defense

A pathogen is a disease-causing agent that disrupts the normal physiology of an infected organism. They

can be either cellular (includes bacteria, fungi and parasites) or non-cellular (includes viruses and prions). A

virus is an infec4ve en4ty that inserts its gene4c material into a host cell in order to mul4ply. A prion is an

infec4ous protein that has folded abnormally into a disease-causing structure. Bacteria are prokaryo4c cells

that reproduce quickly and compete with host cells for space or nutri4on. Disease-causing fungi typically

colonise body surfaces, while parasites are organisms that feed on a host to the detriment of host survival.

They can include either single-celled microparasites (protozoa) or mul4cellular macroparasites (helminths).IMMUNE SYSTEM

The immune system can be divided into three basic lines of defence against pathogenic infec4ons:

• The first line of defence are the surface barriers that prevent the entry of pathogens into the host body

• The second line of defence are the non-specific defence mechanisms ac4vated a^er infec4on occurs

• The third line of defence are the specific responses that target an4gens produced by the pathogens

NON-SPECIFIC DEFENCES SPECIFIC DEFENCES

First line of defence Second line of defence Third line of defence

• Physical barriers

• Phagocy4c leukocytes

• Lymphocytes (B and TH cells)

• Chemical barriers

• Inflammatory response

• An4bodies (via plasma cells)

• Microbiological barriers

• Complement proteins

• Memory cells

SURFACE BARRIERS

Most animals possess three dis4nc4ve types of barriers to prevent pathogens from accessing body 4ssue.

Physical barriers func4on as obstruc4ons that impede access to internal 4ssues, while chemical barriers

consist of the chemical compounds released onto surfaces (or into cavi4es) to hinder pathogenic survival.

Physical Barriers:

• Intact skin consists predominantly of dead cells that line the body surfaces to prevent pathogen entry

• Mucous membranes consist of living cells that line internal cavi4es and secrete trapping fluids (mucus)

• Internal surfaces may be ciliated to aid in the removal of pathogens (via physical ac4ons like coughing)

Chemical Barriers:

• Gastric secre4ons contain strong stomach acids (pH < 2) that func4on to destroy ingested pathogens

• Sweat and tears contain biochemical agents (e.g. lysozymes, lac4c acid) that inhibit microbial growth

• Mucus secreted into the diges4ve and genitourinary tracts also contain biochemical defence agents

Microbiological Barriers:

• Natural flora (commensals) lines the gut, taking up space and preven4ng colonisa4on by pathogens

CLOTTING

If surface barriers are penetrated and pathogens gain access

to body 4ssues, then a clo>ng cascade is ac4vated to restore

an intact external layer. Clo>ng is ini4ated by the release of

cloHng factors from damaged cells or platelets. These factors

cause platelets to become s4cky and form a solid plug, while

also triggering coagula4on by conver4ng an inac4ve enzyme

precursor (prothrombin) into an ac4vated enzyme (thrombin).

This will in turn convert soluble fibrinogen strands in the blood

into insoluble fibrin fibres. The fibrin then associates with the

platelet plug to form a fibrous clot at the region where the skin

has been broken. When the damage site has been completely

repaired, enzymes will dissolve the clot, leaving behind a layer

of skin to act as an impermeable barrier to further infec4on.

Clo1ng Factors

Prothrombin Thrombin

Fibrinogen Fibrin

DAMAGED VESSEL CLOT FORMATIONINNATE IMMUNE SYSTEM

The second line of defence against infec4ous disease is the innate immune system, which is non-specific:

• It does not differen4ate between different types of pathogens (it does not recognise an4gens)

• It responds to an infec4on the same way every 4me (i.e. it has no immunological memory)

The primary component of the innate immune system are the phagocy4c leukocytes, which internalise and

digest broad types of pathogens based on generic characteris4cs (pathogen-associated molecular paderns).

