tachyzoites are the rapidly dividing form of the parasite.

  • They are responsible for acute infection and dissemination through the body.

  • They invade host cells and replicate intracellularly.

Bradyzoites

  • Bradyzoites are slow-growing forms found inside tissue cysts.

  • They are associated with chronic infection.

  • Tissue cysts are commonly found in muscle and neural tissue.

  • Bradyzoites are highly important for immune evasion because they can remain dormant for long periods.

Sporozoites

  • Sporozoites are found inside environmentally resistant oocysts.

  • They infect epithelial cells after ingestion.

6. Disease Caused by T. gondii

  • Most infections are asymptomatic in immunocompetent individuals.

  • Symptomatic disease can include:

    • lymphadenopathy

    • encephalitis

    • myocarditis

    • hepatitis

    • sepsis-like disease

High-risk groups

Pregnant women

  • Congenital infection can damage the fetus.

  • Can cause neurological defects and blindness.

Immunocompromised individuals

  • Particularly dangerous in AIDS patients.

  • Dormant bradyzoite cysts can reactivate.

  • Reactivation commonly causes toxoplasmic encephalitis.

7. Immune Recognition of T. gondii

  • The innate immune system recognises parasite nucleic acids using pattern recognition receptors.

  • Human TLR7 and TLR9 recognise:

    • parasite RNA

    • G-rich parasite DNA

IL-12 Production

  • Recognition of the parasite stimulates IL-12 production.

  • IL-12 is one of the most important cytokines in resistance to T. gondii.

  • IL-12 activates:

    • NK cells

    • CD4 helper T cells

    • CD8 cytotoxic T cells

8. Elimination of T. gondii

IFN-γ

  • IFN-γ is the key cytokine controlling T. gondii infection.

  • It activates antimicrobial mechanisms inside infected cells.

TNF-α

  • TNF-α works alongside IFN-γ to enhance inflammation and parasite killing.

Inducible Nitric Oxide Synthase (iNOS)

  • IFN-γ stimulates iNOS production.

  • Nitric oxide damages the parasitophorous vacuole surrounding the parasite.

  • This inhibits parasite replication and promotes parasite killing.

9. Immune Evasion by T. gondii

Inhibition of Host Signalling

  • T. gondii interferes with host signalling pathways to reduce immune activation.

  • ROP proteins such as ROP16 and ROP55 manipulate host immune responses.

  • The parasite suppresses IL-12 signalling to weaken immunity.

Bradyzoite Cyst Formation

  • The most important immune evasion strategy is formation of bradyzoite tissue cysts.

  • Bradyzoites enter a dormant state inside tissues.

  • Dormancy allows the parasite to avoid immune clearance.

  • These cysts can reactivate later if immunity weakens.

10. T. gondii as a Model Organism

  • T. gondii is commonly used as a model organism for studying malaria parasites.

  • Both belong to the Apicomplexa group.

  • Both have sexual and asexual lifecycles.

Advantages of T. gondii for research:

  • easier to culture

  • larger parasite size

  • easier genetic manipulation

11. Malaria — Plasmodium Species

Epidemiology

  • Malaria remains one of the world’s most important infectious diseases.

  • In 2023 there were approximately:

    • 263 million cases

    • 597,000 deaths

  • Most deaths occur in sub-Saharan Africa.

12. Lifecycle of Plasmodium

Mosquito Stage

  • Sexual reproduction occurs in the female Anopheles mosquito.

Liver Stage

  • Sporozoites infect hepatocytes after entering the bloodstream.

  • Parasites undergo asexual replication in the liver.

Blood Stage

  • Merozoites infect red blood cells.

  • Repeated RBC infection and destruction causes disease symptoms.

13. Important Human Malaria Species

  • Plasmodium falciparum

  • Plasmodium vivax

  • Plasmodium ovale

  • Plasmodium malariae

Most severe species

Plasmodium falciparum

  • Causes the majority of severe malaria and malaria deaths.

  • Associated with cerebral malaria.

14. Symptoms of Malaria

Common symptoms include:

  • fever

  • chills

  • sweating

  • headache

  • nausea

  • muscle pain

Severe complications

Severe anaemia

  • Caused by destruction of red blood cells.

Cerebral malaria

  • Caused mainly by P. falciparum.

  • Can lead to coma and death.

15. Immune Response to Malaria

Recognition

  • Parasite molecules are recognised by:

    • TLR7

    • TLR9

    • TLR2

  • This activates:

    • MAPK signalling

    • NF-κB

    • inflammatory cytokine production

Immune Cells Involved

  • macrophages

  • dendritic cells

  • NK cells

  • B cells

  • T cells

Elimination Mechanisms

  • oxidative burst

  • cytokine-mediated killing

  • antibody production

  • phagocytosis

16. Antigenic Variation in Malaria

PfEMP1

  • PfEMP1 is a major virulence protein expressed on infected RBCs.

