recruit specific and more powerful adaptive immune responses to help fight the infection. Innate immune responses rely on the ability of host cells to recognize characteristic features of microbial molecules called pathogen‑associated molecular patterns, or PAMPs, which can be associated with a pathogen’s proteins, lipids, sugars, or nucleic acids. PAMPs are mainly recognized by pattern recognition receptors (PRRs), including the Toll‑like receptors (TLRs) found on or in both plant and animal cells. In vertebrates, some PRRs are secreted and can activate complement when they bind microbial PAMPs. The complement system, which can also be activated by antimicrobial antibodies bound to pathogens, consists of a group of blood proteins that are activated in sequence to help fight infections, by disrupting the pathogen's membrane, stimulating an inflammatory response, or targeting the microbe for phagocytosis—mainly by macrophages and neutrophils. The phagocytes use a combination of degradative enzymes, antimicrobial peptides, and oxygen‑derived toxic molecules to kill invading pathogens; in addition, they secrete various signal molecules that help trigger an inflammatory response.
Cells infected by a virus produce and secrete type I interferons (IFNα and IFNβ), which induce a complex set of host‑cell responses that inhibit viral replication. The interferons also enhance the killing activity of natural killer (NK) cells. An NK cell kills infected host cells because they express large amounts of surface proteins that activate the NK cell; the killing is especially efficient when infected cells express reduced amounts of class I MHC proteins, which, when present in normal amounts on a host cell surface inhibit the killing activity of NK cells.
Dendritic cells of the innate immune system functionally link innate immune responses to adaptive immune responses. The cells become activated when their PRRs pick up microbes and their products at sites of infection and phagocytose them. The activated cells cleave the microbial proteins into peptide fragments, which bind to newly made MHC proteins, which transport the fragments to the cell surface. The activated dendritic cells then carry the peptide–MHC complexes to a lymph organ, where they activate appropriate T cells to make specific adaptive immune responses against the microbes.
OVerVIeW OF The ADApTIVe IMMUNe SYSTeM
A dramatic “big bang” in immune defense mechanisms occurred when jawed vertebrates evolved and acquired an adaptive immune system. This sophisticated defense system depends on B and T lymphocytes (B and T cells), which, during their development, rearrange particular DNA sequences in various combinations so that, together, the cells can produce an almost limitless variety of B and T cell receptors and antibodies. Collectively, these proteins can bind to essentially any molecule, including small chemicals, carbohydrates, lipids, and proteins; individually, they can distinguish between molecules that are very similar—such as between two proteins that differ in only a single amino acid, or between two optical isomers of the same small molecule. By this strategy, the adaptive immune system can recognize and respond specifically to any pathogen, including new mutant forms. However, because the genetic rearrangement process produces both receptors that can bind to self molecules as well as receptors that can bind to foreign molecules, vertebrates have had to evolve special mechanisms to ensure that B and T cells do not react against the host’s own molecules and cells—a process called immunological self‑tolerance.