Biology - Chapter 5: Cell Recognition and the Immune System

7 stages of cell-mediated immunity

1. Pathogens invade body cells / taken in by phagocytosis
2. Phagocyte places antigens from pathogen on cell-surface membrane
3. Receptors on specific helper T cell (Th cell) fit exactly onto these antigens - complementary
4. Attachment activates T cells to divide rapidly by mitosis and form a clone of genetically identical cells - clonal selection
5. Some cloned cells form more Th cells, secrete cytokines which stimulates macrophages (phagocytes) to carry out phagocytosis and B cells to carry out humoral immunity
6. Some cloned cells form cytotoxic T cells (Tc cells), which have perforin on their cell membrane - this protein creates holes in the CSM of pathogens so substances are able to move into/out of the cell freely, so the pathogen's metabolic reactions stop and the cell dies
7. Some form memory cells so in the event of a future infection by the same pathogen, the pathogen will be killed faster

Why are T cells most effective against viruses?

Viruses replicate inside living cells - fewer living infected cells means fewer viruses multiply and infect more cells

4 stages of humoral immunity

1. Helper T cell binds to antigen, activating specific, complementary B cell
2. It divides by mitosis - clonal selection so ALL secrete same antibody (monoclonal antibodies)
3. Some form plasma cells, which secrete antibodies complementary to the antigens so bind to them, destroying the pathogen (primary immune response)
4. Some form memory cells, which divide into plasma cells upon reinfection and secrete the complementary antibodies faster to destroy the pathogen sooner (secondary immune response)

How are MCA used to treat cancer? (2 ways)

DIRECT MCA THERAPY:
1. MCA are produced - specific to antigen on cancer cells
2. MCA are given to a patient, attach to receptors on cancer cells - BLOCKS THE RECEPTORS
3. This blocks the chemical signals that stimulate uncontrolled growth of cancer cells

ALTERNATIVELY - INDIRECT MCA THERAPY:
1. Radioactive / cytotoxic drug attached to MCA
2. MCA bind to cancer cells - drug kills them

Vaccination

The injection of a weakened or mild form of a pathogen to produce immunity

Why do vaccines only result in a slight response?

Only a small amount of antigen is introduced

How does HIV lead to AIDS (and eventually, death)? (3)

1. Helper T cells are destroyed, so there are none/no longer enough to activate B cells to divide by mitosis and secrete antibodies + stimulate production of cytotoxic T cells + memory cells infected/destroyed
2. Individual becomes susceptible to pathogens/cancers
3. Pathogens reproduce, damage cells, release toxins

Why do monoclonal antibodies only attack one type of cell? (4)

1. The antibodies have a specific tertiary structure
2. The antibodies have a binding site that is complementary to only one antigen
3. This antigen is only found on that type of cell
4. So the antibody can only bind to that type cell to form antigen-antibody complex

Pathogen

A microorganism that causes disease

2 types of defence mechanisms in the body

1. General, immediate defences (e.g. the skin as a barrier to pathogens, phagocytosis)
2. More specific, less rapid but longer lasting defences (cell-mediated responses with T lymphocytes and humoral responses with B lymphocytes)

How do you describe the body's own cells and molecules?

Self

How do you describe foreign cells and molecules?

Non-self

What are antigens made of, where are they found and why?

Proteins on the cell-surface membrane or cell wall - they have enormous variety and a highly specific tertiary structure

6 things protein molecules allow the immune system to identify

1. Pathogens
2. Cells from other organisms / transplants
3. Cells infected by viruses
4. Abnormal / cancer / tumour cells
5. APCs
6. Toxins

Are specific lymphocytes produced in response to an infection?

