Parasites (Smyth) Flashcards
What is the definition of a parasite?
“An organism which lives in or on another organism (its host) and benefits by deriving nutrients at the other’s expense”
What are the 2 types of parasites?
An obligate parasite is totally dependent on the host to complete its life cycle, while a facultative parasite is not.
What are endoparasites?
ENDOPARASITES
“All those that live inside the host (including all parasitic worms-helminths)”
- Sometimes definition of “parasitic disease” is restricted to diseases due to this group
Eg. 1. Protists (known also as microparasites)
Tend to rely on a third organism, which is generally known as the carrier or vector for either transmission or for a maturation set in their life cycle, where the latter this is an intermediate/ secondary host
Protists : Trypanosoma brucei (T.brucei)
Host: Man; Cattle; Horses
Carrier: Tsetse fly (Glossina)
Disease: African trypanosomiasis/ Sleeping
Sickness: Nagana
What are Helminths?
Helminths (known also as parasitic worms/ macroparasites) Inhabiting spaces in the host’s body-
NOT ALL INTESTINAL
Types:
Tapeworms (Cestodes) e.g. young/ intermediate form of
Pork Tapeworm (cysticercus) -reside in brain, eyes, muscles, and skin Adult in human gut
Flukes (Trematodes) e.g. Schistosoma (reside in blood vessels)
Fasciola - in liver or lung - (intermediate in snails)
Roundworms (Nematodes) e.g. Heartworm (reside in the pulmonary artery)
What are ectoparasites?
ECTOPARISITES
“Parasites that live on the outside of the host, either on the skin or the outgrowths of the skin”
Lice, Fleas, Ticks, Leeches, Some mites, Biting Flies.
Protozoa and helminths parasitology lifespan
Protozoa and helminths are eukaryotic - this makes treating infections difficult
They live at the expense of their host and have evolved with it and its immune system.
Parasitic infections are distinguished from bacterial or viral infections by their complex life cycles and long duration inside or on the host.
This duration is due in part by their ability to evade the immune system and avoid immune destruction.
Most parasites undergo radical developmental changes throughout their life cycle, are antigenically complex, and host specific
In general they do not wish to kill their host
How do parasites cause disease?
Directly - damage by the parasite
Host Immune system induced damage
Death of the parasite can cause even stronger immune responses
- Immune effects
- Pathogenic degeneration eg calcification
Other agents carried by the parasite
- viruses (ASFV)
- bacteria
- other parasites eg mosquitos and malaria
T Helper subset in parasite invasion
Most parasites are susceptible to both Innate and adaptive immunity (and have produced strategies to escape both)
Micro and macro endoparasites induce different immune responses
Different parasites drive a bias to a specific subset of CD4+ T helper cells:
- Tho - naive T helper forms the others
- Thl - intercellular infective agents, micro-endoparasites
(macrophage driven responses) - Th2 - extracellular infective agents, macro-endoparasites (eosinophil driven responses)
Th17
Treg
Tth
These alter not only which form of T or B cell response is seen but also other inflammatory changes
What is the typical Type I immune response to protist infection and how does it involve pattern recognition receptors and cytokines?
Triggering Antigens:
- Protozoa antigens trigger pattern recognition receptors (PRRs) like Toll-like receptors (TLRs) 2 and 9.
Receptor Response:
- TLRs respond to glycoprotein repeat sequences and unexpected repeat DNA sequences during phagocytosis.
Antigen Presenting Cells (APCs):
- Involves dendritic cells, macrophages.
Cytokine Release:
- Stimulated APCs release interleukin-12 (IL-12), initiating a pro-inflammatory response.
IL-12 Actions:
- Activates natural killer (NK) cells to produce more interferon-gamma (IFN-γ).
- Activates already formed Type I cells to produce more IFN-γ.
- Drives naive CD4 T cells towards the T helper 1 (Th1) pathway.
IFN-γ Actions:
- Activates resting macrophages to become M1 macrophages, enhancing phagocytosis and granule release.
