Parasites Flashcards
Microbes have co-exsited with us since the beginning, what is important to remember?
Most microbes are not disease causing, there’s a balance between pathology/disease and harmony/benefit.
Actually, parasites causing pathogenicity/disease is an exception rather than a rule.
Define parasitism.
Parasitism – where one organism either harms or lives at the expense of the host.
There are two big groups of parasites, which?
Protozoa and Helminths (worms).
Describe protozoa as a group.
Protozoa are uinicellular eukaryotic organisms (size: microns). They can be both intracellular, extracellular or both (in different life stages). Examples include: Malaria, Toxoplasma, Leishmania, Trypanosoma.
Describe Helminths as a group.
Helminths/worms are multicellular eukaryotic organisms (size: microns to meters!), they are strictly extracellular. Examples include: Filaria, Schistosoma, Trichinella, Ascaris.
What distinguishes parasites from other types of infection?
- Parasites are eukaryotes, more closely related to us.
- They have complex life cycles in and outside the host, which puts pressure om the immune system having to respond before metamorphosis and expressing other antigens and to new antigens in the new stage, leaving the immune response one step behind. Also the location of different life stages can differ. (Some parasites only live one or a few stages in a human host, whereas other go through different stages in the host)
- Sexual recombination: can lead to big diversity.
The most effective immune response will depend on the type of organism, the location of the infection, and the life cycle stage of the parasite.
Where are parasitic infections most common?
In tropical climates, which are common breeding grounds for many arthropod vectors that carry parasitic infection, such as mosquitoes, flies, and ticks.
There are four dogmas/paradigms in host/parasite interactions, which?
- A host will mount a defense against a parasite.
- The parasite must have components available to evade this defense (always a counterattack to the immune response).
- Host specificity is determined by the host’s ability to mount an effective defense and which parasite can evade that defense.
- Within this interplay between defense and response most of the disease is caused by the host immune mechanisms.
Name four characteristics of parasitic Infections.
Parasitic infections:
- Often long lived / chronic infections.
- Metamorphosis through multiple antigenically
distinct life cycles
- have immune evasion mechanisms
- are a significant public health problem, especially in developing countries (poverty, malnutrition, low sanitation, concomitant infections)
Which cells in the innate and adaptive immune system are key in the control of parasitic infections?
Innate: Macrophages, dendritic cells (DC), neutrophils and eosinophils can kill both protozoa and worms, mainly by phagocytosis, ROI (reactive oxygen intermediates) and NO (Nitric oxide) secretion and cytokine activation (IL-12) Also NK cells secrete IFN-g which enhances macrophage activity.
Adaptive: Both T and B cells important,
- T cells are fundamental to the development of immunity Both CD4 and CD8 T cells can be necessary for protection
-Th1 cells provide protection against intracellular protozoa by
secreting IFN-g which activates macrophages and DCs.
-Th2 and Treg responses are characteristic of helminthic infections.
-Th1/2 polarized responses either protect or exacerbate disease (too much never good)
Antibodies produced by B cells contribute through many effector functions: Complement (C’) fixation (direct damage), Neutralization (blocking surface receptors to hinder infection), Opsonization (enhance phagocytosis) and ADCC (cytotoxicity). But! many evasion mechanisms are used to evade these effector functions.
How many protozoans are there and how many of them are known pathogens?
We know of about 30 000 protozoans, out of which 73 are pathogenic (again, an exception rather than a rule!)
Which are the most common protozoan parasites?
Malaria 4-500 million carriers worldwide
Toxoplasma 1, 2 billion
Trypanosomas 18 million
Leishmania 12 million
Name and explain a common survival strategy in pathogenic protozoa.
Antigenic variation is a common survival strategy in pathogenic protozoa.
Antigenic variation the ability to “switch” the antigens expressed, which is possible through having multigene families that code for these variable antigens (coat proteins having the same function but different structure). Antigenic variation is the major reason to why parasitic infections are long lived, because there is a continuous battle between the parasite and the immune system. When the immune system produces antibodies for one antigen, the parasite (protozoa mainly) decrease in numbers, go through an antigenic shift and goes up in numbers, then antibodies towards that antigen is produced which lower the numbers again, switch antigen and so on. These waves of parasitemia characterizes many protozoan infections, where trypanosomes (causing African sleeping sickness - 100% fatal) stand out with over 1000 protein variants (variant
surface glycoprotein (VSG)). Antigenic variation
in Trypanosomes is not restricted by any other function than immune evasion (really shows the co-evolution).
Which protozoa causes malaria?
The protozoa causing malaria is Plasmodium
falciparum.
Which people are most susceptible to malaria infection?
