Immune Response to Infectious Diseases - Parasites PDF

Immune Response to Infectious Diseases - Parasites Learning Objectives On completion of this session you should be able to 1) Describe how the immune system recognises and responds to parasite pathogens. 2) Identify various strategies employed by parasite pathogens to evade detection and...

Immune Response to Infectious Diseases - Parasites Learning Objectives On completion of this session you should be able to 1) Describe how the immune system recognises and responds to parasite pathogens. 2) Identify various strategies employed by parasite pathogens to evade detection and elimination by the immune system. Eukaryotic Parasites 1) Include helminth worms and protozoa 2) Parasites manipulate the immune Trichinella response and long lasting protection spiralis is difficult to attain roundworm in the intestine 1. Helminth worms: Large multicellular organisms (nematodes, trematodes and cestodes Cause intestinal or systemic infection Usually lead to chronic infections Schistosoma fluke lasting years Helminths – immune response Immune response mediated by antibodies, Th2 cells, mast cells, eosinophils, complement and phagocytes IgE binds to parasite and mast cells Mast cells degranulate releasing potent inflammatory mediators and recruiting eosinophils Eosinophils bind to IgE and release eosinophil basic protein which damages the cell wall of the parasite -> death IgG, complement and phagocytes may also have a role Functions of TH2 cells Carlson, B. M. (2019). Chapter 8-The Lymphoid System and Immunity. The Human Body, 209-239. Protozoa 2. Unicellular eukaryotic organisms e.g. Trypanosoma brucei - African Sleeping Sickness Plamodium - malaria Lives in blood stream of host Type of immune response that develops to protozoan infection depend in part on the location of the parasite within the host Any protozoans have life cycle stages in which they are free in the bloodstream, during these stages the humoral antibody is most effective Many of these same pathogens are also capable of intracellular growth; during these stage, cell-mediated immune reactions are effective in host defence T. brucei life cycle Response to T. brucei 1) Removed by complement mediated lysis and phagocytosis 2) Parasite is difficult to irradicate 3) Evade immune system by altering expression of surface proteins 4) T. brucei is coated with antigenic glycoproteins that mask underlying antigens 5) Parasite has ~1000 genes encoding glycoprotein and only one form is expressed at one time Plasmodium life cycle Stevenson, et al. (2004). Nature Reviews Immunology, 4(3), 169-180. Malarial ligands that induce innate responses and their respective receptors Stevenson, et al. (2004). Nature Reviews Immunology, 4(3), 169-180. Presumed mechanisms of adaptive immunity to malaria 1) Antibodies block invasion of sporozoites into liver cells 2) Interferon-γ (IFN-γ) and CD8+ T cells inhibit parasite development in hepatocytes 3) Antibodies block invasion of merozoites into erythrocytes 4) Antibodies prevent sequestration of infected erythrocytes by preventing binding to adhesion molecules on the vascular endothelium 5) IFN-γ and CD4+ T cells activate macrophages to phagocytose intra- erythrocytic parasites and free merozoites 6) Antibodies neutralize parasite glycosylphosphatidylinositol and inhibit induction of the inflammatory cytokine cascade 7) Antibodies mediate complement-dependent lysis of extracellular gametes, and prevent fertilization of gametes and the development of zygotes Stevenson, et al. (2004). Nature Reviews Immunology, 4(3), 169-180. Linking innate and adaptive immunity to blood-stage malaria Stevenson, et al. (2004). Nature Reviews Immunology, 4(3), 169-180. Immune evasion 1) Parasite periodically changes expression and sheds glycoprotein 2) This blocks antibodies and binds to receptors on immune cells thereby suppressing immune response 3) Other protozoa e.g. Plasmodium evade the immune system in a similar way by altering antigenic expression Immune evasion of parasites Summary 1. The immune system employs intricate mechanisms to recognise and respond to parasite pathogens. 2. Parasite pathogens have evolved various strategies to evade detection and elimination by the immune system.