Host-Parasite Part 1 Flashcards
Define parasite
- Lives in host organism
- Benefits from depriving nutrients
Name 2 types of parasite
1. Obligate parasite
* Completely depends on host to survive- reproduction, growth and development
* Host complete life cycle
2. Faculatitive parasite
* Can live independently of a host
* But has ability to parasitize host when opportunitu arises
* Host does not need to complete life cycle
Groups of Parasitive organisms
Endoparasite
Live inside host cell
Endoparasite: Protist - Trypanosoma brucei (T.brucei)
- microparasite
- Relies on third organisms to aid transmission and complete life cyle
- Vector/carrier = tsetse fly
- > feeds on infected host (cattle, human or horses)
- > T.brucie enters bloodstream of tsetfy
- > rapidly mutlplies and migrates to salivary glands
- Upon feeding again, tsetse injects the protist (saliva) into host and infects it
- Protist undergoes different stages in life cycle
- > correlated progress of disease
SLEEPING SICKNESS IN HUMANS
What are parasitic worms called?
Helminths
Helminths are considered as?
Macroparasite
Name the 3 types of Helminths?
- Tapeworm (cestodes)
- Fluke (Trematodes)
- Roundworm (Nematodes)
Give example of Tapeworm and what it infects?
- Long segmented body
- Cysticerous (Pork tape worm)
- > Young/intermediate
- Affects brain,eyes, muscles and skin
- Adult
- > affects gut
Give example of Fluke and what it infects?
- Flat leaf-like
- Genus schistosoma
- > blood vessel (host)
- Fasciola
- > liver/lung
- > intermediate only resides in snails
Give example of roundworks and where it resides in host?
- Elongated, cylinderical structure
- Heatworm
- > pulmonary artery ->dogs
- Gives rise to cardiovascular issues
Define ectoparasites
- parasites that live on surface/skin/outgrowth of skin
Examples
* Ticks
* Mites
* Fleas
* Lice
Helminths and Protozoa are what group of organisms?
Eukaryotes
> cellular complexity
> difficult to treat infections
What relationship do parasites have with their host organism?
- Symbiotic relationship
Why go parasite generally have complex life cycles?
- Have different developmental forms
- changes in morphology > structure and form
- challenging target for immune recognition and treatment
- Contributes to disease progression
Key features of parasites
- Ability to evade immune system
- High antigen complexity and specificity to host cell
- Limited lethaliy - does not aim to kill the host
- > as parasite depends on host cells well being
- > Evolved with hosts and its immune system
Why are parasite able to stay in host for a long time?
- Evades immune system
- Avoids immune destruction
What is a weak point of parasite that we can exploit?
- Due to close relationship to host
- > lost/gained metabolic pathways
- > dependent upon host
- Weak point we can exploit
Mechanisms by which parasites can harm host
- Direct damage
- > feed -> tissue damage ->physical blockages
- Host immune system induced damage
- > inflammatory reactions
- > release of toxic substances ->harmful to host
- Death of parasite
- > Inflammatory response
- > calcificatiom/fibrosis
- Serve as cariers
- > virus/bacteria
- > other parasite (mosquito and malaria)
Ixodes ricinus
- Dear tick
- > lyme disease
- Infection caught bite from infected tick
Th1
- Against intracellular pathogens
- Against micro-endoparasites (protist)
- Macrophage driven process
Th2
- Against extracellular pathogens
- Against macro-endoparasites
- Eosinophil-driven immune responses
Protist infections
Trypanozoa brucei
Example: Trypanozoa brucei
* On its surface - lectin (sugar molecules)
* Host cells (dentritic/macropages) can reconise lectin using pattern recognition receptor (PRR)
* >Toll-like receptor (TLR)
* >Lectin receptor
> > innate response
Possible diagram questions: Protist microparasite
Protist infections – aim activate macrophages and NK cells
- Intracellular pathogen
- > protozoan antigens
- Binds to PRR on dendritic/macrphage cells
- Productions of cytokines
- Interleukin- 12 (IL-12)
- > Drives naive Th2 to mature in to active Th2
- > Activates Th2
- Activates natural killer cells>Induces expression of cytokine IFN-gamma
IFN-gamma
* Pro-inflammatory response
* Drives maturation of naive Th2 alongside IL-12
* Activates resting macrophages -> active macrophages
* >mediate phagocytosis
Possible diagram question- Protist microparasite infection
Innate response to Plasmodium falciparum
- Microparasite= Plasmodium falciparum
- Innate response to merazoite/Trophozoite (form of parasite)
- > surface molecule= GP1
- GP1 binds TLR2
- > Activated TLR9
- > binds to dsDNA (parasite)
- Upon binding- release of cytokines
* >IL-12 ->NK -> IFN-gamma ->activates macrophages - > IL-12-> act Th2
Activated macrophages
* Release of pro-inflammatory cytokines
* >IL-1
* >IL-6
* >TNF-alpha
*»_space;hallmark for fever of malaria infections
Protist infections
- MHCII independent activation
- > INNATE
- NK cell and macrophages - main cell types
However
* Percentge of Th-1 cells- induced by IL-12
* and IFN-gamma activate protozoal specific B cells- acquired immunity
*»_space;induce IgG2 and IgG3 in B cells
* (innate and adaptive meet)
Macroendoparasitic infections
Macroendoparasitic infections mechanisms
- IL-10 and TNF-alpha blocks IL-12 pathway
- IL-4 is stimulator of type 2 T cell
Difference between Protozoal and Helminth infections
Protists
* TH1 response (IFNγ)
* Inflammatory
* IL12, IFNγ
* Activated macrophage’ oxidative burst
* NK cells
* Antibody response mainly (+)
* IgG2
* IgG3
Helminths
* TH2 response (IL4)
* IL 10 and TGFβb limit acute inflammation via macrophages
* Rather Basophil and Eosinophil activation
* Antibody response mainly (++)
* IgG1 (mouse)
* IgG4 (man)
* IgE -class switch
Basophils and mast cells do have a role in inflammation
Ig subtypes
Protozoa
* IgG2
* IgG3
Helminths
* IgG1
* IgG4
* IgE
IgG subtype structures
IgE Structure
What is IgE?
