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?