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The evolution and genetics of innate immunity

Key Points

  • The innate immune response fights infections from the moment of first contact and is the fundamental defensive weapon of multicellular organisms.

  • Studies in Drosophila and in mammals are central to the appreciation that innate immunity is phylogenetically ancient, and that defensive strategies have been conserved at the molecular level.

  • The Toll family of receptors, of which Drosophila Toll is the prototype, is a paralogous system for innate immune sensing.

  • Recent genome sequencing projects have allowed the analysis of 88 Toll sequences from Drosophila, mammals and plants, providing new insights into the evolution of Toll receptors.

  • The function of Toll receptors differs between mammals and Drosophila, raising intriguing questions about the mechanisms of Toll signal reception and the relationship between inflammation and development.

  • A conserved evolutionary strategy of innate immunity involves the use of antimicrobial peptides to protect epithelial surfaces and fluid compartments.

  • There is mounting evidence of similarities between the mechanisms of immunity and apoptosis.

  • Many human diseases result from the failure of processes in the innate immunity response, either caused by a primary defect or by medical treatment.

  • The study of various organisms provides a greater understanding of immunity and indicates therapeutic strategies for dealing with infection and disease in humans.

Abstract

The immune system provides protection from a wide range of pathogens. One component of immunity, the phylogenetically ancient innate immune response, fights infections from the moment of first contact and is the fundamental defensive weapon of multicellular organisms. The Toll family of receptors has a crucial role in immune defence. Studies in fruitflies and in mammals reveal that the defensive strategies of invertebrates and vertebrates are highly conserved at the molecular level, which raises the exciting prospects of an increased understanding of innate immunity.

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Figure 1: The immune response in Drosophila and in mammals.
Figure 2: Evolution of the Toll interleukin-1-receptor domain.

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Acknowledgements

D.A.K.'s lab is supported by the National Institutes of Health. B.B. is an investigator of the Howard Hughes Medical Institute.

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DATABASE LINKS

CR3

Pgrp

Gnbp

Toll

Dorsal

Cactus

Drosomycin

imd

Dif

Rel

IKK

spätzle

nec

18 wheeler

Toll-6

Toll-7

IRAK

Pelle

IL-18R

ST2

TLR4

MYD88

SIGIRR

Toll-9

Easter

Snake

Gd

Pipe

Nudel

Windbeutel

Cecropin

Diptericin

Defensin

Attacin

Drosocin

Metchnikowin

Andropin

Lysozyme

RpS6 air8

hop

hop Tum

TepI

RpS6

TRAF6

TAK1

NIK

Dredd

FADD

TRADD

FLICE

Apaf1

Dark

FURTHER INFORMATION

Toll signalling in Drosophila

Flybase

Jackson lab

ENCYCLOPEDIA OF LIFE SCIENCES

Immune system

Immune mechanisms against extracellular pathogens

Antimicrobial proteins and peptides

Metchnikoff, Elie (Ilya)

Ehrlich, Paul

Drosophila embryo: dorsal–ventral specification

Glossary

CLONAL EXPANSION

The proliferation of a lymphocyte clone bearing an antibody or T-cell receptor that is specific for a particular antigen.

CLONAL ELIMINATION

The removal, generally in the thymus, of a T cell bearing a receptor that recognizes molecules within the host. Such cells, if not eliminated, would otherwise cause autoimmune disease.

GRANULOCYTES

White blood cells, encompassing neutrophils, eosinophils and basophils, which are dedicated to the ingestion and destruction of microorganisms (bacteria, for example).

CYTOKINES

A wide array of proteins, functionally similar to classical endocrine hormones, that mediate signalling between cells. Cytokines have a vital role in communication between different cells of the immune system. Although usually secreted, they might occasionally be anchored to cell surfaces. They often act at close range, but also circulate and exert their effects at a distance.

HAEMOCOEL

The haemocoel is the blood space of arthropods and molluscs. It is a very large, blood-filled cavity, which occupies most or all of the body.

HUMORAL IMMUNITY

B-cell-mediated immunity in mammals that fights bacteria and viruses in body fluids with antibodies that circulate in blood plasma and lymph, fluids formerly called humours. In insects, humoral immunity refers to the immune response that produces antimicrobial peptides, particularly at high concentrations in the haemolymph (blood).

MACROPHAGES

Phagocytic cells that respond to non-self material (for example, bacteria, protozoa or tumour cells) to release substances that stimulate other cells of the immune system. They are also involved in antigen presentation and are derived from monocytes, which circulate in the blood.

GRAM-NEGATIVE

Bacteria that fail to take up Gram stains during histological preparation for identification: typically bacteria present in the bowel rather than the throat and respiratory tissues. Examples of infections caused by this class of bacteria include the plague, tularemia, cholera and typhoid fever.

REL ONCOGENE

The Rel oncogene was originally found in an avian reticuloendotheliosis virus; it is the prototype of a family of transcription factors that includes NF-κB, c-rel, Relish, Dif and Dorsal.

GRAM-POSITIVE

Bacteria that take up Gram stains during histological preparation for identification: typically bacteria present in the throat and respiratory tissues. Infections caused by this class of bacteria include anthrax and listeriosis.

MAXIMUM PARSIMONY

A mathematical method for determining the evolutionary relationship between proteins, wherein account is taken of the minimum number of mutations that are required to effect transition from one member of the family to another.

BILATERIA

Members of the animal kingdom that possess bilateral symmetry — the property of having two similar sides, with definite upper and lower surfaces, and anterior and posterior ends.

PROTHROMBIN

(clotting factor II). One of the 13 chemical components of the blood that create the clotting mechanism. Prothrombin is a blood plasma protein and is synthesized in the liver.

COMPLEMENT

Group of blood proteins that circulate and reside in the tissues, the actions of which 'complement' the work of antibodies. They 'burst' bacteria by creating pores in the bacteria's membrane. Complement proteins can also cover the surfaces of bacteria and act as flags for phagocytes. Proteolytic cleavage fragments of complement proteins act as local signals for inflammation.

CASPASE

Enzymes that are responsible for the breakdown of the cell during apoptosis by cleaving numerous cellular proteins. They are synthesized as inactive procaspases that are later activated by proteolytic cleavage into active caspases.

PUPARIUM

A case formed by the hardening of the last larval skin, in which the pupa is formed.

IATROGENIC

Disease caused by the physician in the course of treating the patient.

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Kimbrell, D., Beutler, B. The evolution and genetics of innate immunity. Nat Rev Genet 2, 256–267 (2001). https://doi.org/10.1038/35066006

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