Flashcards in Immunology of Parasitic Disease Deck (50):
What is concomitant immunity?
What helminth has this immunity?
It is where the skin stage larval schistosomes are killed by Antibody-Dependent Cell Cytotoxicity (ADCC) but the adult worms escape elimination
Schistosome = Blood fluke
What is ADCC?
Antibody-dependent cell cytotoxicity is an IgE mediated response against specific parasites. The response degranulates EOSINOPHILS
What is antigenic mimicry?
What is an example of a parasite that uses this immune evasion strategy?
It is when a parasite acquires host hemmaglutinins and MHC so the immune system perceives it as "self" and doesn't attack it.
Schistosomes use this strategy
What isTra antigenic variation?
What parasite uses this strategy?
It is when the protozoa spontaneously changes its antigenic phenotype to escape immune destruction.
Trypanosomes (African Sleeping Sickness, Chaga's) use this strategy
What is the larval stage of the schistosome (blood fluke)?
Where is it released from?
What is the infectious stage of the schistosome?
Where does it enter the host?
Cercaria is the schistosome larvae and it is released from FRESH water snails
The infectious stage of the schistosome is the schistosomula and it is the skin stage
What is the infectious stage of malaria? Where does it enter the host?
What is the dormant liver stage of malaria called?
What is the RBC stage of malaria called?
Sporozoite is the infectious stage that enters the host via mosquito bite
Hypnozoite = dormant liver
Merozoite = erythrocytic stage
What is the most important host mechanism (cell) for clearing parasite infection?
Which cells play the largest role for protozoa?
CD4 cells because they will release cytokines and activate cells to clear the parasite.
Th1- IFNg activates macrophages to clear protozoa
Th2 - eosinophilia and hypergammaglobulinemia of IgE to clear helminths?
How do schistosomes enter the human host?
Where in the human host do schistosomes reside?
After what point will the schistosome be impervious to immune attack?
The schistosome enters through the skin and travels to the lungs. Once it enters the lungs it is impervious to immune attack.
Then they reside in the lumen of mesenteric blood vessels(blood fluke)
What four cells are the dominant effectors for clearing a schistosome?
The hematological hallmark of a helminth infection is ____________ and __________________.
eosinophilia and hypergammaglobulinemia of IgE
What allows for schistosome immune resistance?
Concomitant immunity where the mammalian host resist REINFECTION of the skin stages of a worm, but are unable to eradicate the original worm.
Describe the life cycle of the schistosome. Begin with the adult worm in the human vessels.
What is the infectious agent?
What part of the life cycle is susceptible to immune response?
Human vessels -> lay eggs-> urine/feces-> fresh water-> snails-> 1000s of offspring from single egg-> Cercaria (INFECTIOUS AGENT)-> penetrate skin-> Schistosoma (VULNERABLE TO IMMUNE ATTACK)--> 24-48 hours -> lung (IMPERVIOUS TO IMMUNE ATTACK)
How does concomitant immunity prevent reinfection by schistosome?
What Th plays a major role?
1. The host has IgE antibodies anchored on mast cells and activated eosinophils.
2. Cercaria sheds antigens that triggers degranulation of cutaneous mast cells by cross-linking
3. Mast cells release ECF (eosinophil chemotactic factor) and histamine to vasodilate and increase vascular permeability
4. IgE binds to schistosomula (skin stage) and acts as a ligand for the eosinophil which causes its degranulation
5. MBP is released and disintegrates the schistomula (ADCC)
Th2 - IL4, IL5, IL13 play a major role
The process of ADCC against the schistosome is T-cell __________________ but not T-cell ______________.
T cell dependent (to activate and class switch B cells)
But not T cell mediated (no CD8)
What type of hypersensitivity response is ADCC against the schistosome?
Type 1 immediate hypersensitivity
Toxoplasma is an obligate ___________ so it is sequestered from direct exposure to immune elements. Removal must be _______________.
Intracellular protozoa (sporozoa).
Elimination depends on ACTIVATED MACROPHAGES and CD8 T cells
What cells do toxoplasma infect?
What species can it live in?
What percent of people are seropositive for toxoplasma?
Any nucleated cell
It is ubiquitous and can live in over 300 mammal species and 30 bird species
80-100% of us are seropositive but we are not all sick because healthy immune systems can clear it
What are we not able to eradicate toxoplasma infections?
Dormancy is a common problem where trophozoites stay in other cells and aren't killed.
Immunosuppression reactivates latent infections.
What is the primary mechanism of resistance to a toxoplasma infection?
The phagocytic killing of toxoplasma by activated macrophages
(if the macrophage is not activated, it will phagocytose the Toxoplasma trophozoite but fail to kill the parasite
What Th cell is critical for immunity of intracellular sporozoa (toxoplasma) infections?
What Ab helps with clearing infection?
Th1 because it releases IFNg which activates macrophages. Activated macrophages are necessary to kill Toxo. Resting macrophages can phagocytose but NOT kill.
IgG opsonizes the parasite and contributes to activated macrophage killing
What specific type of toxoplasma infected cell are CD8 T cells capable of killing?
liver cells infected with toxoplasma
Why is sterile immunity rare for Toxoplasma infections?
Macrophages clear extracellular parasites and CD8 kill MHCI cells that have been infected, but toxoplasma can reside in certain cells that lack MHCI in the brain and eye and escape detection. This allows for reservoir of latent infection.
What percent of the world lives in malaria endemic areas?
How many are infected?
How many die yearly?
What specifically causes the death?
50% are infected.
Over 200 million are infected and 2 million die a year.
25% of childhood deaths in Africa (every 12 seconds, one dies)
Death is caused by cerebral malaria
What is the major malarial vector?
