M4 Communicable Diseases

Question 1

What are communicable diseases caused by?

Answer 1

Infective organisms known as pathogens.
Pathogens include bacteria, viruses, fungi and protoctista.
Each has particular characteristics that affect the way they are spread and the ways we can attempt to prevent/cure the diseases they cause.

Question 2

What is a communicable disease?

Answer 2

A disease that can be passed from one organism to another.
In animals they are most commonly spread from one species to another, but can also be spread between species.
Communicable diseases in plants are sped directly plant to plant.
Vectors, which carry pathogens from one organism to another, are involved in the spread of a number of important plant and animal diseases.

Question 3

Describe bacteria

Answer 3

• There are more bacteria than any other organism, a small proportion of these are pathogens.
• Bacteria are prokaryotes, so they have a cell structure that is very different from eukaryotic organisms they infect (they do not have a membrane-bound nucleus or organelles).
• Bacteria can be classier by their basic shape - rod shaped (bacilli), spherical shaped (cocci), comma shaped (vibrios), spiralled (spirilla) and corkscrew (spirochaetes).
• Or bacteria can be classified by their cell walls, the main two types react differently with Gram staining. Gram positive bacteria look purple-blue under light microscope. Gram negative bacteria appear red. This is useful as the type of cell wall affects how bacteria react to different antibiotics.

Question 4

Describe viruses

Answer 4

• Viruses are non-living infectious agents. They are 50 times smaller in length than the average bacterium.
• The basic structure is some genetic material (DNA or RNA) surrounded by a protein.
• Viruses invade living cells, where the genetic material of the virus takes over the biochemistry of the host cell to make more viruses.
• Viruses reproduce rapidly and evolve by developing adaptations to their host, which makes them successful pathogens. All naturally occurring viruses are pathogenic - they cause disease in every other type of organism, even bacteria (bacteriophages).

Question 5

Describe protoctista (Protista)

Answer 5

• Protoctista are a group of eukaryotic organisms with a wide variety of feeding methods.
• They include single-celled organisms and cells grouped into colonies.
• A small percentage of protoctista act as pathogens, causing devastating communicable diseases in both animals and plants.
• The protists that cause disease are parasitic. Pathogenic protists may need a vector to transfer them to their hosts, or they may enter the body through polluted water.

Question 6

Describe fungi

Answer 6

• Fungal infections are not a major problem in animals, but they can cause devastation in plants.
• Fungi are eukaryotic organisms that are often multicellular. They cannot photosynthesise and they digest their food extracellularly before absorbing the nutrients. Many fungi are saprophytes - they feed on dead and decaying matter.
• However some fungi are parasitic, feeding on living plants and animals. These are the pathogenic fungi which cause communicable diseases.
• Because fungal infections often affect the leaves of plants, they stop them photosynthesising and so can quickly kill the plant.
• When fungi reproduce they produce millions of tiny spores which can spread huge distances, meaning they can spread rapidly and widely through crop plants.
• Fungal diseases of plants can cause hardship and starvation in many countries across the world.

Question 7

How do viruses attack and damage host tissues?

Answer 7

• Viruses take over the cell metabolism.
• The viral genetic material gets into the host cell and is inserted into the host DNA.
• The virus then uses the host cell to make new viruses which then burst out of the cell, destroying it and then spread to infect other cells.

Question 8

How do protoctista attack and damage host tissues?

Answer 8

• Some protoctista also take over cells and break them open as the new generation emerge, but they do not take over the genetic material of the cell.
• They simply digest and use the cell contents as they reproduce.

Question 9

How do fungi attack and damages host tissues?

Answer 9

• Fungi digest living cells and destroy them.
• This combined with the response of the body to the damage caused by the fungus gives the symptoms of disease.
• Some fungi produce toxins which affect the host cells and cause disease.

Question 10

How do bacteria attack and damage the host tissues?

Answer 10

• Most bacteria produce toxins that poison or damage the host cells in some way, causing disease.
• Some bacterial toxins damage the host cells by breaking down the cell membranes, some damage or inactivate enzymes and some interfere with the host cell genetic material so the cells cannot divide. These toxins are a by-product of the normal functioning of the bacteria.

Question 11

What are some diseases caused by bacteria?

Answer 11

Tuberculosis (TB)
Bacterial meningitis
Ring rot (potatoes and tomatoes)

Question 12

What are some diseases caused by viruses?

