Immunology: Comparative Immunology of Mammals


The mammalian immune system comprises a complex, coordinated and finely controlled series of interactions involving cells and molecules which has evolved to protect the host against disease. Mammals consist of a highly diverse group of animals in which the immune system has been subjected to a variety of selective pressures. This is reflected in differences in the organisation and function of their immune systems, and is seen especially in those gene families characterised by complexity and polymorphism, such as those encoding immunoglobulins (Ig), T‐cell receptors (TCR), major histocompatibility complex (MHC) molecules and natural killer (NK) cell receptors. The evolution of these components in a range of mammalian groups and species will be the main focus of this article.

Key Concepts:

  • The mammalian immune system has evolved to protect the host against disease.

  • The system is complex, involving specialised tissues, cells, soluble mediators and membrane‐bound molecules.

  • The mammalian adaptive immune response is characterised by extreme specificity in terms of antigen recognition.

  • This specificity is largely determined by genes encoding the major histocompatibility complex (MHC) molecules, immunoglobulins (Igs) and T‐cell receptors (TCRs).

  • Selection pressure by pathogens is believed to drive the generation of polymorphism in functional MHC genes.

  • MHC molecules present antigen to TCR and some additionally interact with NK cell receptors.

  • NK cells act as both effector and regulatory cells of the immune response.

  • Different mammalian groups and species have evolved a wide range of strategies to cope with rapidly changing pathogens, all aimed at protecting the host from disease.

Keywords: immunity; mammals; immunoglobulin; lymphocytes; evolution; NK cell receptors; MHC; TCR

Figure 1.

Components of the mammalian adaptive immune system. (a) Three components have evolved to provide specificity and diversity in the mammalian adaptive immune response. MHC class I and class II molecules consist of two molecules, but differ in structure. The MHC class I α chain consists of three domains and is associated with β2‐microglobulin, constant to all MHC class I molecules. MHC class II molecules consist of two chains each with two domains. Areas of high variability in the amino acid sequence of the chains relate to the peptide‐binding grooves, as indicated in red. The T‐cell receptor (TCR) consists of α and β chains that have a constant and variable (V) region. Note that some T cells express the γδ chains as an alternative. Immunoglobulin molecules consist of two heavy (H) and two light (L) chains, each with constant and variable regions. Hypervariable regions of the TCR and immunoglobulin that recognise antigen and confer specificity are shown in red. (b) Cellular expression of these components. Antigen‐presenting cells synthesise MHC class I and class II molecules, but not the TCR or immunoglobulin. T cells synthesise the TCR and MHC class I molecules, but not class II (unless activated, and only then in certain species as shown in Table ). B cells synthesise immunoglobulin, MHC class I and class II molecules. Immunoglobulin is expressed on the cell surface and is also secreted as an effector molecule. Polymorphism and specificity combine to generate effective adaptive immunity. There is co‐dominant expression of MHC alleles. Combined with (usually) multiple MHC loci, each cell expresses an array of MHC molecules on its surface capable of binding a wide variety of peptides. It should be noted that the diversity in the TCR and cell‐surface antibody molecules is expressed in a different manner. T and B cells are clonal and express molecules with a single specificity, so diversity arises from the number of different clones. This has evolved to ensure a high degree of specificity in the effector immune response.



Alitheen NB, McClure S and McCullagh P (2010) B‐cell development: one problem, multiple solutions. Immunology and Cell Biology 88: 445–450.

Apanius V, Penn D, Slev PR, Ruff LR and Potts WK (1997) The nature of selection on the major histocompatibility complex. Critical Reviews in Immunology 17: 179–224.

Averdam A, Petersen B, Rosner C et al. (2009) A novel system of polymorphic and diverse NK cell receptors in primates. PLoS Genetics 5: e1000688.

Ballingall KT, Ellis SA, MacHugh ND, Archibald SD and McKeever DJ (2004) The DY genes of the cattle MHC: expression and comparative analysis of an unusual class II MHC gene pair. Immunogenetics 55: 748–755.

Belov K, Miller RD, Ilijeski A, Hellman L and Harrison GA (2004) Isolation of monotreme T‐cell receptor alpha and beta chains. Immunogenetics 56: 164–169.

Birch J and Ellis SA (2007) Complexity in the cattle CD94/NKG2 gene families. Immunogenetics 59: 273–280.

Castro‐Prieto A, Wachter B and Sommer S (2011) Cheetah paradigm revisited: MHC diversity in the world's largest free‐ranging population. Molecular Biology and Evolution 28: 1455–1468.

