Pertahanan Parasit Thd Imun Host

8/18/2019 Pertahanan Parasit Thd Imun Host

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Sistem pertahanan parasit

terhadap sistem imun host

Silvia Fitrina Nasution, MBiomed


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enomena os -paras edefence

• The immune system is one of an organism's most complex systems

and shows many signs of coevolution with parasites.

• Some of the major questions in the eld of evolutionary ecology havebeen to understand :

– why immune responses are not always maximally ecient

–

why immune responses vary among host species – and why immune responses vary with many other factors! such as

environment! stage of the host's life cycle or infection by di"erentparasite types

• The corresponding question has also been as#ed with respect to

parasites: – why are the parasites not always maximally infective or in$ict

maximum damage%

– &hy are the parasites cannot always exert maximum virulence %because there are costs of deploying or evolving a strong

response by host immune defences


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*n regard to host defence against parasite! behaviourallyhost has been choosing a site to live or being active atcertain times of day and season to avoid parasites

*n fact! parasites have evolutionarily countered suchstrategies by for example :

adapting their transmission pathways to increase thechances of an encounter with the next host.

in many cases! the behaviour of intermediate hosts isactively rigged by the parasite to meet the next host inits life cycle

+ain entrance to tissues or by which they manipulatethe signalling networ# of the immune system.

particular aspect to understand all these facts is ,the role of parasite actions against the host's defence systems”

enomena os -paras edefence


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The diversity of immune evasion mechanisms

Some of the major aspects in the evolutionary ecology of host-parasite interactions and to classify immune evasion

mechanisms by #ind and target as is done in the following andillustrated by a few examples /aul Schmid01empel! 23345 :

• Classication by mode of action

Passive evasion : /arasites can passively evade theimmune system in a variety of ways

65 /arasites can hide away from the immune system byinvading immune0privileged tissue such as the centralnervous system or the eye

25 /arasites can become (invisible) to the immune system

75 /arasites can change their surface identity as the T0cells

and antibodies of the vertebrate's immune systemrecogni8e specic epitopes by changing the antigenicsurface of a parasite! stored some variants of g! ormutation of parasite epitops5.

9or example! Plasmodium falciparum has

approximately 3 stored variants and Trypanosoma brucei has several hundred of variant antigens

http://rstb.royalsocietypublishing.org/search?author1=Paul+Schmid-Hempel&sortspec=date&submit=Submithttp://rstb.royalsocietypublishing.org/search?author1=Paul+Schmid-Hempel&sortspec=date&submit=Submithttp://rstb.royalsocietypublishing.org/search?author1=Paul+Schmid-Hempel&sortspec=date&submit=Submithttp://rstb.royalsocietypublishing.org/search?author1=Paul+Schmid-Hempel&sortspec=date&submit=Submit


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Active modulation and interference

The major group of immune evasion mechanisms impliesactive interference with the host's immune responses.

9or such interference! parasites produce or code in the

case of viruses5 for molecules that are able to bloc# ormodulate specic steps in the host's immune response! aswell as general cellular functions that are crucial for hostdefence e.g. cell motility5

These modulatory molecules are deployed in di"erent

ways. 9or example! bacterial adhesins and invasins thatmanipulate host cells to facilitate entry of the bacteria canbe membrane0bound proteins e.g. Streptococcus

pyogenes Streptococcus 5< =itchell 23375.

The diversity of immune evasionmechanisms

http://rstb.royalsocietypublishing.org/content/364/1513/85.fullhttp://rstb.royalsocietypublishing.org/content/364/1513/85.full


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• Classication by targets of immune evasion

– /arasites evade the rst step of the immune response! i.e. the recognition step! with active and

passive mechanisms. – /assive avoidance of recognition is shown by bacteria that modify or shield their /=/s parasite0

associated molecular patterns5>#ey surface elements that the immune system recogni8es.

• 9or example : Plasmodium! schistosomes and nematodes have been reported to producecompeting ligands to impede recognition by the host

– ctive evasion of recognition is illustrated by schistosomes! which produce ?0type lectins that cansequester the host's recognition tags.

– ?omplement is part of the innate immune system and consists of serum proteins and cellmembrane receptors that act together to #ill an invader@parasite. *t is activated by three di"erentbiochemical cascades! which are targeted by parasites.

• For ex: Leishmania! inhibits the complement cascade by degrading host proteins or by activerelease of signalling compounds

– /arasites have evolved a variety of ways to evade macrophages and other immune cells! for

example! by modulating the host's cell cytos#eleton to bloc# proper phagocytosis.• Ax : Bops proteins are deployed by Yersinia pestis to interfere with macrophages

– /arasites also prevent immune cell fusion by retaining crucial host signals and many specicallymanipulate the internal organi8ation of cell vacuoles

• Ax : Toxoplasma modies its host vacuole membrane with its own proteins to prevent furtherimmune responses

• Leishmania and Toxoplasma downregulate apoptosis to prolong cell life for prolonged own

development! perhaps by the production of homologues of regulatory proteins

The diversity of immune evasionmechanisms


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functioning immune response is dependent on its signallingnetwor#.

*n response to an infection! host signalling molecules! such ascyto#ines! chemo#ines or interferons! are produced by variouscells.

/arasites! in turn! interfere with this signalling in many ways!for example : Leishmania inhibits interleu#in5 *C062 indendritic cells D?s5 and macrophages! but leaves other pro0inflammatory cyto#ine pathways such as E90FG5 intact! it also

induces *C063 to avoid clearance

=any parasites can also lodge in phagocytic host cells thatwould normally engulf and destroy them. 9or #illing! the host's

cells produce reactive oxygen radicals! change the p1 in the

parasite 0 holding vacuoles or mobili8e degrading proteases.