No - all 10 million types of lymphocytes already exist, but the lymphocyte that is complementary to the pathogen is stimulated to divide to build up its numbers to a level where it can be effective in destroying it

4 steps of how lymphocytes recognise cells that belong to the body - in fetuses

1. Lymphocytes collide with other cells (exclusively with baby's own material as placenta protects it from infection)
2. Some lymphocytes have receptors that are complementary to baby's own cells
3. Those lymphocytes die / are suppressed
4. Remaining lymphocytes are those that fit and only respond to foreign material

3 steps of how lymphocytes recognise cells that belong to the body - in adults

1. Lymphocytes produced in bone marrow only encounter self-antigens
2. Lymphocytes that show an immune response to self-antigens undergo programmed cell death (apoptosis) before they differentiate into mature lymphocytes
3. No clones of those lymphocytes appear in the blood, leaving only those that will respond to foreign material

Antigen

A foreign protein on the surface of a cell (cell membrane) that is recognised as non-self by the immune system and stimulates an immune response.

2 types of white blood cell

1. Phagocytes
2. Lymphocytes

7 steps of phagocytosis

1. Phagocyte is attracted to pathogen by chemical products it secretes (e.g. toxins)
2. Cytoplasm moves around pathogen - phagocyte engulfs it
3. Pathogen is enclosed in phagosome (phagocytic vaucole)
4. Lysosomes fuse with phagosome
5. Lysosomes contain enzymes (lysozymes)
6. Lysozymes hydrolyse the pathogens and its material is absorbed into the phagocyte
7. Phagocyte sticks antigens on surface so antigens from pathogen are displayed on cell membrane

Immunity

The ability of organisms to resist infection by protecting against disease-causing microorganisms or their toxins that invade their bodies.

What produces lymphocytes?

Stem cells in the bone marrow

2 types of lymphocytes:

1. B-lymphocytes: mature in the bone marrow, associated with humoral immunity (antibodies in bodily fluids)
2. T-lymphocytes: mature in the thymus gland, associated with cell-mediated immunity

Why can T-lymphocytes distinguish invader cells from normal cells? (4)

- Phagocytes present some of pathogen's antigens on their cell-surface membrane after phagocytosis
- Body cells invaded by a virus present some of viral antigens on their cell-surface membrane
- Transplanted cells from individuals of the same species have different antigens on the cell-surface membrane
- Cancer cells differ from normal cells, present antigens on cell-surface membrane

Antigen-presenting cells

Cells that display foreign antigens on their cell membrane

Why are there a vast number of different types of T cell?

The receptors on each T cell respond to a single antigen

How do cytotoxic T cells kill infected cells? (3)

1. Produce perforin, a protein that makes holes in the cell-surface membrane
2. Holes mean that phospholipid bilayer can no longer control the movements into/out of the cell - cell becomes freely permeable to all substances
3. Cell's metabolic reactions stop and it dies

What type of B cells are responsible for the primary immune response?

Plasma cells

What type of B cells are responsible for the secondary immune response?

Memory cells

Plasma cells vs Memory cells

Plasma:
- secrete specific antibodies into blood plasma
- survive for a few days
- responsible for primary immune response; immediate defence

Memory:
- do not produce antibodies directly
- have a longer lifespan
- responsible for secondary immune response; long-term immunity

Antibody

Proteins with specific binding sites made by B cells

5 features of antibodies

- Made of 4 polypeptide chains
- Heavy chain: pair of polypeptides, which are longer
- Light chain: pair of polypeptides, which are shorter
- Variable region: binding site - different on different antibodies
- Constant region: rest of the antibody that binds to receptors on cells (e.g. B cells)

What forms when the variable region of an antibody binds onto its complementary antigen?