Answer 12

HIV/AIDS
Influenza (animals)
Tobacco Mosaic Virus (plants)

Question 13

What are some diseases caused by protoctista?

Answer 13

Malaria
Potato/tomato late blight

Question 14

What are some diseases caused by fungi?

Answer 14

Black sigatoka (bananas)
Ringworm (cattle)
Athletes foot (humans)

Question 15

Describe ring rot

Answer 15

• A bacterial disease of potatoes, tomatoes and aubergines caused by a Gram positive bacterium.
• It damages leaves, tubers and fruit.
• It can destroy up to 80% of the crop and there is no cure, once a bacterial ring rot infects a field it cannot be used to grow potatoes for at least 2 years.

Question 16

Describe tobacco mosaic virus (TMV)

Answer 16

• A virus that infects tobacco plants and around 150 other species.
• It damages leaves, flowers and fruit, stunting growth and reducing yields and can lead to an almost total crop loss.
• Resistant strains are available but there is no cure.

Question 17

Describe potato blight

Answer 17

• Caused by a fungus-like protoctist oomcyete.
• The hyphae penetrate host cells, destroying leaves, tubers and fruit, causing millions of pounds of crop damages each year.
• There is no cure but resistant strains, careful management and chemical treatments can reduce infection risk.

Question 18

Describe black Sigatoka

Answer 18

• A banana disease caused by a fungus, which attacks and destroys the leaves.
• The hyphae penetrate and digest the cells, turning the leaves black.
• If plants are infected it can cause a 50% reduction in yield.
• Resistant strains are being developed, good husbandry and fungicide treatment can control the spread of the disease but there is no cure.

Question 19

Describe tuberculosis (TB)

Answer 19

• A bacterial disease of humans, cows, pigs, badgers and deer commonly caused by Mycobacterium tuberculosis and M. bovis.
• TB damages and destroys lung tissue and suppresses the immune system, so the body is less able to fight off other diseases.
• The global rise of HIV/AIDS has had a big impact on the numbers of people suffering from diseases such as TB, because people infected by HIV/AIDS are much more likely to develop TB infections.
• In people TB is both curable (by antibiotics) and preventable (by improving living standards and vaccination).

Question 20

Describe bacterial meningitis

Answer 20

• A bacterial infection of the meninges of the brain (protective membranes on the surface of the brain) which can spread into the rest of the body causing septicaemia (blood poisoning) and rapid death.
• It mainly affects young children and teenagers.
• Antibiotics will cure the diesel if delivered early. Vaccines can protect against some forms of bacterial meningitis.

Question 21

Describe HIV/AIDS (acquired immunodeficiency syndrome)

Answer 21

• Caused by HIV (human immunodeficiency virus) which targets T helper cells in the immune system of the body.
• It gradually destroys the immune system so that affected people are open to other infections.
• HIV/AIDS can affect humans and some non-human primates.
• HIV is a retrovirus with RNA as it’s genetic material. It contains the enzyme reverse transcriptase, which transcribes the RNA to a single strand of DNA to produce a single strand of DNA in the host cell. This DNA interacts with the genetic material of the body cell.
• The virus is passed from one person to the next in bodily fluids, through unprotected sex, shared needles, contaminated blood products and mothers to babies during breast feeding.

Question 22

Describe influenza (flu)

Answer 22

• A viral infection of the ciliated epithelial cells in the gas exchange system.
• It kills them, leaving the airways open to secondary infection. Flu can be fatal, especially to young children, old people and people with chronic illnesses.
• Many of these deaths are from serve secondary bacterial infections.
• There are 3 main strains - A, B and C. Strain A viruses are the most virulent and are classified further by the proteins on their surface.
• Flu viruses mutate regularly. Vulnerable groups are given a flu vaccine annually.

Question 23

Describe malaria

Answer 23

• Caused by the protoctista Plasmodium and spread by the bites of infected Anopheles mosquitoes.
• The Plasmodium parasite has a complex life cycle with two hosts - mosquitoes and people.
• They reproduce inside the female mosquito. The female needs to take two blood meals to provide her with protein before she lays her eggs - this is when the Plasmodium is passed on to people.
• It invades the red blood cells, liver and even brain.
• There is no vaccine against malaria and limited cures.
• Preventative measures can be taken by controlling the vector, such as by insecticides and removing standing water where mosquitoes breed.
• Simple measures such as mosquito nets, window and door screens and long sleeve clothing can prevent them biting people and spreading the disease.

