Pathogen Recognition by Innate Immune Cells

Pattern Recognition Receptors

• Innate immune cells depend on germline-encoded, invariant receptors, called pattern recognition receptors (PRR) that recognize evolutionarily conserved components of pathogens.
• One of the most important classes of PRR is the Toll-like receptors (TLRs), which recognize conserved structural motifs known as pathogen-associated microbial patterns (or PAMPs) or danger-associated molecular patterns (DAMPs).
• PAMPs are components of microbial pathogens (such as Lipopolysaccharide (LPS), peptidoglycan, and flagellin).
• DAMPs are endogenous molecules released from cells that die via immunologic cell death.
• Signaling downstream of PRR leads to the transcription of interferons and cytokines, two classes of proteins that signal between immune cells.

Used with permission from Macmillan Publishers Ltd: Nature Reviews Microbiology, 5, 491-504, copyright 2007.

Cells in the innate immune system

• Neutrophils, or polymorphonuclear neutrophilic leukocytes (PMNs), are short-lived granulocytes in the blood that are recruited to the peripheral tissues in response to an infection. They are mobilized by GM-CSF, and are recruited to sites of infection by interleukin-8, where they produce reactive oxygen species.
• Macrophages are phatocytic cells that engulf pathogens and act as antigen-presenting cells. They also release cytokines that increase the permeability of blood vessels and chemokines that direct the migration of the neutrophils to the site of infection. There are 2 subsets of macrophages (M1 and M2) which have opposite roles in promoting or suppressing inflammation and are thought to have divergent roles in tumor biology.
• Dendritic cells (DCs) are the prototypical antigen-presenting cell type, because they have very effective intracellular machinery for degrading foreign pathogens to present to T cells. Once DCs upregulate co-stimulatory molecules and migrate to the lymph nodes, they provide the three signals needed to activate naïve T cells (antigen, co-stimulation and cytokine signals).
• Mast cells are granulocytes that recruit eosinophils and basophils and are involved in the response to parasites as well as allergic reactions. 
• Natural killer cells (NK cells) are lymphocytes that are part of the innate immune system because they lack antigen-specific receptors. 
  • NK cells circulate in the blood and kill abnormal cells, such as virally-infected cells and tumor cells. Their effector mechanisms are similar to effector mechanisms used by CD8+ cytotoxic T cells, and include the release of perforin, which produces holes in the target cells, and granzymes, which are serine proteases released from granules.