PHAGOCYTOSIS

Phagocytes are white blood cells (leukocytes) that can engulf foreign bodies. Phagocytes are non-specific

and can only respond to broad categories of pathogens. Phagocytes are recruited to infected 4ssues when

damaged cells release chemotac4c chemicals. The phagocyte uses cellular extensions called pseudopodia

to travel from the bloodstream via amoeboid movement. A pathogen is then surrounded by pseudopodia

internalised within a vesicle (via endocytosis). The vesicle is then fused to lysosomes and the pathogen is

digested. The an4genic fragments from the pathogen may then be presented on the cell membrane of the

phagocyte (becoming an anLgen presenLng cell) in order to s4mulate the third line of defence (adap4ve).

LYMPHATIC SYSTEM

The lympha4c system is a secondary transport system that func4ons to

drain fluid from all around the body. The fluid within this system is called

lymph and is rich in white blood cells. The lympha4c system will filter the

fluid at sites called lymph nodes and remove pathogens to avoid infec4on.

When a phagocy4c leukocyte engulfs a pathogen and becomes an an4gen

presen4ng cell, it will be transported to the lympha4c system in order to

present the an4genic fragment to lymphocytes (adap4ve immune cells).

Lympha4c systems therefore func4on as an important link between the

innate and adap4ve systems as it connects phagocytes and lymphocytes.

Lymph

ADAPTIVE IMMUNE SYSTEM

The third line of defence against infec4ous disease is the adap4ve immune system, which is specific:

• It recognises specific an4gens in order to differen4ate between different types of pathogens

• It produces a heightened response upon re-exposure to a pathogen (i.e. has immunological memory)

The principal components of the adap4ve immune system are the lymphocytes residing in lymph nodes.

ANTIGENS

An4gens are molecular markers (typically glycoproteins) that are usually located on the outer surfaces of

pathogens. These an4genic fragments are unique to the pathogen and can be used to target the pathogen

specifically. An4gens will be targeted by specific proteins called anLbodies (an4gen = an4body generator).LYMPHOCYTES

The body contains millions of different B and T lymphocytes that each

recognise a single, specific an4gen. Only the appropriate lymphocyte

can be ac4vated by a par4cular an4genic fragment to divide and form

iden4cal clones (clonal selec4on / expansion). As each pathogen may

contain many dis4nct an4genic fragments on their surface, a par4cular

pathogen may s4mulate several different B and T lymphocytes to form

clones (this is called polyclonal ac4va4on). The prolifera4on of specific

B cells first require ac4va4on by a specific helper T cell (helper T cells

coordinate the en4re adap4ve immune response). Helper T cells are

introduced to an4genic fragments by an4gen presen4ng cells in the

lymph nodes. The helper T cells will then release cytokines to ac4vate

naïve B lymphocytes that have also encounter the an4gen. The B cells

divide and differen4ate to form a large quan4ty of short-lived plasma

cells and a lesser quan4ty of memory cells. Plasma cells will produce

an4bodies that target the an4gen and facilitate pathogen elimina4on.

APC TH

an4gen presenta4on

B B

selected not selected

ANTIBODIES

An4bodies are proteins produced by B lymphocytes (and plasma cells) that

are specific to a par4cular an4gen. They are composed of four polypep4de

chains that are connected by disulphide bonds to form Y-shaped molecules.

Each an4body is composed of two heavy and two light chains, but differ in

their variable region which is specific for a given an4gen. The remainder of

the an4body is constant and serves as a recogni4on site for immune cells.

An4bodies facilitate pathogen destruc4on in a number of different ways,

including via precipita4on, agglu4na4on and complement ac4va4on, but

the primary way an4bodies act to eliminate pathogens is via opsonisaLon.