Ciccarese S, Lanave C and Saccone C (1997) Evolution of T‐cell receptor gamma and delta constant region and other T‐cell‐receptor related proteins in the human–rodent–artiodactyl triplet. Genetics 145: 409–419.

Codner GF, Birch J, Hammond JA and Ellis SA (2012a) Constraints on haplotype structure and variable gene frequencies suggest a functional hierarchy within cattle MHC class I. Immunogenetics 64: 435–445.

Codner GF, Stear MJ, Reeve R, Matthews L and Ellis SA (2012b) Selective forces shaping diversity in the class I region of the major histocompatibility complex in dairy cattle. Animal Genetics 43: 239–249.

Connelley T, Aerts J, Law A and Morrison WI (2009) Genomic analysis reveals extensive gene duplication within the bovine TRB locus. BMC Genomics 10: 192.

Das S, Nozawa M, Klein J and Nei M (2008) Evolutionary dynamics of the Ig heavy chain variable region genes in vertebrates. Immunogenetics 60: 47–55.

Dobromylskyj M and Ellis SA (2008) Complexity in cattle KIR genes: transcription and genome analysis. Immunogenetics 59: 463–472.

Doxiadis GG, de Groot N, Otting N, Blokhuis JH and Bontrop RE (2011) Genomic plasticity of the MHC class I A region in rhesus macaques: extensive haplotype diversity at the population level as revealed by microsatellites. Immunogenetics 63: 73–83.

Flajnik MF (2002) Comparative analyses of immunoglobulin genes: surprises and portents. Nature Reviews Immunology 2: 688–698.

Guethlein LA, Abi‐Rached L, Hammond JA and Parham P (2007) The expanded cattle KIR genes are orthologous to the conserved single‐copy KIR3DX1 gene of primates. Immunogenetics 59: 517–522.

Guzman E, Price S, Poulsom H and Hope J (2011) Bovine γδ T cells: cells with multiple functions and important roles in immunity. Veterinary Immunology & Immunopathology (in press).

Hammond JA, Guethlein LA, Abi‐Rached L, Moesta AK and Parham P (2009) Evolution and survival of marine carnivores did not require a diversity of killer cell Ig‐like receptors or Ly49 NK cell receptors. Journal of Immunology 182: 3618–3627.

Hughes AL and Nei M (1988) Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 355: 167–170.

Janeway CA and Medzhitov R (2002) Innate immune recognition. Annual Review of Immunology 20: 197–216.

Nei M and Rooney AP (2005) Concerted and birth and death evolution of multi‐gene families. Annual Review of Genetics 39: 121–152.

Niedermann G, Grimm R, Geier E et al. (1997) Potential immunocompetence of proteolytic fragments produced by proteasomes before evolution of the vertebrate immune system. Journal of Experimental Medicine 185: 209–220.

Nikolich‐Zugich J, Slifka MK and Messaoudi I (2004) The many important facets of T‐cell repertoire diversity. Nature Reviews Immunology 4: 123–132.

Niku M, Liljavirta J, Durkin K, Schrodeus E and Iivanainen A (2012) The bovine genomic DNA sequence data reveal three IGHV subgroups, only one of which is functionally expressed. Developmental and Comparative Immunology 37: 457–461.

Parham P (2005) Influence of KIR diversity on human immunity. Advances in Experimental Medicine and Biology 560: 47–50.

Parham P, Adams EJ and Arnett KL (1995) The origins of HLA‐A, B, C polymorphism. Immunological Reviews 143: 141–180.

Parham P, Norman PJ, Abi‐Rached L and Guethlein LA (2012) Human‐specific evolution of KIR recognition of MHC class I molecules. Philosophical Transactions of the Royal Society of London. Series B 367: 800–811.

Reynaud C‐A, Dufour V and Weill J‐C (1997) Generation of diversity in mammalian gut‐associated lymphoid tissues. Journal of Immunology 159: 3093–3095.

Sambrook JG, Sehra H, Coggill P et al. (2006) Identification of a single killer immunoglobulin‐like receptor (KIR) gene in the porcine leukocyte receptor complex on chromosome 6q. Immunogenetics 58: 481–486.

Schenten D and Medzhitov R (2011) The control of adaptive immune responses by the innate immune system. Advances in Immunology 109: 87–124.

