Parasite Invasion Flashcards
What type of epithelia is skin?
Stratified squamous epithelium
What type of epithelia is mucosal?
Simple columnar epithelium
Where is mucosal epithelium found?
Lining the inner surfaces of various internal organs and body cavities
Which out of skin and mucosal epithelium is easier to penetrate by pathogens and why?
Mucosal is simple epithelium, which is much easier for parasites to invade compared to the stratified epithelium of skin.
Mucosal linings like in the gut are intended for absorption, whereas skin is made to be impenetrable.
What are “tight junctions” in epithelial cells?
Transmembrane protein structures that attach epithelial cells tightly together, to minimise entry of pathogens
What are desmosomes?
Transmembrane protein structures that connect to intermediate filaments within the cell, forming a spot-like attachment.
Allows tissues to withstand mechanical stress and maintain their structural integrity.
What are three common ways pathogens disrupt tight junctions?
- Toxin-mediated disruption
- Inflammation-induced signalling
- Manipulation of actin cytoskeleton
How does toxin-mediated disruption work (with example)?
Pathogens secrete toxins that bind to or mimic host proteins involved in tight junctions, directly leading to disassembly or increased permeability.
Example is Clostridium perfringens enterotoxin (CPE)
How does inflammation-induced signalling work (with example)?
Pathogens trigger inflammatory responses that down regulate/mislocate tight junction proteins, increasing epithelial permeability.
Example is cytokine TNF-a which can be triggered by Salmonella and Shigella.
How do pathogens manipulate actin cytoskeleton to gain entry into host cells (with example)?
Tight junctions are anchored to actin cytoskeleton.
Pathogens can inject effectors that disrupt actin filaments, weakening tight junctions.
Example is EPEC which injects Map effectors that disrupt actin
What are the three main mechanisms of parasite entry?
- Induced phagocytosis (Trojan Horse)
- Active penetration
- Paracytosis
How does induced phagocytosis work?
Some pathogens induce/allow take up by phagocytic cells (e.g. macrophages) and survive in them by resisting degradation.
Alternatively, pathogens can induce lysosome-mediated endocytosis (which is a parasite-directed form of phagocytosis) which allows them to be internalised by non-phagocytic cells.
Example of parasite induced phagocytosis (into phagocytic cells)
Leishmania spp. targets macrophages by binding to receptors ->
Macrophages engulf promastigote parasite ->
Parasite prevents phagosome-lysosome fusion ->
Leishmania differentiates into amastigotes and replicates within macrophage
Example of parasite induced phagocytosis (into non-phagocytic cell)
Trypanosoma cruzi can get entry into both phagocytic and non-phagocytic cells. It does this via lysosome-mediated endocytosis, involving host actin manipulation
How does active invasion different from induced phagocytosis?
Active invasion is driven entirely by the parasite, using its own machinery, independent of host phagocytosis
Does T. cruzi use active invasion or induced phagocytosis?
T. cruzi uses a parasite-directed endocytic process similar to induced phagocytosis, involving host lysosomes and actin, but it is not true active invasion.
What is active invasion?
When parasite gains entry into a host cell using its own machinery, without requiring the host to trigger internalisation
What is an example of a parasite that uses active invasion, and how?
Toxoplasma gondii binds to host cell surface receptors ->
Secretes effectors (from RON proteins) to insert into host membrane ->
Forms a “moving junction ->
Uses actomyosin motor to pull itself into cell through junction
What does Toxoplasma’s entry strategy allow it to do?
Infect almost all nucleated cells
What is paracytosis?
Invasion of host by passing between cells
What is an example of a parasite that uses paracytosis, and how?
Schistosomes can enter directly through skin by penetrating between skin (stratified squamous) epithelial cells.
It uses proteolytic enzymes to disrupt tight junctions and extracellular matrix proteins, and their highly motile tails help them burrow through
What form are schistosomes in when they burrow into skin?
Cercariae
What are the proteases released by cercariae during paracytosis?
Elastases
What is myosin A in T. gondii invasion?
MyoA is the motor that drives forward movement into the host cell using:
- Actin filaments
- and ATP-powered contraction
