immunity to microbes (mechanisms of defense against bacterial infections)
TRANSCRIPT
Immunity to microbes
(mechanisms of defense against bacterial infections)
Goal
bacteria - extracellular- intracellular
viruses
parasites- protozoa- helmints
fungi
To understand basic principles of defense againstinfections induced by:
Important features of defense against infectious agents
Establishment, course and outcome of infection depend on ability of pathogen to evade or resist immune response
Mediated by the mechanisms of both innate and adaptive immunity
Specialization of the immune system allows optimalresponse to each type of microbe
Tissue injury and disease are often result of immune response to pathogens
Bacteria
- outside cell (extracellular bacteria)
Unicellular prokaryotes
Survive and replicate:
- inside cell (intracellular bacteria)
- induction of inflammation
Induce disease by:
- production of toxins
Extracellular bacteria
Replicate outside cell (in circulation, tissues and lumens)
Induce inflammation (often with pus formation)
- e.g. staphylococci and streptococci
Produce toxins:
- exotoxins (diphteria, tetanus...)
- endotoxin (LPS)
Mechanisms of defense againstextracellular bacteria
Mechanisms of innate immunity
- complement activation by alterative and lectin pathway
- phagocytosis (neutrophils and macrophages)
- inflammation (induction of TNF, IL-1, chemokines etc.)
Complement
activation by
alterative and lectin pathway
Phagocytosis and killing of
microbes
Pathogen recognition
Zipping of membrane around microbe
Phagocytosis and killing of
microbes
Ingestion of microbe
Phagocytosis and killing of
microbes
Fusion of phagosomewith lysosome
Phagocytosis and killing of
microbes
Phagocyte activation
Phagocytosis and killing of
microbes
Killing of microbe
Phagocytosis and killing of
microbes
Inflammation
- complement activation by clasical pathway (IgG and IgM)
- neutralization of toxins (IgG and IgA)
- opsonization and phagocytosis (IgG)
Humoral immunity
Mechanisms of adaptive immunity
B cells and antibodies
CD4+ helper T cells
Mechanisms of defense againstextracellular bacteria
Mechanisms of defense against extracellular bacteria
(B cells)
Neutralization of toxins
Opsonization and phagocytosis
- B cell help (various citokines)
- macrophage activation (IFN-γ) – TH1
- neutrophil activation (IL-17) – TH17
- induction of inflammation (TNF)
- complement activation by clasical pathway(IgG and IgM)
- neutralization of toxins (IgG and IgA)
- opsonization and phagocytosis (IgG)
Humoral immunity
Mechanisms of adaptive immunity
B cells and antibodies
Mechanisms of defense againstextracellular bacteria
CD4+ helper T cells
Naivna CD4+TNaïve CD4+T
IFN-
IL-4IL-5
IL-17A
TH1
TH2
Macrophage
stimulation
Eosinophilstimulation
Neutrophilstimulation
TH17
Naivna CD4+TNaïveCD4+T
Defence against intracellular pathogens
Defence against helmints
Defence against some extracellular bacteria and fungi
TH1
TH2
TH17
Mehanisms of immune evasion
- polysaccharide capsule (S. pneumoniae...)
Mechanisms of defense againstextracellular bacteria
Mehanisms of immune evasion
- polysaccharide capsule (S. pneumoniae...)
- genetic variation of surface antigens (Neisseria sp, E. coli...)
- production of IgA proteases (Neisseria sp., S. pyogenes...)
- inhibition of complement activation (many bacteria)
Mechanisms of defense againstextracellular bacteria
Injurious effects of immune response
- inflammation (SIRS, septic shock)
- superantigens (S. aureus, S. pyogenes...)
Mechanisms of defense againstextracellular bacteria
Mechanism of superantigen action
T-cell
Antigen-presenting cell
Activation of 5-20% T cells
Massive cytokine production
Injurious effects of immune response
- inflammation (SIRS, septic shock)
- superantigens (S. aureus, S. pyogenes...)
- “molecular mimicry” (S. pyogenes and Rheumatic fever)
Mechanisms of defense againstextracellular bacteria
Survive and replicate in cells
Induce chronic infections
Facultative intracellular (e.g. Mycobacterium sp.)
Strict intracellular (Chlamydia and Ricketsia)
Intracellular bacteria
Escape from antibody, complement etc.
Enter cells via receptors or phagocytosis
Intracellular bacteria
Mechanisms of defense against
intracellular bacteria
- phagocytosis (inefficient unless stimulated)
- NK cells (production of IFN-γ and stimulation of macrophages)
Mechanisms of innate immunity
Stimulation of macrophages by NK cells
Mechanisms of defense against
intracellular bacteriaMechanisms of adaptive immunity
Cell-mediated immunity
CD8+ cytotoxic T cells
CD4+ helper T cells (TH1)
- B-cell help to produce opsonizing antibodies (IFN-γ)
- macrophage activation (IFN-γ) – TH1
- induction of inflammation (TNF)
Macrophage activation by
TH1 cells
- destruction of infected cells (containing bacteria in cytoplasm)
Mechanisms of defense against
intracellular bacteriaMechanisms of aquired immunity
Cell mediated immunity CD4+ helper T-cells (TH1)
- Support of B-cells to produce opsonizing antibodies (IFN-γ)
- Macrophage activation (IFN-γ) – TH1
- Induction of inflammation (TNF)
CD8+ cytotoxic T-cells
Cooperation between CD4+ and CD8+ T-cells in elimination of intracellular bacteria
Mechanisms of defense against
intracellular bacteria
- inhibition of phagolysosome formation (M. tuberculosis...)
Mehanisms of immune evasion
Mechanisms of defense against
intracellular bacteria
Mechanism of immune evasion by Mycobacteria
- inhibition of phagolysosome formation (M. tuberculosis...)
- escape from phagolysosome (L. monocytogenes....)
Mehanisms of immune evasion
- inhibition of ROS i NO (M. leprae...)
Mechanisms of defense against
intracellular bacteria
Injurious effects of immune response
-chronic inflammation (DTH) and granuloma formation (tuberculosis)
Mechanisms of defense against
intracellular bacteria
Thanks for your attention!
Questions?