Question 24

Describe ring worm

Answer 24

• A fungal disease affecting mammals including cattle, dogs, cats and humans.
• Different fungi infect different species. It causes a grey-white crusty, infectious, circular areas of skin. It is not damaging but may be itchy.
• Anti-fungal creams are an effective cure.

Question 25

Describe athletes foot

Answer 25

• A human fungal disease, a form of ringworm that grows on and digests the warm, moist skin between toes.
• It causes cracking and scaling, which is itchy and may become sore.
• Anti-fungal creams are an effective cure.

Question 26

How does direct transmission of pathogens spread disease in animals?

Answer 26

1. Direct contact - any contact of bodily fluids (STIs), direct skin-to-skin contact (ringworm) and microorganisms from faeces transmitted on hands.
2. Inoculation - through a break in skin, (HIV/AIDS during sex), through an animal bite (rabies) and through a puncture wound or sharing needles.
3. Ingestion - taking in contaminated food or drink, or transferring pathogens to the mouth from the hands.

Question 27

How are pathogens spread through indirect transmission in animals?

Answer 27

1. Formites - inanimate objects such as bedding, socks or cosmetics can transfer pathogens (athletes foot)
2. Droplet infection (inhalation) - minute droplets of saliva and mucus are expelled from your mouth as you talk, cough or sneeze. If these contain pathogens, when healthy individuals breathe in droplets they may become infected.
3. Vectors - a vector transmits communicable pathogens from one host to another. They are often, but not always animals. Water can also act as a vector of disease

Question 28

Factors affecting the transmission of communicable diseases in animals

Answer 28

• Overcrowded living and working conditions
• Poor nutrition
• A compromised immune system, including having HIV/AIDS
• Poor disposal of waste, providing breeding sites for vectors
• Climate change - can introduce new vectors and diseases
• Culture and infrastructure - in many countries traditional medical practices can increase transmission
• Socioeconomic factors - eg. lack of trained health workers and insufficient public warning during an outbreak of disease.

Question 29

Describe transmission of pathogens between plants

Answer 29

Direct transmission:
- Direct contact of a healthy plant with any part of a diseased plant eg. ring rot, tobacco mosaic virus (TMV)

Indirect transmission:
- Soil contamination: infected plants often leave pathogens (bacteria or viruses) or reproductive scores from protoctista or fungi in the soil. These can infect the next crop.

Vectors:
- Wind: bacteria, viruses and fungi may be carried in the wind.
- Water: spores swim in the surface film of water on leaves; raindrop splashes carry pathogen and spores.
- Animals: insects and birds carry pathogens and spores from one plant to another as they feed.
- Humans: pathogens and spores are transmitted by hands, clothing, formites, farming practices and by transporting plants and crops around the world.

Question 30

Factors affecting the transmission of communicable diseases in plants

Answer 30

Planting varieties of crops that are susceptible to disease
Over-crowding increases the likelihood of contact
Poor mineral nutrition reduced resistance of plants
Damp, warm conditions increase the survival and spread of pathogens and spores
Climate change - increased rainfall and wind promote the spread of diseases; changing conditions allow animal vectors to spread to new areas; drier conditions may reduce the spread of disease.

Question 31

How to prevent the spread of communicable diseases in plants

Answer 31

• Leave plenty of room between plants to minimise the spread of pathogens
• Clear fields as thoroughly as possible, remove all traces of plants from the soil at harvesting.
• Rotate crops, the spores or bacteria will eventually die if they do not have access to the host plant.
• Follow strict hygiene practices, such as washing hands, washing boots and sterilising storage sacks.
• Control insect vectors.

Question 32

How do plants recognise an attack

Answer 32

• Plants are not passive, they respond rapidly to pathogen attacks.
• Receptors in the cells respond to molecules from the pathogens, or to chemicals produced when the plant cell well is attacked.
• This stimulates the release of signalling molecules that appear to switch in genes in the nucleus.
• This in turn triggers cellular responses, which include producing defensive chemicals, sending alarm signals to unaffected cells to trigger their defences, and physically strengthening the walls.

