Summary Infectious Agents & Immunology
Biomedical sciences year 2
Part 2 Infectious agents
---------------------------------------------------------------------------------------------------------------------------------------
(LT1: 2.1 It takes 2)
Humans co-existist with micro-organisms (viruses, bacteria, parasites, fungi). Microbiota are the
microorganisms important for ones health. Infections result from interplay pathogen vs defenses host.
Infectious Agents:
- Single protein: prion (induce change in protein topology)
- Set of proteins: viruses (carry nucleic acid, functional interaction with live cells)
- Single cell: bacteria, protozoa (prokaryote, eukaryote)
- Multicellular organism: fungi, parasites
! LT2: 2.2 Life cycle parasites
What is a parasite?
A parasite is an organism that lives in or on and takes its nourishment from another organism (it can’t
live or reproduce independently). They are eukaryotic, invertebrate animals (mono- or multicellular)
that vary in type, size and route of infection.
Antigenic variation is the evasion strategy of parasites where they actively switch the expression of
different antigens to delay the clearing of an infection by the immune system.
Most important human parasites:
- protozoan unicellular Plasmodium (malaria); P falciparum on Anophilus mosquito
- macroscopic multicellular Schistosoma (schistosomiasis); Bilharzia
Life cycle Plasmodium (Malaria, Anopheline mosquito)
I. Sporozoite
1. Infected female anopheline mosquito bites, injecting
sporozoites (in saliva) into the bloodstream
2. Sporozoites migrate to the liver, where they multiply asexually
in the liver cells.
II. Merozoite
3. Parasites (merozoites) are released from liver cells in
vesicles into the blood and infect erythrocytes.
4. Merozoites multiply until the erythrocytes burst and release
more merozoites which can reproduce asexually.
III. Gametocyte
5. Some merozoite offspring mature into the sexual form of the parasite called gametocytes.
These circulate in the bloodstream.
IV. Gametes
6. When uninfected mosquito bites, it gets infected with gametocytes which develop into mature
sec cells (gametes).
V. Ookinetes/Oocysts
7. Fertilized female gametes develop into active ookinetes that burrow through the mosquito’s
midgut wall and form oocysts on exterior surface
VI. Oocyst/Sporozoites
8. Inside the oocyst active sporozoites develop. When the oocyst bursts, these are released into
the body cavity and travel to the salivary glands. (If it bites a person, this will be infected
again.
,Life cycle schistosoma worm (Schistosomiasis, Snails)
I. Cercariae
1. Infected snails release cercariae into sweet water, Cercariae penetrate the skin and shed
forked tail, forming schistosomula.
II. Schistosomula
2. Schistosomula migrate throughout body's tissues through blood circulation and mature into
schistosomes and adult worms (they pair off)
III. Adult worms
3. Adult worms can exist in various locations where they produce eggs that pass from intestinal
veins to lumen of the gut.
IV. Miracidia
4. Worm eggs are released into the external environment through feces and urine, which in
fresh water form miracidia.
5. Miracidia hatch and infect snails.
(Snails are easy to infect because they have a rudimentary immune system and soft
skin that is easy to penetrate, has to be compatible (molecular basis is still unknown))
V. Mother sporocyst
6. After infiltration of snail, the miracidium removes the ciliated plates and develops ino mother
sporocyst and creates daughter sporocysts (=clonal replication).
7. Daughter sporocysts can produce either daughter sporocysts or cercariae.
Pathology
Plasmodium (malaria): (Merozoite stage)
- Anemia (bursting of erythrocytes)
- Cerebral malaria, organ failure (edema through adherence to small blood vessels→
obstruction).
- Placental malaria (interferes with child growth)
Schistosoma: (Eggs) (cercariae → rash)
- Chronic infection and inflammation
- Organ failure: where eggs are trapped, Eggs can get stuck in the capillaries of the liver which
causes inflammation and cell death
- Liver damage (chronic): Inflammatory granulomas form in the liver when parasitic cells get
into the liver but can’t get out
- Bloody feces/urine
The same parasite can look very different and interact with very different environments during different
life stages.^
Treatment:
- 90% suppression in malaria makes no sense (full replication cycle)
- 90% suppression in schistosomiasis is useful (90% less eggs etc etc)
Worms can live for years/decades
- Nowadays overreactive immune system in rich countries
- In Africa there are no allergies because people have worms which create an IgE response
already and keep the immune system precise
- Parasites can downregulate the immune system (chronic infection results in Th2-type
response which is down-modulated after 2-3 months). The modulation of the immune system
is done by molecules secreted by the worms. Parasitic infections are often limited to the
(sub-)tropics due to hygiene, density of population etc.
