3.2.4 Cell recognition and the immune system

Antigen definition?

Foreign protein or other molecule that stimulates an immune response, and are specific to a particular cell or virus type.

What are examples of non-specific immunity?

Barriers to entry such as skin, stomach acid, mucus, scabs, and phagocytes which carry out phagocytosis.

What are the two types of specific immune responses?

Cell mediated responses such as T lymphocytes, and humoral responses like B lymphocytes.

What do antigens allow the immune system to do?

Identify pathogens, non-self material like cells from organisms of the same species, toxins including those produced by certain pathogens like the cholera bacterium, and abnormal body cells.

How do antigens allow for self- cell recognition?

Each cell type has specific molecules - antigens - usually proteins that identify it as they have a specific 3D tertiary structure.

What is the disadvantage of cell recognition in terms of organ donation?

In people who have had organ transplants the immune system recognises them as foreign even though they have come from individuals of the same species. To minimise this, tissues are matched as closely as possible to the recipient and immunosuppressant drugs may be used

What are phagocytes?

Cells that ingest and destroy pathogens before they cause harm, this is not specific.

Explain the stages of phagocytosis:

1. Chemicals released by pathogens act as attractants causing the phagocyte to move towards the pathogen.

2. Phagocytes contain receptors on their c.s membrane that recognise and attach to chemicals on the pathogen’s surface.

3. They engulf the pathogen to form a phagosome vesicle

4. Lysosomes move towards the vesicle and fuse with it. Lysozymes are present within the lysosome. They destroy ingested pathogens by hydrolysis.

5. Useful products may be recycled, other products are released when the vesicle fuses with the cell membrane.

What happens in foetal development to prevent lymphocytes attacking their own cells?

In early foetal development all lymphocytes with complimentary self receptors die or are inactivated, so the body is left with lymphocytes that can only respond to non self foreign matter

Why are there only a few lymphocytes of each type?

Because there are many many lymphocytes present that are all different, and upon infection, the one with the specific antibodies is triggered to build up its numbers to destroy it, which explains why there is a lag time between pathogen exposure and body defences controlling it.

How do lymphocytes recognise cells belonging to the body?

• In the fetus, millions of lymphocytes are constantly colliding with other cells. Infection in the fetus is rare as it is protected from the outside world.

• Lymphocytes therefore collide almost always with its own body material.

• Some lymphocytes have receptors that are complimentary to the body’s own cells.

• These lymphocytes die/ are suppressed

• Only ones remain that fit foreign material, so only respond to foreign material.

• In bone marrow, lymphocytes produced in the bone marrow initially only encounter self-antigens.

• Any lymphocytes showing an immune response undergo programmed cell death before they mature, so no clones appear in the blood, leaving only those that respond to non-self antigens.

What is a specific immune response?

Responses that depend on lymphocytes produced in bone marrow, and specific lymphocytes react to specific antigens, and this is slower in action but provide long term immunity.

What are the two types of lymphocytes

• B lymphocytes mature in the bone marrow, and are associated with humoral immunity, which is immunity involving antibodies that are present in body fluids like blood plasma.

• T lymphocytes mature in the thymus gland, are are associated with cell mediated immunity, involving body cells.

Both are produced in bone marrow by stem cells.

How can T lymphocytes distinguish invader cells from normal cells via antigens?

• Phagocytes that have engulfed and hydrolysed a pathogen presents some of its antigens on their own cell-surface membrane, becoming an antigen presenting cell (APC).

• Body cells invaded by a virus present some of the viral antigens on their own cell surface membrane.

• Transplanted cells have different antigens, and cancer cells also display different antigens.

What are antigen presenting cells?

Cells that display foreign antigens on their surface

Explain the stages of cell mediated immunity:

• Phagocyte digests pathogen and displays some of its antigens on its cell surface membrane, becoming an APC.

• Helper T cells detect the antigens, and receptors on them fit exactly onto them because they have a complimentary shape

• This attachment activates the T cell to divide rapidly by mitosis and from a clone of genetically identical T cells.

What are the roles of the cloned T cells in the cellular response?

• Develop into memory cells that enable a rapid response to future infections by the same pathogen

• Stimulate phagocytes to engulf pathogens by phagocytosis

• Stimulate B cells to mature by releasing cytokines

• Develop into cytotoxic T cells

Explain the role of cytotoxic T cells:

Infected body cells also present antigens. Tc cells bind to presented antigen.

Perforin is released, which makes holes in the cell surface membrane making it freely permeable to all substances.

Enzymes introducing controlled cell death are released by Tc cell, causing it to die.

What does humoral immunity involve?

Antibodies - soluble in the blood and tissue fluid

How does clonal selection of B cells work?

B cell is triggered when it encounters its matching antigen.

B cell antibody attaches to the complementary antigen, antigen enters the cell by endocytosis and gets presented on its surface.

