Last minute quick view - Immunology + Parasitology

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In the Name of Allah, the Most Beneficent the Most Merciful. Just in case you're too lazy to open the notes, personally I find the notes very difficult to read. Hope this helps.

Immune Evasion by Parasites

Parasites have developed many ways to escape from the human immune system so they can thrive successfully while living in the human body.

1. Escape from Immune Effectors

1. Intracellular parasites avoid destruction:

E.g.      Toxoplasma gondii enters the human macrophage without using the phagocytic pathway

Leishmania parasites enter macrophages by binding onto the cell receptors. They also has the enzyme superoxide dismustase, which inhibit the respiratory burst

Trypanosome cruzi escapes form the phagosome in the human macrophage into the cytoplasm before fusion of the phagosome and lysosome happens.

Plasmodium parasites are protected inside RBCs.

2. Extracellular parasites hide away from immune detections and attack:

i.                     Through formation of protective cysts:

e.g.       Entamoeba histolytica

             Toxoplasma gondii

             Trichinella spiralis

ii.                   Living within the intestinal lumen:

e.g.        Intestinal worms

iii.            Living in places like:

                e.g.        in the eye – Oncocerca volvulus

                              in the bile duct – fasciola hepatica

                             collagen nodules – Oncocerca volvulus

3. Resists complement destructions:

e.g.       Leishmania major – Its lipophosphoglygogen surface coat can shed the complement system once the system is attached (this resistance correlates with virulence).

Trypanosome cruzi has a glycoprotein that resembles the DAF (decay-accelerating factor) that limit the complement action.

2. Avoidance of recognition

This is done by changing the antigenicity and immunogenicity of the parasites.

1.       Switch of antigen expression

This is done mainly by African Trypanosomes. The parasites continuously change their antigen profile, weakening the immune system and making it ineffective.

2.       Antigenic diversity among different strains and different stages.

e.g.   Leishmania

        Toxoplasma

        Plasmodium

3.       Synthesis of immunodominant molecules with repeated sequences

This repeating reduces the immunogenicity (plasmodium species). Or, the repeating sequences can be shared by many antigens on the species. So the immune system will not bother recognizing repeating sequences and the parasite is safe. (smoke-screen effect)

4.       Shedding of surface antigens

Helminths and Plasmodium secrete a lot of antigens to mop up the antibodies.

5.       Antigen mimicry

Schistosomula coat it with the ABO blood group glycolipids and MHC molecules derived from the host.

Adaptation of host antigens and synthesis of surface proteins similar to the host proteins are combinations of strategies being used by parasites such as:

e.g.   Fasciola hepatica

        Ascaris

        Tapeworms

3. Immunosuppression

1.       Release of immunosuppressive mediators (enzymes and peptides)

These either cleave the antibodies or interfere with proper complement activation.

e.g. Schistosomes

      Trichinella spiralis

Trypanosoma cruzi (T. cruzi elaborates suppressive substances that act on CD4+ proliferation and IL-2 expression)

Plasmodium falciparum antigenic product interferes with IL-2 production and their receptor expression.

2.       Induction of suppressor cells

Plasmodia species and African Trypanosomes induce suppressor macrophages that inhibit IL-1 production.

Trypanosoma cruzi and Leishmania induce suppressor macrophages that inhibit IL-2 production.

3.       Utilization of immune effectors by parasites

e.g. Direct infection of CD4+ and CD8+ cells by Trypanosome cruzi

Consumption of IL-2 by Leishmania.

4.       Non-specific polyclonal activation of both T and B lymphocytes

This will lead to exhaustion of immune system in producing high concentration of IgG and IgM that activate effector cells but has no significant effect against parasite antigens. This mechanism is known in:

e.g.   Schistosomes

        Plasmodium falciparum

        African trypanosomes

5.       Induction of blocking antibodies

Antibodies produced against one stage of a parasite may have a blocking effect on the antibodies raised against other stages sharing the same antigenic epitopes.

e.g. IgM antibodies produced against the carbohydrate antigens released by Schistosome eggs in the early infections are able to block the IgG antibodies produced in the schistosomula stage.

Immunological consequences of parasitic infections

Immune system activated by the parasites may have significant negative effects on the host.

1. The increased number and heightened activity of macrophages and lymphocytes in the liver and spleen cause enlargement of those organs.

                          e.g.        Malaria

              African Trypanosomes

              Visceral Leishmaniasis

2. Granuloma formation around the Schistosome eggs within the liver is caused by T-cell dependent activities.
3. Elephantiasis is caused by immunopathological responses to adult filariae in the lymphatics.
4. Formation of immune complexes – in quartan malaria, immune complexes formed may deposit in the kidney, causing nephrotic syndromes.
5. The IgE in worm infections can cause severe damage on the hose due to the release of mast-cell mediators.

e.g.       Hydatid cysts, if ruptured, can cause severe allergic response (anaphylactic shock)

Asthma-like reactions in Toxocara canis infections and Tropical Pulmonary Eosinophilia when there are worms migrating in the lung.

6. Auto-antibodies arise as a result of polyclonal activation. The antibodies against RBCs, lymphocytes, and DNA are produced in cases of trypanosomiasis and malaria.
7. Antibodies against the parasites may cross react with the host antigen, such as in the case of Trypanosoma cruzi infection, organs are enlarged (organomegaly – megaesophagus, megacolon, ect.), this condition is thought to be due to auto-immune effect of antibodies and cytotoxic T cells on the nerve ganglia of antibodies.
8. Excessive production of cytokines may enhance the manifestations of disease. Fever, anemia, diarrhea and pulmonary changes in acute malaria (resembles endotoxemia) are probably caused by TNFα.
9. Several immunological mechanisms may combine in producing pathological effects e.g. anaemia of malaria.
10. The non-specific immunosuppression that is so widespread may explain why people with parasitic infection are especially susceptible to bacterial and viral infections.

e.g.       the patients suffering from auto-immune diseases and allergies are ‘cured’ after infected by worms

            Burkitt’s lymphoma – susceptibility is associated with malaria