2025-2026 Immunology Guy Caljon
IMMUNOLOGY OF TROPICAL INFECTIOUS
DISEASES
THE INVERTEBRATE HOST
INVERTEBRATES AS PARASITE HOSTS AND DISEASE VECTORS
• Various pathogens transmitted by blood feeding arthropods
o Mites: Rickettsia sp.
o Ticks: Lyme disease, babesiosis, theileriosis, TBEV
o Lice: Epidemic typhus (Rickettsia), trench fever, recurrent fever
o Mosquitoes:
§ Protozoa: malaria
§ Arboviruses: yellow fever, dengue, chikungunya, zika, WNV
§ Nematodes: Wuchereria, Brugia (lymphatic filariids)
• Reduviid bugs: Chagas disease
• Dipters: leishmaniasis and human African trypanosomiasis
• When taking a blood meal, the arthropods can take up a pathogen or transmit a pathogen to another
vector à the pathogen must enter the arthropod through the blood meal and go to a place where it
can be transmitted again
• Parasite life cycles depend on specific interactions with the vector:
• Besides parasites, insects harbor a microbiome, including bacterial symbionts in the midgut à
interesting since we can modify the microbiome of insects and render them for example resistant to
certain pathogens J
ESTABLISHMENT IN THE ARTHROPOD GUT
• Arthropods cuticula is made of beta 1,4-N-acetylglucosamine
à it is water resistant and therefore forms a barrier for pathogens
• The inside and outside of the gastrointestinal tract (GIT) of insects is
covered with a layer of chitin (carbohydrate) and a layer of lipid
o The lipid layer prevents the insect from drying out
o The entire GIT is chitin-based, except for the midgut, where many proteins are digested
• The pathogen enters the arthropod when during its blood meal from an infected host à it must
migrate from the human environment (the blood meal) to the insects’ midgut
à There are typical physiological barriers/triggers during this migration
• Malpighian tubules are primitive kidneys that help in the dehydration of the blood meal (= fast
removal of water that is present in the blood meal)
o The insect is quite small and cannot keep this much water
1
,2025-2026 Immunology Guy Caljon
• The blood bolus, containing the pathogen moves to the digestive part (pharynx à esophagus à crop
à midgut) à this pathogen must then overcome the environment of the midgut:
o Temperature change: the pathogen experiences a shift from the hosts body temperature
(37°C) to that of the arthropod, which affects its survival
o High pH
o High proteolytic activity (trypsin/chymotrypsin)
o Gut microbiota (competition or direct killing of pathogen)
• It must then be able to cross the midgut to colonize other arthropod organs (like haemocoel or
salivary glands) à the peritrophic matrix (PM) also functions as a barrier
o The PM is a protective mesh-like structure composed of chitin and proteoglycans that allow
nutrients to pass while blocking many pathogens
o The ectoperitrophic space (area between the PM and epithelium) is a strategic target for
pathogens because it provides access to host cells
ARTHROPOD IMMUNE SYSTEM
IMMUNE CELLS
• Haemocoel = the body cavity (space) which
contains hemolymph (blood/lymph)
• This haemolymphe contains hemocytes play a
key role in the immune response of insects
o Haemocytes » white blood cells
o They can be circulating (mobile) or
sessile (stationary)
• There’s also the fat body = primitive liver = made of lipid storage cells and plays a crucial role in the
immune response activation and production of antimicrobial peptides (AMPs) that help infections
• Arthropod immune system: hemolymph/hemocytes
There are different types of hemocytes:
o Plasmatocytes:
§ Phagocytosis (engulfment of small pathogens)
§ Encapsulation (trapping of larger pathogens by paving a cell layer around the
pathogen)
§ AMP production
o Lamellocytes:
§ Encapsulation
§ Melanization (production of melanin to create a black capsule around the pathogen
to prevent its spread and kill it)
o Oenocytoids or crystal cells:
§ Melanization
§ Contains high concentrations of
prophenoloxidase (helps with
melanization)
Hillyer Dev Comp which
Immunolcrystallizes
2016 inside the
cell
Produced in larval lymphoid organ
§ Storage and release of enzymes upon
Plasmatocytes (phagocytosis,
infection encapsulation, AMPs),
Lamellocytes (encapsulation,
à they’re all produced melanization)
in the larval lymphoid organ in the
Crystal cells or oenocytoids (melanization)
thorax of the insect, this organ is no longer present in adults
→ POcells
