Immunity, vaccination, Mabs + autoimmune diseases (Chapter 11)

Question 1

What is active immunity?

Answer 1

Immunity gained after an antigen (e.g. pathogen) has entered the body, an immune response has occurred and ABs have been produced by plasma cells

Question 2

What is natural active immunity?

Answer 2

Immunity gained by being infected i.e. when lymphocytes are activated by antigens on the surface of pathogens that have entered the body, therefore memory cells have been produced

Question 3

What is artificial active immunity?

Answer 3

Vaccination - when an immune response is activated artificially either by injecting antigens into the body or taking them by mouth

Question 4

How does the immune response which leads to active or natural active immunity differ?

Answer 4

The immune responses are similar, and the effect of long term immunity is the same

Question 5

What is passive immunity?

Answer 5

Immunity gained without an immune response ∴ B and T cells have not been activated and plasma cells have not produced any ABs (ABs are provided externally)

Question 6

What is artificial passive immunity?

Answer 6

When ABs/antitoxins are injected normally in the case of a disease which can be fatal before the body’s natural primary response can take place

Question 7

What happens if someone is infected with tetanus?

Answer 7

They are given an injection of ABs against the tetanus toxin (antitoxins) which have been collected from blood donors who have recently been vaccinated against tetanus

Question 8

Although antitoxins provide immediate protection, why is the protection only temporary?

Answer 8

The ABs are not produced by the body’s own B cells and are ∴ regarded as foreign and so removed from circulation by phagocytes

Question 9

Why do antitoxins provide artificial passive immunity?

Answer 9

Because the ABs have not entered the body by a natural process but have come from another person who has encountered the antigen

Question 10

What is natural passive immunity?

Answer 10

When ABs pass from mother to child across the placenta or in breast milk

Question 11

Why are infants not entirely unprotected against pathogens, even though their immune system is less effective?

Answer 11

ABs from the mother cross the placenta during pregnancy and remain in the infant for several months e.g. ABs to protect from measles last 4 or more months in the infant’s blood

Question 12

What is an example of natural passive immunity?

Answer 12

Colostrum (thick, yellowish fluid produced by a mother’s breasts for the first 4/5 days of birth) contains an AB called IgA which acts in the gut to prevent growth of bacteria/viruses and also circulates in the blood

Question 13

What is natural immunity?

Answer 13

Immunity gained by being infected (active) or by receiving ABs from the mother across the placenta or in breast milk (passive)

Question 14

What is a vaccine?

Answer 14

A preparation containing antigens which is used to stimulate an immune response artificially

Question 15

What is active immunity?

Answer 15

Immunity gained either by vaccination (active) or by injecting ABs (passive)

Question 16

What might a vaccine contain?

Answer 16

1) a live/dead/attenuated (harmless) organism
2) a harmless form of a toxin (toxoid)
3) a preparation of surface antigens

Question 17

How are some vaccinations made?

Answer 17

By genetic engineering

Question 18

How are vaccinations given?

Answer 18

1) by injection into a vein/muscle

2) taken orally

Question 19

What is vaccination?

Answer 19

Giving a vaccine containing antigens for a disease, either by injection/by mouth (artificial active immunity)

Question 20

Why does vaccination try to mimic a natural infection e.g. by using live microorganisms?

Answer 20

• Immunity derived from a natural infection is often extremely good at providing protection, bc the immune system has met living organisms which persist inside the body for some time, so the immune system has time to develop an effective response
• The microorganisms reproduce (quite slowly) so that the immune system is continually presented with a large dose of antigens

Question 21

What is herd vaccination?

Answer 21

Vaccinating all or most of the people in a population

Question 22

Why are vaccines that do not mimic an infection less effective?

Answer 22

They are made from dead bacteria/viruses that do not replicate in the body

Question 23

What happens in a vaccine is less effective?

Answer 23

Booster injections are needed to stimulate secondary responses that give enhanced protection

Question 24

What are the 4 problems with vaccines?

Answer 24

1) Poor response to vaccine
2) Live virus + herd immunity
3) Antigenic variation
4) Antigenic concealment

Question 25

Why do some people not respond (very well) to vaccines and what is the effect of this?

Answer 25

1) Some people have a defective immune system meaning that they do not develop the necessary B and T cell clones
2) Malnutrition, especially protein-energy malnutrition because they do not have enough protein to make ABs or clones of lymphocytes
- Effect: these people are at a high risk of developing infectious diseases and transmitting them to people with no immunity

Question 26

Why might a live virus vaccination be a problem and why is herd immunity a solution to this problem?

Answer 26

• People vaccinated with a live virus may pass it out in their faeces during the primary response and infect others
• ∴ better to vaccinate a large no. of people at the same time to give herd immunity, or to ensure that all children are vaccinated within a few months of birth
• Herd immunity interrupts transmission in a population, o that those who are susceptible never encounter the infectious agents concerned

Question 27

Why is antigenic variation a problem with vaccination?

