Transcript lecture_27_Mar_19_invert_immunity

Transmission by Insect vectors
Insect ingested (double pored tapeworm)
1) As insect bloodfeeds, parasites in the salivary glands injected into the host along
with the saliva (Plasmodium, Arboviruses).
2) As insect bloodfeeds, parasites in the mouthparts recognize the host as suitable
and forcibly exit the mouthparts and enter the host (filarial nematodes).
3) As insect feeds in engorges and defecates, parasites in feces enter host
(Chagas disease)
4) As insect feeds it regurgitates compounds from its crop and the parasites enter
the host (Plague bacterium)
5) Parasites in 3 and 4 remain in the GI tract and do not come in contact with the
tissues that are important in the invertebrate immune response to these
parasites.
For the others…. Why do the insects tolerate the presence of the parasites?
Why do they not kill them?
How might they kill these parasites?
Why should vectors protect themselves from parasites?
Do human parasites affect their vectors?
Fitness Costs Associated with Parasite Infection
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reduced nutrients available to host
reduced synthesis of vitellogenin in fat body (Hogg et al. 1997)
ovary uptake of vitellogenin is impaired (Hogg et al. 1997)
increase in hemolymph yolk proteins
resorption of developing follicles (Carwardine and Hurd 1997)
reduced fecundity (Ahmed et al. 1999)
reduced fertility (Hacker 1971, Hogg and Hurd 1995)
bloodfeeding behavior affected (Anderson et al. 1999)
The Vector-Parasite
Relationship
1) Why do insects tolerate parasites and pathogens?
2) How do insects protect themselves against parasites and
pathogens?
3) Why do insects not kill all parasites and pathogens?
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G
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F
D
C
B
I
A
E
H
Why do the insects not kill their parasites???
To answer this we first must understand how insects CAN
protect themselves, and then determine why these protective
measures are not used or are not effective against the
pathogens
INNATE IMMUNITY OF INSECTS
Innate immunity refers to a nonspecific defense mechanisms that a host uses
immediately or within several hours after exposure to a stimulus. This is the
immunity one is born with and is the initial response by the body to eliminate
microbes and prevent infection.
Unlike adaptive immunity, innate immunity does not recognize every possible
antigen. Instead, it is designed to recognize a few highly conserved structures
present in many different microorganisms. The structures recognized are called
pathogen-associated molecular patterns (PAMPs). Most defense cells have
pattern-recognition receptors for these common pathogen-associated molecular
patterns to allow for an immediate response against invading microorganisms.
Pathogen-associated molecular patterns can also be recognized by a series of
soluble pattern-recognition receptors in the blood that function as opsonins
and initiate the complement pathways.
Examples of innate immunity include anatomical barriers, mechanical removal,
bacterial antagonism, pattern-recognition receptors, antigen-nonspecific defense
chemicals, the complement pathways, phagocytosis, inflammation, and fever.
pathogen-associated molecular patterns (PAMPs): conserved molecular
patterns on microbes
lipopolysaccharide (LPS) from the gram-negative bacteria cell wall;
peptidoglycans found abundantly in the gram-positive cell wall and to a lesser degree
in the gram-negative cell wall
lipoteichoic acids found in the gram-positive cell wall;
mannose-rich glycans (common in microbial glycoproteins and glycolipids);
Β-glucans on fungi
To recognize these microbial molecules, various body defense cells have on their
surface a variety of receptors called pattern-recognition receptors capable of
binding specifically to conserved portions of these molecules.
Pattern-Recognition Receptors (Including Toll-Like Receptors)
1. Pattern Recognition Receptors (PRR )
Recognize pathogen associated molecular patterns (PAMP);
conserved molecular patterns on microbes
Toll-Like Receptors (TLR):
First discovered in Drosophila
Eleven receptors identified in mice and humans
Ligands are
PAMP
(pathogenassociated
molecular
patterns)
Receptors
are
PRR
(patternrecognition
receptors)
Nobel
prize
2011
Immune Response of Insects
Presence of Pathogens
Recognition?
communication
Hemocytes?
Fat body
Molecules of
Molecules of
communicacion
Serine
Proteases
?
Hemocytes
Transferrin
Activation via Toll,
IMD, y IRD
ProPO
Serine
Proteases
Tyrosine
Production of
Immune peptides
PO
DDC
DCE
Melanotic encapsulation
Phagocytosis
Antimicrobial compounds
Defensins
Cecropins
Proline-Rich Peptides
Glycine-Rich Peptides
Others?