The diversity of immune evasion mechanisms


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Immune evasion and pathogenic eects

/athogenic mechanisms can often! but not always! betraced bac# to molecules that inhibit or manipulate thehost's immune defences>suggesting that themechanisms deployed to evade the host's immune

response overlap with those that lead to pathogenesis

9or example! a major pathogenic condition associatedwith bacterial infections is septic shoc#! which resultsfrom the combined action of host cyto#ines!components of complement and the coagulationcascade as the host's immune system responds and ismisguided by the bacterium


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Similarly! parasite0derived proteases aid inmigration across host tissue barriers! degradation ofhost blood proteins! direct evasion of host immunitybut are also instrumental in in$ammation and

pathogenesis Gacterial capsules provide protection from the host's

immune responses by impeding the recognitionprocess through antibodies in vertebrate hosts.

The capsules and the aborted process of hostphagocytosis lead to enhanced in$ammatoryreactions! associated with tissue damage andpathogenic e"ects in the host



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*mmune evasion does not always lead toincreased pathogenic e"ects.

9or example : *mmune evasion by helminths leadsto a downregulation of the in$ammatory response

and! hence! to a lower degree of virulence

Such downregulations are probably most commonin parasites depending on long0lasting infections

+enerally! immune evasion is a modulator ofvirulence! yet! as such a core process that a"ectshow virulence evolves.



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• n illustrative example of this di"erence inmechanisms is the acquisition of iron by pathogenicbacteria

• 9or example : bacteria produce so0called siderophores

to sequester iron from the host immune evasionmolecules tha involved in resource extraction

• *ron extraction is associated with a reduction of hosttness by way of resource depletion

• *n some cases though! iron is mobili8ed from host cellsby parasite0induced tissue destruction Hatledge I Dover 23335! which so causes direct pathogenice"ects

Pathogenesis and virulences

http://rstb.royalsocietypublishing.org/content/364/1513/85.fullhttp://rstb.royalsocietypublishing.org/content/364/1513/85.fullhttp://rstb.royalsocietypublishing.org/content/364/1513/85.fullhttp://rstb.royalsocietypublishing.org/content/364/1513/85.full


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Some parasites even manage to feed on thehost's immune response

for example! Leishmania uses host cyto#ines asgrowth factors or tapeworms use antibodies asnutrients Damian 644J5

the mechanisms underlying immuneevasion are typically not the same asthose underlying resource extractionfrom the host.



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*mmune evasion causes virulence bypathogenesis!

while resource extraction leads tovirulence by resource depletion e.g.loss of fecundity5.

The immune evasion hypothesis

suggests that virulence bypathogenesis is the major factor< theparasite may also face a trade0o"

with resource depletion.



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Immune evasion andtolerance

?learance of the parasite from the host is a threshold process>theparasite is either cleared or not

This capacity is a"ected by parasite immune evasion! immune evasionalso has threshold properties

Gy contrast! a gradual control of the infection by the host is often thoughtto be the cause of long0lasting! chronic infections! where the pathogen is#ept at a level below damage

This issue is related to the concept of (tolerance)

Tolerance is considered to be the ability of the host to reduce or bu"er thee"ect of an infection on host tness

?onsidering the possible involvement of immune evasion! however!tolerance may instead re$ect the parasite's ability to persistently evadethe host's defences! as to remain inside the host and to achieve eventualtransmission

plethora of host immune mechanisms have been described for parasitesthat cause chronic infections e.g. Trypanosoma! Plasmodium! nematodes!some bacteria and viruses5


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Ke#ebalan spesi# parasit

6. Eaturally acquired immunity Terjadi pada parasit yang sulit beradaptasi

dengan hospes

*nfe#si pertama seluruhnya atau hampirseluruhnya tereliminasi

1ospes terprote#si terhadap infe#siberi#utnya dalam jang#a wa#tu yang lama

?ontoh : ?utaneous leishmaniasis!penya#it #ronis yang diobati amebiasis!malaria! dll5


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2. /remunisi Terjadi pada parasit yang beradaptasi dengan

hospes #ronis5

/arasit tetap ada pada hospes dengan jumlahsedi#it

1ospes terprote#si terhadap infe#si beri#utnyadan gejala #linis

Tida# berla#u untu# immunocompromised host ?ontoh : malaria! to#soplasmosis!

tripanosomiasis! dll



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7. ?oncomitant immunity Terjadi pada parasit yang beradaptasi

dengan host

&alaupun hospes tetap terinfe#si olehstadium dewasa5! tetapi sudah #ebalterhadap stadium infe#tif beri#utnya

contoh : s#istosomiasis! malaria! laria!dll



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/arasite)s *mmune Avasion

/ada hospes yang imuno#ompeten! parasit mempunyai

#emampuan untu# tetap hidup dan ber#embangbia#

Gerbagai me#anisme sudah terbu#ti dapat menyebab#an parasitterhindar dari sensitisasi sistem imun hospes yang dapat bersifatfatal

=e#anisme tersebut dapat dila#u#an oleh parasit maupun

#eadaan respon imun hospes dengan cara : /emisahan secara anatomi

=odi#asi antigen parasit

Lariasi antigen

Hegenerasi antigen permu#aan

=as#ing antigen

=odi#asi imun respon hospes

*munosupresi

/olyclonal lymphocyte activation

=odication of leucocyte function

*mmune complexes

Pertahanan Parasit Thd Imun Host

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