PATHOGENESIS & IMMUNE MECHANISM IN PARASITE INFECTIONS

PATHOGE NESIS

A parasite may live in or on the tissues of its host w/o causing evident harm. However, in a mayority of cases, the parasite has the capacity to produce damage.

The lesion may be localized at the site where the parasite has become established, or it may extend to distant parts of the hosts body.
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Trauma nutrition robbing The pathogenic effects of parasite

lytic necrosis

toxin production interaction of the host immune/

inflammatory responses
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TRAUMA
Physical trauma, or destruction of cells, tissue or organs by mechanical or chemical means, is common in parasite infections. Damage due to :
invasion (eg : Scabies) migration (eg : VLM, Gnathostoma) attachment (eg : Trichuris, Giardia) obstruction (eg : Ascaris, Filaria)
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NUTRITION ROBBING

Helminths can contribute to malnutrition by decreasing nutrient intake, increasing nutrient excretion and/or nutrient utilization. Giardia robs its host in a different way. Its concave side on ventral surface cover intestinal absorptive surface of their hosts and interfere their hosts absorption of nutrients.

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LYTIC NECROSIS Enzymes elaborated by many parasite make it them possible to digest food i/t immediate environment and to transform nutriment into their own protoplasma or store it for the production of energy. E.g. : E. histolytica is not only lysis tissues for nutritional needs but also for penetration into tissues o/t colon/extraintestinal viscera Necrosis of parasited host cells during invasion, growth & multiplication (eg : malaria, Toxoplasma)
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TOXIN PRODUCTION Parasite toxins that causes pathogenic effects is found in malaria. Lysis o/t parasited red blood cells unleashes large amounts of toxic waste products into the blood, to which the host responds with a sharp rise in TNF & probably other fever causing fever. Synchrony of red cell lysis & consequent eruption of TNF accounts for periodicity of typical paroxysms of chills & fever in malaria.
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INTERACTIONS of the HOST IMMUNE/ INFLAMATORY RESPONSES A number of cases previously thought due to toxins released by parasites are now understood as caused by the hosts reaction to parasite products. e.g. : T. cruzi develops clusters of cardiac muscle cells of its host. When the parasite degenerate, the inflammatory response damages supporting cells of the nerve ganglia that control peristalsis & heart contraction. Parasite Ag on the hosts own cells, particularly in the endocardium, cause autoimmune reactions & the hosts cells are attacked as foreign by the immune system.
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Immunity to Parasites

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When a host invaded by a parasite the host may or may not show resistance.

IMMUNE MECHANISM

If the host does show resistance, this may be innate or acquired.

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Important General Features of Immunity to Parasites. Defence against parasites is mediated by both innate and specific/adaptive immunity. The innate immune response to parasites plays an important role in determining the nature of the specific immune response. The immune response is capable of responding in distinct and specialized ways to different parasites in order to combat these infectious agents most effectively.
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Important General Features of Immunity to Parasites. The survival and pathogenicity of parasites in a host are critically influenced by their ability to evade or resist protective immunity. Tissue injury and disease consequent to infections may be caused by the host response to the parasite and its products rather than the parasite itself.
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Innate Immunity to Parasite The principal innate immune response to protozoa is phagocytosis but many of these parasites are resistant to phagocytic killing & may even replicate within macrophages. Phagocytosis is a process of engulfment of an invading particle within an invagination o/t phagocytes cell membrane. Nonspecific physical and chemical barriers that contribute to resistance against infection Does not exhibit immunological memory Mediated several classes of cells and tissues, with close interactions with the adaptive response
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Innate Immunity to Parasites Protozoa and helminthic parasites that enter the blood stream or tissue are often able to survive and replicate because they are resistant to host innate immune responses. Parasites in human host are usually resistant to complement. Macrophages can phagocytose protozoa, but the tegument of helminthic parasites makes them resistant to the cytocidal effects of both neutrophils and macrophages.
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Acquired Immunity to Parasite An acquired immune response is stimulated by a spesific foreign substance called an Ag & circularly an Ag is any substance that will stimulate an immune response. Different protozoa & helminths vary greatly in their structural & biochemical properties, life cycles & pathogenic mechanisms acquired immune responses. The principal defense mechanism against protozoa that survive within macrophagee is CMI, particularly macrophage activation by TH1 cell-derived cytokines.
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The Immune System

The principal function of the immune system is to protect the host against pathogenic microbes
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Humoral immune responses

B cells and antibodies

Specific/Adaptive immunity

Cytotoxic T cell (Tc) Cell mediated immune responses Helper T cells (Th)

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Specific/Adaptive Immunity to Parasites

Parasite antigen

Worm infections elicit Th2 protective immune responses. Protozoan infections elicit Th1 protective 11/18/2010 DEWI M D immune responses.

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Specific/Adaptive Immunity to Parasites Different parasites elicit quite distinct specific immune responses. Cell-mediated immunity is the principal defense against protozoa that survive within macrophages. Protozoa that replicate inside cells and lyse host cells stimulate specific CTL responses, similar to cytopathic viruses. IgE antibodies and eosinophils mediate defense against many helminthic infections.
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Cell Mediated Immunity

Mediated by Ag-specific T cells; cell-mediated immunity (CMI) Th1 driven; cytokines IFN-, TNF, IL-12 Effectors: activated macrophages and monocytes, (some cytotoxic CD8+ T cells) Granulomas, tuberculintype reactions (Filariasis)
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Cytotoxic T Cells Lyse Infected Cells

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Cytotoxic/Cytolytic Reactions Involving Parasites

Malaria Blackwater Fever hemolysis of erythrocytes

Malaria excess anemia; both infected and uninfected erythrocytes opsonized and phagocytosed Chagas disease : cardiomyopathy, megacolon, megaesophagus
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Immune Complex Reactions

Ag-Ab complexes form in circulation or in tissue Circulating complexes deposit in tissue Complexes activate C cascade >> induce acute inflammatory responses Granulocyte degradative enzymes damage tissue Cerebral Malaria, Nephrotic syndrome of chronic malaria
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IgE and Eosinophils

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Immune Response

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Destruction of Large Parasites by ADCC

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Evasion of Immune Mechanisms by Parasites Evolutionary adaptations give parasites their ability to evade and resist immune responses. Some parasites survive and replicate inside cells. Others develop cysts that are resistant to immune responses. Antigen masking is an effective form of immune response evasion by some parasites. Parasites can develop a tegument that is resistant to damage by antibodies and complement or CTLs.
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Evasion of Immune Mechanisms by Parasites Some parasites have mechanisms for surface antigen variation. There are two forms of antigenic variation: Stage specific, Parasites with complicated life histories may express certain antigens only at a particular stage of development (Exp Sporozoite Malaria) Continuous variation of major surface antigens (change their surface antigens, ex Trypanosoma)
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