Host-Parasite Part 1 Flashcards
(40 cards)
1
Q
Define parasite
A
- Lives in host organism
- Benefits from depriving nutrients
2
Q
Name 2 types of parasite
A
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
3
Q
Groups of Parasitive organisms
Endoparasite
A
Live inside host cell
4
Q
Endoparasite: Protist - Trypanosoma brucei (T.brucei)
A
- 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
5
Q
What are parasitic worms called?
A
Helminths
6
Q
Helminths are considered as?
A
Macroparasite
7
Q
Name the 3 types of Helminths?
A
- Tapeworm (cestodes)
- Fluke (Trematodes)
- Roundworm (Nematodes)
8
Q
Give example of Tapeworm and what it infects?
A
- Long segmented body
- Cysticerous (Pork tape worm)
- > Young/intermediate
- Affects brain,eyes, muscles and skin
- Adult
- > affects gut
9
Q
Give example of Fluke and what it infects?
A
- Flat leaf-like
- Genus schistosoma
- > blood vessel (host)
- Fasciola
- > liver/lung
- > intermediate only resides in snails
10
Q
Give example of roundworks and where it resides in host?
A
- Elongated, cylinderical structure
- Heatworm
- > pulmonary artery ->dogs
- Gives rise to cardiovascular issues
11
Q
Define ectoparasites
A
- parasites that live on surface/skin/outgrowth of skin
Examples
* Ticks
* Mites
* Fleas
* Lice
12
Q
Helminths and Protozoa are what group of organisms?
A
Eukaryotes
> cellular complexity
> difficult to treat infections
13
Q
What relationship do parasites have with their host organism?
A
- Symbiotic relationship
14
Q
Why go parasite generally have complex life cycles?
A
- Have different developmental forms
- changes in morphology > structure and form
- challenging target for immune recognition and treatment
- Contributes to disease progression
15
Q
Key features of parasites
A
- 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
16
Q
Why are parasite able to stay in host for a long time?
A
- Evades immune system
- Avoids immune destruction
17
Q
What is a weak point of parasite that we can exploit?
A
- Due to close relationship to host
- > lost/gained metabolic pathways
- > dependent upon host
- Weak point we can exploit
18
Q
Mechanisms by which parasites can harm host
A
- 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)
19
Q
Ixodes ricinus
A
- Dear tick
- > lyme disease
- Infection caught bite from infected tick
20
Q
Th1
A
- Against intracellular pathogens
- Against micro-endoparasites (protist)
- Macrophage driven process
21
Q
Th2
A
- Against extracellular pathogens
- Against macro-endoparasites
- Eosinophil-driven immune responses
22
Q
Protist infections
Trypanozoa brucei
A
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
23
Q
Possible diagram questions: Protist microparasite
Protist infections – aim activate macrophages and NK cells
A
- 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
24
Q
Possible diagram question- Protist microparasite infection
Innate response to Plasmodium falciparum
A
- 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
25
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**
* >>induce Ig**G2** and Ig**G3** in B cells
* (innate and adaptive meet)
26
# Macroendoparasitic infections
Macroendoparasitic infections mechanisms
* IL-10 and TNF-alpha blocks IL-12 pathway
* IL-4 is stimulator of type 2 T cell
27
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**
28
Ig subtypes
Protozoa
* IgG2
* IgG3
Helminths
* IgG1
* IgG4
* IgE
29
IgG subtype structures
30
IgE Structure
31
What is IgE?
* Immunoglobulin (antibody)
* Least abundant isotype - 0.05% in blood
* Role: Against Helminth and Allergy
32
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
33
IgE and Allergy
* Immune System overreacts to harmless substances: **allergens**
* IgE bound to Mast cell receptor and Basophil receptor
34
IgE Receptors
* High affinity IgE receptor
* >**FcεRI**
* Expressed: Mast cells, Basophils
* IL-5 induces FcεRI expression on Eosinophils
35
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
36
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
37
Explain the mechanism of degranulation using the diagram
1. Helminth antigen binds to IgE bound high affinity IgE receptor
2. Activates family of Kinases- Lyn (Src) and Syk
3. Stimulates adaptor protein= **LAT** and gets phosphorylated
4. Stimulated downstream signalling of PLCy = Phospholipase C gamma = **enzyme**
5. Enzyme cleaves PIP2 ->DAG (diacylglycerol) and IP3 ( inositol trisphosphate) **Important secondary messengers**
6. IP3 binds to receptors on endoplasmic reticulum
> release intracellular Ca2+ from ER stores
7. DAG remains associated with membrane. Along with Ca2+ leads to PKC (protein kinase C) mediated phosporylation
8. Causes **DEGRANULATION** (granule exocytosis)
9. Extracullar Ca2+ causes direct degranulation
10. >>release of bioactive molecules contained in granules of Basophil and Eosinophil
38
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
39
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 facto*r > highly vasodilatory
** newly formed cytokines**
* eosinophil chemotactic factor > stimulated degranulate
* interleukin-4 >Th2 immune > more IgE
**Interleukin-4 critical cytokine in production of IgE**
Italics- cause smooth muscle constriction (not blood vessel)
>asthma
40
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