Variable

Constant

MEMORY CELLS

When B and T lymphocytes divide and differen4ate, a small propor4on

of clones will differen4ate into memory cells. Memory cells remain in

the body for years (or even a life4me). If a second infec4on with the

same an4gen occurs, memory cells will produce a secondary immune

response that is faster and more potent, such that the symptoms of

infec4on do not normally appear. Because the individual no longer

presents with the symptoms of infec4on upon exposure, the person

is said to have developed immunological memory and is now immune.

An$body Levels

Time

IMMUNODEFICIENCY

Immunodeficiency is a condi4on in which the immune system is either compromised or absent. As a result,

the body cannot fight off pathogens and becomes increasingly suscep4ble to opportunis4c infec4ons. The

human immunodeficiency virus (HIV) can cause acquired immunodeficiency syndrome (AIDS) by specifically

infec4ng the helper T lymphocytes. With a reduc4on in the number of TH cells, an4bodies are unable to be

produced and immunity is lowered. HIV is transmided through the exchange of bodily fluids – including via

unprotected sex, blood contact (e.g. unsafe needle injec4ons) or maternal transmission during pregnancy.ZOONOSES

A zoonosis is an infec4ous disease that can be transmided from other species

to humans. The pathogen can be transferred directly from a non-human host

or may be transmided by an unaffected intermediate species (referred to as a

vector). The infected animals can act as a reservoir for the pathogen, allowing

it to survive even if it is eradicated in humans – facilita4ng the re-emergence

of diseases in popula4ons where they had been eliminated. Zoono4c diseases

are occurring with greater frequency due to increased urbanisa4on of regions

heightening the exposure of humans to infected animals. Examples of zoono4c

diseases include bovine tuberculosis, rabies and Japanese encephali4s.

ANIMAL

DISEASES

ZOONOSIS

HUMAN

DISEASES

Disease Pathogen Animal Source Mode of Transmission

Tuberculosis Bacterium (M. bovis) Ca:le Unprocessed milk

Rabies Virus (R. lyssavirus) Wild animals / pets Direct contact (bite / scratch)

Japanese encephaliFs Virus (JEV) Pigs Biological vector (mosquitoes)

ANTIBIOTICS

Bacterial pathogens can be trea4ng with compounds that specifically target prokaryo4c features (e.g. 70S

ribosomes). These compounds are called anLbioLcs. Some bacteria have developed an4bio4c resistance

genes (via muta4ons), that enable them to survive an4bio4c treatment. The bacteria can even pass these

genes to suscep4ble colonies by bacterial conjuga4on (plasmid exchange), making an4bio4cs ineffec4ve.

VACCINATION

Vaccina4on involves the injec4on of a biological prepara4on (vaccine) to provide ac4ve acquired immunity

to a specific infec4ous disease. Vaccines consist of aOenuated pathogens – either the an4genic fragments

or the nucleic acid sequences that code for the an4gens. The body will respond to a vaccine by ini4a4ng a

primary response that results in the produc4on of memory cells. When an individual is then exposed to the

actual pathogen, the memory cells will trigger a more potent secondary immune response that prevents

disease symptoms from developing (the individual is now considered to be immunised against the disease).

HERD IMMUNITY

Vaccina4ons confer immunity to vaccinated individuals but also indirectly

protects the non-vaccinated people via herd immunity. When a sufficiently

large percentage of a popula4on is immune to infec4on, there is a reduced

risk of infec4on for individuals who lack immunity. Herd immunity limits the

spread of a pathogen to individuals who are par4cularly elderly, extremely

young or may be immune compromised. The propor4on of a popula4on that

needs to be vaccinated to confer herd immunity will be influenced by a range

of factors – such as popula4on density, mode of transmission and infec4vity.

NON-IMMUNE

INFECTED

VACCINATED

OUTBREAKS

An epidemic is an outbreak that occurs over a given 4me period within a par4cular community or region,

while a pandemic occurs across a wider geographical area (e.g. global). Emerging trends can be measured

via percentage changes (e.g. vaccine efficiencies) or percentage differences (e.g. age group comparisons).