Young children with immature immune system and pregnant people who are immunocompromised, are most susceptible to malaria.
When you take a blood sample of a person infected with malaria, you will only find protozoa of the first life stage (sporozoites) in the blood, why?
Malaria infects red blood cells, which usually circulate through the spleen a lot. Malaria uses the evasion mechanism called sequestration, basically hiding, because they want to avoid the spleen, which is the first line of defense for blood borne pathogens. They do this by expressing an adhesion protein called PfEMP1 (which they also have many variants of to evade the immune system by antigenic variation) which bind to surface receptors of blood vessel endothelial cells to adhere, and thus allows them to sequester or “hide” from the spleen.
Which are the key players in sensing/recognizing plasmodium (malaria)?
The mechanisms for sensing/recognition of malaria is the same as for other intracellular pathogens, PRRs. Mainly TLRs, RLRs and NLD. TLRs sense e.g. plasmodial DNA (TLR9) and RNA (TLR7), NLR sense intracellular PAMPs like Haemozoin (crystallized form of heme, produced by the protozoa feeding on hemoglobin) and DAMPs like urate and RLRs mainly recognizing plasmodium DNA.
Activated PRRs induce activation of multiple pathways to clear parasites, for example secretion of proinflammatory cytokines like IFN-g and IL-12 (stimulating NK-cells) and activation of T and B cell responses.
Considering that many protozoa are intracellular, which carries risks like the cell dying of apoptosis to kill the infection, they have evolved many special evasion strategies, name two.
- Leishmania is acid resistant, which makes it possible to live inside of the lysosome. They have their way in already paved out, as macrophages engulf them (to try to kill them) but then they thrive in the lysosome.
- Toxoplasma produce their own cocoon which can’t fuse with lysosome
- Many inhibit cytokine secretions, like IL-12 so NK cells are not activated.
- Inhibition of apoptosis (leishmania, toxoplasma)
- inhibition of DC migration (leishmania, toxoplasma) or DC antigen presentation.
How many helminths are there and how many of them are known pathogens?
There are somewhere around 50 000 known helminths and only ~50 are parasitic, most are not fatal, they are masters of living with the immune system. Chronic/life-long infections are common.
Although talked about very little, helminth infections are very common:
Ascaris (spolmask) 800 million carriers worldwide
Whipworm 600 million
Hookworm 575 million
Schistosoma 200 million
Filaria 120 million
Strongyloides 30-100 million
What is the most common evasion tactic for worms?
The most common evasion mechanism for worms is anatomical seclusion, normally to immunopriviledged sites like the eyes, brain, placenta and intestinal mucosa with less immunoactivity/tolerance.
Give examples of two other evasion tactics used by worms.
Other evasion tactics used by worms are:
-Coating with host protein:
-Molecular mimicry
-surface shedding/ replacement
- downregulation of host immune system: immunomodulation e.g. production of proteases that supress chemokines, Serpins that supress proteases produced by host and anti-oxidants that supress NO toxicity (secreted by eosinophils).
Three factors play into the pathogenesis of a parasite, which?
- Pathogenic potential of parasite: Parasites are highly host-adapted eukaryotes: most infections
generate little or no symptomatology/pathology - Immune response of host: most severe parasitic pathology has immune/inflammatory component
- ”external” complications: if you’re immunocompromized (child, pregnant, malnutrition, concurrent disease etc) plays into pathology.
Worms (and protozoa) can induce both non-inflammatory and inflammatory pathways, when are the inflammatory more common?
The inflammatory pathways are more likely induced when the parasite is dead, as there are no evasion strategies like hidden antigens anymore.
Are there standardized vaccines for parasitic infections available?
No, mainly because of the many evasion strategies like antigenic variation (protozoa) and coating with host protein and molecular mimicry (worms).
Give one example of the immune response and effector mechanism in response to one helminth and one intracellular protozoa.
Helminths: TH2 cells –> IL-4, IL-5–> IgE, eosinophils –> Eosinophils kill IgE-coated parasites (form of ADCC)
Malaria: CD8+ T cells –> secretion of cytokines like IFN-g and TNF –> activate macrophages and neutrophils to kill parasites
How are most fungal infections controlled?
Most fungal infections are controlled by innate responses, especially PRR recognition of common surface structures, neutrophils, and complement, as evidenced by increased susceptibility to fungal infection in individuals with defects in one or more of these components, including during systemic immunosuppression.
Both humoral and cellular pathways are engaged against fungal infections, as evidenced by memory responses and increased susceptibility in immune-compromised individuals, where the primary modes of clearance of mycoses appear to
be mediated by T 1, and possibly T 17, cells.
Fungal infections page 1241
