Lecture 2 – Innate Immunity 1: Cells, Pattern Recognition, and Receptor Signaling
Jim Mahoney, Ph.D.
(immediate, broad, stereotypic, genomic) vs
(slow, specific, somatically
generated, sometimes anti-self) immunity. Innate is evolutionarily older than adaptive
(only exists in vertebrates after jawed fishes). All circulating blood cells of all types come
pluripotential hematopoietic stem cells
(PHSC) in bone marrow and fetal liver.
Macs, PMNs, basos, eosinos are all derived from the myeloid progenitor (downstream of
PHSC). T and B cells are from the lymphoid progenitor.
include tight junctions/epithelial barrier, mucus layers, and
antimicrobial peptide secretion (disrupting bacterial membranes). Antimicrobial peptides
act by inserting into the bacterial membrane or by acting as chemoattractants.
are found in neutrophils and NK&B cells, especially in response to TLR and NOD
are expressed in the epithelium.
are in the saliva.
Recognition of pathogenic structures
, recognized by
) is done
stereotypically (i.e., against structures that the pathogen needs in order to survive, such as
CpG DNA, dsRNA, LPS, yeast cell wall, N-formyl-Met, etc.).
are recruitment, opsonization, phagocytosis, intracellular
killing, and ‘sounding the alarm’.
Innate Immune Cells
Neutrophils (70% of WBCs), macrophages (7%), NK cells, γδ T cells.
live for just a day, are active in acute inflammation, and kill via
radical oxygen. Immature neutrophils are
, and high numbers of these generally
indicate a bacterial infection. PMNs have azurophilic granules (lysosomes and defensins)
and specific granules (complement receptors, adhesion molecules). These sentinel cells
live for weeks/months, are active in chronic inflammation, present
antigen, release cytokines, and use radical oxygen and NO to kill. Immature macrophages
, and high circulating levels of these may indicate a viral infection.
After phagocytosis, monocytes may exhibit tolerogenic or immunogenic signals.
cells, by releasing cytotoxic granules, kill host cells that have become infected
or tumor-ish. They recognize via ‘activating receptors’ (often chemokine receptors) but
are inhibited by MHC-I.
Finally, some γδ T cells release cytokines for inflammation. B-1 cells make
natural (nonspecific) serum antibodies that target PAMPs broadly. NK T cells recognize
bacterial lipids, not proteins, and release cytokines in response.
PAMPs and PRRs