Immunology

Question 1

Immune response

When the body is invaded by any pathogen, a series of responses ensure that the pathogen is rapidly identified (as non self), and destroyed before too much damage is caused to the affected organism.

Question 2

Each type of cell has specific molecules on its plasma cell-surface membrane that identify it.
These molecules include proteins and enable the immune system to identify:

· Pathogens
· Cells from other organisms of the same species
· Abnormal body cells
· Toxins

Question 3

Antigen:

An antigen is a molecule (usually a protein) that stimulates an immune response that results in the production of a specific antibody. (Antibody generator)

Question 4

The surface of all own cells (self) and foreign cells or pathogens (non self) are covered in specifically shaped antigens. These antigens help identify each particular type of cell to the host organism.

Therefore, if the antigens are not recognised, the body will treat that cell/pathogen as non-self and initiate an immune response which will lead to the destruction of the cell / pathogen / protein.

Glycoproteins & Glycolipids are both examples of antigens.

Question 5

Phagocytes:

Phagocytes are a groups of white blood cells which can distinguish between cells which do or do not display the self-antigens
Phagocytes will ingest / engulf and destroy any cell that presents a non-self-antigen. This process is called phagocytosis.

This process is non-specific and works the same for any cell / pathogen that displays a (non-self) antigen. However, it would take far too long to destroy all the invading pathogens in the event of an infection, which may result in damage to tissues and organs. As a result, we also have more efficient systems which involve specific immunity.

Answer 5

Phagocytes are also capable of detecting chemical signals produced by pathogens. Early in an infection, this group of white blood cells move to the site of infection, engulf and begin to hydrolyse pathogens

Question 6

Non-Specific Immunity

1 + 2) Pathogen is engulfed by the phagocyte
3) Engulfed pathogen enters the cytoplasm of the phagocyte in a vesicle which is now called a phagosome.
4) Lysosomes fuse with phagosome releasing hydrolytic digestive enzymes (lysozymes)
5) Lysosome enzymes hydrolyse the pathogen
6+7) Waste materials are released from the cell by exocytosis and antigens presented on the cell surface membrane and the phagocyte becomes an antigen presenting cell

Question 7

Specific Immunity

A specific response to a specific antigen on the surface of a cell or pathogen that has been recognised as non-self

Question 8

T Lymphocytes – Cell-mediated immunity (Primary response)

T Cells are responsible for the stage of an immune response called the cellular response.

The cellular response occurs in the following stages:
1) Antigen presenting
2) Clonal selection
3) Role of T cells

Question 9

1) Antigen presenting

T (Helper) cells can respond directly to the (specific) pathogen or its antigens or they respond to antigen presenting cells, that presents the specifically complementary antigen.

The antigen presenting cell presents the pathogen’s antigen on its cell surface membrane.

Answer 9

Antigens can also be presented by infected body cells, not just phagocytes or pathogens. T helper cells can also detect the faulty antigens on abnormal cells (e.g. cancer cells)

Question 10

Cellular Response:

1) Phagocyte engulfs & hydrolyses the pathogen and presents the antigen on the cell surface membrane

2) T Helper cell with specific receptor molecule binds to presented antigen

3) Once T Helper cell binds to the presented antigen it is activated. It then rapidly clones by mitosis.

Question 11

2) Clonal selection

a) A specific TH cell binds to presented antigen via its complementary receptor.

b) TH cell is activated and clones to produce many TH cells with complementary receptors to the antigen.

Answer 11

This method is required as there would not be enough room in the body to have lots of every T cell for every antigen you may encounter. The increased number of cells would increase the total energy demands of the organism.

Question 12

3) Role of T cells

When the specific TH cell has been activated, the cloned daughter cells differentiate into 2 different types of T cell

1) T Helper cell
2) Cytotoxic Killer T cell

Question 13

T Helper Cell

1) Specific TH cell binds to the antigen presenting cell
2) Release cytokines that attract phagocytes to the area of infection.
3) Release cytokines that activate Cytotoxic Killer T cell
4) Activates a specifically complementary B cell
5) Form memory TH cells

Question 14

Cytotoxic Killer T Cell

1) Locates and destroys infected body cells that present the correct antigen
2) Binds to antigen-presenting-cells
3) Releases perforin (protein) which creates holes in the cell surface membrane which destroys the Antigen Presenting Cell

Question 15

B cells - Humoral Response (Primary response)

The humoral response involves the activation of B cells to produce antibodies.

B cells must be stimulated by their complementary TH cell by the release of cytokines.