Question 33

Describe how plants recognise/defend against an attack

Answer 33

1. Some molecules from the pathogen are recognised directly by the plant cell.
2. When pathogenic enzymes break down the cell wall the breakdown products are recognised.
3. Signalling molecules alert nucleus to attack.
4. Polysaccharides (callose and lignin) made to strengthen the cell walls.
5. Defensive chemicals give the alarm to other cells before they are attacked.
6. Some defensive molecules directly attack the pathogen.

Question 34

Describe the physical defences of plants against pathogens

Answer 34

When plants are attacked by pathogens they rapidly set up extra mechanical defences. They produce high levels of a polysaccharide called callose, which contains beta-1,3 linkages and beta-1,6 linkages between glucose monomers:
- within minutes of an initial attack, callose is synthesised and deposited between the cell walls and the cell membrane in cells next to the infected cells. These callose papillae act as barriers, preventing the pathogens entering the plant cells around the site of infection.
- large amounts of callose continue to be deposited in cell walls after the initial infection. Lignin is added, making the mechanical barrier to invasion even thicker and stronger.
- callose blocks sieve plates in the phloem, sealing off the infected part and preventing the spread of pathogens.
- callose is deposited in the plasmodesmata between infected cells and their neighbours, sealing them off from the healthy cells and helping to prevent the pathogen spreading.

Question 35

Describe the chemical defences of plants against pathogens

Answer 35

Many plants produce powerful chemicals that either repel the insect vectors of disease or kill invading pathogens. Some of these chemicals are so powerful that we extract them and use them to help control insects, fungi and bacteria:
- insect repellents eg. pine resin
- insecticides eg. caffeine (toxic to insects and fungi)
- antibacterial compounds including antibiotics eg. phenols
- antifungal compounds eg. phenols
- anti-oomycetes, enzymes made by some plants that break down glucans; polymers found in the cell walls of oomycetes
- general toxins, some plants make chemicals that can be broken down the form cyanide compounds when the plant cell is attacked

Question 36

How do mammals immune systems work?

Answer 36

They have two lines of defence against invasion by pathogens.
The primary non-specific defences against pathogens are always present or activated rapidly.
Mammals have a specific immune response, which is specific to each pathogen but is slower to respond.

Question 37

Describe human barriers of entry to pathogens

Answer 37

• The skin covers the body and prevents the entry of pathogens. It has a skin flora of healthy microorganisms that outcompete pathogens for space on the body surface. The skin also produces sebum, an oily substance that inhibits the growth of pathogens.
• Many of the body tracts, including the airways of the gas exchange system, are lined by mucous membranes that secrete sticky mucus. This traps microorganisms and contains lysozymes, which destroy bacterial and fungal cell walls. Mucus also contains phagocytes, which remove remaining pathogens.
• Lysozymes in tears and urine, and the acid in the stomach also help prevent pathogens getting into our bodies.

Question 38

Describe blood clotting and wound repair

Answer 38

• If you cut yourself, the skin is breached and pathogens can enter the body.
• Blood clots rapidly to seal the wound. When platelets come into contact with collagen in the skin or the wall of the damaged blood vessel, they adhere and begin secreting several substances:
  • thromboplastin, an enzyme that triggers a cascade of reactions resulting in the formation of a blood clot
  • serotonin, which makes the smooth muscle in the walls of the blood vessels contract, so they narrow and reduce the supply of blood to the area.
• The clot dries out, forming a hard, tough scab that keeps pathogens out. This is the first stage of wound repair. Epidermal cells below the scab start to grow, sealing the wound permanently, while damaged blood vessels regrow.
• Collagen fibres are deposited to give the new tissue strength. Once the new epidermis reaches normal thickness, the scab sloughs off and the wound is healed.

Question 39

Describe the inflammatory response

Answer 39

• The inflammatory response is a localised response to pathogens resulting in inflammation at the site of a wound.
• Inflammation is characterised by pain, heat, redness and swelling of tissue.
• Mast cells are activated in damaged cells issue and release chemicals called histamines and cytokines.
  • Histamines make the blood vessels dilate, causing localised heat and redness. The raised temperature helps prevent pathogens reproducing.
  • Histamines make blood vessel walls more leaky so blood plasma is forced out, once forced out of the blood it is known as tissue fluid. Tissue fluid causes swelling (oedema) and pain.
  • Cytokines attract white blood cells (phagocytes) to the site. They dispose of pathogens by phagocytosis.

