Immunity to microbes

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

Goal

bacteria - extracellular- intracellular

viruses

parasites- protozoa- helmints

fungi

To understand basic principles of defense againstinfections induced by:

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

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

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

Destruction of infected cells by NK cells

Destruction of infected cells by NK cells

Destruction of infected cells by NK cells

- 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

Neutralization of viruses

Protective mechanisms of antibodies

- 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)

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

CD8+ CTLTarget cell

apoptosis

granzymes

Mechanism of killing by CTLs

CD8+ CTLTarget cell

FasL Fas apoptosis

Mechanism of killing by CTLs

Mechanisms of innate and adaptive immunity against viruses

- antigenic variation (influenza virus, HIV...)

Mechanisms of immune evasion

Mechanisms of defense against viruses

Antigenic variations of influenza virus

- antigenic variation (influenza virus, HIV...)

Mechanisms of immune evasion

Mechanisms of defense against viruses

- inhibition of antigen processing and presentation (many viruses)

Inhibition of antigen

processing and

presentation by viruses

- 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

Inhibition of immune response through production ofvirokines and viroreceptors

- 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

- 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

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

Mehanisms of innate immunity

Protozoa and helmints – mostly resistant

- complement and phagocytosis (protozoa)

- eosinophils and macrophages (helmints)

Mechanisms of defense against parasites

-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

Immunity against helmints

(TH2 response)

Immunity against helmints(function of eosinophils)

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

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

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

Thanks for your attention!

Questions?