Host-Parasite Part 2 Flashcards
Name one disease causes by parasite
Lymphatic Filariasis
What are the 3 parasites that Lymphatic filariasis?
- Wuchereria bancrofti -106 million cases
- Brugia malayi -12.5 million cases
- Brugia timori
What is filariasis caused by?
Nematodes
Parasitic disease:Filariasis
The 2 major stages in the life cycle of Wuchereria bancroft
- Human Stages
- Mosquito Stages
Larva forms in human stage
L3,L4,L5
Larva forms in Mosquito stages
L1-L3
Diagram question
Explain the life cycle of Wuchereria bancroft?
- Mosquito blood meal
>L3 larvae enter ->lymphatics - Adults in Lymphatics ) L3,L4,L5
>Grows and mates (7-10cm) upto 7 years - Female adults->sheathed microfilariae
>migrates ->lymph and blood channels
4.Mosquite blood meal (ingests microfilariae)
>Microfilariae ->gut of mosquito
>Hatches from sheath ->L1 - Microfilariae sheds sheaths penetrate-> mosquito’s midgut ->thoracic muscles
6+7. L1 differentiates -> L3 Larvae - L3 migrates to head and mosquito’s proboscis
In the W.bancroft, the mosquito is said to be?
Intermediate Host
How many months does the L3-L4-L5 process take?
6 months
Diagram question
Lympathic filariasis- Explain immune Response against Nematode (L3) using diagram
How does the L3 Larvae evade the immune system?
- Uses immune response to biting to enter bloodstream
- Blocks Toll-like receptors
- Inhibit T cell activation
- Promotes regulatory T cells
Immune evasion-Responses to Insect Bites
- Biting triggers mast cell degranulation
- > Release of histamine-> vasodilation
- > Blood vessel wall becomes permeable to L3
- > entry route into the bloodstream and migration towards host cell
Immune evasion: Block Toll-like receptors
- Inteferes with TLR - Langerhan cell and dendritic cells (APCs) on skin
- Via parasitic protiens
- Avoids recognition
Immune evasion- Inhibiting T-cell Receptor (TCR)
- Larvae 3- produce ES-62 protein
- > glycoprotein attached to phospholipids
- binds on membrane of T cell and taken in
- > inhibits PKC signalling pathway (responsible for TCR activation)
- T cell not activated
- Target larvae not destroyed
Larvae: Promoting Regulatory T cells
- Promotes T cells to differentiate ->T regulatory cells
- Role: Immune suppression including parasites
- How?
- > interaction with antigen presenting cells
- > > key role in determining fate of T cells
What protein is produced by L3 Larvae to inhibit TCR
ES-62 protein
How does the L3 modify the immune system?
- IL-10 :Class switching to IgG4
- Blocks binding IgE to FceRI
- Competes with the binding site (IgG4 binds to FecRI)
- Results in dampened immune system
- > Reduced IL-4
- > Reduced IgE
- Survival stratedy for Parasite- no mast degranulation, no complement system, no antibody dependent cell-mediated cytotoxicity (ADCC)
Why is limiting the immune response crucial for both parasite and host cell?
Parasite survival
* Strong immune system would inhibit stages in its life cycle
* >infection, reproduction and infection
Host
* Strong immune response -> tissue damage and pathology if not regulated
* >histamine -> inflammation and tissue damage
Dying worms
* Adult larvae/microfilariae
* Antigen released -> host lymphatic system
* Host recognises-> attack
* Prolonged- > damage to lympathic system + surrounding tissue
* Overtime> Fimbrotic blockage and calcification
* >impairs tissue and organ function
What is lymphatic stone function
- Lymphatic don’t function
- No drainage of tissue fluid
- >Elephantiases
What is the second micro parasitic group called?