, Interventions, parasite drugs
The aim is to eliminate parasitic infections like malaria and schistosomiasis. There are current
therapies that have some issues and therefore, new therapies are needed.
→ What are the therapeutic targets for a new drug?
Drug or vaccine is required with selective toxicity that driscriminates between host and parasite
targets. Vaccines stimulate protective immune response of the host to fight invading pathogen.
Required knowledge:
- Understanding of parasite life cycle (to find best target stage/protein)
- Understand immune mechanisms stimulated by parasite (humoral/cellular response)
Parasites evasion strategies
It is hard to fight parasites targeting their surface proteins:
➢ Antigenic diversity: existence of different forms of the Same basic single gene copy within a
population of parasites. (as a result of selective pressure)
○ (multiple parasites with different surface proteins; not all parasites express exactly the
same epitopes when exposed to antibodies, immune to only one strain)
➢ Antigenic variation: maintenance of multiple copies of a repertoire of a basic gene-forms in
the genome of an individual parasite.
○ (same parasite can change its surface proteins when necessary; when a clone dies
off, a different one comes up) (ex african trypanosomes/sleeping sickness)
➢ Parasites suppress immune system
Changes in appearance exist due to recognition of pathogen proteins (antigens) by the host immune
system. Antigenic variation mechanisms:
Trypanosomes: produce variable surface flycoproteins (VSG) (transmitted by tse-tse fly) which is an
extracellular blood-borne parasite and therefore has to change its protein coat continuously to evade
the immune response(antibody-attack)
Sequestration: the parasite is never present in only one organ
Presence of intermediate host: in addition to infecting definitive host (humans) they also have an
intermediate host (snail/mosquito/duck/etc).
Dutch/duck schistosomiasis: schistosoma of ducks try to enter the skin but are not compatible, the
cercariae die in the skin, causes itch.
Biomedical sciences year 2
Part 2 Infectious agents
---------------------------------------------------------------------------------------------------------------------------------------
(LT1: 2.1 It takes 2)
Humans co-existist with micro-organisms (viruses, bacteria, parasites, fungi). Microbiota are the
microorganisms important for ones health. Infections result from interplay pathogen vs defenses host.
Infectious Agents:
- Single protein: prion (induce change in protein topology)
- Set of proteins: viruses (carry nucleic acid, functional interaction with live cells)
- Single cell: bacteria, protozoa (prokaryote, eukaryote)
- Multicellular organism: fungi, parasites
! LT2: 2.2 Life cycle parasites
What is a parasite?
A parasite is an organism that lives in or on and takes its nourishment from another organism (it can’t
live or reproduce independently). They are eukaryotic, invertebrate animals (mono- or multicellular)
that vary in type, size and route of infection.
Antigenic variation is the evasion strategy of parasites where they actively switch the expression of
different antigens to delay the clearing of an infection by the immune system.
Most important human parasites:
- protozoan unicellular Plasmodium (malaria); P falciparum on Anophilus mosquito
- macroscopic multicellular Schistosoma (schistosomiasis); Bilharzia
Life cycle Plasmodium (Malaria, Anopheline mosquito)
I. Sporozoite
1. Infected female anopheline mosquito bites, injecting
sporozoites (in saliva) into the bloodstream
2. Sporozoites migrate to the liver, where they multiply asexually
in the liver cells.
II. Merozoite
3. Parasites (merozoites) are released from liver cells in
vesicles into the blood and infect erythrocytes.
4. Merozoites multiply until the erythrocytes burst and release
more merozoites which can reproduce asexually.
III. Gametocyte
5. Some merozoite offspring mature into the sexual form of the parasite called gametocytes.
These circulate in the bloodstream.
IV. Gametes
6. When uninfected mosquito bites, it gets infected with gametocytes which develop into mature
sec cells (gametes).
