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Summary BMLS10 Immunology review for K2 test
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LS10 Immunology reviewLesson 2 Defense against bacteria
Chemical and physical barriers (1st)
★ e.g. Lysozyme and defensins or the epithelial cells that are
joined by tight junctions
★ Lysozymes function as an antimicrobial agent by cleaving to the
peptidoglycan component of bacterial cell walls, which leads to
cell death
★ Defensins can kill bacteria or inhibit growth by membrane
disruption by forming a pore
The complement system → classical, alternative, and lectin (terminal)
★ Functions in lytic/membrane attack complex, chemotaxis, or
opsonization
★ Chemotaxis is where c3a and c5a recruit phagocytic cells to the site of infection and
promote inflammation
★ Opsonization is where phagocytes with receptors for c3b engulf and destroy the
pathogen
★ Lysis happens due to the completion of the complement cascade which leads to the
formation of MAC (membrane attack complex) which disrupts the cell membrane and
causes cell lysis
Innate immune system (2nd)
★ Involves phagocytes which recognize PAMPS and ILCs, these are lymphoid cells that
lack antigen-specific receptors, they are present in the barrier tissue e.g. skin, intestine,
and lung
→ ILCs are important in bacterial infections!
★ ILC-1 (for intracellular bacteria) secretes IFNy, this enhances macrophage function
★ ILC-3 secretes IL-17 and IL-22 → IL-17 induces stromal cells to secrete chemokines
which attract neutrophils (and monocytes), and IL-22 induces epithelial cells to secrete
antimicrobial peptides
→ Phagocytes
★ Macrophages are found in tissue, are long-living, and are the first phagocytes at the
infection site (are recruited by c3a and c5a)
★ Monocytes are found in the blood and are long-living (classical and patroling)
★ Neutrophils are found in the blood, are short-lived, and are attracted to the site of
infection by IL-17
, ★ Immature dendritic cells (DC) are long-lived, there are conventional DCs and
plasmacytoid DCs
Pattern recognition receptors (PRRs)
★ They recognize molecular patterns on bacteria/cells e.g. PAMPs (pathogen-associated)
and DAMPs (danger associated)
★ Examples of PRRs: C-type lectin family that recognize microbial sugars e.g. mannose
and Toll-like receptors that recognize multiple different ligands
★ PRRs function in the phagocytosis/killing of microorganisms, cytokine production
(IL1, IL6, TNFa, TNFb), and induce co-stimulatory molecules in dendritic cells and
macrophages
Killing of microorganisms
★ Degranulation of lysosomes, lysosomes contain hydrolytic enzymes.
Once a macrophage engulfs bacteria by phagocytosis, it fuses with a
lysosome where the pathogen is destroyed using those enzymes.
(oxygen-independent)
★ Respiratory burst is where phagocytes release a large number of
reactive oxygen species (ROS) into the phagosome to kill the ingested
bacteria
★ NETosis (only neutrophils!) can be caused
by epithelial and endothelial cells which
are infected, by activated platelets, and
inflammatory cytokines → NETs are
networks of extracellular fibers that are
composed of neutrophilic DNA which
bind pathogens, then granule components
are released which degrade bacterial toxic
factors, and kill bacteria
★ The Nitric oxide pathway (only macrophages), is induced by IFN-y, IL-1, or TNFa
which causes the production of nitric oxide which is toxic for microorganisms and thus
kills them → more effectively than respiratory burst!
, Dendritic cells are the bridge between the innate and adaptive immunity
★ Once a dendritic cell recognizes a PAMP and there is antigen
display then there will be T-cell activation
★ The antigen displays the MHC-peptide complex
★ PAMPs upregulate co-stimulatory molecules e.g. CD40, CD80,
CD86
★ Then there will be secretion of T-cell differentiating cytokines for
T-cell activation
Adaptive immune system (3rd)
★ Here there is T-cell activation to either get CD4+ T-helper cells
or CD8+ cytotoxic T-cells and B-cell activation for plasma
differentiation to make antibodies
★ 3 signals are needed for T-cell activation: 1. TCR binds to an
MHC/peptide complex (DC) 2. Co-stimulation by CD80/CD86
will bind to CD28 on the T-cell 3. Cytokine production by dendritic cells
What can T-cells do against bacteria?
★ Th1 stimulates macrophages as it secretes IFNy which enhances the nitric oxide
pathway and allows CD40-CD40L interaction (B-cell activation)
★ Th17 produces IL-17 which recruits neutrophils and IL-22 which induces
anti-microbial peptides (only extracellular bacteria!!)
★ Tfh gives help to the B-cell to produce IgG and allows opsonization of microbes
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