Answer 27

When major changes in antigen structure (antigenic shift) occur, memory cells will no longer recognise the virus ∴ the protective immunity given by vaccination against a previous strain is ineffective against the new one

Question 28

Why are there not yet any effective vaccines against diseases caused by protoctists e.g. malaria?

Answer 28

• Protoctists are eukaryotes with many more genes than bacteria and viruses have, ∴ they can have many hundred/thousands of antigens on their cell surface

Question 29

How many life cycle stages does plasmodium pass through while in a human host?

Answer 29

3

Question 30

Why is it difficult to create a vaccine against malaria?

Answer 30

• Each stage of the life cycle has its own specific antigens ∴ effective vaccines would have to contain antigens to all 3 stages
• OR the antigens would have to be specific to the infective stage, which would only work if the immune system could give an effective response in the short period of time (few hours) between the mosquito bite and infection of the liver cells

Question 31

Why is antigenic concealment a problem with vaccination?

Answer 31

• Some pathogens evade attack by the immune system by living inside cells, therefore concealing their antigens from antibodies
• Some of these pathogens then also suppress the immune system as they are inside T cells or macrophages (parasitising them)
• ∴ difficult to develop effective vaccines bc there is such a short period of time for an immune response to occur before the pathogen hides

Question 32

Why is it difficult to develop a vaccination against cholera?

Answer 32

Vibrio cholerae remains in the intestine where it is beyond reach of many ABs

Question 33

What are the difficulties with a vaccine against TB?

Answer 33

1) only derived from the strain that affects cattle (M.bovis)
2) 70-80% effective
3) effectiveness of vaccine without exposure decreases with age
4) caused by two different strains of bacteria with two different antigens
5) the bacteria can live inside cells
6) if someone with latent TB is vaccinated, it doesn’t stop the active form of TB developing later on from the latent form

Question 34

How does vaccination prevent disease?

Answer 34

Memory cells are produced without infection, so that if someone ever gets infected with the real pathogen, the body can produce ABs rapidly from the memory cells, before symptoms even occur (i.e. no primary response, only secondary response)

Question 35

How did ring vaccination occur in the case of smallpox?

Answer 35

When a case of smallpox was reported, everyone in the household, 30 surrounding households and any relatives was vaccinated

Question 36

How did ring vaccination work in the case of smallpox?

Answer 36

It protected everyone who could have come into contact with the disease, reduced chances of transmission and contained the disease

Question 37

How did characteristics of the variola virus help the eradication of smallpox to succeed?

Answer 37

1) it was stable and did not mutate or change its surface antigens ∴ the same vaccine was used everywhere and it was cheap to produce
2) it did not linger in the body after infection and become active later (like TB)
3) it did not infect animals ∴ it was easy to break the transmission cycle

Question 38

How did characteristics of the vaccine help the eradication of smallpox to succeed?

Answer 38

1) the vaccine was live (∴ effective) and made from a harmless strain of a similar virus
2) the vaccine was freeze-dried and could be kept at high temps for as long as 6 months ∴ suitable for the tropics
3) it was easy to administer, largely due to development of stainless steel, reusable, bifurcated needle (two prongs)

Question 39

What are two other reasons that the eradication of smallpox succeeded?

Answer 39

1) infected people were easy to identify
2) many 16-17 year olds become enthusiastic vaccinators and suppliers of information about cases which was especially valuable in remote areas

Question 40

What two social factors make it difficult for vaccination programmes to succeed?

Answer 40

1) unstable political situations e.g. since the late 1970s and 80s in Africa and Latin America
2) difficult to organise public health facilities in developing countries with poor infrastructure, few trained personnel and limited financial resources, especially in periods of civil unrest or war

Question 41

Why has a programme of one-dose vaccination not eliminated measles in any country, despite high coverages of populations?

Answer 41

1) poor response to the vaccine for children who need several boosters to develop full immunity
2) in large cities with high birth rates and shifting populations, it can be hard to give boosters, follow up cases and trace contacts
3) migrants and refugees can form reservoirs of infection, experiencing epidemics within their communities and spreading the disease to surrounding populations
4) measles is highly infectious ∴ need 93-95% herd immunity to prevent transmissions (some only have 75% coverage)
5) the current vaccine only has a 95% success rate, ∴ whole population needs to be vaccinated

Question 42

What are autoimmune diseases and why do they occur?

Answer 42

• Diseases in which the body can mount immune responses against itself, leading to severe symptoms
• They occur bc the immune system attacks one or more self-antigens, usually proteins

Question 43

How do autoimmune diseases arise?

Answer 43

1) during the maturation of T cells in the thymus, many millions of cells are destroyed because they have T cell receptors that are complementary to self-antigens
2) however, some of these T cells evade destruction and can be activated to stimulate an immune response against the body’s own proteins
3) this starts an attack often involving ABs and killer T cells against parts e.g. organs of the body or the whole body

Question 44

What is Myasthenia Gravis (MG)?