(no new immune = Pro-Phenol
are created)oxidase
but there can be proliferation of existing immune cells
Du Pasquier, Reference Module in Biomedical Sciences 2014
à arthropods
Circulating vshave a short
sessile life span:(immune
hemocytes there’s no function
need of continuous
+ O2) replenishment of immune cells
Hemocytes can proliferate upon infection in adult arthropods
Fat body (storage glycogen + AMP production) 2
4
, Arthropod immune system: hemolymph/hemocyte
2025-2026 Immunology Guy Caljon
• Circulating hemocytes: hemolymphHillyer
is pumped around
Dev Comp in the
Immunol 2016insect through contraction of the
primitive heart (muscular
Produced tube) à spread
in larval of immune
lymphoid cells and O2
organ
o This heart contains 7 abdominal segments: for each segment there’s an opening (ostia) in the
heart/tubePlasmatocytes (phagocytosis, encapsulation, AMPs),
o The heart Lamellocytes (encapsulation,
pumps hemolymph anterograde melanization)
(forward) and retrograde (backward) ensuring
Crystal
circulation cells or oenocytoids (melanization)
•
→ PO = Pro-Phenol oxidase
Sessile hemocytes: found in these ostia where they wait and capture pathogens trying to circulate =
Du Pasquier, Reference Module in Biome
functions as a filter for pathogens
Circulating vs sessile hemocytes (immune function + O2)
Hemocytes can proliferate upon infection in adult arthropods
Fat body (storage glycogen + AMP production)
4
IMMUNE PATHWAYS
• The innate immune system in arthropods shares similarities with vertebrates, relying on pathogen
recognition receptors (PRRs) to detect pathogen-associated molecular patterns (PAMPs)
• However, instead of an adaptive immune system, arthropods rely on highly efficient innate immune
pathways
• The three major pathways are:
1. Toll Pathway: mainly recognizes Fungi & Gram-positive bacteria
o Key components:
1) Recognition: Spätzle (cytokine) is activated during the infection
2) Signaling: Toll receptor (it does NOT directly recognize PAMPs)
3) Activation: signaling molecules are activated and induce the transcription of
antimicrobial peptides (AMPs)
o Mechanism: Spätzle (cytokine) is activated through a serine protease cascade triggered by
pathogen recognition à Spätzle then binds to the Toll receptor à this activates Tube & Pelle
(like MyD88 adaptor complex in humans) à phosphorylation of cactus (inhibitor) allows Rel1
(NF-kB like molecule) to migrate to the nucleus à transcription of AMPs, which fight
infections
o Regulation: highly regulated to prevent unnecessary immune activation
3
, 2025-2026 Immunology Guy Caljon
2. Imd pathway (immunodeficiency pathway): mainly recognizes Gram-negative bacteria &
protozoa
o Key components
1) Recognition: PGRP-LC (Peptidoglycan Recognition Protein) directly recognizes PAMPs
2) Activation: signaling molecules are activated and induce the transcription of AMP
genes
o Mechanism: PGRP-LC recognizes peptidoglycans from Gram-negative bacteria or protozoan
components à activates Imd & Fadd & Dredd which leads to the activation of Rel2 (NF-kB
like) that triggers the transcription of AMPs
o Application for vector control: if we introduce highly immunogenic Gram-negative bacteria
into an insect population, it could stimulate the Imd pathway, making insects more resistant
to protozoan infections (e.g., malaria parasites in mosquitoes)
3. Jak/Stat pathway (janus-activated kinase pathway): mainly recognizes viruses
o Key components
1) Recognition: Upd or Vago (IL-6 like cytokines) is activated during the infection & bind
Dome receptor
2) Signaling: Dome receptor (it does NOT directly recognize PAMPs)
3) Activation: signaling molecules are activated and induce the transcription of
antimicrobial peptides (AMPs)
o Mechanism: Upd or Vago are activated and bin the Dome receptor à this triggers Jak
Arthropod immune system
phosphorylation, activating Stat à transcription of AMPs, which fight infections
• These pathways are very regulated: constant inflammation will kill the insect
3 main immunity pathways, tightly controlled by negative regulators
Fungi, G+ G-, protozoa Virus
Proteolytic
activation IL-6 like + Vago
MyD88 adaptor
NF-kB like
Hillyer Dev Comp Immunol 2016
9
4
IMMUNOLOGY OF TROPICAL INFECTIOUS
DISEASES
THE INVERTEBRATE HOST
INVERTEBRATES AS PARASITE HOSTS AND DISEASE VECTORS
• Various pathogens transmitted by blood feeding arthropods
o Mites: Rickettsia sp.
