(mechanisms of defense against viral, parasitic and fungal infections) Immunity to microbes (mechanisms of defense against viral, parasitic and fungal infections)

Goal To understand basic principles of defense against infections induced by: bacteria - extracellular - intracellular viruses parasites protozoa helmints fungi

Viruses Simple structure (subcellular level) Obligate intracellular agents - unable to replicate outside cells - enter cells via receptors Induce diseases through - damage of cells in which they replicate - induction of immune response Infections - acute - chronic (active and latent)

Mechanisms of defense against viruses Mechanisms of innate immunity inhibition of infection and induction of antiviral state type I interferons (IFN-α and β) - killing of infected cells (NK cells)

Antiviral action of type I interferons Uninfected cells Infected cells Expression of class I MHC molecules Expression of enzimes that inhibit viral replication Protection from infection Killing of infected cells by CTLs

Destruction of infected cells by NK cells

Destruction of infected cells by NK cells

Destruction of infected cells by NK cells

Mechanisms of defense against viruses Mechanisms of adaptive immunity Humoral immunity B cells and antibodies - neutralization (IgG and IgA), ADCC (IgG) and opsonization (IgG) Cell-mediated immunity

Neutralization of viruses

Protective mechanisms of antibodies

Mechanisms of defense against viruses Mechanisms of adaptive immunity Humoral immunity B cells and antibodies - neutralization (IgG and IgA), ADCC (IgG) and opsonization (IgG) Cell-mediated immunity CD8+ and CD4+ T cells - killing of infected cells (CD8+ T cells) - activation of CD8+ T cells and and B cells (CD4+ helper T cells)

Mechanism of killing by CTLs

Mechanism of killing by CTLs

Mechanism of killing by CTLs

Mechanism of killing by CTLs

Mechanism of killing by CTLs

Mechanism of killing by CTLs perforin granzymes Target cell CD8+ CTL apoptosis

Mechanism of killing by CTLs Target cell CD8+ CTL apoptosis FasL Fas

Mechanisms of innate and adaptive immunity against viruses

Mechanisms of defense against viruses Mechanisms of immune evasion - antigenic variation (influenza virus, HIV...)

Antigenic variations of influenza virus

Mechanisms of defense against viruses Mechanisms of immune evasion - antigenic variation (influenza virus, HIV...) - inhibition of antigen processing and presentation (many viruses)

Inhibition of antigen processing and presentation by viruses

Mechanisms of defense against viruses Mechanisms of immune evasion - antigenic variation (influenza virus, HIV...) - inhibition of antigen processing and presentation (many viruses) - inhibition of immune response (many viruses)

Inhibition of immune response through production of virokines and viroreceptors

Mechanisms of defense against viruses Mechanisms of immune evasion - antigenic variation (influenza virus, HIV...) - inhibition of antigen processing and presentation (many viruses) - inhibition of immune response (many viruses) - infection of immune cells (HIV...) - establishment of latency (HSV, HIV...) - inhibition of apoptosis (Herpes and Pox viruses...)

Mechanisms of defense against viruses Injurious effects of immune response - tissue damage due to CD8+ CTL activity (HBV...) - immune complexes formation (HBV...) - „molecular mimicry” (many viruses and various autoimmune diseases)

Parasites - complex eukaryotic organisms - most common infectious diseases (30% of world population) - complex life cycles - protozoa (unicellular) – intra- and extracellular agents - helmints (multicellular warms) – extracellular agents - often induce chronic infections - constant exposure (endemic areas) - direct exposure or via vectors - need for vaccines (immunoparasitology)

Mechanisms of defense against parasites Mehanisms of innate immunity Protozoa and helmints – mostly resistant - complement and phagocytosis (protozoa) - eosinophils and macrophages (helmints)

Mechanisms of defense against parasites Mehanisms of adaptive immunity Protozoa B-cells, CD4+ TH1 and CD8+ T cells - antibodies (B-cells) – Entamoeba sp., Plasmodium sp. IFN-γ production and macrophage stimulation (CD4+TH1 cells) - Leishmania sp. - cytotoxicity (CD8+ T cells) – Plasmodium sp. Helmints B-cells and CD4+ TH2 cells - stimulation of B-cells to produce IgE (IL-4) - stimulation of eosinophils (IL-5 and IgE) - degranulation of mast cells (IgE)

Immunity against helmints (TH2 response)

Immunity against helmints (function of eosinophils)

Mechanisms of defense against parasites Injurious effect of immune response - granuloma formation and fibrosis (Schistosoma sp.) - immune complex formation (Plasmodium sp.) Mechanisms of immune evasion - existence of different forms/stages (Plasmodium sp...) - alteration of surface antigens (Trypanosoma sp....) - complement resistance (many parasites) -“concealing” – cysts (Toxoplasma sp.), residence in gut (intestinal parasites)

Fungi extracellular agents (some survive phagocytosis) - yeast (unicellular) - molds (multicellular) - local and systemic mycoses most systemic infection - opportunistic some endemic (dimorphic fungi) - risk factor - immunodeficiency (neutropenia)

Mechanisms of defanse against fungi Mechanisms of innate immunity Fungi – mostly susceptible - phagocytosis (neutrophils) - complement Mechanisms of adaptive immunity Cell-mediated immunity - macrophage and neutrophil activation (CD4+ TH1 and TH17 cells) Injurious effect of immune response - granuloma formation and fibrosis (Histoplasma capsulatum) Mechanisms of immune evasion - inhibition of phagocytosis (C. neoformans...)

Thanks for your attention! Questions?