Helper T cells bind to the processed antigens and stimulate the B cell to divide by mitosis to form clones of identical B cells that all produce the antibody specific to the antigen. These are referred to as monoclonal antibodies.

Allows for the body to produce many antibodies for antigens.

What do cloned B cells develop into?

• Plasma cells secrete antibodies usually into blood plasma, living only a few days but make 2000 antibodies every second. These antibodies lead to antigen destruction, so are responsible for the primary immune response. Plasma cells then form memory cells.

• Memory cells are responsible for secondary immune response, and live for decades. Cells do not produce antibodies, but circulate in blood and tissue fluid. When they encounter the same antigen later they divide rapidly and develop into plasma cells and more memory cells. These produce antibodies needed, and so they provide long term immunity as an increased quantity of antibodies is secreted at a faster rate than the primary response.

Outline the process of the secondary immune response:

Antibodies are produced rapidly and in high concentrations, and each cloned plasma cell makes monoclonal antibodies.

Causes a rapid destruction of the invading antigens resulting in the infected person not feeling any symptoms, and life long immunity develops.

Outline the structure of an antibody:

They are made up from 4 polypeptide chains, and the chains of one pair are long (heavy chains) and the other pair’s chains are shorter (light chains). Each antibody has a specific binding site fitting very precisely into a specific antigen to form an antigen-antibody complex. The binding sites are variable regions, and is made of a specific amino acid sequence to form a specific 3D shape. The rest of the antibody is the constant region. The 4 chains are held by disulfide bridges.

Draw an antibody

How do antibodies lead to the destruction of the antigen?

• Constant region serves as a marker that stimulates phagocytes to engulf bacterial cells to which they are attached

• They cause agglutination of bacterial cells through cross linking, forming clumps of cells so it is easier for phagocytes to engulf them.

What are monoclonal antibodies?

Identical antibodies produced from one B lymphocyte, and are specific to one type of antigen with a complimentary shape.

How do mABs work in cancer treatment?

• Ones can be produced that are specific to antigens on cancer cells, they are given to a patient where they attach to the receptors and block chemical signals that stimulate uncontrolled growth.

• They can also be used via attaching a radioactive or cytotoxic drug to the monoclonal antibody - can be used in smaller doses which is cheaper and does not cause as many side effects.

How are mABs used in medical diagnosis?

Used to diagnose flu, hepatitis and chlamydia where they produce a more rapid result. People with prostate cancer often produce more of a protein called prostate specific antigen, so a test can be used to measure the level of PSA in the blood.

How are mABs used in pregnancy tests?

Used to detect the presence of hCG in the urine (pregnancy hormone).

If pregnant, the complementary antibody and hCG bind together and move along the test strip. The free antibodies now cannot move as they are bound to fixed antibodies and cause a colour change.

Free antibodies move to control, and fixed antibodies bind to a different part of free antibody to cause a colour change

If not pregnant no colour change occurs because free antibodies don’t bind to hCG but a line still appears in control strip.

Ethical issues of monoclonal antibodies?

• Involves mice in production and they are given cancer which may be unethical

• There have been unexpected side effects such as volunteers suffering organ failure, which raises the question over their use in drug trials

• There have been deaths from their use in MS treatment

• The costs must be weighed with the benefits, and society must make decisions on their use combined with current knowledge.

What is the ELISA test?

• Stands for enzyme linked immunosorbant assay, and is a technique for determining the quantity of a chemical using monoclonal antibodies and an enzyme.

• Assay is very sensitive allowing for the detection of minute quantities

Outline the method for direct ELISA testing:

• Attach antibody with complementary site to antigen to a well, then rinse to remove unattached antibodies

• Add test sample, and complementary antigens will bind, rinse to remove unattached antigens.

• Add enzyme linked antibody which binds to antigen, and rinse to remove excess (in indirect this will be an antibody that can bind to the first antibody).

• Add colourless substrate - enzyme will act on it to produce a colour change

• Colour shows antigen is present and intensity is relative to amount of antigen.

What is passive immunity?

Produced by the introduction of antibodies into individuals from an outside source, and produces immunity immediately. No memory cells are formed and there is no lasting immunity

What is active immunity and its types?

Produced by stimulating the production of antibodies by the individuals’ own immune system. Direct contact with the pathogen or its antigen is necessary. Has 2 types: natural active immunity results from an individual getting infected with a disease under normal circumstances, body produces its own antibodies. Artificial active immunity is vaccination - induces an immune response in an individual without them having symptoms

How does a vaccine work?

Introduces antigens into the the body, which stimulates an immune response and produces pathogens, but only a small amount of antigen is introduced so the response is small. Memory cells remain in the blood and allow a greater and quicker response to future infection.

Define vaccination:

Injection of antigens from dead microorganism to produce memory cells

What are features of successful vaccination programme?

