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Innate Immunity

The ability of a multicellular organism to defend itself against invasion by pathogens (bacteria, fungi, viruses, etc.) depends on its ability to mount immune responses. All metazoans (probably) have inborn defense mechanisms that constitute innate immunity. Vertebrates have not only innate immunity but also are able to mount defense mechanisms that constitute adaptive immunity. This table gives some of the distinguishing features of each type of immunity.

Innate Immunity Adaptive Immunity
Pathogen recognized by receptors encoded in the germline Pathogen recognized by receptors generated randomly
Receptors have broad specificity, i.e., recognize many related molecular structures called PAMPs (pathogen-associated molecular patterns) Receptors have very narrow specificity; i.e., recognize a particular epitope
PAMPs are essential polysaccharides and polynucleotides that differ little from one pathogen to another but are not found in the host. Most epitopes are derived from polypeptides (proteins) and reflect the individuality of the pathogen.
Receptors are PRRs (pattern recognition receptors) In jawed vertebrates, the receptors are B-cell (BCR) and T-cell (TCR) receptors for antigen [Link]
Immediate response Slow (3–5 days) response (because of the need for clones of responding cells to develop — Link)
Little or no memory of prior exposure Memory of prior exposure [Link]
Occurs in all metazoans? Occurs in vertebrates only
Discussed on this page Discussed at these links:

The Cells of the Innate Immune System

A variety of different types of cells participate in innate immunity. What they all have in common is that the receptors by which they recognize pathogens are limited in their specificity. This is in contrast to the B cells and T cells of the adaptive immune system that generate receptors — BCRs and TCRs respectively — that are exquisitely specific for the pathogen.

The players:

Pathogen-Associated Molecular Patterns (PAMPs)

Pathogens, especially bacteria, have molecular structures that


Pattern Recognition Receptors (PRRs)

There are three groups:
  1. secreted molecules that circulate in blood and lymph;
  2. surface receptors on phagocytic cells like macrophages that bind the pathogen for engulfment;
  3. cell-surface receptors that bind the pathogen initiating a signal leading to the release of effector molecules (cytokines).

1. Secreted PRRs

Example: Circulating proteins (e.g., C-reactive protein) that bind to PAMPs on the surface of many pathogens. This interaction triggers the complement cascade leading to the opsonization of the pathogen and its speedy phagocytosis.

2. Phagocytosis Receptors

Macrophages have cell-surface receptors that recognize certain PAMPs, e.g., those containing mannose. When a pathogen covered with polysaccharide with mannose at its tips binds to these, it is engulfed into a phagosome.

3. Toll-Like Receptors (TLRs)

Macrophages, dendritic cells, and epithelial cells have a set of transmembrane receptors that recognize different types of PAMPs. These are called Toll-like receptors (TLRs) because of their homology to receptors first discovered and named in Drosophila.

Mammals have 12 different TLRs each of which specializes — often with the aid of accessory molecules — in a subset of PAMPs. In this way, the TLRs identify the nature of the pathogen and turn on an effector response appropriate for dealing with it. These signaling cascades lead to the expression of various cytokine genes.


In all these cases, binding of the pathogen to the TLR initiates a signaling pathway leading to the activation of NF-κB. [Link to discussion]

This transcription factor turns on many cytokine genes such as those for

All of these effector molecules lead to inflammation at the site.

And even before these late events occur, the binding of enhances phagocytosis and the fusion of the phagosomes with lysosomes.

Innate Immunity can trigger Adaptive Immunity

This can occur in several ways:


Macrophages and dendritic cells are phagocytes and are also responsible for "presenting" antigens to T cells to initiate both cell-mediated and antibody-mediated adaptive immune responses. (Dendritic cells also engulf self-antigens, e.g., body cells that have died by apoptosis, but because these have no PAMPs associated with them, there is no second signal to activate the T cells.)


The interaction of PAMPs and TLRs on dendritic cells causes them to secrete cytokines, including


B cells are also antigen-presenting cells — Link. They bind antigen with their BCRs and engulf it into lysosomes. They then transport the digested fragments to the cell surface incorporated in class II histocompatibility molecules just as macrophages and dendritic cells do.

B cells also have TLRs. When a PAMP such as LPS binds the TLR, it enhances the response of the B cell to the antigen.

It has been known for many years that for vaccines to be effective, the preparation must contain not only the antigen but also materials called adjuvants. Several adjuvants contain PAMPs, and their stimulus to the innate immune system enhances the response of the adaptive immune system to the antigen in the vaccine.


Pathogens coated with fragments of the complement protein C3 are not only opsonized for phagocytosis but also bind more strongly to B cells that have bound the pathogen through their BCR. This synergistic effect enables antibody production to occur at doses of antigen far lower than would otherwise be needed.

Some workers feel that, in fact, adaptive immunity is not possible without the assistance of the mechanisms of innate immunity.

Antimicrobial Peptides

In addition to their innate pathogen-recognition systems, vertebrates (including ourselves), invertebrates (e.g., Drosophila), even plants and fungi secrete antimicrobial peptides that protect them from invasion by bacteria and other pathogens. In fact, probably all multicellular organisms benefit from this form of innate immunity.

For humans, the best-studied antimicrobial peptides are the


All our epithelial surfaces are protected by defensins.

Curiously, some defensins (β-defensin) also affect coat color (in dogs and mice) and in other ways mimic the effects of melanocyte-stimulating hormone (MSH).


Hepcidin is a peptide of 25 amino acids with a secondary structure (beta sheet) like that of the defensins. It is secreted by the liver and controls the level of iron in the blood and ECF by regulating its release from intracellular stores. Hepcidin secretion is increased in response to invasion by pathogens (fungi and bacteria). Many of these require iron for their virulence and by blocking the release of iron into the blood, hepcidin starves them of this essential factor.


The best known human cathelicidin is LL37, a peptide of 37 amino acids synthesized by macrophages, neutrophils, adipocytes, and epithelial cells (providing antimicrobial protection to our skin and the lining of our urinary tract). Unlike the defensins, its secondary structure is alpha helix.

Like defensins, the gene for LL37 can be turned on by activated TLRs. In macrophages, for example, cathelicidin synthesis within the cell promotes killing of engulfed bacteria like M. tuberculosis, the agent of TB. Activation of the cathelicidin gene requires the presence of the active form of vitamin D (1,25 [OH]2 vitamin D3). This may explain:

Antimicrobial Peptides and the GI Tract

The contents of the GI tract (especially the colon) are loaded with bacteria. But most of these cause no trouble thanks to a variety of defenses. Among these is the barrier of antimicrobial peptides that exists from mouth to anus.
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5 March 2016