- Stimulates the formation of cytotoxic T cells.
Increases NK cell activity.
Effectors:
- Activated Macrophages (M1): Destroy free agents and infected cells.
- Cytotoxic T Cells and NK Cells: Destroy infected host cells.
What is the innate immune response to Plasmodium falciparum (type 1 infection) and its role in malaria’s hallmark fever?
Stimulation of TLRs: Merozoites stimulate Toll-like receptors (TLRs), specifically TLR2 (binds GPI) and TLR9 (binds parasite dsDNA).
IL-12 Activation: This stimulation leads to the activation of IL-12.
Th1 and NK Cells: IL-12 activates Th1 and NK lymphocytes, which release interferon-gamma (IFN-γ).
Macrophage Stimulation: IFN-γ stimulates macrophages.
Cytokine Secretion: Stimulated macrophages secrete pro-inflammatory cytokines IL-1, IL-6, and TNF-α.
Fever: These cytokines contribute to the hallmark fever of malaria infections.
Recurrent Fever: The synchronized release of merozoites `from ruptured RBCs is the major cause of recurrent fever in malaria.
What is the immune response to helminth infections and how does it differ from the Type I response?
Antigen Presentation: Helminth antigens feed into antigen-presenting cells (APCs), leading to activation of naive CD4 T helper cells.
Type II Helper Response: Unlike the Type I response, helminth infections induce a Type II helper response.
Cytokine Release:
- IL-4 and IL-25: Drive the Type II helper response.
- TGF-β and IL-10: Block the release of IL-12 from APCs (macrophages and dendritic cells), preventing a Type I response.
Effector Cells and Cytokines:
- IL-4, IL-9, and IL-3: Increase the number and activity of mast cells and basophils.
- IL-5: Drives the production of eosinophils.
- IL-13 and IL-4: Activate B cell class switching to produce immunoglobulin E (IgE) and IgG1 and IgG4.
Outcome: Predominantly Type II helper cells (Th2) and their associated cytokines mediate the immune response, leading to the activation of various effector cells tailored to combat helminth infections.
Protist:
- TH1 response (IFNy)
- Inflammatory
- IL12, INF
- Activated macrophages oxidative burst
- NK cells
Antibody response mainly:
- IgG2
- IgG3
Helminths
- TH2 response (IL4)
- IL-10 and TGFßb limit acute inflammation via macrophages
- Rather Basophil and Eosinophil activation
Antibody response mainly:
- IgG1 (mouse)
- IgG4 (man)
- IgE
IgE structure
- Structure is similar to Ig G
- Has 4 constant region domains.Heavy chain
- Mol. Wt. 1,90,000
- Half life: 2 days
- Heat labile (inactivated at 56°C in 1 hour)
- Normal serum concentration 0.3 ug/ml
- Mostly present extra cellularly
- Does not cross placenta
What role does IgE play in the immune response to helminth infections?
IgE Production: During helminth infections, interleukins IL-4 and IL-13 drive B cell class switching to produce IgE.
Binding to Mast Cells and Basophils: IgE binds to high-affinity FcεRI receptors on the surface of mast cells and basophils.
Antigen Recognition: When IgE bound to these cells recognizes helminth antigens, it triggers degranulation.
Degranulation: Release of histamines, proteases, and other inflammatory mediators.
Histamines: Increase vascular permeability and smooth muscle contraction, aiding in expulsion of helminths.
Proteases: Damage the surface of the helminths.
Eosinophil Recruitment and Activation: IgE also aids in the recruitment and activation of eosinophils.
Role of FcεRII
Role of FcεRII (CD23): FcεRII, a low-affinity IgE receptor, is found on B cells, monocytes, and other immune cells.
Regulation of IgE Levels: FcεRII helps regulate the levels of IgE in the body, preventing excessive immune responses.
Antigen Presentation: FcεRII can facilitate the presentation of helminth antigens to T cells, enhancing the adaptive immune response.
IgE Transport: FcεRII assists in the transport and distribution of IgE throughout the immune system.
