Parasitology short plans Flashcards
How do leishmania and toxoplasma modulate the host immune response, and how does this affect disease progression?
• Both intracellular, different cell types big differences. Altered modulation different disease types (with host genetics, environment). Comparison, LOD scores etc.
• Antiparasitic immune response
o Leishmanicidal: phagocytosis, complement
o Toxoplasma: TLRs, NFkB, cytokines and etc, JAK STAT, IRGs, tryptophan, iNOS and CD8.
• Delivery of modulating proteins
o ROPs, and across lipid bilayer.
• Modulation to avoid killing. Survival essential to pathology.
o Complement – L.d. uses, Tg avoids.
o Vacuole – avoid iNOS, alter metabolism. IRGs for Tg.
• Modulation to alter overall – essential to immunopathologies
o Cytokines – ROPs and GRAs for Tg. Trojan horse and induction for leish.
o Causing apoptosis – T cells central to immunopathologies. Altering TLR signalling? Complex.
o Conversion to bradyzoite – stimulated by immune system.
Discuss the potential benefits and and adverse consequences of IgE in Th2 infections.
• Benefits
o Directed. Less wasteful, ADCC, directs innate.
o Memory – decreased acquisition e.g. hookworm. Potential for vaccines but ASP-2.
o Cross reactivity – decreased acquisition in schisto.
• Adverse
o Reliance on class switching easily manipulated
o Allergy – misdirection. Types of proteins, epi evidence, intervention evidence.
• Not necessary, but beneficial.
Discuss the relationship between allergy and the immunological response against metazoan parasite infection in mammals
1) Intro
2) Evidence for protective role of helminth infections in allergic disease
a. Intervention studies
b. Epi studies
c. Mouse model
3) IgE key mediator in both. Action, cross-reactivity in schisto.
4) Helminth modulation of the Th2 response
5) Helminth induction of T cell hyporesponsiveness
Discuss the different morbidities resulting from infection with schistosomiasis.
Acute – swimmer’s itch, katayama fever, neurological disease.
Primary morbidities – subtle morbidities, primary chronic manifestations, secondary chronic manifestations.
Primary chronic manifestations. Site of eggs. Deposition, alteration of immune response. Difference in site; intestinal, hepatic, bladder, female genital schisotosomiasis. Alteration of immune response hepatosplenomegaly vs periportal fibrosis.
Secondary chronic manifestations – immune complexes, malignancy.
v
Different ways parasitic worms damage their mammalian host.
Direct - ascaris and hookworm. Entry, migration, blockage, laceration.
Indirect - subtle morbidities, susceptibility to other infections.
- immunopathologies: reaction to metabolites, schisto, filarial nematodes.
Suppression of allergy.
IgE in helminth and allergy
Raised
Targets
Helminth co-evolution
Helminth regulation and immunosuppression.
Discuss the interactions with of the Leishmania spp with the immune system.
Modulation: apoptosis, overcoming leishmanicidal activity, altering signalling, modulation of cellular function.
Immunopathologies. CL; Th1/2 skewing, progression, neutrophils and T cells.
VL; proinflammatory, arms of response, things affecting progression.
Compare tryps and plasmodium immune evasion
Sequestration vs VSG
Antigenic variation, generation of diversity
Other ways to avoid Abs (polymorphism, redundancy, tandem repeats)
Plasmodium: immunomodulation - dendritic cells, macrophages, T cells and B cells.
Tryps: TLTF and trypanolytic factors.
Molecular malaria pathogenesis.
• Blood stage asexual reproduction cycle – draw cycle
• Basic symptoms. Fever. Headache, nausea, vomiting, general malaise.
• Syndromes.
o Many involve sequestration: first describe this
o Cerebral malaria – importance. Cytoadherence, inflammation, occlusion, vasoconstriction, BBB loss. Role of NO – highly controversial. Why a specific problem in the brain?
o Severe malarial anemia – destruction, decreased production, co-infections.
o Metabolic acidosis.
o Placental malaria
• Protection against malaria? Sickle cell and etc. Duffy binding-like proteins.
Discuss motility and invasion in the apicomplexa.
• The glideosome - toxoplasma
o General stuff known – basics, actin, myosin, types of motility
o All apicomplexans have an apical complex vital for motility. Apical polar, secretory organelles, conoid, myosin motors.
o Microneme proteins – how they act, binding, general structure of glideosome, release
o Control
• Invasion: a multistep process. Several alternative pathways, with sialic acid dependent one most often used, but others also possible.
o Motility, initial attachment, motility across cell surface, apical attachment – highly polarised.
Deployment of MICs.
Conoid.
Rhoptry secretion
Moving junction formation and action.
o Invasion
o Closure and separation.
• Importance of invasion – target of immune system, therapy target, vaccine target.
Schistosomiasis, immunity and reinfection
Schistosomiasis, immunity and reinfection.
• At the end of last century, schistosomiasis increased
• Parasite survival.
o Immune evasion - tegument
o Immune modulation
o Use of the immune system
Is there immunity?
Studies from around the world show peak levels of infection at around 12. Possible reasons:
• Patterns of exposure.
o Lack of reinfection due to lack of exposure? Studies in fishing communities
• Immunity
o Difficult to detect as sterile immunity to parasites never occurs.
o Acquired immunity or innate resistance?
Acquired immunity would relate to duration of exposure, given multiple immune evasion mechanisms. If directly age related, might be associated with innate changes.
Damming of Senegal River
Precipitous fall at puberty
Measuring immune responses in infection and reinfection studies shows that resistance to reinfection is correlated with TH2 responses
Susceptibility correlated with host locus including TH2 cytokine genes
TH cell dependent anti-fecundity immunity, reducing egg production.
• Immunity in animals
o Acquired resistance important in regulating infection intensity in cattle.
o Pigs eliminate within a few months, and are relatively resistant to later challenges.
Mechanisms of immunity