Antigen-antibody complex

How do antibodies lead to the destruction of the antigen (bacterial cells) (3)

1. On surface of B cells, bind with complementary antigen, form antigen-antibody complex
2. Each antibody binds to two bacterial cells, causing them to agglutinate, forming clumps of bacterial cells - easier for phagocytes to locate and engulf them as they are less spread out in the body
3. Also serve as markers, stimulate phagocytes to engulf bacterial cells that they are attached to

Monoclonal antibodies

Antibodies with the same tertiary structure and are produced from cloned/identical B cells

Advantages and disadvantages of using MCA

Advantages (3):
- MCA are not toxic and are highly specific so only target desired cells and have fewer side effects
- MCA used in indirect MCA therapy are used in smaller doses, so are cheaper and have reduced side effects
- MCA used in medical diagnosis produce much more rapid results

Disadvantages (3):
- MCA produced using mice by having the mice make MCA and tumour cells - involves deliberately inducing cancer in mice, ethical issues with animal rights
- Some die due to multiple sclerosis as a side effect of MCA - patients must give informed consent and be aware of risks associated with MCA
- If drug trials for MCA are not conducted safely, then it can be dangerous

How are MCA used in medical diagnosis?

1. MCA complementary to antigens of pathogen / abnormal cells produced
2. MCA injected / ingested - bind to antigens
3. Levels of MCA used to as warning to high levels of pathogen / abnormal cells

2 types of immunity

1. Passive immunity:
- produced by introduction of antibodies from an outside source
- no direct contact with pathogen/antigen is needed to induce immunity
- fast-acting
- no lasting immunity as antibodies are broken down + no memory cells are formed

2. Active immunity:
- produced by stimulating production of antibodies by plasma cells or memory cells
- direct contact with pathogen/antigen is needed to induce immunity
- takes time to develop
- long-lasting immunity as antibody is produced in response to antigen
- natural: infection with disease
- artificial: vaccination - induces immune response without suffering symptoms of disease

What does a vaccine contain?

One or more types of antigen from the pathogen, which stimulate an immune response

5 features of a successful vaccination programme

1. Suitable vaccine is economically available in sufficient quantities to immunise most of vulnerable population
2. Few side effects, if any (a lot of unpleasant ones would discourage people from being vaccinated)
3. Means of producing, storing and transporting vaccine must be available (technologically advanced equipment, hygienic conditions)
4. Means of administering vaccine properly at appropriate time must be possible (training staff to administer it at different centres throughout population)
5. Must be possible to vaccinate vast majority of vulnerable population to bring about herd immunity

Herd immunity

When a sufficiently large proportion of the population has been vaccinated to make it difficult for a pathogen to spread within that population, so vulnerable people and unvaccinated people are less likely to come in contact with infected people.

Why is herd immunity important?

Never possible to vaccinate everyone in a large population - due to vaccine, pathogens cannot replicate / not carried in vaccinated people, so non-vaccinated people are more likely to contact vaccinated people

Why should vaccination be carried out at one time?

So that for a certain period, there are very few individuals in the population with the disease and the transmission of pathogens is interrupted

6 reasons why a vaccine may not eliminate a disease

1. It fails to induce immunity in certain individuals (e.g. faulty immune system)
2. Individuals develop disease after being vaccinated before immunity levels are high enough to prevent it
3. Pathogens may mutate frequently and antigens change suddenly rather than gradually, so vaccines are no longer effective
4. Pathogens may have many varieties so it is impossible to develop a vaccine that is effective against all of them
5. Certain pathogens 'hide' from immune system (e.g. inside cells)
6. Individuals may object to vaccine for religious, ethical or moral reasons

7 ethical issues of using vaccines

1. Vaccine production and development involves use of animals
2. Vaccines have side effects, may cause long-term harm
3. How to carry out trials and who to test the vaccines on
4. Testing a new vaccine in a country where target disease is common despite unknown health risks as many benefits if most of population is treated
5. Compulsory vaccines so enough are vaccinated for herd immunity
6. Costs - continue carrying out expensive vaccination programmes even if disease is almost eradicated, could use money for a different disease
7. Balancing health risks of a vaccine with advantages of controlling a disease for benefit of whole population

How do vaccines work (5)

1. Vaccine contains antigens / dead or weakened pathogens - this is injected
2. Memory cells are made
3. Upon second exposure to pathogen, memory cells become active and divide into plasma cells, which produce antibodies
4. They produce these rapidly + produce more antibodies than first exposure
5. Antibodies destroy pathogens

How do vaccines lead to the production of antibodies? (5)

1. Vaccine contains antigen
2. Phagocytes presents antigens on its surface
3. Specific helper T cell (with receptor on surface) detects antigens and binds to them
4. This stimulates B cells with receptors complementary to antigen to divide by mitosis, forming clones to give plasma cells
5. These produce large amounts of the same antibody

Why might you give more injections of a vaccine?

