5. Microorganisms: parasites Flashcards
Define parasites
Parasite - organism that lives on / in a host organism - gets its food from / at the expense of its host
Three main classes of parasites that cause disease in humans:
- protozoa
- helminths
- ectoparasites
What are the types of parasites based on their host exploitation?
- Obligate parasites: need to spend at least a part of life cycle in parasitic relationship - ex: Ascaris lumbricoides, Plasmodium falciparum
- Facultative parasites: generally free living but can become parasitic if enter a suitable host - ex: Naegleria fowleri
What are the types of hosts?
- Definitive host: parasite reaches sexual maturity
- Intermediate host: required for parasite development but no sexual development occurs
- Incidental host: can be infected but doesn’t play a role in parasite lifecycle
- Paratenic host: no development takes place but parasite remains alive + infective to another host
DIPI
What are the main routes that parasites use to enter the host?
- Broken skin barrier - wounds
- Oral pathway
- Unprotected sex
- Vector’s bite
What are helminth parasites?
Helminths - parasitic worms, usually intestinal
What are the 3 taxonomically important helminth groups?
3 taxonomically important helminth groups:
- nematodes (roundworms)
- cestodes (tapeworms)
- trematodes (flukes)
What are the challenges for combating helminth infections?
Helminths are good at evading + supressing immunity:
- long-lived - don’t kill the host
- large size - difficult for immunity to kill
- takes long to develop immunity + protective memory
- suppress immunity - reduced pathology
Co-evolved with humans - good at manipulating the immune system
Explain the hygiene hypothesis
Hygiene -> allergies - untrained immunity
What are protozoan parasites?
Protozoan parasites - microscopic, one-celled parasites - Apicomplexa disease causing - ex: malaria, cryptosporidiosis
Explain malaria as a protozoan parasite disease
Malaria:
- Plasmodium spp parasite - 5 species infect humans
- Anopheles mosquitos - definitive hosts
- Parasite migrates and invades a variety of host tissues in their lifecycle
- Malaria - acute disease: rapid parasite replication in the liver
Explain Taxoplasma parasites
Taxoplasma:
- unicellular protozoan parasites
- definitive hosts - cats
- intermediate hosts - warm-blooded animals, including humans
- infects brain, eyes, heart, lungs - flu-like symptoms, usually imm system fights on its own
Humans can be infected by:
- contaminated cat faeces
- eating infected meat
What is the host defense against microbial infection?
Innate immunity:
- External: skin, mucous, secretion
- Internal: phagocytic cells, NK cells, antimicrobial peptides, inflammatory response, Complement system
Adaptive immunity:
- Humoral response (B cells)
- Cell-mediated response (T cells)
Why parasites don’t kill the host?
Parasites (like some other microorg) don’t kill the host too quickly / at all - to fully exploit the host
What are the main environments where parasites reside in human hosts?
- live freely in bloodstream
- live in protected areas (ex gut, brain)
- hide in host cells
What are the modes of parasite living inside hosts?
- extracellularly - outside of the cell (ex bloostream)
- intracellulary - inside of the cell (ex in RBC)
What are the challenges encountered by protozoal parasites while invading human hosts?
Challenges encountered by protozoal parasites:
- parasite migration and motility to infect specific cells / hosts
- transmission from one host to other hosts
- gaining nutrients - may need to adapt to new environment while at different lifecycle stages
- avoiding being killed by immune system
- maintaining balance between different life cycle stages: proliferation / forming long-term infection / undergoing transmission
Describe the lifecycle of Plasmodium parasite
Plasmodium - intracellular parasites - invade RBCs
What are the advantages and disadvantages of Plasmodium invading host cells?
Plasmodium - intracellular parasite - invades RBCs
Advantages:
- gain nutrients
- shielded from immune system
- RBCs - host cells - readily available and accessible to mosquito vector
=> Plasmodium transmission is very effective
Disadvantages:
- must convert terminally differentiated RBCs into cells with nutrient uptake systems
- remodelling RBC membrane by parasite - increased cell rigidity
=> infected RBCs can be detected -> removed by spleen
How do Apicomplexan parasites migrate and invade host cells?