- Immunoglobulin (antibody)
- Least abundant isotype - 0.05% in blood
- Role: Against Helminth and Allergy
How is immunity to Helminths mediated?
- Already bound on Mast cells, Basophils and Eosinophiles
- Binds to Helminths antigen
- > IgE binds to surface of Helminths
- causes aggregation of receptors> signalling pathway
- > activates Eosinophils
IgE and Allergy
- Immune System overreacts to harmless substances: allergens
- IgE bound to Mast cell receptor and Basophil receptor
IgE Receptors
- High affinity IgE receptor
- > FcεRI
- Expressed: Mast cells, Basophils
- IL-5 induces FcεRI expression on Eosinophils
Explain IgE activity in Mast cell, Basophil and Eosinophil?
- Cross-linking and aggregation of receptors
- Triggers intracellular signalling cascadee
- > Degranulation of mast cells and basophils
- > > release granules> extracellular environment
- causes calcium increase in cells> release vacuoles degranulating
- > Releases inflammatory mediators
- > > Histamines
- > > Cytokines
- > > Chemokines
Hypersensitivity Reactions
>Allergic responses
How is IgE regulated?
- CD23 receptors
- Low affinity lectinreceptor for IgE
- > Binds to sugars of IgE
- Has a second receptor = lectin
- Surface of Eosinophils, mature B cells and macrophages
- Regulation of IgE levels
- Prevents degranulation
- > influence concentration of IgE levels in blood plasma
Explain the mechanism of degranulation using the diagram
- Helminth antigen binds to IgE bound high affinity IgE receptor
- Activates family of Kinases- Lyn (Src) and Syk
- Stimulates adaptor protein= LAT and gets phosphorylated
- Stimulated downstream signalling of PLCy = Phospholipase C gamma = enzyme
- Enzyme cleaves PIP2 ->DAG (diacylglycerol) and IP3 ( inositol trisphosphate) Important secondary messengers
- IP3 binds to receptors on endoplasmic reticulum
> release intracellular Ca2+ from ER stores - DAG remains associated with membrane. Along with Ca2+ leads to PKC (protein kinase C) mediated phosporylation
- Causes DEGRANULATION (granule exocytosis)
- Extracullar Ca2+ causes direct degranulation
- > > release of bioactive molecules contained in granules of Basophil and Eosinophil
Eosinophils
- 1% of white blood cells
- granules IgE/FcεRI releases
- > Eosinophil peroxidase, Ribonuclease -> cytotoxic activity
- > Major basic protein (MBP)
- > > cytotoxic membrane binding->destruction
- > > induces degranulations of Mast cells and Basophils
8-12hrs (Bloodstream)
8-12days (Tissues)
>absence of stimulation
>Increase in allergic and chronic parasitic settings
Problem - will also destroy your tissues
>explains increased levels to allergy chronic reactions
Basophil
- 0.1% of WBC
- Pre-formed mediators (from granules)
- histamine**>vasodilation
- serotonin >vasodilation
- heparin> stop blot clot formations
newly formed lipid mediators:
* prostaglandin D2 >
* leukotriene C4 >
platelet-activating factor > highly vasodilatory
** newly formed cytokines**
* eosinophil chemotactic factor > stimulated degranulate
* interleukin-4 >Th2 immune > more IgE
Interleukin-4 critical cytokine in production ofIgE
Italics- cause smooth muscle constriction (not blood vessel)
>asthma
Explain the positive feedback loop of IgE, Eosinophil and Basophil/Mast cell. Why is can it be a concern and how can IgE expression be regulated?
- Parasitc antigen/allergen binds the IgE bound to FceRI (high affinity IgE receptor)
- > degranulation: release of ribonuclease, lipase…
- Produces Major Basic Protien (MBP) which activated basophil > degranulation> histamine, serotinin…
- Basophil recuits IL-4 > class switching of B cells to IgE
- Basophil produces eosinophil chemotatic factor (ECF) that brings more eosinophil site of infection
- > > involved in this postive feedback
Control and Regulation
* CD23 - FceRII
* >low IgE affinity > binds to IgE when present in high concentrations
* Competes active site of FceRI
Why is regulation important?
* Overproduction chronic damage to tissue