Seich AI, Basatena NK, Macnamara A et al. (2011) KIR2DL2 enhances protective and detrimental HLA class I‐mediated immunity in chronic viral infection. PLoS Pathogens 7(10): e1002270.

Siddle HV, Deakin JE, Coggill P et al. (2009) MHC‐linked and un‐linked class I genes in the wallaby. BMC Genomics 10: 310.

Siddle HV, Marzec J, Cheng Y, Jones M and Belov K (2010) MHC gene copy number variation in Tasmanian devils: implications for the spread of a contagious cancer. Proceedings of the Royal Society B: Biological Sciences 277: 2001–2006.

Sinkora M, Stepanova K, Butler JE et al. (2011) Ileal Peyer's patches are not necessary for systemic B cell development and maintenance and do not contribute significantly to the overall B cell pool in swine. Journal of Immunology 187: 5150–5161.

Stear MJ, Bishop SC, Mallard BA and Raadsma H (2001) The sustainability, feasibility and desirability of breeding livestock for disease resistance. Research in Veterinary Science 71: 1–7.

Storset AK, Slettedal IO, Williams JL, Law A and Dissen E (2003) Natural killer cell receptors in cattle: a bovine killer cell immunoglobulin‐like receptor multigene family contains members with divergent signalling motifs. European Journal of Immunology 33: 980–990.

Su C and Nei M (1999) Fifty‐million‐year‐old polymorphism at an immunoglobulin variable region gene locus in the rabbit evolutionary lineage. Proceedings of the National Academy of Sciences of the USA 96: 9710–9715.

Takahashi T, Yawata M, Raudsepp T et al. (2004) Natural killer cell receptors in the horse: evidence for the existence of multiple transcribed LY49 genes. European Journal of Immunology 34: 773–784.

Toka FN, Kenney MA and Golde WT (2011) Rapid and transient activation of γδ T cells to IFN‐γ production, NK cell‐like killing, and antigen processing during acute virus infection. Journal of Immunology 186: 4853–4861.

Verma S and Aitken R (2012) Somatic hypermutation leads to diversification of the heavy chain immunoglobulin repertoire in cattle. Veterinary Immunology & Immunopathology 145: 14–22.

Wan Q‐H, Zeng CJ, Ni XW, Pan HJ and Fang SG (2009) Giant panda genomic data provide insight into the birth‐and‐death process of mammalian major histocompatibility complex class II genes. PLoS One 4(1): e4147.

Wang X, Parra ZE and Miller RD (2011) Platypus TCRμ provides insight into the origins and evolution of a uniquely mammalian TCR locus. Journal of Immunology 187: 5246–5254.

Yokoyama WM and Plougastel BF (2003) Immune functions encoded by the natural killer gene complex. Nature Reviews. Immunology 3: 304–316.

Yuhki N and O'Brien SJ (1990) DNA variation of the mammalian major histocompatibility complex reflects genomic diversity and population history. Proceedings of the National Academy of Sciences of the USA 87: 836–840.

Further Reading

Boehm T, Hess I and Swann JB (2012) Evolution of lymphoid tissues. Trends in Immunology 33: 315–321 (Epub ahead of printing).

Du Pasquier L and Litman GW (eds) (2000) Origin and Evolution of the Vertebrate Immune System. Berlin: Springer.

Klein J (1997) Homology between immune responses in vertebrates and invertebrates: does it exist? Scandinavian Journal of Immunology 46: 558–564.

Kurosawa Y and Hashimoto K (1997) How did the primordial T cell receptor and MHC molecules function initially? Immunology and Cell Biology 75: 193–196.

Magor KE and Vasta GR (1998) Ancestral immunity comes of age. Immunology Today 19: 54–56.

Novacek MJ (1992) Mammalian phylogeny: shaking the tree. Nature 356: 121–125.

Parham P (2008) The genetic and evolutionary balances in human NK cell receptor diversity. Seminars in Immunology 20: 311–316.

Pastoret P‐P, Griebel P, Bazin H and Gouaerts A (eds) (1998) Handbook of Vertebrate Immunology. London: Academic Press.

Rodriguez RM, Lopez‐Vazquez A and Lopez‐Larrea C (2012) Immune systems evolution. Advances in Experimental Medicine and Biology 739: 237–251.

Rook GAW and Stanford JL (1998) Give us this day our daily germs. Immunology Today 19: 113–116.

Web Links

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Ellis, Shirley A(Aug 2012) Immunology: Comparative Immunology of Mammals. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001284.pub3]