Download Mechanisms of adaptive immunity

Immunity to microbes
(mechanisms of defense against
bacterial infections)
Goal
To understand basic principles of defense against
infections induced by:
bacteria
- extracellular
- intracellular
viruses
parasites
- protozoa
- helmints
fungi
Important features of defense against
infectious agents
Mediated by the mechanisms of both innate and
adaptive immunity
Specialization of the immune system allows optimal
response to each type of microbe
Establishment, course and outcome of infection depend on
ability of pathogen to evade or resist immune response
Tissue injury and disease are often result of immune
response to pathogens
Bacteria
Unicellular prokaryotes
Survive and replicate:
- outside cell (extracellular bacteria)
- inside cell (intracellular bacteria)
Induce disease by:
- induction of inflammation
- 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 against
extracellular 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
Phagocytosis and
killing of
microbes
Zipping of membrane
around microbe
Phagocytosis and
killing of
microbes
Ingestion of microbe
Phagocytosis and
killing of
microbes
Fusion of phagosome
with lysosome
Phagocytosis and
killing of
microbes
Phagocyte activation
Phagocytosis and
killing of
microbes
Killing of
microbe
Inflammation
Mechanisms of defense against
extracellular bacteria
Mechanisms of adaptive immunity
Humoral immunity
B cells and antibodies
- complement activation by clasical pathway (IgG and IgM)
- neutralization of toxins (IgG and IgA)
- opsonization and phagocytosis (IgG)
CD4+ helper T cells
Mechanisms of defense against extracellular bacteria
(B cells)
Neutralization of toxins
Opsonization and phagocytosis
Mechanisms of defense against
extracellular bacteria
Mechanisms of adaptive immunity
Humoral immunity
B cells and antibodies
- complement activation by clasical pathway(IgG and IgM)
- neutralization of toxins (IgG and IgA)
- opsonization and phagocytosis (IgG)
CD4+ helper T cells
- B cell help (various citokines)
- macrophage activation (IFN-γ) – TH1
- neutrophil activation (IL-17) – TH17
- induction of inflammation (TNF)
Naïve
Naivna
CD4+T
TH1
IFN-
Macrophage
stimulation
TH2
IL-4
IL-5
Eosinophil
stimulation
TH17
IL-17A
Neutrophil
stimulation
Naïve
Naivna
CD4+T
TH1
Defence against
intracellular pathogens
TH2
Defence against helmints
TH17
Defence against some
extracellular bacteria and fungi
Mechanisms of defense against
extracellular bacteria
Mehanisms of immune evasion
- polysaccharide capsule (S. pneumoniae...)
Mechanisms of defense against
extracellular bacteria
Mehanisms of immune evasion
- polysaccharide capsule (S. pneumoniae...)
- genetic variation of surface antigens (Neisseria sp, E. coli...)
- inhibition of complement activation (many bacteria)
- production of IgA proteases (Neisseria sp., S. pyogenes...)
Mechanisms of defense against
extracellular bacteria
Injurious effects of immune response
- inflammation (SIRS, septic shock)
- superantigens (S. aureus, S. pyogenes...)
Mechanism of superantigen action
T-cell
Activation of 5-20%
T cells
Massive cytokine
production
Antigen-presenting cell
Mechanisms of defense against
extracellular bacteria
Injurious effects of immune response
- inflammation (SIRS, septic shock)
- superantigens (S. aureus, S. pyogenes...)
- “molecular mimicry” (S. pyogenes and Rheumatic fever)
Intracellular bacteria
Survive and replicate in cells
Enter cells via receptors or phagocytosis
Escape from antibody, complement etc.
Induce chronic infections
Facultative intracellular (e.g. Mycobacterium sp.)
Strict intracellular (Chlamydia and Ricketsia)
Intracellular bacteria
Mechanisms of defense against
intracellular bacteria
Mechanisms of innate immunity
- phagocytosis (inefficient unless stimulated)
- NK cells (production of IFN-γ and stimulation of macrophages)
Stimulation of macrophages by NK cells
Mechanisms of defense against
intracellular bacteria
Mechanisms of adaptive immunity
Cell-mediated immunity
CD4+ helper T cells (TH1)
- B-cell help to produce opsonizing antibodies (IFN-γ)
- macrophage activation (IFN-γ) – TH1
- induction of inflammation (TNF)
CD8+ cytotoxic T cells
Macrophage
activation by
TH1 cells
Mechanisms of defense against
intracellular bacteria
Mechanisms 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
- destruction of infected cells (containing bacteria in cytoplasm)
Cooperation between CD4+ and CD8+ T-cells in elimination of
intracellular bacteria
Mechanisms of defense against
intracellular bacteria
Mechanisms of defense against
intracellular bacteria
Mehanisms of immune evasion
- inhibition of phagolysosome formation (M. tuberculosis...)
Mechanism of immune evasion
by Mycobacteria
Mechanisms of defense against
intracellular bacteria
Mehanisms of immune evasion
- inhibition of phagolysosome formation (M. tuberculosis...)
- escape from phagolysosome (L. monocytogenes....)
- 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)
Thanks for your attention!
Questions?