Institute for Microbiology, Medical Faculty of Masaryk University and St. Anna Faculty Hospital in Brno Miroslav Votava FACTORS OF PATHOGENICITY AND VIRULENCE – addendum: The Essentials of Immunology Lecture for 2nd-year students April 21 st, 2008

Defense against infection Two tightly linked defense systems: 1. Innate immunity (nonspecific one) 2. Acquired (specific, adoptive) immunity Both systems hand in hand a) prevent microbes from colonizing of bodily surfaces b) bar their penetration into tissues c) inhibit their spread through the body d) neutralize their toxins e) aim for their liquidation and removal of their remains

Innate immunity Properties: Innate immunity acts nonspecifically against whole microbial groups (bacteria, viruses etc.) it is inherited, therefore it exists from the birth it is present in all members of given species it is no match for obligate pathogens it works instantly – which is extremely important it acts uniformly even during repeated contact Tools: barriers of colonization and penetration – skin, mucosae, normal microflora, protective reflexes barriers of spread and tools liquidating microbes cellular – mainly phagocytosis cellular – mainly phagocytosis humoral – complement, lysozyme, cytokins (IF) etc. humoral – complement, lysozyme, cytokins (IF) etc.fever inflammation – calor, dolor, rubor, tumor, functio laesa

Acquired immunity Properties: Acquired immunity affects specifically particular microbe only it forms only during the life after the contact with this agent it develops in particular individual only it protects also against virulent strains of obligate pathogens but it starts to operate relatively late, after immune reaction has developed it has a memory, so after repeated contact with the same microbe it acts more quickly and efficiently Tools: antigen-presenting cells (phagocytes; antigen = foreign structure on the microbial surface) T cells (lymphocytes) and activated macrophages (cell-mediated immunity) B cells (lymphocytes) = producers of antibodies (humoral immunity)

Protection by cell-mediated immunity Indispensable in the defense against intracellular parasites (mycobacteria, listeriae, brucellae, francisellae, viruses, some fungi, protozoa) Nonimmune macroorganism: Microbes remain alive and multiply in phagocytes, which disseminate them through the body Immune macroorganism: immune lymphocytes Th1 react with microbial antigens and produce cytokines (IFN-γ, TNFα etc.), which attract and activate macrophages Activated macrophages go on the rampage: they release enzymes and may damage neighboring tissue (delayed hypersensitivity) they phagocyte more vividly engulfed microbes are reliably killed In virus infections and tumors the afflicted cells are recognized and killed by cytotoxic Tc lymphocytes

Protection by antibodies Bacterial infections: support of phagocytosis – opsonization of encapsulated bacteria (IgG) inhibition of adherence to epithelium – mucosal antibodies IgA neutralization of bacterial toxins (IgG) bacteriolysis by complement (IgM, IgG) transfer of immunity across the placenta (IgG) Parasitic infections: expulsion of helminths (IgE) Viral infections: neutralization of virus infectivity (IgG, IgA)