More antigen, so more memory cells, so more antibodies produced + will be produced quicker if infected

Describe the structure of HIV (6):

- Genetic material (RNA)
- Reverse transcriptase (enzyme)
- Capsid (protein coat)
- Lipid envelope
- Attachment proteins
- Matrix

AIDS

Acquired Immune Deficiency Syndrome

Why is HIV a retrovirus?

It has the enzyme reverse transcriptase and can make DNA from RNA

In HIV, what does reverse transcriptase do?

Produces DNA from RNA

How does HIV replicate (6)?

1. Attachment protein binds to receptors on helper T cell (CD4)
2. Capsid fuses with CSM, releases the RNA into the cell's cytoplasm
3. Reverse transcriptase converts virus's RNA to a complementary strand of DNA
4. This HIV DNA is inserted into the host's DNA in the nucleus of the cell
5. HIV DNA transcribed into mRNA using host cell's enzymes: makes viral proteins (e.g. capsid and reverse transcriptase) from viral DNA
6. Viral proteins are assembled into new viruses and are released from the cell

Does HIV kill individuals directly?

No - it prevents the immune system from functioning normally, so the infections and cancers the HIV positive person develops leads to their death.

ELISA test

Enzyme Linked Immunosorbent Assay - uses antibodies to detect presence and quantity of a protein in a sample

Why is the ELISA test useful?

It can be used to detect the quantity of a protein in a sample as it is extremely sensitive so can detect very small amounts of a molecule

How does the indirect ELISA test work? (7)

1. Apply sample to a surface (slide) to which all antigens in the sample will attach
2. Wash surface several times to remove any unattached antigens
3. Add antibody complementary to antigen we are trying to detect and leave two to bind together
4. Wash surface to remove excess antibody
5. Add second antibody complementary to first antibody - has enzyme attached to it
6. Add substrate complementary to enzyme - enzyme acts on substrate, results in colour change as coloured product forms
7. Amount of antigen present is relative to the intensity of colour that develops

What diseases can the ELISA test be used to detect?

HIV, TB, hepatitis

Why are antibiotics ineffective against viruses? (3)

1. Viruses do not have a murein cell wall like bacteria do (have capsid protein instead), so do not have any sites where antibiotics can work
2. Viruses don’t have metabolic processes
3. Viruses don’t have bacterial structures / enzymes

Why should you still continue to test for a disease even if someone has been vaccinated? (3)

- Disease may be caused by different types of pathogen, not just the ones in the vaccine
- Some might've been infected before receiving the vaccine
- In case vaccine doesn't work

How does the direct ELISA test work? (4)

1. It uses a single antibody complementary to the shape of the antigen being tested
2. Antibody has enzyme attached to it
3. Add substrate complementary to enzyme - enzyme acts on substrate, results in colour change as coloured product forms
4. Amount of antigen present is relative to the intensity of colour that develops

Direct vs Indirect ELISA test (3)

1. Direct uses only one type of antibody, while indirect uses 2 antibodies (primary and secondary antibodies)
2. Direct is less time-consuming than indirect
3. Direct is less sensitive than indirect

Antigenic variation

When the antigens on the surface of a pathogen changes

Why are older people more likely to be affected by pathogens?

Their immune systems are less effective

2 things to check in order to diagnose AIDS

AIDS-related symptoms + number of helper T cells

If a mother infected with HIV gives birth, why might the baby test positive for HIV antibodies?

Children receive antibodies from their mothers, so will always test positive

After infection with HIV, why might the number of HIV particles in the blood decrease a year+ after infection?

The virus remains dormant