Lecture 5 : Pathogenicity Overview

1. Lecture 5 : PathogenicityOverview THE BODY’S DEFENCES • Physical And Chemical Defences • The Innate Immune System • The Adaptive Immune System VIRULENCE AND ADAPTATION • The Processes Of Adaptation POPULATION RESPONSES TO INFECTION

2. The Body’s Defences • Infection is common, but disease is rare. • The likelihood of a disease developing depends upon various factors, such as: the size of the infecting dose; the virulence of the causal agent; and the effectiveness of the body's defence mechanisms. • Louis Pasteur: ‘the germ is nothing, the terrain is everything’.

3. Physical And Chemical Defences • Physical defences – skin, membranes, nose hairs, mucous. • Chemical defences – sweat, tears, saliva, stomach acid. • Biological defences – commensal bacteria, the immune system

4. The Innate Immune System • There are two types of immune system: • the innate immune system – defences present from birth. • The adaptive immune system – specific defences in response to an invading microorganism. • The innate immune system: phagocytes (macrophages, neutrophils), complement, interferon.

5. Adaptive Immune System(1) • Triggered by antigens – i.e. ‘foreign’ proteins found within bacteria, viruses, pollen, etc. • Two types of response: • Humoral (or serum) – B-lymphocytes create proteins called antibodies (or immunoglobulin) which lock onto the antigens. • Cellular – ‘killer’ T-lymphocytes kill; ‘helper’ T-lymphocytes activate phagocytes or B-lymphocytes.

6. Adaptive Immune System(2) • The adaptive immune system has two notable properties: • Specificity – it responds to a specific antigen by producing a specific antibody or activating specific T-lymphocytes. • Memory – it retains a memory of previous antigens, and can respond more rapidly when invaded again. • This is why we rarely get certain disease more than once – i.e. we develop immunity. • This is the principle behind immunisation – vaccines trigger the adaptive immune system without causing illness.

7. Virulence And Adaptation • There are three possible outcomes when a population is infected by a new agent: • The host’s immune system overwhelms the agent • The agent overwhelms and kills the host without being transmitted • The agent replicates within the host and is transmitted to a new host. The hosts may die or recover. • We generally only notice the third possibility. • New infections may produce a high death rate, but over the course of time the host and agent adapt to one another and the disease normally becomes less virulent.

8. Processes Of Adaption • Adaption arises from the processes of natural selection. • Hosts that are genetically more resistant survive in greater numbers to transmit their genes to the next generation. • Natural selection favours agents that develop mechanisms for successful transmission to a new host. One possibilty is to become less virulent so that the host will survive longer. • These processes can be best observed in species that reproduce quickly. Myxomatosis in Australian rabbits provides a good example.

9. Myxomatosis(1) • Eurpean rabbits introduced into Australia in 1859 but they bred so rapidly that they became a pest. • It was decided to kill them in 1950 by infecting them with myxomatosis – a commensal of a different species of Brazilian rabbit, but fatal to European rabbits. • Myxomatosis is transmitted in Australia by mosquitoes when they bite virus-rich lumps in the skin of the rabbits. • Myxomatosis wiped out 99 per cent of the rabbits within 3 months. • However …

10. Myxomatosis(2) • The less virulent strains of the virus had more chance of being transmitted, so the disease became less virulent. • The surviving rabbits meanwhile passed on their genes and became more resistant. • The death rate fell to 60-70 per cent, and the number of rabbits began to increase. • However, the less virulent strains of the virus did not produce sufficient lumps in the more resistant rabbits to be transmitted, so natural selection favoured more virulent strains of the pathogen. • A balance was eventually achieved as host and agent adapted to one another (coevolution).

11. Population Responses • Populations can be divided into three categories wrt to diseases that confer immunity: • Susceptibles • Infectives • Immunes • If a disease is very infectious, a high percentage of the population become infected and either die or survive as immunes. A high percentage of surviving adults will be immune so children will make up the majority of susceptibles. Highly infectious diseases therefore tend to become a disease of childhood and may become milder. • This, however, is moderated by geography.

12. Effects Of Population Size • Diseases in small populations cannot find sufficient hosts and burn themselves out. • In larger populations the disease may be able to find a continuous supply of new hosts and become endemic – i.e. continuously present. • If the disease is highly infectious but generates immunity, the fresh hosts are provided by non-immune children. • In smaller populations after a disease burns itself out, the non-immune population gradually builds up and may become infected from outside to produce an epidemic. • An epidemic on an inter-continental scale is called a pandemic.