Innate Cells – Jan. 14
- The main cells of the innate immune system are phagocytes (neutrophils, macrophages, immature
dendritic cells) and lymphocytes (natural killer cells). The phagocytes destroy extracellular
pathogens by phagocytosis. The lymphocytes destroy intracellular pathogens (especially viruses) by
- Phagocytosis is the major way that extracellular pathogens are destroyed and is important against
bacteria. Receptors on phagocytes (PRRs) bind to the pathogen (PAMPs) to trigger phagocytosis. The
cell membrane extends around the microbe, envelopes it, and internalizes it, forming a phagosome.
The phagosome fuses with a lysosome containing anti-microbial mediators, forming a
phagolysosome. The phagolysosome kills the pathogen. Killing occurs within a phagolysosome so
that it does not damage the phagocyte. The lysosome contains acids and enzymes that quickly kill the
- Enzymes in the phagolysosome: 1. Defensins, Lysozyme – Damage pathogen cell wall, which destroys
the integrity of the bacteria. 2. NADPH oxidase – Produces toxic oxygen metabolites. superoxide →
H2O2 + HOCl (= respiratory burst). People that lack NADPH oxidase are unable to destroy bacteria.
3. Nitric oxide synthetase – Produces toxic nitric oxide (NO). Another thing to note is that the pH
inside the phagolysosome is very acidic (4-5), whereas the pH outside it in the cytoplasm is around
- One phagocyte will phagocytose several extracellular pathogens simultaneously.
- Mechanisms a bacterium might use to resist phagocytosis: 1. Bacteria cover up PAMPs. They put a
coating around the surface so they can’t be seen by PRRs. These are called encapsulated bacteria.
2. Block uptake into the phagocyte. 3. Escape from phagosome. 4. Some bacteria can resist being
destroyed by lysosomal contents. They can block the lysosome from fusing to the phagosome.
- Intracellular bacteria can enter by phagocytosis and then survive/replicate inside the phagocyte. If
they replicated in the phagosome, then they are hard to deal with. If they escape from the phagosome
and then replicate in the cytoplasm, adaptive immunity can deal with it (we have poor innate
immunity against these bacteria). If they are not dealt with, they can escape from the phagocyte and
infect new cells.
- Innate immunity may limit growth of intracellular bacteria, but it usually fails to eradicate it. Cell-
mediated adaptive immunity is the major immune response against intracellular bacteria.
- The main phagocytes are neutrophils, macrophages, and immature dendritic cells.
- Neutrophils: Most abundant white blood cell (leukocyte) (60-70%). Rapidly differentiate from stem
cells in response to infection, and double in count. You can diagnose if someone has an infection
because the neutrophil count will be really high. Neutrophils leave the blood and migrate rapidly to
infected tissue. They are short-lived (live for about 6 hours). Neutrophils bind to PAMPs on a
pathogen through their PRRs. They engulf and digest bacteria via phagocytosis.
- Neutropenia: The normal count of neutrophils 1500 neutrophils per uL of blood. Neutropenia is low
neutrophil count (less than 500 cells per uL of blood). People with neutropenia are at a high risk of