Question 16

B Cell Activation

1) A specific T Helper cell with the correct receptor binds to presented antigen and then locates AND activates a specifically complementary B cell. The specific T Helper releases cytokine chemicals that signal the specific B cell to clone by mitosis (clonal selection)

2) The B cell then differentiates into two types of cell:

a) Plasma cells -
Produce and secrete vast quantities of specific antibodies into the blood plasma
b) Memory (B) cells -
Remain in the body to respond to pathogen rapidly and extensively should there be a future re-infection

Answer 16

The whole process from initially recognising a pathogen as non self, up to producing antibodies is called the Primary response.

Question 17

Antibodies:

Protein made in response to foreign antigen – has binding sites which bind specifically to an antigen. A specific antibody is produced by a specific ‘Plasma cell’

Question 18

Antibodies are complex proteins with a quaternary structure (4°), made up of four polypeptide chains. The overall shape of the antibody is “Y-shaped”

Question 19

Antibody Structure:

-The main part of the antibody is the same in all antibodies this is the constant region;

-The variable regions have a different primary structure and therefore a different tertiary structure (different shapes);

-It is the variable region and therefore binding site that is specific which is different for each antibody;

-Specific antibodies are only complementary to one antigen

-Due to their specific binding sites, antibodies only bind to specific antigens forming a (permanent) antigen-antibody complex.

Question 20

How do antibodies assist in the destruction of pathogens?

1) AGGLUTINATION: Specific antibodies bind to the antigens on pathogen and clump them together.

2) OPSONISATION: marking pathogens so phagocytes recognise and destroy the pathogen more efficiently.

3) LYSIS: Bind to antigens and lead to destruction of the pathogen’s membrane.

4) ANTI-TOXIN & ANTI-VENOM: Bind to toxins or venom (both usually proteins) to prevent these molecules from binding to their complementary target receptors.

5) Prevent pathogen replication

Question 21

Memory cells

As well as producing plasma cells and antibodies, B cells also produce memory cells as part of the humoral response. These memory cells are not involved directly in destroying the invading pathogen.

The role of the memory cell is to remain in the circulation in case of future re-infection by the same pathogen.

Question 22

Memory Cells:

1) If the memory cells encounter the antigen again, they are rapidly activated (by cytokines secreted by specific TH cell) and divide rapidly by mitosis.

2) The genetically identical cloned memory cells differentiate into plasma cells and more memory B cells.

3) The plasma cells produce lots of the specific antibodies for the invading pathogen, in a short period of time.

Question 23

Secondary response:
The activation of memory cells to produce antibodies.

Question 24

The secondary response is both RAPID and EXTENSIVE.

The antigen is normally eliminated before it can cause disease or any symptoms develop

Question 25

Antigenic Variability

Some pathogens have antigens which mutate and change shape (e.g. Flu, HIV).

When this occurs, the pathogen will not be recognised by the memory cells from the previous infection, (no longer complementary to receptors) and the individual will not be able to initiate a secondary response

Question 26

Immunity

There are two main ways immunity can be gained:

1) Passive
2) Active

Question 27

Passive Immunity:

1) No exposure to ANTIGEN
2) Antibodies are received from elsewhere i.e. are not produced by the individual
3) Can be given by mother or an antiserum (injection of antibodies)
4) No production of Memory cells

Question 28

Active Immunity:

Active Antibodies produced in response to exposure to an ANTIGEN
This type of immunity is provided by the memory cells that are produced after a primary immune response to a pathogen

Question 29

Vaccination

Vaccines contain antigens from dead, weakened or attenuated pathogens.

The pathogen is engulfed by a phagocyte and displayed on an antigen-presenting cell.

A specific T helper cell binds to the antigen on the antigen presenting cell.

The specific T helper cell stimulates a specific B cell (by releasing cytokines).

B cell divides by mitosis to produce plasma cells and memory cells.

Plasma cells produce and release antibodies

Memory cells recognise the antigen on second infection.

Answer 29

Vaccines are not effective against pathogens which show antigenic variability.

Question 30

Vaccination Ethics

Some vaccines are known to cause side effects. However, these are usually mild and cause fewer problems/complications than the disease itself.

However, in some individuals, these side effects may result in complications which have severe (permanent) effects on the individual.

It is the decision of individuals (with medical advice) to decide whether to vaccinate or not.

Question 31

Herd immunity:
If enough individuals in the population are vaccinated (85%), then there is little chance of the disease spreading, therefore even non-vaccinated individuals will be protected.

Question 32

Uses of monoclonal antibodies

· Research
· Pregnancy testing kits and ELISA test
· Diagnosis (showing presence of a particular antigen)
· Targeting drugs
· Killing specific cells
· Isolating specific chemicals.

Question 33

Ethical Issues:

-Development and testing involve use of animals. Does this infringe rights of animals?

