Immunology
Week 2 Defence against bacteria
Kahoot
- What are PAMPs?
Foreign signals present on micro organisms.
- Which cells belong to the adaptive immune system?
Only T-cells and B-cells.
- Which cells are seen as the bridge between the innate and adaptive immune
system?
The dendritic cells.
- Where does the T-cell receptor bind to?
To the MHC/peptide complex. The CD4 and CD8 are on the T-cell!
- How does a NK-cell recognise its target?
The absence of MHC1 and presence of DAMPs.
- What is meant by respiratory burst?
The formation of superoxide in phagocytes.
- Which antibody has the most antigen binding sites?
IgM.
- How many signals are necessary for B-cell activation?
3, cytokines, co-stimulation and recognition of antigen.
- What cells secrete IgE?
Plasma cells.
The immune response against bacteria.
The first line of defense
Physical barriers
- Horned layer of the skin.
- Commensal bacteria on the skin.
- Fatty acids on the skin.
- Multiple layers of the epithelium.
- Stomach acid.
- Mucus.
- Cilia.
, - Vomiting, diarrhea. Longitudinal flow.
- Coughing and sneezing.
Chemical barriers
- The complement system.
- Fatty acids.
- Defensins.
- Lysozyme.
- Surfactants.
The complement system
The complement system is 3 pathways that all lead to the splicing of C3.
1. Classical. Antibody
2. Alternative. Spontaneously
3. Lectin. Lectin
Functions:
- Lytic/membrane attack complex (C5-C9).
- Chemotaxis (C5a/C3a attracts immune cells).
- Opsonization, by breakdown product of C3.
The classical pathway starts from day one when there is a new bacteria.
C3a is important for chemotaxis.
C3b is important for opsonization. With just C3b it will not be taken up.
The second line of defense.
The innate immune system.
- phagocytes: recognise PAMPS/DAMPS with their PRR.
, - Innate lymphoid cells (ILC) secrete all kinds of cytokines that help other cells of the
immune system. They are present in barrier tissues (mucosa).
Group 1 and 3 ILCs are important in the defense against bacteria.
Group 1 ILC
- INTRAcellular bacteria.
- Secrete IFN𝛾: enhances macrophage function.
Group 3 ILC
- Secrete IL-17: Induces stromal cells to secrete chemokines, which attracts
neutrophils and monocytes.
- Secrete IL-22: indices epithelial cells to secrete antimicrobial peptides.
Phagocytes
Macrophages:
- Major phagocyte population, many different names: microglia.
- In tissues.
- Long living (3+ months).
- First at the infection site.
Monocytes:
- In blood.
- Long living.
- Differentiate into inflammatory monocytes or macrophages.
- Classical.
- Patrolling: monocytes with a crucial role in the endothelium.
Neutrophils:
- In blood.
- Short living.
- Attracted to the site of infection.
Immature dendritic cells (DC).
- Conventional/classical: cDCs, not large scale killing of microorganisms but primarily
antigen presentation and inducing immune response.
- Plasmacytoid: pDCs, produce Type 1 IFN (IFN𝛼 and IFN𝛽).
Macrophages are first at the site of infection, followed by a large number of neutrophils. They
are attracted by different factors.
- Bacterial components: f-Met-Leu-Phe
- Complement products: (C3a+C5a).
- Locally released cytokines and chemokines from macrophages, stromal and
epithelial cells. These cells are induced by ILC3.
Pattern recognition receptors (PRRs) recognise molecular patterns on bacteria/cells.
- PAMPs: pathogen associated molecular patterns.
- DAMPs: danger associated molecular patterns.
, When pathogens are past the physical barriers the cells of the innate immune system are
able to recognize them by their PRRs.
Membrane bound receptors
Receptor Recognizes
Toll-like (TLR4) LPS, intra and extracellular ligands
C-type lectin Microbial sugars, mannosylated ligands.
Cytoplasmic sensor receptors
Receptor Recognizes
NOD-like (NLRP3) NLRP3 signaling leads to the production of
proinflammatory cytokines like IL-1.
RIG-like cytoplasmic viral RNAs. IFNa is produced
by viral infected cells because of RIG
inducing.
Functions of PRRs
- Signaling leads to phagocytosis and killing of microorganisms.
- Cytokine production like IL-1, IL-6, IFNa and TNFb.
- Induction of co-stimulatory molecules in dendritic cells and macrophages.
Killing of microorganisms
1. Degranulation of lysosomes
The pathogen is brought into the cell by phagocytosis. The phagosome fuses with
the lysosome, creating the phagolysosome. In the phagolysosome the pathogen is
broken down by proteolytic enzymes and antimicrobial proteins.
- Lysozymes: Break the peptidoglycan layer of the bacterial cell wall.
- Defensins: The positively charged defensins get into the negatively charged
cell membrane of the bacteria creating holes.
- Hydrolytic enzymes: These enzymes cleave the peptide bonds and degrade
proteins, hydrolyze nucleic acids, and break down carbohydrates in the
pathogen's cell walls or membranes.
This process is oxygen INDEPENDENT.
