Immunity to microbes (mechanisms of defense against viral, parasitic and fungal infections)
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Transcript of Immunity to microbes (mechanisms of defense against viral, parasitic and fungal infections)
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Immunity to microbes
(mechanisms of defense against viral, parasitic and fungal infections)
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Goal
bacteria - extracellular- intracellular
viruses
parasites- protozoa- helmints
fungi
To understand basic principles of defense againstinfections induced by:
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Viruses
- unable to replicate outside cells
Simple structure (subcellular level)
Obligate intracellular agents
- enter cells via receptors
- acute
Infections
- chronic (active and latent)
- damage of cells in which they replicate
Induce diseases through
- induction of immune response
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Mechanisms of defense against viruses
- inhibition of infection and induction of antiviral state type I interferons (IFN-α and β)
- killing of infected cells (NK cells)
Mechanisms of innate immunity
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Antiviral action of type I interferons
Expression ofclass I MHC molecules
Expression of enzimes that inhibit viral replication
Uninfected cells
Infectedcells
Protection frominfection
Killing of infected cells by
CTLs
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Destruction of infected cells by NK cells
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Destruction of infected cells by NK cells
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Destruction of infected cells by NK cells
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- neutralization (IgG and IgA), ADCC (IgG) and opsonization (IgG)
Mechanisms of defense against viruses
Mechanisms of adaptive immunity
Humoral immunity
B cells and antibodies
Cell-mediated immunity
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Neutralization of viruses
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Protective mechanisms of antibodies
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- neutralization (IgG and IgA), ADCC (IgG) and opsonization (IgG)
- activation of CD8+ T cells and and B cells (CD4+ helper T cells)
CD8+ and CD4+ T cells
Mechanisms of defense against viruses
Mechanisms of adaptive immunity
Humoral immunity
B cells and antibodies
Cell-mediated immunity
- killing of infected cells (CD8+ T cells)
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Mechanism of killing by CTLs
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Mechanism of killing by CTLs
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Mechanism of killing by CTLs
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Mechanism of killing by CTLs
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Mechanism of killing by CTLs
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perforin
CD8+ CTLTarget cell
apoptosis
granzymes
Mechanism of killing by CTLs
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CD8+ CTLTarget cell
FasL Fas apoptosis
Mechanism of killing by CTLs
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Mechanisms of innate and adaptive immunity against viruses
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- antigenic variation (influenza virus, HIV...)
Mechanisms of immune evasion
Mechanisms of defense against viruses
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Antigenic variations of influenza virus
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- antigenic variation (influenza virus, HIV...)
Mechanisms of immune evasion
Mechanisms of defense against viruses
- inhibition of antigen processing and presentation (many viruses)
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Inhibition of antigen
processing and
presentation by viruses
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- antigenic variation (influenza virus, HIV...)
- inhibition of antigen processing and presentation (many viruses)
- inhibition of immune response (many viruses)
Mechanisms of immune evasion
Mechanisms of defense against viruses
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Inhibition of immune response through production ofvirokines and viroreceptors
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- 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 immune evasion
Mechanisms of defense against viruses
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- tissue damage due to CD8+ CTL activity (HBV...)
- immune complexes formation (HBV...)
- „molecular mimicry” (many viruses and various autoimmune diseases)
Injurious effects of immune response
Mechanisms of defense against viruses
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Parasites
- protozoa (unicellular) – intra- and extracellular agents
- complex eukaryotic organisms
- helmints (multicellular warms) – extracellular agents
- most common infectious diseases (30% of world population)
- complex life cycles
- constant exposure (endemic areas)
- need for vaccines (immunoparasitology)
- direct exposure or via vectors
- often induce chronic infections
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Mehanisms of innate immunity
Protozoa and helmints – mostly resistant
- complement and phagocytosis (protozoa)
- eosinophils and macrophages (helmints)
Mechanisms of defense against parasites
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-IFN-γ production and macrophage stimulation (CD4+TH1 cells) - Leishmania sp.
Protozoa
Helmints
- cytotoxicity (CD8+ T cells) – Plasmodium sp.
Mehanisms of adaptive immunity
- antibodies (B-cells) – Entamoeba sp., Plasmodium sp.
B-cells, CD4+ TH1 and CD8+ T cells
B-cells and CD4+ TH2 cells
- stimulation of eosinophils (IL-5 and IgE)
- stimulation of B-cells to produce IgE (IL-4)
- degranulation of mast cells (IgE)
Mechanisms of defense against parasites
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Immunity against helmints
(TH2 response)
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Immunity against helmints(function of eosinophils)
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Injurious effect of immune response
Mechanisms of immune evasion
- granuloma formation and fibrosis (Schistosoma sp.)
- alteration of surface antigens (Trypanosoma sp....)
- complement resistance (many parasites)
-“concealing” – cysts (Toxoplasma sp.), residence in gut (intestinal parasites)
- immune complex formation (Plasmodium sp.)
- existence of different forms/stages (Plasmodium sp...)
Mechanisms of defense against parasites
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Fungi
- yeast (unicellular)
- molds (multicellular)
- extracellular agents (some survive phagocytosis)
- most systemic infection - opportunistic some endemic (dimorphic fungi)
- risk factor - immunodeficiency (neutropenia)
- local and systemic mycoses
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Mechanisms of defanseagainst fungi
Fungi – mostly susceptible
Mechanisms of innate immunity
- phagocytosis (neutrophils)
Mechanisms of adaptive 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...)
- complement
Cell-mediated immunity
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Thanks for your attention!
Questions?