Antimicrobial
Activity
E. coli 3 hr: Phagocytosis
Immune Response of Insects
Presence of Pathogens
Recognition?
communication
Hemocytes?
Fat body
Molecules of
Molecules of
communicacion
Serine
Proteases
?
Hemocytes
Transferrin
Activation via Toll,
IMD, y IRD
ProPO
Serine
Proteases
Tyrosine
Production of
Immune peptides
PO
DDC
DCE
Melanotic encapsulation
Phagocytosis
Antimicrobial compounds
Defensins
Cecropins
Proline-Rich Peptides
Glycine-Rich Peptides
Others?
Antimicrobial
Activity
Melanotic encapsulation
Immune Response of Insects
Presence of Pathogens
Recognition?
communication
Hemocytes?
Fat body
Molecules of
Molecules of
communicacion
Serine
Proteases
?
Hemocytes
Transferrin
Activation via Toll,
IMD, y IRD
ProPO
Serine
Proteases
Tyrosine
Production of
Immune peptides
PO
DDC
DCE
Melanotic encapsulation
Phagocytosis
Antimicrobial compounds
Defensins
Cecropins
Proline-Rich Peptides
Glycine-Rich Peptides
Others?
Antimicrobial
Activity
Mosquito Antimicrobial Peptides
lysozyme
Bomanin
Jacob
cecropin
defensin
gambicin
Advantages of Insect Innate Immune System
* Antimicrobial peptide generation is very fast
* Peptides are potent with wide spectrum of activity
* Small peptides diffuse quickly
* Insect immune peptides do not need special cells for production
Where do peptides act? How can parasites survive?
The majority of insect immune peptides are expressed in
hemocytes and fat body tissues and secreted into the
hemolymph
Parasites can:
1) Evade immune response
2) Inactivate immune response
3) Avoid contact with immune response
defensin
What happens with Intracellular Parasites?
DENv comprise 4 antigenically distinct
serotypes: DENv-1, -2, -3, -4
• 2.5 billion people at risk
• 50-100 million new infections/year
• ~500,000 cases of DHF, DSS
• No vaccine, no drugs
Transmitted by mosquitoes
• Aedes aegypti, Aedes albopictus,
Aedes polynesiensis
Intracellular viruses are not freely
exposed to classical components
of the vector immune response
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Apoptosis: Programmed Cell
Death
• Cellular response to damage,
age, and stress
– Intracellular infection
• Cells respond to viral infection
by initiating apoptotic cell
death
• Powerful immune response
– severely limit virus
production
– reduce or eliminate the
spread of progeny virus
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We believe:
Dengue enters cells-
Mosquito activates apoptosis
virus over expresses IAP1
Apoptosis inhibited until virus has replicated
Cells allowed to burst- releasing virions
How can we prove/disprove/study this?
• Cali, Colombia:
•
>120,000 dengue cases
• 115 deaths
• Naturally DENv resistant field
population of Aedes aegypti
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Costs associated with Parasitism:
Reduced nutrients available to host
Reduced synthesis of vitellogenin in the fat body
Uptake of vitellogenin by the ovary is impaired
Increased concentration of egg yolk proteins
Resorption of developing follicles
Reduced fecundity & fertility
Bloodfeeding behaviour may be altered
Fitness Costs Associated with Immune Response
Melanization
*
*
*
*
reduced fertility
increased time to oviposition
reduced longevity
competition for resources needed for egg
* development and melanin synthesis
Immune peptides and Phagocytosis
* No apparent reduction in fertility
* No significant reduction in longevity
* Competition for resources?
TRADE OFFS
Phenylalanine
PAH
Tyrosine
Competition
Defense
Egg Development
Undergoing immune response
(Ferdig et al. 1993)
Controls
Why study insect immune responses?
•Understand general insect immunity: the innate responses that insects use to protect
themselves from pathogens
•By understanding how this system works we may exploit it to enhance the success of
management strategies
•Invertebrates have no antigen:antibody system, and lack a memory function. But their
innate immune response is extremely similar to that of the vertebrate acute
phase response. We can look at the origin and progenitor responses that have
arisen through different evolutionary periods and which form the only immune
response in invertebrates.
• Identify several novel immune peptides that have potent antimicrobial activity. These
have a broad spectrum of activity, and can be produced and released with no
known toxicity to eukaryotic organisms.
Rhodnius prolixus
T. Cruzi
Anopheles gambiae
P. falciparum
Armigeres subalbatus
Brugia pahangi
develops
Brugia malayi
killed