MLM_Introduction to Host-Parasite Interaction 2024-2025 PDF

Introduction to host-pathogen interaction Prof. Mohamed Ridha Barbouche M.D., Ph.D. Department of Microbiology, Immunology and Infectious Diseases, Arabian Gulf University  Host-microbe interaction The human body is interacting and...

Introduction to host-pathogen interaction Prof. Mohamed Ridha Barbouche M.D., Ph.D. Department of Microbiology, Immunology and Infectious Diseases, Arabian Gulf University  Host-microbe interaction The human body is interacting and challenged daily by a variety of micro- organisms. These could be, - either normal flora or microbiota, living in stable niches and peacefully coexisting with their host to achieve a mutually beneficial relationship. - or pathogens which are microbes capable of causing host damage through direct microbial action or inappropriate host immune response. Types of host-microbe relationships  Pathogens affecting human host Bacteria: small prokaryotic single-celled organisms with a single DNA circular chromosome and characteristic cell walls e.g. E. coli Viruses: smaller than bacteria with DNA or RNA genome; obligate parasites which cannot replicate outside host cells e.g. CMV, HIV Protozoa: single-celled eukaryotic organisms with several organelles and simple or complex life cycles e.g. P. falciparum, leishmania Helminths: small to large metazoan or multicellular organisms, or worms with simple to complex life cycles e.g. A. lumbricoides Fungi: eukaryotes with cell walls containing chitin, cellulose or both and form germinative spores e.g. C. albicans Arthropods: organisms with jointed appendages; mostly ectoparasites e.g. S. scabiei ‘’Prions: small, proteinaceous ‘’infectious’’ particles, lacking a nucleic acid genome e.g. in CJD or BSE’’ The outcome of an infectious process involves complex interactions between host and microbes and leads to either: - Eviction (elimination of the pathogen). - Asymptomatic carriage (pathogen is contained, latent infection or carrier status, potential source of infection). - Clinical symptoms following incubation period (acute or chronic disease).  Pathogen (Invador) Host (Defender) - Bacteria, viruses, parasites (protozoa, - Immune system (organs, cells, soluble factors). helminths) and fungi that cause host damage and disease. - Barriers (physical, chemical and biological). - Contagious potential (inoculum size, mode of - Innate immunity (sensing receptors, transmission, entry site, adherence to phagocytosis and microbicide activity, receptors, invasion of tissues). complement, cytokines, inflammation, NK, antigen presenting cells). - Virulence factors and pathogenicity (direct or indirect). - Adaptive immunity (T cells and subsets, B cells, Immunoglobulins, memory). - Evasion mechanisms to host immunity. - Immune suppression may lead to opportunistic - Acquisition of drug resistance capacity. infections (weak pathogens but severe disease).  Pathogen associated antigens - Antigen is any substance that triggers an immune response. - This response is intended to naturally protect the body from harmful entities, such as disease-causing microbes. - In humans, some of the immune responses activated by the presence of antigens are innate immunity, antibody formation and induction of T cell- mediated immunity.  Pathogen associated antigens -cont.- - Pathogen associated molecular patterns (PAMP) are molecules with conserved motifs that and serve as ligands for host pattern recognition molecules (PRR) such as Toll-like receptors, triggering innate immune responses. - Pathogen associated specific antigen epitope (antigenic determinant) is part of an antigen that is recognized specifically by adaptive T and B cells receptors (TCR, sIg), triggering adaptive immune responses. Organs of the immune system Lymphatic circulation Cells of the Immune System Soluble factors  The three lines of defense Physical, chemical and biological surface barriers Keep the invader outside the host tissues. Innate immunity General host defense responses aimed to destroy the invader before it becomes established in tissues. Adaptive immunity Specific host defense responses aimed to target a determined antigenic epitope of the invader (specificity) and to remember it (memory).  Surface Barriers Physical: Intact skin Mucosa and cilia Chemical: Secretions (sebum, saliva, tears, gastric, bile salts…), low pH of urine, lysozyme… Biological Normal flora (commensal microbiota) living on body surfaces and in cavities of digestive, respiratory and genital tracts. It protects against colonization by pathogens through saturation of corporeal sites, competition towards essential nutriments and production of toxic components for pathogens.  Innate immunity - Innate immune mechanisms that non specifically target the pathogens and aim to eliminate them. - Binding of PRRs (TLRs) by PAMPs triggers immediate inborn defense responses. - These responses mainly involve: fever (cytokines stimulate brain cells to release prostaglandins which act on hypothalamus, fever enhances the immune response by speeding up metabolism and phagocyte activity) inflammation phagocytes Complement NK cells (cytotoxic cells that kill infected cells missing self MHC molecules) Inflammation Phagocytes (neutrophils, monocytes/macrophages, some dendritic cells) Complement The complement system, also known as complement cascade, is a part of the innate immune system that complements the ability of antibodies and phagocytic cells to clear microbes from an organism, promote inflammation, and attack the pathogen's cell membrane. Adaptive Immunity Adaptive Immunity -cont.- Cell-mediated immunity (cellular immunity) Antibody-mediated immunity (humoral immunity) Adaptive Immunity -cont.- Primary and secondary B cells immune responses Ig M IgG Innate Immunity and Adaptive Immunity compared Nature of the invader determines host immune responses - Extracellular bacteria (neutralization by antibodies, activation of complement, opsonization and phagocytosis) - Intracellular bacteria (phagocytosis, killing in the phagolysosome, T CD4 helper type 1) - Viruses (type I interferons, NK, neutralizing Abs during viremia, T CD4 helper type 1, T CD8 CTL) - Protozoa (phagocytosis, T CD4 helper type 1, T CD8 CTL) - Helminths (T CD4 type 2, eosinophils, IgE, ADCC). - Fungi (phagocytosis, neutrophils, T CD4 type 1, inflammation). Pathogens evasion mechanisms to host immune responses - Viruses (surface antigens variability through mutations, inhibition of immune responses) - Parasites (anatomic sequestration (cysts), tegument resistant to antibodies and complement or to CTL) - Bacteria (inhibition of complement activation, resistance to phagocytosis for extracellular bacteria and inhibition of phagolysosome fusion).