Question 40

Describe how fevers inhibit the growth of pathogens

Answer 40

When a pathogen invades your body, cytokines stimulate your hypothalamus to reset the thermostat and your temperature goes up. This is a useful adaptation because:
- most pathogens reproduce best at or below 37°C. Higher temperatures inhibit pathogen reproduction.
- the specific immune system works faster at higher temperatures.

Question 41

What are phagocytes?

Answer 41

• Phagocytes are specialised white blood cells that engulf and destroy pathogens.
• There are two main types of phagocytes - neutrophils and macrophages.
• Phagocytes build up at the site of an infection and attack pathogens. Sometimes you can see pus in a spot, cut or wound. Pus consists of dead neutrophils and pathogens.

Question 42

What are the stages of phagocytosis?

Answer 42

1. Pathogens produce chemicals that attract phagocytes.
2. Phagocytes recognise non-human proteins on the pathogen. This is a response not to a specific type of pathogen, but simply a cell or organism that is non-self.
3. The phagocyte engulfs the pathogen and encloses it in a vacuole called a phagosome.
4. The phagosome combined with a lysosome to form a phagolysosome.
5. Enzymes from the lysosome digest and destroy the pathogen.

• Macrophages take longer to engulf and destroy a bacterium compared to a neutrophil, as when a macrophage has digested a pathogen, it combines antigens from the pathogen surface membrane with special glycoproteins in the cytoplasm called the major histocompatibility (MHC) complex, with moves these pathogen antigens to the macrophage’s own surface membrane, becoming an antigen-presenting cell (APC)
• These antigens now stimulate other cells involved in the specific immune response.

Question 43

Describe the role of cytokines

Answer 43

• Phagocytes that have engulfed a pathogen produce chemicals called cytokines.
• Cytokines act as cell-signalling molecules, informing other phagocytes that the body is under attack and stimulating them to move to the site of infection or inflammation.
• Cytokines can also increase body temperature and stimulate the specific immune system.

Question 44

Describe the role of opsonins

Answer 44

• Chemicals that bind to pathogens and ‘tag’ them so they can be more easily recognised by phagocytes.
• Phagocytes have receptors on their cell membranes that bind them to common opsonins, and the phagocyte then engulfs the pathogen.
• There are a number of different opsonins, but antibodies such as immunoglobulin G (IgG) and immunoglobulin M (IgM) have the strongest effect.

Question 45

What are antibodies?

Answer 45

• Antibodies are Y-shaped glycoproteins called immunoglobulins, which bind to a specific antigen on the pathogen or toxin that has triggered the immune response. There are millions of different antibodies, and there is a specific antibody for each antigen.
• Antibodies are made up of two identical long polypeptide chains called the heavy chains, and two much shorter identical chains called the light chains. The chains are held together by disulfide bridges, and there are also disulfide bridges within the polypeptide chains holding them in shape.
• Antibodies bind to antigens with a protein-based ‘lock-and-key’ mechanism. The binding side is an area of 110 amino acids on both the heavy and light chains, known as the variable region. It is a different shape on each antibody and gives the antibody its specificity. The rest of the antibody molecule is always the same, so it is called the constant region.
• When an antibody binds to an antigen it forms an antigen-antibody complex.
• The hinge region of the antibody provides the molecule with flexibility, allowing it to bind two separate antigens, one at each is its antigen-binding sites.

Question 46

How do antigens defend the body?

Answer 46

1. The antibody of the antigen-antibody complex acts as an opsonin so the complex is easily engulfed and digested by phagocytes.
2. Most pathogens can no longer effectively invade host cells once they are part of an antigen-antibody complex.
3. Antibodies act as agglutinins causing pathogens carrying antigen-antibody complexes to clump together. This helps prevent them spreading through the body and makes it easier for the phagocytes to engulf a number of pathogens at the same time.
4. Antibodies can act as anti-toxins, binding to the toxins produced by pathogens and making them harmless.

Question 47

The specific immune system is based on white blood cells called lymphocytes. What are the main types of T lymphocytes (mature in the thymus gland)?