• Suitable vaccine must be economically available in sufficient quantities to immunise most of the vulnerable population

• Must be very few side effects

• Means of producing storing and transporting must be available - needs high tech equipment, hygienic conditions and cold transport.

• Vaccine needs to be administered properly at the appropriate time - training staff etc.

• Herd immunity must be produced

How does herd immunity work?

Arises when a sufficiently large proportion of the population has been vaccinated to make it difficult for the pathogen to spread. When the majority is vaccinated it is highly improbable that a susceptible individual will come into contact with an infected person. This is beneficial as you can never vaccinate everyone in a population, as it may be dangerous to vaccinate those at risk of side effects. Percentage cover is the amount of individuals who must be immune to prevent an epidemic, and varies from disease to disease.

Why might a vaccination not eliminate a disease?

• Vaccine may not induce immunity in some people

• People may get the disease straight after the vaccine before their immunity levels are high, so could infect others

• Pathogen could mutate frequently so vaccines become ineffective. Called antigenic variability and means the immune system does not produce the antibodies to destroy the pathogen

• May be many varieties of a pathogen - vaccine not effective against them all

• Some hide from the immune system by going into body cells or out of reach places

• Some are antivaxxers and don’t want to be vaccinated

What are the ethical issues of vaccines?

• Production often uses animals

• Some cause long term side effects

• Clinical trials pose risks and ethical issues

• To be effective the vaccine needs to be used on the majority but it may not be acceptable to make everyone have it if they have different religious or ethical beliefs

• Individual health risks from vaccination must be balanced against the advantages of controlling the disease

What does HIV cause?

AIDS (acquired immune deficiency syndrome)

How is HIV transmitted?

Through bodily fluids being exchanged in se+ual intercourse or contaminated needles.

Describe and explain the structure of the HIV particle:

The outside is made of a lipid envelope taken from the previous host T helper cell surface membrane, and has embedded attachment glycoproteins for recognition of host cells. Inside the protein layer is the capsid also made of protein that compartmentalises RNA and some enzymes. One enzyme is reverse transcriptase involved in HIV replication.

What is a retrovirus?

One that has converts RNA into DNA using reverse transcriptase.

Explain the process of HIV replication:

1. Following infection HIV enters the bloodstream and circulates around the body.

2. A protein on HIV readily binds to a protein called CD4, which occurs on many cells, but HIV most frequently binds to helper T cells

3. Protein capsid fuses with the cell surface membrane, and the RNA and enzymes of HIV enter the helper T cell.

4. HIV reverse transcriptase converts the virus’s RNA into DNA

5. Newly made DNA moves into the nucleus where it is inserted into the cell’s DNA

6. HIV DNA in nucleus makes messenger RNA using the cell’s enzymes. This contains the instructions for making new viral proteins and the RNA to go into the new HIV.

7. mRNA passes out of the nucleus through a nuclear pore and uses the cell’s ribosomes to make HIV particles

8. Particles are released from T h cell with a piece of the cell surface membrane forming the lipid envelope.

How does HIV cause AIDS?

The virus attacks helper T cells, and this causes AIDs as it interferes with their functioning. In a person with AIDS they may have between ¼ to 1/6 of the normal numbers of T helper cells.

What is the knock on effect of having low helper T cell numbers in AIDS?

The immune system cannot stimulate B cells to produce antibodies or stimulate cytotoxic T cells that kill infected cells. Memory cells may be infected and destroyed, so the body is unable to produce an adequate immune response and becomes susceptible to other infections and cancers. There are many secondary diseases they may suffer from that ultimately causes death.

Why does HIV not directly cause death?

Because it infects the immune systems and prevents it functioning normally, so those infected by HIV are unable to respond effectively to other pathogens, and this is what causes ill health and death.

What are the signs and symptoms of HIV and AIDs?

HIV has a long latency of 8-10 years where there are no symptoms, but the individual is infectious. The person then may show mild symptoms of the AIDs related complexes like tiredness, fever, weight loss. Then there are more serious symptoms, and there are no defences against opportunistic infections.

How is HIV prevented?

Safe seX education like using condoms and not sharing needles

Why is it hard to produce a vaccine for HIV?

Mutation rates are extremely high in the virus, so there is high genetic variety and antigenic variability, so many different variants are generated.

Why are antibiotics ineffective against viral diseases like AIDs?

Some antibiotics work by preventing bacteria making normal cell walls. Normally, the murein cell wall prevents osmotic lysis because the cell membrane pushes against it as it expands, and the cell wall is inelastic so prevents further entry of water. Antibiotic inhibit enzymes required for synthesis of linkages in cell walls which weakens them and causes the cell to burst. However, viruses lack their own metabolic pathways, so antibiotics are ineffective as there are no pathways to disrupt. They have a protein coat and not a murein cell walls, so antibiotic cannot disrupt this, and antibiotics cannot reach viruses when inside a host cell.