Cell recognition and the immune system

What is an antigen?

a foreign protein that stimulates an immune response

Where are antigens found?

As proteins on the surface of cells

Why are antigens important?

Allow us to recognise self from non self and can trigger an immune response

Why can proteins act as specific antigens?

proteins have a specific tertiary structure / shape

What are 5 sources of antigens?

1. Own body cells
2. Pathogens
3. Abnormal body cells
4. Toxins
5. Cells from other individuals in the same species.

How can your immune cells encounter cells from other individuals in the same species?

•Pregnancy
•Some Vaccines
•Organ Transplant
•Blood Transfusion

Stem cell transplant

Describe how an immune response can be triggered? (2)

•Cells with non-self antigens can enter the body

•These immune cells have receptors and recognise these

What does a non-specific response consist of?

physical barriers and phagocytosis

List and describe how physical barriers act as non-specific response. (3)

• skin - protective covering that most pathogens cannot penetrate

• lysosomes in tears - prevents pathogens from entering eyes

• hydrochloric acid in the stomach - low pH so enzymes of most pathogens are denatured and the pathogen killed

What are primary defences against disease?

•Those that stop a disease from entering the body

What are secondary defences against disease?

•Defences that kill pathogens that have entered the body

What is the cellular response?

the t-cells and other immune system cells that they interact with e.g phagocytes form the cellular response

What is the humoral response?

B-cells, clonal selection and the production of monoclonal antibodies

What are pathogens?

microorganisms that cause disease

What are the 2 types of phagocytes?

neutrophils and macrophages

What do macrophages do that neutrophils can't?

Antigen presentation

What is phagocytosis?

the cellular process of engulfing and digesting pathogens

Describe the process of phagocytosis

- Phagocyte recognises foreign antigens on the pathogen and binds to the antigen
- Phagocyte engulfs pathogen, containing it in a phagosome.
- Lysosome fuses with phagosome and releases lysozymes into the phagosome
- These hydrolyse the pathogen
- Phagocyte becomes antigen presenting and stimulates specific immune response

Where is the phagosome in the phagocyte?

In the cytoplasm

What happens to the soluble products from the breakdown of a pathogen in phagocytosis?

are absorbed into the cytoplasm of the phagocyte

What do phagocytes release?

cytokines, which attract more phagocytes to the site of infection

Describe how a phagocyte destroys a pathogen present in the blood. (3)

1. Engulfs pathogen

2. Forming phagosome and fuses with lysosome

3. Enzymes hydrolyse

What are the 2 types of lymphocytes?

B lymphocytes and T lymphocytes

What is an antibody?

A protein specific to an antigen produced by B cells

Describe the structure of antibodies

Glycoproteins consisting of 4 polypeptide chains -two heavy and two light, that are bound by disulphide bridges, and thus have a quaternary structure.

What is the constant region of an antibody?

the part that is the same on all antibodies, it binds to receptors on cells such as B cells

What is the variable region of an antibody?

it is the region that contains the antigen binding site, it is different and specific.

How many binding sites does antigens have?

2 binding sites complimentary in shape to antigens and bind to form antibody-antigen complexes.

How many antigens can one antibody bind to?

2

What are the 4 main functions of antibodies in the human body?

- Act as opsonins - tagging foreign bodies for phagocytosis
- Stick pathogens together (agglutination) - prevents them spreading around the body
- Stick to pathogens - prevents them invading host cells
- (antitoxins) stick to bacterial toxins - prevents them from harming body cells

Where are t lymphocytes produced?

bone marrow

Where do T lymphocytes mature?

thymus gland

What types of cell do T helper cells bind to, to be activated?

antigen presenting phagocytes

T lymphocytes can only recognise antigens which are on the surface of other body cells. What are the 4 situations in which this can happen?

- Infected cell presenting viral antigens
- Cancer cells presenting abnormal antigens
- Transplanted cells with different antigens to host cells
- Phagocytes presenting pathogen's antigens

What are the different types of T lymphocytes?

• T helper cells

• Cytotoxic T cells

• T memory cells

What is the function of T helper cells?

- differentiate into memory T cells
- stimulate B cells to divide by mitosis
- stimulate phagocytosis by phagocytes
- activates cytotoxic T cells

How do T helper cells trigger phagocytes to increase their rate of phagocytosis?

By producing cytokines called interleukins

What is the function of cytotoxic cells?

kills infected cells

How do cytotoxic T cells kill abnormal cells?

Attaches to cell and releases a protein called perforin which destroys the cell by forming holes in the cell membrane.