  • It is encoded by approximately 60 different var genes.

Key mechanism

  • Only one var gene is expressed at a time.

  • When antibodies recognise one PfEMP1 variant, the parasite switches expression to another variant.

  • This allows immune evasion and persistent infection.

17. Sequestration and Cerebral Malaria

Sequestration

  • Infected RBCs adhere to endothelial cells and avoid splenic clearance.

  • Infected RBCs can also bind to uninfected RBCs, called rosetting.

Important proteins

  • PfEMP1

  • RIFIN

  • STEVOR

Consequences

  • capillary blockage

  • severe inflammation

  • reduced blood flow

  • tissue damage

Cerebral malaria

  • Blockage of brain capillaries leads to neurological disease.

  • Severe inflammation contributes to coma and death.

18. Trypanosomes

Human African Trypanosomiasis

  • Also called sleeping sickness.

  • Caused by Trypanosoma brucei.

  • Transmitted by the tsetse fly.

19. Important Species

Trypanosoma brucei gambiense

  • Causes chronic disease progression.

Trypanosoma brucei rhodesiense

  • Causes more acute disease.

20. Lifecycle Forms of Trypanosomes

Slender Form

  • Dividing form in bloodstream.

  • Responsible for tissue invasion.

Stumpy Form

  • Non-dividing transmission form.

  • Taken up by tsetse flies.

Metacyclic Form

  • Infective form transmitted to humans.

21. Clinical Progression of Sleeping Sickness

Stage 1 — Haemolymphatic Stage

Symptoms include:

  • fever

  • headache

  • lymphadenopathy

  • chancre at bite site

Stage 2 — CNS Stage

  • Parasites invade the central nervous system.

  • Causes:

    • sleep disturbances

    • neurological dysfunction

    • behavioural changes

    • coma

    • death

22. Immune Evasion by Trypanosomes

Antigenic Variation

  • Trypanosomes frequently change their surface glycoproteins.

  • This prevents antibodies from clearing the infection.

  • New antigenic variants continuously emerge.

  • This leads to chronic infection and waves of parasitaemia.

23. Key Comparison of Parasite Evasion Strategies

Parasite

Main Immune Evasion Strategy

Toxoplasma gondii

Dormant tissue cysts

Plasmodium falciparum

Antigenic variation + sequestration

Trypanosoma brucei

Surface antigen switching

Potential Viva Questions & Answers

Question 1

“Describe the lifecycle and immune evasion mechanisms of Toxoplasma gondii.”

Answer

  • Toxoplasma gondii is an intracellular protozoan parasite with cats as the definitive host.

  • Humans become infected through contaminated food, water, cat faeces or undercooked meat.

  • Tachyzoites are responsible for acute infection, while bradyzoites form dormant tissue cysts.

  • The immune response involves TLR7 and TLR9 recognition, IL-12 production and IFN-γ activation.

  • IFN-γ activates iNOS, which inhibits parasite replication.

  • The parasite evades immunity by suppressing IL-12 signalling and forming dormant bradyzoite cysts that persist chronically.

Question 2

“Explain how Plasmodium causes severe malaria and evades the immune system.”

Answer

  • Plasmodium falciparum causes the most severe form of malaria.

  • The blood stage of infection causes destruction of red blood cells and severe anaemia.

  • The parasite evades immunity through antigenic variation of PfEMP1 proteins encoded by var genes.

  • Only one PfEMP1 variant is expressed at a time, allowing immune escape.

  • Infected red blood cells also adhere to endothelial cells and avoid splenic clearance.

  • This sequestration causes capillary blockage and severe inflammation.

  • In cerebral malaria, blockage of brain capillaries leads to neurological disease, coma and death.

Question 3

“Compare innate and adaptive immune responses against protozoan parasites.”

Answer

  • Innate immunity provides a rapid non-specific response using macrophages, dendritic cells, cytokines and NK cells.

  • Pattern recognition receptors detect parasite molecules and trigger inflammation.

  • Adaptive immunity is slower but highly specific.

  • B cells produce antibodies while T cells kill infected cells and coordinate immune responses.

  • CD4 helper T cells activate other immune cells through cytokines.

  • CD8 cytotoxic T cells kill infected host cells containing intracellular parasites.

  • Adaptive immunity also generates memory responses that improve protection during reinfection.

Question 4

“Describe the pathogenesis and immune evasion strategies of African sleeping sickness.”

Answer

  • African sleeping sickness is caused by Trypanosoma brucei and transmitted by the tsetse fly.

  • The disease first causes a haemolymphatic stage with fever, headache and lymphadenopathy.

  • Parasites later invade the central nervous system causing sleep disturbances and neurological disease.

  • Severe infection can progress to coma and death.

  • Trypanosomes evade immunity through antigenic variation of surface glycoproteins.

  • Continuous switching of surface antigens prevents effective antibody clearance and allows chronic infection.