Answer 44

An autoimmune disease that targets the neuromuscular junctions between motor neurones and skeletal muscle cells (grave muscular weakness)

Question 45

What happens normally at a neuromuscular junction?

Answer 45

1) motor neurones transmit nerve impulses to muscle cells
2) where the motor neurones terminate, they release AC into the small gaps between neurones and muscle fibres
3) AC binds with receptors on the CSMs of muscle fibres
4) the interaction of AC and its receptor stimulates Na+ channels to open and the influx of Na+ begins a series of events resulting in muscle contraction

Question 46

What happens in people with MG?

Answer 46

1) they have helper T cells that are specific for cell surface receptors for AC
2) under certain conditions, these cells stimulate a clone of B cells to differentiate into plasma cells and secrete ABs that bind to the receptor ∴ blocking transmission of impulses from motor neurones
3) muscle fibres ∴ absorb the receptor-AB complexes and destroy them as they are not being used
4) without the AC receptors, muscle cells and ∴ muscles do not receive any stimulation and so the muscle tissue begins to break down

Question 47

What is AC?

Answer 47

A cell signalling molecule

Question 48

What is the typical symptom of MG?

Answer 48

Muscle weakness that gets worse with activity and improves with rest ∴ normally worst at end of day or after exercise

Question 49

What are to effective treatments for MG and why?

Answer 49

1) a drug that inhibits the enzyme in synapses that breaks down AC, ∴ increasing [AC] in synapses so that its action in stimulating muscle fibres to contract lasts for longer
2) surgical removal of the thymus gland, bc it is the site of maturation of the helper T cells that stimulate B cells to produce ABs to AC receptors

Question 50

Although MG is not an inherited condition, how is it linked to alleles?

Answer 50

People with certain alleles of genes involved in cell recognition are at a higher risk of developing MG than those without these alleles

Question 51

Give 3 examples of other autoimmune diseases

Answer 51

1) multiple sclerosis
2) rheumatoid arthritis
3) type 1 diabetes

Question 52

Why are ABs desirable for use in diagnosis and treatment of diseases?

Answer 52

They have high degrees of specificity

Question 53

What is required to produce ABs

Answer 53

Very large numbers of a particular B cell clone, all secreting monoclonal (identical) antibodies

Question 54

What was the problem with producing ABs on a large scale?

Answer 54

B cells that divide by mitosis do not produce ABs and plasma cells that secrete ABs do not divide

Question 55

What is a hybridoma?

Answer 55

A cell which divides by mitosis and secretes ABs

Question 56

How can Mabs be produced?

Answer 56

1) a small no. of plasma cells producing a particular AB is taken from the spleen of a mouse who was injected with the antigen
2) these plasma cells are then fused with cancer cells, which divide indefinitely, producing a hybridoma cell
3) the cells are then checked and tested that they produce the right AB and then cloned

Question 57

How can Mabs be used to locate the position of blood clots in a person thought to have DVT?

Answer 57

1) hybridoma cells are made to secrete the antifibrin AB (antigen = human fibrin, protein found in blood clots)
2) a radioactive chemical that produces gamma radiation is attached to each AB molecule to make radioactively labelled ABs
3) the labelled ABs are introduced into the patient’s blood
4) as the Mabs are carried around the body in the bloodstream, they bind to any fibrin molecules
5) the radioactivity emitted by these Mabs is used to detect their exact position in the body using a gamma-ray camera, indicating the position of any blood clots

Question 58

What are 4 ways that Mabs are used in diagnosis?

Answer 58

1) to locate blood clots in person thought to have DVT
2) to locate cancer cells, which have proteins on their CSMs that differ from the proteins on normal body cells and can ∴ be detected by ABs
3) to identify the exact strain of virus/bacterium that is causing an infection, speeding up the choice of the most appropriate treatment for the patient
4) in blood typing before transfusion and tissue typing before transplants

Question 59

How many times are Mabs administrated when used in diagnosis?

Answer 59

Once

Question 60

What is the problem when using Mabs as treatment?

Answer 60

• They need to be administered more than once
• Bc the ABs are produced by lab animals e.g. mice, when introduced into humans, they trigger an immune response as they are foreign (non-self) and act as antigens

Question 61

How has the problem of Mabs being non-self been largely overcome by humanising them?

Answer 61

1) altering the genes that code for the heavy and light polypeptide chains of the ABs so that they code for human sequences of amino acids, rather than mouse/rabbit sequences
2) changing the type and position of the sugar groups that are attached to the heavy chains to the arrangement found in human ABs

Question 62

Give 4 examples of Mabs that have have significant success in treatment involving modifying immune responses

Answer 62

1) tratstuzumab
2) ipilimumab
3) infliximab
4) rituximab

Question 63

What is infliximab used for and how does it work?

Answer 63

• Used to treat rheumatoid arthritis

- It binds to a protein secreted by T cells that causes damage to the cartilage in joints and blocks its action

Question 64

How can Mabs be used to treat cancers?

Answer 64

They can bind to cancer cells, marking them out for destruction or activate the immune system to attack cancer cells