o Ticks: Lyme disease, babesiosis, theileriosis, TBEV
o Lice: Epidemic typhus (Rickettsia), trench fever, recurrent fever
o Mosquitoes:
§ Protozoa: malaria
§ Arboviruses: yellow fever, dengue, chikungunya, zika, WNV
§ Nematodes: Wuchereria, Brugia (lymphatic filariids)
• Reduviid bugs: Chagas disease
• Dipters: leishmaniasis and human African trypanosomiasis
• When taking a blood meal, the arthropods can take up a pathogen or transmit a pathogen to another
vector à the pathogen must enter the arthropod through the blood meal and go to a place where it
can be transmitted again
• Parasite life cycles depend on specific interactions with the vector:
• Besides parasites, insects harbor a microbiome, including bacterial symbionts in the midgut à
interesting since we can modify the microbiome of insects and render them for example resistant to
certain pathogens J
ESTABLISHMENT IN THE ARTHROPOD GUT
• Arthropods cuticula is made of beta 1,4-N-acetylglucosamine
à it is water resistant and therefore forms a barrier for pathogens
• The inside and outside of the gastrointestinal tract (GIT) of insects is
covered with a layer of chitin (carbohydrate) and a layer of lipid
o The lipid layer prevents the insect from drying out
o The entire GIT is chitin-based, except for the midgut, where many proteins are digested
• The pathogen enters the arthropod when during its blood meal from an infected host à it must
migrate from the human environment (the blood meal) to the insects’ midgut
à There are typical physiological barriers/triggers during this migration
• Malpighian tubules are primitive kidneys that help in the dehydration of the blood meal (= fast
removal of water that is present in the blood meal)
o The insect is quite small and cannot keep this much water
1
,2025-2026 Immunology Guy Caljon
• The blood bolus, containing the pathogen moves to the digestive part (pharynx à esophagus à crop
à midgut) à this pathogen must then overcome the environment of the midgut:
o Temperature change: the pathogen experiences a shift from the hosts body temperature
(37°C) to that of the arthropod, which affects its survival
o High pH
o High proteolytic activity (trypsin/chymotrypsin)
o Gut microbiota (competition or direct killing of pathogen)
• It must then be able to cross the midgut to colonize other arthropod organs (like haemocoel or
salivary glands) à the peritrophic matrix (PM) also functions as a barrier
o The PM is a protective mesh-like structure composed of chitin and proteoglycans that allow
nutrients to pass while blocking many pathogens
o The ectoperitrophic space (area between the PM and epithelium) is a strategic target for
pathogens because it provides access to host cells
ARTHROPOD IMMUNE SYSTEM
IMMUNE CELLS
• Haemocoel = the body cavity (space) which
contains hemolymph (blood/lymph)
• This haemolymphe contains hemocytes play a
key role in the immune response of insects
o Haemocytes » white blood cells
o They can be circulating (mobile) or
sessile (stationary)
• There’s also the fat body = primitive liver = made of lipid storage cells and plays a crucial role in the
immune response activation and production of antimicrobial peptides (AMPs) that help infections
• Arthropod immune system: hemolymph/hemocytes
There are different types of hemocytes:
o Plasmatocytes:
§ Phagocytosis (engulfment of small pathogens)
§ Encapsulation (trapping of larger pathogens by paving a cell layer around the
pathogen)
§ AMP production
o Lamellocytes:
§ Encapsulation
§ Melanization (production of melanin to create a black capsule around the pathogen
to prevent its spread and kill it)
o Oenocytoids or crystal cells:
§ Melanization
§ Contains high concentrations of
prophenoloxidase (helps with
melanization)
Hillyer Dev Comp which
Immunolcrystallizes
2016 inside the
cell
Produced in larval lymphoid organ
§ Storage and release of enzymes upon
Plasmatocytes (phagocytosis,
infection encapsulation, AMPs),
Lamellocytes (encapsulation,
à they’re all produced melanization)
in the larval lymphoid organ in the
Crystal cells or oenocytoids (melanization)
thorax of the insect, this organ is no longer present in adults
→ POcells