What is the function of T memory cells?

provide long term immunity - able to rapidly differentiate into cytotoxic T cells if the body is infected with the same pathogen again.

Describe the process of cell mediated immunity

• Phagocyte presents antigens from engulfed pathogen on its membrane.

• Specific helper T cells have receptors complimentary to these antigens

• Attachment activates the T cell to divide by mitosis, forming a clone of genetically identical T cells.

Where are B lymphocytes produced and matured?

bone marrow

Describe the structure of B lymphocytes

Surface membrane attached to antigen receptors

What is endocytosis?

process by which the cell takes in materials that are too large to pass through

By what process do B cells take up antigens (which are bound to an antibody)?

endocytosis

Describe the process of humoral immunity

1. B cell binds to antigen of pathogen and engulfs them in endocytosis
2. B cell presents antigens on it's surface
3. T helper cells bind to these antigens, activating the B cell to divide by mitosis to give a clone of plasma cells (clonal selection and expansion)
4. Cloned plasma cells produce and secrete specific antibodies for the antigens of the pathogen that has entered the body.

What is the function of B lymphocytes?

Creates plasma cells and B memory cells

What is the function of plasma cells?

secrete antibodies

How long do plasma cells survive for?

a few days

What is the function of B memory cells?

Remain in the blood for years and provide long term protection - can rapidly turn into plasma cells and release antibodies

How long do memory cells survive for?

decades

What is the primary immune response?

Production of antibodies and memory cells from new B-cells, after antigen enters body for the first time.

What is the secondary immune response?

Memory T-cells activated and divide into correct T-cells to kill cells presenting the antigen.

How do antibodies lead to the destruction of a pathogen?

Forms antigen-antibody complex resulting in agglutination, enhancing phagocytosis

What causes antigen variability?

1. Random genetic mutation changes DNA base sequence.
2. Results in different sequence of codons on mRNA
3. Different primary structure of antigen = H-bonds, ionic bonds & disulfide bridges form in different places in tertiary structure.
4. Different shape of antigen.

What is a monoclonal antibody?

Antibody produced from a single clone of cells

What are some applications of monoclonal antibodies?

• targeting medication to specific cell types by attaching a therapeutic drug to an antibody

• medical diagnosis

• pregnancy testing (form of medical diagnosis)

How can monoclonal antibodies be used to target medication to cancer cells?

1. Monoclonal antibodies made to be complementary to antigens on cancer cells

2. Anti-cancer drug attached to antibody

3. Antibody binds to cancer cells (forming antigen-antibody complex)

What is the advantage of using monoclonal antibodies to treat cancer?

Fewer side effects - fewer normal body cells killed

How are monoclonal antibodies used in medical diagnosis?

• monoclonal antibody interacts with certain chemical associated with a certain disease

• levels of antibody-protein complex measured

• suggests certain disease if levels are abnormal

How are monoclonal antibodies used in pregnancy tests?

• In pregnancy test, hCG binds to monoclonal antibody which is bound to dye

• another fixed antibody traps the hCG-antibody-dye complex and forms a line

• Any spare antibodies move along and bind to another fixed antibody (control line)

What are some ethical issues associated with the use of monoclonal antibodies?

• Animal testing - cancer in mice

• Although effective treatment for cancer and diabetes, it has caused deaths when used in treatment of Multiple Sclerosis so patients need to be informed of risk and benefits before treatment so they can make informed decisions

• Dangers of clinical trials

Define active immunity

Immune system making its own antibodies.

What are the two types of active immunity?

Natural active immunity- individual becomes infected under normal circumstances.

Artificial active immunity- Basis of vaccination

Define passive immunity

Receiving antibodies from elsewhere - not made by the body.

What are the two types of passive immunity?

natural passive immunity - babies receiving antibodies from mother

artificial passive immunity - receiving antibodies from medical procedures

Why is passive immunity temporary?

because the donor's antibodies are eventually destroyed

What is a vaccination and how does it work?

Vaccination involves introducing small quantities of dead or inactive forms of a pathogen into the body to stimulate the white blood cells to produce antibodies. If the same pathogen re-enters the body the white blood cells respond quickly to produce the correct antibodies, preventing infection.

What is vaccination an example of?

Artificial active immunity

What is herd immunity?

When a majority of a population are vaccinated against a disease. This means that even people who have not been vaccinated are less likely to get it because there are fewer people to catch it from.

What is the limitation of herd immunity?

