Fitness Correlates of Heritable Variation in Antibody

Responsiveness in a Wild Mammal

A. Graham, A. Hayward, K. Watt, J. Pilkington, J. Pemberton, D. Nussey

Science 2010

Vera Vollenweider

Overview

1. Introduction

The Immune System

2. Hypothesis

3. Research Questions

4. Methods

5. Results

6. Summary

The Immune System

Antibodies generated by activated B cells protect the body against pathogens

Immune tolerance describes a state of unresponsiveness of the immune system to self-antigens

Autoimmunity results from some failure of the hosts immune system to distinguish self from nonself, causing destruction of self-proteins, cells, and organs by auto-antibodies

Antibodies that bind self nuclear and cytoplasmic antigens are called antinuclear antibodies (ANA)

The Immune System

Immune systems of different individuals are heterogeneous in the strength, specificity, and efficacy of responses to infection

Much of the variation is under genetic control Individuals vary in their genetic susceptibility to generate self-

targeted immune responses (autoimmunity)

Why has natural selection failed to eliminate alleles that promote autoimmunity?

Hypothesis Individuals with strong immune responses experience fitness benefits

of immunity but are also likely to suffer its costs There are trade-offs between antibody-response, survival, and

reproduction

Food limitation and high parasite abundance decreases strength and self-reactivity of immune response

Antibody responses

SurvivalReproductive success

Research Questions

1. Do wild mammals also mount self-directed antibody responses?2. Do ANA concentrations reflect general antibody responsiveness?3. Is the variation in ANA concentration among individuals genetically

based?4. Is there an association between ANAs and different components of

fitness?

Methods Unmanaged population of Soay sheep

in Hirta (Scotland) Blood plasma samples collected during

August of 11 years: 2622 plasma samples 1476 sheep

Measured antinuclear antibodies (ANAs)

High ANA concentrations =

strong response to self-antigens

Results IDo wild mammals also mount self-directed antibody responses?

Two factors hypothesized to decrease self-reactivity of the immune system:

Food limitation High parasite abundance

114 out of 410 (27.8%) of adult females were positive for ANA 21 out of 144 (14.6%) of adult males were positive for ANA

ANA concentration increased with age from lambs to adults

Adult females had significantly higher ANAs than adult males (P < 0.001)

Result IIDo ANA concentrations reflect general antibody responsiveness?

Further immunological analysis with all ANA-positive sheep:i. Concentrations of total IgGii. Concentrations of antibodies to ribonucleoproteiniii. Concentrations of antibodies to Teladorsagia circumcincta

All positively correlated with ANAs

Result IIIIs the variation in ANA concentration among individuals genetically based?

A significant proportion of ANA heterogeneity was attributed to additive genetic effects:

One-third of the among-individual variation and One-eighth of the total phenotypic variance were genetically based

Among-individual variation in ANA concentration is partly genetically based

Results IVIs there an association between ANAs and different components of fitness?

1. Survival 2. Fecundity

1. Survival

Population dynamics characterized by years of rising and high density followed by winter crashes

Environment-dependent association of survival with high ANAs in adult female sheep

2. Fecundity

Male Female

Males and females with high ANAs in August were less likely to have sired or produced a lamb the previous year

Summary

Positive ANA concentration leads to higher survival rates but reduced reproduction in female sheep

Survival-ANA association is environment and sex dependent Reduced fecundity in ANA-positive females is accompanied by

improved survival of their neonates

A mechanism for the maintenance of immunoheterogeneity, possibly including autoimmune susceptibility genes, by natural selection

Density-dependent selection on horn phenotype

T. Clutton-Brock, K. Wilson, I. StevensonPhil. Trans. R. Soc. Lond. B 1997

Morphology

Gender

Polled (P)

Scurred(S)

Normal (N)

Male 0 % 12 % 88 %

Female 41 % 24 % 35 %

Development of horn has a genetic component

Horn morphology is related to components of fitness

Morphology

Gender

Polled (P)

Scurred(S)

Normal (N)

Male 0 % 12 % 88 %

Female 41 % 24 % 35 %

S male show lower mating success

Morphology

Gender

Polled (P)

Scurred(S)

Normal (N)

Male 0 % 12 % 88 %

Female 41 % 24 % 35 %

S of both sexes show higher survival in years when population density and mortality are high

S male show lower mating success

Morphology

Gender

Polled (P)

Scurred(S)

Normal (N)

Male 0 % 12 % 88 %

Female 41 % 24 % 35 %

S male show lower mating success

S female show higher conception rates

S of both sexes show higher survival in years when population density and mortality are high

Density-dependent natural selection acting on simple polymorphic variation in a free-living population

ReferencesPictures:(1) http://en.wikipedia.org/wiki/Hirta#mediaviewer/File:Outer_Hebrides_UK_relief_location_map.jpg(2) soaysheepbreeders.com(3) autoimmunityblog.com(4) www.roche.com(5) http://en.wikipedia.org/wiki/Hirta#mediaviewer/File:Outer_Hebrides_UK_relief_location_map.jpg(6) http://en.wikipedia.org/wiki/Shawangunk_Grasslands_National_Wildlife_Refuge#mediaviewer/File:Shawangunk_Grasslands_NWR.

jpg(7) http://www.flemingyachts.com/venture3/entry4.html(8) http://www.nematode.net/NN3_frontpage.cgi?navbar_selection=speciestable&subnav_selection=Heterodera_schachtii(9) http://saltmarshranch.com/about-soay/small-sheep-small-acreage.shtml(10) http://markgtelfer.co.uk/2011/05/08/counting-sheep-and-lack-of-sleep/(11) http://www.nature.com/hdy/journal/v104/n2/fig_tab/hdy2009109f1.html

LiteratureGraham, AL Hayward, AD Watt, KA Pilkington, JG Pemberton, JM Nussey, DHAF Graham, Andrea L. Hayward, Adam D. Watt, Kathryn A. Pilkington, Jill G. Pemberton, Josephine M. Nussey, Daniel H.TI Fitness Correlates of Heritable Variation in Antibody Responsiveness in a Wild Mammal, Science 2010CluttonBrock, TH Wilson, K Stevenson, IRAF CluttonBrock, TH Wilson, K Stevenson, IRTI Density-dependent selection on horn phenotype in Soay sheep, PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCESRI 1997Moorcroft, P. R., Albon, S. D., Pemberton, J. M., Stevenson, I. R. & Clutton-Brock, T. H. 1996. Densitydependent selection in a fluctuating ungulate population. Proc. R. Soc. Lond. B263, 31-38

Fitness Correlates of Heritable Variation in Antibody Responsiveness in a Wild MammalOverviewThe Immune SystemFoliennummer 4The Immune SystemHypothesisResearch QuestionsMethodsResults IFoliennummer 10Result IIResult IIIResults IV1. Survival2. FecunditySummaryDensity-dependent selection on horn phenotypeFoliennummer 18Foliennummer 19Foliennummer 20Foliennummer 21Foliennummer 22References