• Human testing. Who should be tested, are they being put at possible risk? Is this justified by possible benefit to society?
• Is it available to all or only those who can afford it?
• Balancing risk of side effects against possible benefit
• Should vaccination programmes be compulsory, if society benefits?
• Should we be aiming to eliminate an organism? (loss of genetic variability)

Question 34

When a vaccine is given to a person, it leads to the production of antibodies against a disease-causing organism. Describe how

Answer 34

1. Vaccine contains antigen from pathogen;
2. Phagocyte/macrophage presents antigen on its surface. 3. Specific T helper cell with specific receptor binds to complementary antigen.
3. T helper cell stimulates specific B cell.
4. (With) complementary antibody on its surface.
5. B cell divides by mitosis to form plasma cells.
6. plasma cells secretes large amounts of antibody
7. Formation of Memory B cells with complementary antibodies remain in blood

Question 35

Describe the difference between active and
passive immunity.

Answer 35

1. Active involves memory cells, passive does not;
2. Active involves production of antibody by plasma cells/memory cells;
3. Passive involves antibody introduced into body from outside/named source;
4. Active long term, because antibody produced in response to antigen;
5. Passive short term, because antibody (given) is broken down;
6. Active (can) take time to develop/work, passive fast acting;

Question 36

ELISA Test

1) Sample containing molecule to be detected binds to antibody due to complementary shape

2) Second monoclonal antibodies (with enzyme attached) added and also binds to molecule.
Then washed – so any unbound antibodies with enzyme washed away (removed from test well).

3) Substrate is added and chemical colour change is visible

4) Colour change = Positive Result
Confirms presence of the molecule.

Question 37

Describe the role of
antibodies in producing a
positive result in an ELISA
test.

Answer 37

1. (First) antibody binds/attaches /complementary (in shape) to antigen;
2. (Second) antibody with enzyme attached is added;
3. (Second) antibody attaches to antigen;
4. (Substrate/solution added) and colour changes;

Question 38

HIV Structure

RNA - Genetic material
Capsid - Contains RNA
Envelope - Outer surface
Enzymes - Proteins that carry out steps in HIV life cycle
Glycoproteins (Attachment proteins) - Proteins embedded in envelope

Question 39

HIV replication – Using TH cells

1. Protein on HIV binds with a protein commonly found on TH cells.
2. Capsid fuses with cell-surface membrane and releases Viral RNA and enzymes into the helper TH cell.
3. The HIV’s reverse transcriptase converts viral RNA into cDNA using host nucleotides.
4. Viral cDNA moves into nucleus of T cell and is inserted into host cell genome (DNA). The person is now INFECTED.
5. Transcription of viral DNA into (viral) mRNA which is translated to produce HIV proteins. The infected TH cell starts to manufacture new HIV virions / particles.
6. Particles break away from TH cell with a section of host cell surface membrane which forms their lipid envelope, with TH receptor proteins embedded (to gain access into more TH cells).
7. Over time this leads to a reduction in the number of TH cells or reduction by inactivation of TH cells.

Question 40

AIDS

· By replicating using the body’s TH cells, HIV reduces an individual’s ability to respond to pathogens, as their cell mediated immunity is compromised.

· An uninfected person should have between 800 and 1200 TH cells mm -3 of blood, compared to a person suffering from AIDS can have as few as 200 TH cells mm -3 of blood.

· Screening (ELISA) for HIV antibodies can be used to determine the HIV status of a patient.

· AIDS is not a pathogen, so cannot be detected using antigens or antibodies. AIDS can be screened for by checking the number of TH cells.

· HIV does not kill directly but by compromising the immune system it leaves people vulnerable to secondary diseases that ultimately cause death. B memory cells MUST be activated by specific TH cells, which may have been destroyed.

· Many AIDS sufferers develop infections of the lungs, intestines, brain and eyes, as well as experiencing weight loss and diarrhoea (symptoms).

Question 41

More HIV
Destruction of more TH cells

Less activation of (specific)
TC / B cell
Less able to destroy (other) pathogen / Cancerous / Infected cell

Question 42

How antibiotics work

· Antibiotics work by preventing bacteria making a normal cell wall (murein/peptidoglycan) by targeting 70s ribosomes (not cytoplasmic 80S ribosomes found in Eukaryotes).

· This means that the bacteria are unable to resist osmotic pressure and the cells burst due to an increase in cell volume of water by osmosis.

· Viruses use host cells organelles to carry out metabolic activities so do not have any viral organelles to disrupt.

· Viruses also have a CAPSID (protein coat) rather than a murein cell wall. This does not allow antibiotics to act on viruses as they do for bacteria.

· As viruses spend most of the time within a host cell, they are also out of reach of antibiotics.