Leishmanioisis
Leishmanioisis
Protist= Trypanosome
Genus=Leishmania
What are the 3 forms of Leishmanioisis
- Cutaneuos
- Mucocutaneous
- Visceral
Most common form
Cutaneous
Most severe form
Visceral
Cutaneous Leishmanioisis
- Affect skin, mucous membrane
- > skin sores and lesions
- > localised skin lesions
Mucocutaneous Leishmanioisis
- Affects skin and mucous membranes
- > destruction legions
- > Nose, mouth and throat
Visceral Leishmanioisis
- Affects internal organs
- > spleen,liver and bone marrow
- Fatal if not treated
What are the 2 developmental forms of protozoan parasite of the genus Leishmania
Amastigote
* Non-motile
* Exist within host cells
Promastigote
* Motile,elongated,flagellated forms
* Found in midgut of sandfly vector
What is kinetoplasts?
- Distinctive organelles-> amastigotes and promastigotes
- specialised within mitochondria
- Characterised: uniqure structure and DNA content (kDNA)
- Contributes to survival and replication
Explain the life cycle of Leishmania
- Sandfly blood meal (infective stage)
>ingest promastigotes into human host cell bloodstream
>Saliva of sandfly- chemotactic factor releasing agents- mediate macrophage and neutrophiles to site of infection - Promastigotes phagocytosed by neutrophil
>within phagolysosome
>evades phagocytosis destruction - Neutrophils short-lived- releases promastigotes. Consumed by macrophages.
- Within macrophages- promastigotes differentiate into amastigote developmental form. (diagnostic stage)
>evade phagocytosis destruction
5.Amastigotes multiple
>imfects macrophage-> dies
>infect other tissues and macrophages
6.Sandfly bloodmeal- picks up parasitised cells containing amastigotes
7.Amastigotes migrate from anterior midgut and differentiate back into promastigote development form
8.Sexually reproduce and migrate forwards from mid-gut to foregut.
9.Cycle repeats.
In the Leishmania life cycle - Which is the primary host and why?
Sandfly
Sexual Reproduction occurs
In the Leishmania life cycle- Which is the secondary host
Humans
Sandfly examples
Phlebotomus – Africa, Asia, Europe
Lutzomyia- New World
Modifying inflammatory pathway
Sandfly biting
Injects promastigote->host bloodstream
Saliva
* chemotactic (brings neutrophil and macrophages to site of infection)
* Blocks sandfly gut
* >increase feeding behaviour
*»_space;high change of transmission
Modifying inflammatory pathway
Phagocytosis by Neutrophils and Macrophages
- Prevent fusion of phagocytic vacuole with tertiary granule
- > superoxide, H+
- > > lethal to parasite
Modifying inflammatory pathways
Persistence in Neutrophils and Apoptosis
- Harbor promastigotes in ‘vacuoles’
- Neutrophil- apoptosis
- > delayed by parasite to persist longer
Modifying inflammatory pathway
Uptake of Parasites by Macrophages
- Activates complement system to be taken up my macrophages
Modifying inflammatory pathways
Differentiation to Amastigotes
- In macrophages- become non-motile
- > to reside and multiply
Modifying inflammatory pathways
Parasite Spread and Multiplication
- Multiply within macrophages
- Infected macrophages- transport amastigotes ->lymph nodes, sleen, liver
- Multplies within these tissues»_space;establishing infection
Schematic depiction of modifying inflammatory pathway
Differing host immune responses leads to disease – MOUSE DATA
Black mice (protective immunity)
* Leishmania infection cleared
* why?
* Type 1 response - activated macrophages
* NO toxic to leishmania
White mice (productive infection)
* Infection persist
* >Type 2 response
* >mediate parasite growth
Pathology- TGFβ (cytokine- transforming growth factor beta)
- Infected macrophage
- e.g Kupffer cells in liver recruit CD4 (Th2) and CD8
- > induce TGFβ and CCL (connective tissue growth factors)
- > leadings to fibrosis- excessive formation of connective tissue
- and granuloma formation- organized collections of immune cells