(no new immune = Pro-Phenol
are created)oxidase
but there can be proliferation of existing immune cells
Du Pasquier, Reference Module in Biomedical Sciences 2014
à arthropods
Circulating vshave a short
sessile life span:(immune
hemocytes there’s no function
need of continuous
+ O2) replenishment of immune cells
Hemocytes can proliferate upon infection in adult arthropods
Fat body (storage glycogen + AMP production) 2
4
, Arthropod immune system: hemolymph/hemocyte
2025-2026 Immunology Guy Caljon
• Circulating hemocytes: hemolymphHillyer
is pumped around
Dev Comp in the
Immunol 2016insect through contraction of the
primitive heart (muscular
Produced tube) à spread
in larval of immune
lymphoid cells and O2
organ
o This heart contains 7 abdominal segments: for each segment there’s an opening (ostia) in the
heart/tubePlasmatocytes (phagocytosis, encapsulation, AMPs),
o The heart Lamellocytes (encapsulation,
pumps hemolymph anterograde melanization)
(forward) and retrograde (backward) ensuring
Crystal
circulation cells or oenocytoids (melanization)
•
→ PO = Pro-Phenol oxidase
Sessile hemocytes: found in these ostia where they wait and capture pathogens trying to circulate =
Du Pasquier, Reference Module in Biome
functions as a filter for pathogens
Circulating vs sessile hemocytes (immune function + O2)
Hemocytes can proliferate upon infection in adult arthropods
Fat body (storage glycogen + AMP production)
4
IMMUNE PATHWAYS
• The innate immune system in arthropods shares similarities with vertebrates, relying on pathogen
recognition receptors (PRRs) to detect pathogen-associated molecular patterns (PAMPs)
• However, instead of an adaptive immune system, arthropods rely on highly efficient innate immune
pathways
• The three major pathways are:
1. Toll Pathway: mainly recognizes Fungi & Gram-positive bacteria
o Key components:
1) Recognition: Spätzle (cytokine) is activated during the infection
2) Signaling: Toll receptor (it does NOT directly recognize PAMPs)
3) Activation: signaling molecules are activated and induce the transcription of
antimicrobial peptides (AMPs)
o Mechanism: Spätzle (cytokine) is activated through a serine protease cascade triggered by
pathogen recognition à Spätzle then binds to the Toll receptor à this activates Tube & Pelle
(like MyD88 adaptor complex in humans) à phosphorylation of cactus (inhibitor) allows Rel1
(NF-kB like molecule) to migrate to the nucleus à transcription of AMPs, which fight
infections
o Regulation: highly regulated to prevent unnecessary immune activation
3
, 2025-2026 Immunology Guy Caljon
2. Imd pathway (immunodeficiency pathway): mainly recognizes Gram-negative bacteria &
protozoa
o Key components
1) Recognition: PGRP-LC (Peptidoglycan Recognition Protein) directly recognizes PAMPs
2) Activation: signaling molecules are activated and induce the transcription of AMP
genes
o Mechanism: PGRP-LC recognizes peptidoglycans from Gram-negative bacteria or protozoan
components à activates Imd & Fadd & Dredd which leads to the activation of Rel2 (NF-kB
like) that triggers the transcription of AMPs
o Application for vector control: if we introduce highly immunogenic Gram-negative bacteria
into an insect population, it could stimulate the Imd pathway, making insects more resistant
to protozoan infections (e.g., malaria parasites in mosquitoes)
3. Jak/Stat pathway (janus-activated kinase pathway): mainly recognizes viruses
o Key components
1) Recognition: Upd or Vago (IL-6 like cytokines) is activated during the infection & bind
Dome receptor
2) Signaling: Dome receptor (it does NOT directly recognize PAMPs)
3) Activation: signaling molecules are activated and induce the transcription of
antimicrobial peptides (AMPs)
o Mechanism: Upd or Vago are activated and bin the Dome receptor à this triggers Jak
Arthropod immune system
phosphorylation, activating Stat à transcription of AMPs, which fight infections
• These pathways are very regulated: constant inflammation will kill the insect
3 main immunity pathways, tightly controlled by negative regulators
Fungi, G+ G-, protozoa Virus
Proteolytic
activation IL-6 like + Vago
MyD88 adaptor
NF-kB like
Hillyer Dev Comp Immunol 2016
9
4