Answer 47

T helper cells
T killer cells
T memory cells
T regulator cells

Question 48

The specific immune system is based on white blood cells called lymphocytes. What are the main types of B lymphocytes (mature in the bone marrow)?

Answer 48

Plasma cells
B effector cells
B memory cells

Question 49

Role of T helper cells

Answer 49

• These have CD4 receptors on their cell-surface membranes which bind to the surface antigens in APCs.
• They produce interleukins, which are a type of cytokine (cell-signalling molecule). The interleukins made by the T helper cells stimulate the activity of B cells, which increases antibody production, stimulates production of other types of T cells and attracts and stimulates macrophages to ingest pathogens with antigen-antibody complexes.

Question 50

Role of T killer cells

Answer 50

• These destroy the pathogen carrying the antigen.
• They produce a chemical called perforin, which kills the pathogen by making holes in the cell membrane so it is freely permeable.

Question 51

Role of T memory cells

Answer 51

• These live for a long time and are part of the immunological memory.
• If they meet an antigen a second time, they divide rapidly to form a huge number of clones of T killer cells that destroy the pathogen.

Question 52

Role of T regulator cells

Answer 52

• These cells suppress the immune system, acting to control and regulate it.
• They stop the immune response once a pathogen has been eliminated, and make sure the body recognises self antigens and does not set up an autoimmune response.
• Interleukins are important in this control.

Question 53

Role of plasma cells

Answer 53

Produce antibodies to a particular antigen and release them into circulation.
An active plasma cell only lives for a few days but produces around 2000 antibodies per second whilst alive and active.

Question 54

Role of B effector cells

Answer 54

Divide to form plasma cell cones

Question 55

Role of B memory cells

Answer 55

• These live for a very long time and provide the immunological memory.
• They are programmed to remember a specific antigen and enable the body to make a very rapid response when a pathogen carrying that antigen is encountered again.

Question 56

What is cell-mediated immunity?

Answer 56

In cell-mediated immunity, T lymphocytes respond to the cells of an organisms that have been changed in some way, eg. by antigen processing of mutation. The cell-mediated response is particularly important against viruses and early cancers.

Question 57

Describe the process of cell-mediated immunity

Answer 57

1. In the non-specific defence system, macrophages engulf and digest pathogens in phagocytosis. They process the antigens from the surface of the pathogen to form antigen-presenting cells (ACPs).
2. The receptors on some of the T helper cells fit the antigens. These T helper cells become activated and produce interleukins, which stimulate more T cells to divide rapidly by mitosis. They form clones of identical activated T helper cells that all carry the right antigen to bind to a particular pathogen.
3. The cloned T cell may:
   - develop into T memory cells, which give a rapid response if this pathogen invaded the body again
   - produce interleukins that stimulate phagocytosis
   - produce interleukins that stimulate B cells to divide
   - stimulate the development of a clone of T killer cells that are specific for the presented antigen and then destroy infected cells

Question 58

What is humoral immunity?

Answer 58

• in humoral immunity the body responds to antigens found outside the cells and to APCs. The humoral immune system produces antibodies that are soluble in the blood and tissue fluid, and are not attached to cells.
• B lymphocytes have antibodies on their cell-surface membrane (immunoglobulin M or IgM) and there are millions of different types of B lymphocyte, each with different antibodies.
• When a pathogen enters the body it will carry specific antigens, or produce toxins that act as antigens. A B cell with the complementary antibodies will bind to the antigens on the pathogen, or to the free antigens. The B cell engulfs and processes the antigens to become an APC.

Question 59

Describe the process of humoral immunity

Answer 59

1. Activated T helper cells bind to the B cell APC. This is clonal selection - the point at which the B cell with the correct antibody to overcome a particular antigen is selected for cloning.
2. Interleukins produced by the activated T helper cells activate the B cells.
3. The activated B cells divides by mitosis to give clones of plasma cells and B memory cells. This is clonal expansion.
4. Cloned plasma cells produce antibodies that fit the antigens on the surface of the pathogen, bind to the antigens and disable them, or act as opsonins or agglutinins. This is the primary immune response and it can take days to become fully effective against a particular pathogen.
5. Some cloned B cells develop into B memory cells. If the body is infected by the same pathogen again, the B memory cells divide rapidly to form plasma cell clones. These produce the right antibody and wipe out the pathogen very quickly, before it can cause the symptoms of disease. This is the secondary immune response.