Download Figure-17 This diagram illustrates the various effector mechanism

Figure-17 This diagram illustrates the various effector mechanism that have been shown
to damage schistosomes in vitro. Complement alone damage worms (1) and also does so
in combination with antibody (2). TH1 cells may act directly inhibiting the degree of
larvae in the lungs. (3) Antibody sensitizes neutrophils (4), macrophages (5), platelets (6)
and eosinophils (7) for antibody-dependant cell-mediated cytotoxicity. Neutrophils and
macrophages probably act by releasing toxic oxygen and nitrogen metabolites, whereas
eosinophils damage the worm tegument by release of major basic protein plus reactive
oxygen intermediates. The response is potentiated by cytokines (e.g. TNFα). IgE
antibody is important both in sensitizing eosinophils and local mast cells, which release a
variety of mediators, including those that activate the eosinophils.
Figure-18 Toxoplasma gondii. Live parasites enter the cell activity into a membranebound vacuole. They are not attacked by enzymes because lysosomes do not fuse with
this vacuole. Dead parasites, however, are taken up by normal phagocytosis into a
phagosomes (by interaction with the Fc receptors on the macrophage if they are coated
with antibody) and they are then destroyed by the enzymes of the lysosomes which fuse
with it.
Trypanosoma cruzi. Survival of these parasites depends upon their stage of development;
trypomastigotes escape from the phagosome and divide in the cytoplasm whereas
epimastigotes do not escape and are killed. The proportion of parasites found in the
cytoplasm is decreased if the macrophages are activated.
Leishmania spp. These parasites multiply within the phagaosome and the presence of a
surface protease helps them resist digestion. If the macrophages are first activated by
cytokines the number of parasites entering the cell and the number that replicates
dimnish.
Figure-19 Electron micrograph of Toxoplasma gondii actively invading the host cell,
during invasion the parasite forms a tight junction with the host cell membrane (arrowed)
and modifies and the newly formed phagosome to inhibit subsequent lysosomal fusion.
Figure-20 The Leishmanial vacuole is lysosomal in nature.
3. Immunofluorescence of Leishmania Mexicana-infected murine macrophages probed
with a rhodamine-conjugated anti-tubulin antibody to illustrate the parasite (stained
yellow/red) and a fluorescein-conjugated monoclonal antibody which reacts with the late
endosomal/lysosomal marker LAMP-1 (stained green).
2. mmunoelectron micrograph of L. Mexicana-infected murine macrophage probed with
gold-labelled anti-cathepsin D demonstrating the lysosomal aspartac proteinase in the
leishmanial vacuole.
Figure-21 Schematic representation of two surface antigens of Leishmania that are
anchored to the membrane by phosphatidylinositol tails (GPI anchors)
(1) This protein antigen, Gp63, has protease activity. That of L Mexicana, together with a
lipophosphoglycan (LPG), binds complement. This enables the promastigote to enter the
macrophage through the C3 complement receptor.
(2) This glycolipid antigen, a lipophosphoglycan, imparts resistance to complementmediated lysis. That of L. major binds C3b, the third component of complement, enabling
the promastigate to enter through the CR1 complement receptor. Antibodies to both
antigens confer protection against murine cutaneous leishmaniasis.
Note that many coat proteins of parasites, such as the variable surface glycoprotein
(VSG) of T. brucei, are now known to be bound to the surface membrane by a GPI
anchor.
Figure-22 Antigenic variation to trypanosomes
immunofluorescent labeling of trypanosome with a variant antigen-type specific
monoclonal antibody (1), Panel (2) shows the same field of view where the nuclei and
kinetoplasts of all the parasites are stained with a dye that binds to DNA. Only some of
the parasites express a given antigen variant (arrowed).
Figure-23 Trypanosome infections may run for several months giving rise to successive
waves of parasitaemia.
Graph (1) shows a chart of the fluctuation in parasitaemia in a patient with sleeping
sickness. Although infection was initiated by a single parasite, each wave is caused by an
immunologically distinct population of parasites (a,b,c,d); protection is not afforded by
antibody against any of the preceding variants. There is a strong tendency for new
variants to appear in the same order in different hosts. Variation does not occur in
immunologically compromised animals (that is, animals treated to deprive them of some
aspect of immune function).
Group (2) shows the time-course of production of antibody against four variants in a
rabbit bitten by a tsetse fly carrying Trypanosome brucei. Antibody to successive variant
appears shortly after the appearance of each variant and rises to plateau. The appearance
of antibody drives the parasite towards another variant type.
Group (3) shows the kinetics of one cycle of antigenic variation. A rat was infected with
a homogeneous population of one variant (a) of T. brucei. The second wave of
parasitaemia develops as the new variant (b) emerges and predominates.
Figure-24 Electron micrograph of an infective larva of Toxocara canis illustrating the
surface coat (Sc) bound with cationized ferritin (CF) overlying the epicuticle (Ep).
Larvae were fixed with glutaraldehyde and osmium tetroxide before processing for
electron micrography.
Figure-25 Free antigens can:
(1) Combine with antibody and divert it from the parasite. The variant surface
glycoprotein of Trypanosoma brucei and the soluble antigens of Plasmodium falciparum,
which are also polymorphic and contain repetitive sequence of amino acids, are thought
to act in this way as a smokescreen to decoy.
(2) Blockade effector cells, either directly or as immune complexes. Circulating
complexes, for example, are able to inhibit the action of cytotoxic cells active against
Schistosoma mansoni.
(3) Induce T- or B-cell tolerance, presumably by blockage of antibody-forming cells
(AFC) or by depletion of the mature antigen-specific lymphocytes through clonal
exhaustion or by induction of anergy.
(4) Cause polyclonal activation. Many parasite products are mitogenic B or T cells, and
the high serum concentrations of non-specific IgM (and IgG) commonly found in
parasitic infections probably result from this polyclonal stimulation. Its continuation is
believed to lead to impairment of B cell function, the progressive depletion of antigenreactive B lymphocytes and thus immunosuppression.
(5) Active T cells, especially TH2 cells, or macrophages, or both, to release
immunosuppressive molecules.
Figure-26 A summary of the various methods which parasites have evolved to avoid host
defence mechanisms. DAF = decay accelerating factor.
Figure-27 There is more destruction of erythrocytaes in malaria than can be accounted
for by number infected by parasites. In addition to those lost by lysis when the schizont
ruptures (1), immunopatholocial mechanisms probably contribute to the anaemia.
Parasite antigens, or immune complexes containing parasite antigen, may bind to
unparasitized erythrocytes and accelerate their clearance by cells of the
macrophage/monocyte lineage in the spleen and liver (2). There is also some
autoantibody produced against normal erythrocytaes which again accelerates their
removal (3). TNFα released in response to infection inhibits red blood cell development
from bone marrow stem cells and alters the kinetics of red cell turnover (4).
Dr. MUSTAFA HASSAN LINJAWI