V. Ookinetes/Oocysts
7. Fertilized female gametes develop into active ookinetes that burrow through the mosquito’s
midgut wall and form oocysts on exterior surface
VI. Oocyst/Sporozoites
8. Inside the oocyst active sporozoites develop. When the oocyst bursts, these are released into
the body cavity and travel to the salivary glands. (If it bites a person, this will be infected
again.
,Life cycle schistosoma worm (Schistosomiasis, Snails)
I. Cercariae
1. Infected snails release cercariae into sweet water, Cercariae penetrate the skin and shed
forked tail, forming schistosomula.
II. Schistosomula
2. Schistosomula migrate throughout body's tissues through blood circulation and mature into
schistosomes and adult worms (they pair off)
III. Adult worms
3. Adult worms can exist in various locations where they produce eggs that pass from intestinal
veins to lumen of the gut.
IV. Miracidia
4. Worm eggs are released into the external environment through feces and urine, which in
fresh water form miracidia.
5. Miracidia hatch and infect snails.
(Snails are easy to infect because they have a rudimentary immune system and soft
skin that is easy to penetrate, has to be compatible (molecular basis is still unknown))
V. Mother sporocyst
6. After infiltration of snail, the miracidium removes the ciliated plates and develops ino mother
sporocyst and creates daughter sporocysts (=clonal replication).
7. Daughter sporocysts can produce either daughter sporocysts or cercariae.
Pathology
Plasmodium (malaria): (Merozoite stage)
- Anemia (bursting of erythrocytes)
- Cerebral malaria, organ failure (edema through adherence to small blood vessels→
obstruction).
- Placental malaria (interferes with child growth)
Schistosoma: (Eggs) (cercariae → rash)
- Chronic infection and inflammation
- Organ failure: where eggs are trapped, Eggs can get stuck in the capillaries of the liver which
causes inflammation and cell death
- Liver damage (chronic): Inflammatory granulomas form in the liver when parasitic cells get
into the liver but can’t get out
- Bloody feces/urine
The same parasite can look very different and interact with very different environments during different
life stages.^
Treatment:
- 90% suppression in malaria makes no sense (full replication cycle)
- 90% suppression in schistosomiasis is useful (90% less eggs etc etc)
Worms can live for years/decades
- Nowadays overreactive immune system in rich countries
- In Africa there are no allergies because people have worms which create an IgE response
already and keep the immune system precise
- Parasites can downregulate the immune system (chronic infection results in Th2-type
response which is down-modulated after 2-3 months). The modulation of the immune system
is done by molecules secreted by the worms. Parasitic infections are often limited to the
(sub-)tropics due to hygiene, density of population etc.
, Interventions, parasite drugs
The aim is to eliminate parasitic infections like malaria and schistosomiasis. There are current
therapies that have some issues and therefore, new therapies are needed.
→ What are the therapeutic targets for a new drug?
Drug or vaccine is required with selective toxicity that driscriminates between host and parasite
targets. Vaccines stimulate protective immune response of the host to fight invading pathogen.
Required knowledge:
- Understanding of parasite life cycle (to find best target stage/protein)
- Understand immune mechanisms stimulated by parasite (humoral/cellular response)
Parasites evasion strategies
It is hard to fight parasites targeting their surface proteins:
➢ Antigenic diversity: existence of different forms of the Same basic single gene copy within a
population of parasites. (as a result of selective pressure)
○ (multiple parasites with different surface proteins; not all parasites express exactly the
same epitopes when exposed to antibodies, immune to only one strain)
➢ Antigenic variation: maintenance of multiple copies of a repertoire of a basic gene-forms in
the genome of an individual parasite.
○ (same parasite can change its surface proteins when necessary; when a clone dies
off, a different one comes up) (ex african trypanosomes/sleeping sickness)
➢ Parasites suppress immune system
Changes in appearance exist due to recognition of pathogen proteins (antigens) by the host immune
system. Antigenic variation mechanisms:
Trypanosomes: produce variable surface flycoproteins (VSG) (transmitted by tse-tse fly) which is an
extracellular blood-borne parasite and therefore has to change its protein coat continuously to evade
the immune response(antibody-attack)
Sequestration: the parasite is never present in only one organ
Presence of intermediate host: in addition to infecting definitive host (humans) they also have an
intermediate host (snail/mosquito/duck/etc).
Dutch/duck schistosomiasis: schistosoma of ducks try to enter the skin but are not compatible, the
cercariae die in the skin, causes itch.