What type of protozoa is it?
Plasmodium falciparum a sporozoa (obligate intracellular pathogen)
What is the life cycle of plasmodium? Start with the Definitive host.
1. Anopheles mosquito (def. host) has a blood meal on the human most and deposits sporozoites
2. After 1 hr, sporozoites infect liver cells
3. Schizeny to multiple and infect other liver cells
4. Some become hyponozoites (dormant in liver cells for years), while others become merozoites and are released from the liver to the bloodstream
5. Merozoites invade RBC, undergo schizogeny, burst the RBC and infect more.
6. Mosquito takes up merozoites from blood
What are the three dominant stages of plasmodium life cycle?
1. Sporozoite stage
2. Liver stage
3. Erythrocytic stage
What are the three immune responses to the sporozoite stage of plasmodium infection (malaria infection)?
It is not in a cell yet so:
1. Ab to promote complement-mediated lysis
2. Ab to opsonize plasmodium and remove it via RES
3. Ab block binding to liver cells
Because it is not in a cell, there is NO CD8 response
What is the immune response to the liver stage of plasmodium infection?
The parasite is intracellular at this point so:
1. The liver will make MHCI with parasitic antigen
2. CTL (CD8) can kill the liver cell
3. CD8 can also produce IFNg to induce NOS to kill plasmodium
What is the immune response to the erythrocyte stage of a plasmodium infection:?
RBC do not express MHCI (only nucleated cell do) but it does express parasite antigens.
1. Ab opsonize the infected RBC and promote removal via RES
2. Ab prevent binding and penetration of extracellular merozoites
Which stages of plasmodium life cycle are subject to humoral immunity?
Which stages are subject to cell-mediated immunity?
Humoral= Sporozoite stage and Erythrocytic stage
Cell-mediated = Liver cell stage
What type of parasite is Trichinella? How do it enter the human host?
What organs are affected?
A roundworm (nematode) that infects the host orally (eating bad pork) and infects the lungs and intestine
What are the three main phases of the trichinella spiralis life cycle?
Which is most vulnerable to immune response?
1. Gut phase (adult worm) ***most susceptible
2. Tissue migratory phase (newborn larvae)
3. Intramuscular larvae encyst in capsules
What is the immune response to Trichinella in the gut phase?
Rapid expulsion is a T-cell dependent (but not mediated), Antigen specific effector mechanism.
1. Initial infection stimulates Th2
2. IgE hypergammaglobulinemia and mast cell proliferation (IL4)
3. Goblet cells increase mucus secretion (IL13) and go through hyperplasia which traps the worm
4. Increased gut motility hampers worms hold on gut wall and it is flushed out
What is T cell priming?
After the primary infection with a pathogen, mucousal mast cells are "armed" with anti-Trichinella IgE and are waiting for reinfection. When they next see Trichinella antigen, they are able to immediately degranulate the mast cells (Type I hypersensitivity response.
What is the immune response to the larval migratory stage of Trichinella?
ADCC by eosinophils and IgE
What is the immune response to the muscle larvae stage of Trichinella?
It is ineffective because the larvae is encysted (a collagen capsule) in the myocyte and is sequestered. It then calcifies
What cell is important for tissue-invasive stages but not gut stages of immunity?
What cells are important for intracellular protozoal infections of tissue, but NOT blood?
What are the three major parasite escape mechanisms?
1. Antigen variation
2. Antigen mimicry
3. Evasion of phagocytosis
What immune system evasion technique is used by trypanosomes (T. cruzi and T brucei)?
Antigenic variation where they spontaneously change their antigen phenotype so Ab no longer recognize them.
Trypanosomes dedicate 10% of their genome to have 100 VSGs (variable surface glycoproteins)
What is antigenic variation?
How does it allow immune system evasion?
What parasite utilizes this technique?
Spontanteous and repeated changing of antigenic phenotypes to frustrate and exhaust the immune system
Trypanosomes (Af. Sleeping sickness, Chagas)
What are the 4 ways parasites evade phagocytosis? Give an example of a parasite that uses each technique?
1. prevent macrophage from binding = pneumococcal
2. Escape from phagosome= trypanosome (Chagas, Af. Sleeping Sickness)
3. Prevent phagolysosomal fusion = toxoplasma
4. Impervious to degradation by lysosome= Leishmania
What cells do Leishmania reside in?
What kind of parasite are they?
They are blood/tissue flagellates that reside in the cells of the RES
1. They use complement receptor on activated macrophages to gain entry to host cells
2. They inhibit oxidative burst, scavenge O2 free radicals
3. Live best at lysosomal pH and are impervious to enzymes
4. Macrophages infected by Leishmania are resistant to activation by IFNg
What is the most common type of antigenic mimicry used by parasites?
How are host antigens acquired?
They mimic blood group antigens** most common
Mimic MHC host antigens
The antigens are acquired passively and not synthesized by the parasite
What host evasion strategy is utilized by schistosomes?
What Th response protects against leishmaniasis?
What Th response produces lethal leishmaniasis?
What is the hygiene hypothesis?
Incidence of autoimmune disease (espoecially type I diabetes and MS-type4 hypersensitivities) are increased in developed countries and decreased in underdeveloped countries.
Parasitic infection reduces the risk of atopic disease by 60% because they induce Treg cells that downregulate allergic diseases
What parasite was given to Crohn's patients to send their ulcerative colitis into remission?
benign, self-limiting whipworm
Th1 response followed by Th2 to schistosome egg antigens in the liver cause granuloma formation and fibrosis of the liver which compresses vessels, causes hemostasis and collateral vessel formation.
Ascites= bloated belly with schistomiasis