Only works if a high enough percentage of people have been vaccinated

List 4 ethical issues associated with the use of vaccines

- Animal testing
- Risk of testing on humans
- Can have side effects
- Expensive - less money spent on research and treatments of other diseases
- Compulsory???

What is the success of a vaccination programme dependant on?

- Cost of the vaccine
- Severity of the side effects
- Ease of production, transportation and administration
- Number of people who need to be vaccinated for herd immunity

Why don't vaccines always eliminate a disease?

- vaccines fail to induce immunity in certain individuals
- develop disease after vaccine but before immunity develops
- pathogen may mutate quickly - antigens change (antigen variability)
- many varieties or strains
- some pathogens conceal themselves within cells

What affects the efficiency of vaccines?

Antigen variability

What is the structure of HIV?

• lipid envelope on the outside

• embedded in which are attachment proteins

• inside the envelope is a protein layer (capsid)

• capsid encloses 2x RNA strands and reverse transcriptase

Describe how HIV is replicated. (4)

1. Attachment proteins attach to receptors on helper T cell

2. RNA enters cell

3. Reverse transcriptase converts RNA to DNA

4. Viral proteins produced

5. Virus particles assembled and released from cell

Describe how the human immunodeficiency virus (HIV) is replicated once inside helper T cells (TH cells). (4)

1. RNA converted into DNA using reverse transcriptase;

2. DNA inserted into (helper T cell)

3. DNA transcribed into (HIV m)RNA

4. (HIV mRNA) translated into (new) HIV/viral proteins (for assembly into viral particles)

Explain how HIV affects the production of antibodies when AIDS develops in a person. (3)

1. Less antibodies produced;

2. Because HIV destroys helper T cells

3. So few B cells activated

How does HIV lead to AIDS?

the HIV virus deactivates helper T cells and thus eliminates the source of most of the interleukins and cytokines that boost the immune reaction to stronger action against many diseases

How do antiviral drugs treat HIV?

Inhibit reverse transcriptase

How is HIV an example of a retrovirus?

Replication of HIV involves conversion of RNA into DNA by reverse transcriptase

Why are antibiotics inefficient against viruses?

• Antibiotics can't enter human cells - but viruses exists in its host cell (they are acellular) - difficult to destroy them without damaging normal body cells

• Antibiotics often work by damaging murein cell walls to cause osmotic lysis - viruses have no cell wall

Describe how phagocytosis of a virus leads to presentation of its antigens. (3)

1. Phagosome fuses with lysosome
2. Virus destroyed by lysozymes
3. Antigens from virus are displayed on the cell membrane

What is the ELISA test used for?

uses antibodies to detect the presence and quantity of an antigen/protein in a sample

What does ELISA stand for?

enzyme linked immunosorbent assay

Describe the process of the ELISA test

- Add sample containing antigens to well and wash to remove any antigens that didn't stick
- Add an antibody that is specific to our antigen and wash to remove any excess antibodies
- Add 2nd antibody attached to an enzyme to bind to the 1st antibody and wash again to remove any unbound 2nd antibody
- Add colourless substrate which is converted by enzyme to produce a coloured product.
- The amount of antigen present is relative to the intensity of colour that develops

Describe the role of antibodies in producing a positive result in an ELISA test. (4)

1. First antibody binds to antigen
2. Second antibody with enzyme attached is added
3. Second antibody attaches to antigen
4. Substrate added and colour changes

Describe and explain the role of antibodies in stimulating phagocytosis. Do not include details about the process of phagocytosis. (2)

Antibodies bind to antigen and cause agglutination/attract phagocytes

Describe how presentation of a virus antigen leads to the secretion of an antibody against this virus antigen. (3)

1. Helper T cell binds to the antigen on the phagocyte

2. This helper T cell stimulates a specific B cell

3. B cell divides by mitosis

4. Forms plasma cells that release antibodies

When a vaccine is given to a person, it leads to the production of antibodies against a disease-causing organism. Describe how. (5)

1. Vaccine contains antigen from pathogen

2. Macrophage presents antigen on its surface

3. T cell with complementary receptor protein binds to antigen

4. T cell stimulates B cell

5. With complementary antibody on its surface

6. B cell secretes large amounts of antibody

7. B cell divides to form clone all producing same antibody.

Describe the difference between active and passive immunity. (5)

• Active involves memory cells, passive does not

• Active involves production of antibody by plasma cells

• Passive involves antibody introduced into body from outside source

• Active long term, because antibody produced in response to antigen

• Passive short term, because antibody given is already broken down

• Active takes time to work, passive fast acting.

What is apoptosis?

programmed cell death