Apicomplexan parasites used gliding motility - in motile stages of lifecycle - substrate-dependent cell motility (conc sensing - not flagella / cilia / shape-shifting) - migrate to host - propel themselves into the host
Use host cell receptors - attach - use actin-myosin for forward / backward movement
What is the sequence of RBC invasion by Plasmodium?
- Recognition and attachment: recognises RBC - attaches to surface - mediated by both surface proteins
- Reorientation and junction formation: one merozoite attached to RBC reorientates - forms tight junction - allows entry into RBC
- Entry and replication: merozoite anters RBC forming parasitophorous vacuole inside - replicates within the vacuole
- Exit: bursts out of RBC / released in exoerythrocytic vesicles without RBC lysis
What must intracellular parasites avoid when escaping host immune system in host cells?
Intracellular parasites - when invade host cells must:
- evade host cell killing mechanism
- prevent host cell apoptosis
How do RBCs create a protected niche for Plasmodium?
RBCs provide niche for Plasmodium:
- abundant + accessible to mosquito vectors
- contain many nutrients
- no MHC for antigen presentation
HOWEVER - infected RBCs may be detected - because parasite alters surface proteins -> destroyed in spleen => Plasmodium destroyed together
What is the Plasmodium membrane protein used in ivading RBCs?
Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) - encoded by ~60 genes in var gene family - for one protein 1 gene is expressed at a time + var genes show high levels of recombination => high PfEMP1 variation
PfEMP1 composed of building blocks: DBL + CIDR binding domains with variable sequences and binding specificities for host endothelial cells
What are the clinical outcomes of Plasmodium infection?
Clinical outcomes of Plasmodium infection - malaria disease -> slows down blood flow + damages liver
What is the trade-of strategy used by Plasmodium in malaria development?
Trade-of between survival and reproduction - to maximise transmission while maintaining infection
What is the lifecycle of African trypanosomes?
African trypanosomes -> African trypanosomiasis - sleeping sickness
What is the main adaptation of African trypanosomes?
African trypanosome parasite can change its coating protein - variant surface glycoprotein (VSG) coat - hides invariant proteins - changes -> evades immune system
What are the mechanisms used for coat changing in African trypanosomes?
Mechanisms:
1. Gene converison: uses a special DNA repair mechanism to replace genes encoding for VSG with a silent version of the same gene - rapidly generate new VSG variants
2. Segmental gene conversion: replaces a part of VSG gene with a silent copy - more VSG variants
3. Telomere exchange: swaps the ends of two different chromosomes - new combination of genes for VSGs - higher variety
4. Transcriptional switch: changes which VSG gene is actively transcribed - rapidly switch to a new protein coat
How do African tryponosomes have an inexhaustible repertoire of antigen variants?
High antigen variability - different coatings - because VSG protein vsg genes undergo high rates of recombination => parasites can establish long-term chronic infection because adapt every time the immune system fights
What is the trade of in African trypanosomes?
Trade of between slender (proliferation) - stumpsy (transmission) forms
How do African trypanosomes differentiate from their proliferative to transmissive form?
Use quorum sensing of stumpy indication factor (sif) - at high sif slender -changes to-> stumpy
What are the three African Trypanosome subspecies infecting humans?
- Trypanosoma brucei brucei
- Trypanosoma brucei rhodesiense (susceptible)
- Trypanosoma brucei gambiense (susceptible)
To which African trypanosome species humans are susceptible? Which genes are responsible?
- Trypanosoma brucei rhodesiense - parasite has serum resistance - associated (SRA) gene
- Trypanosoma brucei gambiense - T. b. gambiense-specific glycoprotein (TgsGP)
=> genes allow escape human immune system, Trypanosoma brucei brucei is lysed by human immune system
What are the main hosts of Trypanosoma species?
Trypanosoma - zoonosis: cows / bores -> mosquito -> human
Why are humans susceptible to certain Trypanosoma species?
APOL1 - human protein - lyses Trypanosome species:
- T. b. brucei: lysed by APOL1 -> humans not susceptible
- T. b. rhodesiense: use serum resistance associated (SRA) proteins - degrade APOL1 -> humans susceptible
- T. b. gambiense: some lysed by APOL1 - TgsGP degrade some APOL1 -> humans susceptible
