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
enzimes that inhibit
viral replication
Protection from
infection
Expression of
class I MHC
molecules
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
CD8+
granzymes
Target cell
CTL
apoptosis
Mechanism of
killing by CTLs
CD8+
Target cell
CTL
FasL Fas
apoptosis
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?