Week 2 Defence against bacteria
Kahoot
- What are PAMPs?
Foreign signals present on micro organisms.
- Which cells belong to the adaptive immune system?
Only T-cells and B-cells.
- Which cells are seen as the bridge between the innate and adaptive immune
system?
The dendritic cells.
- Where does the T-cell receptor bind to?
To the MHC/peptide complex. The CD4 and CD8 are on the T-cell!
- How does a NK-cell recognise its target?
The absence of MHC1 and presence of DAMPs.
- What is meant by respiratory burst?
The formation of superoxide in phagocytes.
- Which antibody has the most antigen binding sites?
IgM.
- How many signals are necessary for B-cell activation?
3, cytokines, co-stimulation and recognition of antigen.
- What cells secrete IgE?
Plasma cells.
The immune response against bacteria.
The first line of defense
Physical barriers
- Horned layer of the skin.
- Commensal bacteria on the skin.
- Fatty acids on the skin.
- Multiple layers of the epithelium.
- Stomach acid.
- Mucus.
- Cilia.
, - Vomiting, diarrhea. Longitudinal flow.
- Coughing and sneezing.
Chemical barriers
- The complement system.
- Fatty acids.
- Defensins.
- Lysozyme.
- Surfactants.
The complement system
The complement system is 3 pathways that all lead to the splicing of C3.
1. Classical. Antibody
2. Alternative. Spontaneously
3. Lectin. Lectin
Functions:
- Lytic/membrane attack complex (C5-C9).
- Chemotaxis (C5a/C3a attracts immune cells).
- Opsonization, by breakdown product of C3.
The classical pathway starts from day one when there is a new bacteria.
C3a is important for chemotaxis.
C3b is important for opsonization. With just C3b it will not be taken up.
The second line of defense.
The innate immune system.
- phagocytes: recognise PAMPS/DAMPS with their PRR.
, - Innate lymphoid cells (ILC) secrete all kinds of cytokines that help other cells of the
immune system. They are present in barrier tissues (mucosa).
Group 1 and 3 ILCs are important in the defense against bacteria.
Group 1 ILC
- INTRAcellular bacteria.
- Secrete IFN𝛾: enhances macrophage function.
Group 3 ILC
- Secrete IL-17: Induces stromal cells to secrete chemokines, which attracts
neutrophils and monocytes.
- Secrete IL-22: indices epithelial cells to secrete antimicrobial peptides.
Phagocytes
Macrophages:
- Major phagocyte population, many different names: microglia.
- In tissues.
- Long living (3+ months).
- First at the infection site.
Monocytes:
- In blood.
- Long living.
- Differentiate into inflammatory monocytes or macrophages.
- Classical.
- Patrolling: monocytes with a crucial role in the endothelium.
Neutrophils:
- In blood.
- Short living.
- Attracted to the site of infection.
Immature dendritic cells (DC).
- Conventional/classical: cDCs, not large scale killing of microorganisms but primarily
antigen presentation and inducing immune response.
- Plasmacytoid: pDCs, produce Type 1 IFN (IFN𝛼 and IFN𝛽).
Macrophages are first at the site of infection, followed by a large number of neutrophils. They
are attracted by different factors.
- Bacterial components: f-Met-Leu-Phe
- Complement products: (C3a+C5a).
- Locally released cytokines and chemokines from macrophages, stromal and
epithelial cells. These cells are induced by ILC3.
Pattern recognition receptors (PRRs) recognise molecular patterns on bacteria/cells.
- PAMPs: pathogen associated molecular patterns.
- DAMPs: danger associated molecular patterns.
, When pathogens are past the physical barriers the cells of the innate immune system are
able to recognize them by their PRRs.
Membrane bound receptors
Receptor Recognizes
Toll-like (TLR4) LPS, intra and extracellular ligands
C-type lectin Microbial sugars, mannosylated ligands.
Cytoplasmic sensor receptors
Receptor Recognizes
NOD-like (NLRP3) NLRP3 signaling leads to the production of
proinflammatory cytokines like IL-1.
RIG-like cytoplasmic viral RNAs. IFNa is produced
by viral infected cells because of RIG
inducing.
Functions of PRRs
- Signaling leads to phagocytosis and killing of microorganisms.
- Cytokine production like IL-1, IL-6, IFNa and TNFb.
- Induction of co-stimulatory molecules in dendritic cells and macrophages.
Killing of microorganisms
1. Degranulation of lysosomes
The pathogen is brought into the cell by phagocytosis. The phagosome fuses with
the lysosome, creating the phagolysosome. In the phagolysosome the pathogen is
broken down by proteolytic enzymes and antimicrobial proteins.
- Lysozymes: Break the peptidoglycan layer of the bacterial cell wall.
- Defensins: The positively charged defensins get into the negatively charged
cell membrane of the bacteria creating holes.
- Hydrolytic enzymes: These enzymes cleave the peptide bonds and degrade
proteins, hydrolyze nucleic acids, and break down carbohydrates in the
pathogen's cell walls or membranes.
This process is oxygen INDEPENDENT.
