Immunity against parasites
Parasitic infections are produced by protozoa and helminths. Most parasites have very complex life cycles that often develop partly in humans or other animals, while other parts of the cycle depend on other invertebrate intermediary organisms, for example insects. The parasites that infect man can affect him in many different ways, some colonize the blood, like trypanosomes, others can live inside the erythrocytes, like Plasmodium, in the liver, like some Leishmania species, the intestine like tapeworms or even the brain like toxoplasma.
The immune response to many parasites has only a limited result due to the complex mechanisms that these microbes have to interfere with it. As an example we can put an infection with a tapeworm that can measure up to a meter in length and yet can live inside our intestine without even causing intestinal inflammation. Parasitic infections are often chronic and affect a large number of people especially in developing countries and is a serious health problem because there are no effective vaccines against them and drug treatments often have limited effectiveness.
The innate immune response to most parasites is very inefficient. Some parasites such as Trichinella spiralis can activate complement, although this is usually not enough to eliminate the pathogen. The most important innate response is that of phagocytosis, although in most cases it is also not completely efficient in eliminating the parasite.
An effective immune response against parasites almost always depends on the activation of adaptive immunity. The type of response to parasites depends very much on the characteristics of their life cycle and physiology, which are extraordinarily variable and complex. Some of them even alternate intracellular and extracellular life cycles infecting different types of tissues and cells, so that in each case the most effective immune response has to be different. In the case of those parasites that have extracellular life cycles, such as Trypanosoma brucei, which lives free in the blood, the most effective response is that of antibodies. These antibodies can be neutralizing, for example the antibodies against Plasmodium can block the parasites preventing their entrance in the erythrocytes, or they can activate effector mechanisms such as complement or phagocytosis to destroy the pathogen. In helminth infections, a Th2-type response with specific IgE synthesis against parasite antigens usually occurs. In this case, professional antigen-presenting cells phagocyte helminth antigens and present parasite peptides in traces of MHC class II molecules to Th2 lymphocyte clones. Th2-lymphocyte clones produce Th2-type cytokines: IL-4, IL-5, IL-10 which are crucial for coordinating this response. On the one hand, B lymphocytes that present specific immunoglobulins of parasitic antigens in their membrane present their peptides to Th2 clones that respond to IL-4 production, cytokine that favors the change of isotype to IgE; for this reason we can find high levels of IgE in parasitic diseases. The IgE produced in this way will bind to the parasite surface and will allow the activation of mast cells and eosinophils that will be key to the elimination of the parasite. IL-5 is also a factor of differentiation and activation of eosinophils, so the elevated levels of IL-5 will increase the number of eosinophils that our bone marrow produces in cases of parasitosis. The mast cells produce release of pro-inflammatory substances in response to the binding of IgE to the parasite, alerting the immune system of its presence, while eosinophils release toxic substances that will allow the elimination of the parasite.
Many parasites have exclusively intracellular life cycles, as in the case of Leishmania, a protozoan that infects all macrophages and lives and replicates within them. The production of antibody against these parasites is ineffective because they internalize inside the phagocytic cells quickly avoiding the action of these antibodies. In these cases, the most effective immune response is the Th1 type, as in the case of viral infections and intracellular bacteria with the activation of IFN-gamma-producing cells that activate infected macrophages so that they can efficiently eliminate parasites that have been phagocytes.
Mechanisms of parasite evasion against the immune response
Most of the parasites have developed very sophisticated mechanisms to escape from the action of the immune system, which makes it very difficult to eliminate them, and therefore many of these infections are chronic. Once again we can see that antigenic variation is a very effective escape mechanism in some parasites. The most notable case is Trypanosoma brucei, the cause of sleeping sickness in Africa. The external part of this parasite is constituted by a protein called VSG (Variable Surface Glucoprotein). This protein is very antigenic and infected individuals produce antibodies against it in an effective way, however the parasite has up to 1000 different genes that encode different versions of this protein and changes over time. When parasites change their VSG, the anticuepos are unable to join the new version and there is an expansion of new parasites, a fact that is repeated again and again as the individual is making antibodies against the different versions of the VSG. Other parasitic evasion mechanisms include interference with the complement e.g. Trypanosoma cruzi, which causes Chagas disease in South America, has a protein homologous to DAF, a factor that regulates complement activation in human cells. Intracellular parasites such as Leishmania, Toxoplasma or Trypanosoma have different mechanisms that make them resistant to the action of phagocytes, using methods very similar to those used by intracellular bacteria. Some parasites physically isolate themselves from the host organism, producing a cyst within which they can survive for years, as is the case with Trichinella spiralis. Others simply have covers so resistant that the immune system cannot damage them, as is the case of the thick cuticle that covers the nematodes. Some parasites such as schistosomes disguise themselves by coating themselves with host proteins, making them invincible to the immune system.
Finally, most parasites interfere with the host’s immune response by producing a certain degree of immunosuppression by different emcanisms, such as producing proteins analogous to immunosuppressive factors such as TGF-BETA.
- Regueiro González J.R., López Larrea C., González Rodriguez S. y Martínez Naves E. Inmunología: Biología y patología del sistema inmunitario. 4ª edición. Editorial Médica Panamerica, 2010.