2.4 Cell recognition and the immune system Flashcards
Define antigen:
Protein marker (often on surface of a cell) that is recognised as foreign by our immune system
Antigens are specific so allow the immune system to identify…
Pathogens (disease causing organisms) e.g. viruses, fungi, bacteria
Cells from other organisms of the same species e.g. organ transplant, blood transfusion
Abnormal body cells e.g. cancerous cells / tumours
Toxins released from bacteria
Why are transplant organs often taken from relatives?
Antigens are genetically controlled - close relative have more similar antigens
What are antigens recognised by?
Lymphocytes which bind to and detect the characteristic shape of an exposed protein
What is the process of phagocytosis?
- Phagocyte detects and moves towards chemical released from pathogen
- Phagocytes surrounds and engulfs the pathogen into a vesicle. The vesicle fuses with the phagosome releasing the pathogen (endocytosis)
- Lysosome also fuse with the phagosome and release hydrolytic enzymes (lysozymes) to digest the pathogen
- Hydrolysed products are absorbed by the phagocyte (exocytosis)
What is the most important molecule on the surface of each cell? Why?
Proteins and glycoproteins
Proteins have enormous variety and a high specific tertiary structure. It is the variety of specific 3D structure that distinguishes one cell from another
What are glycoproteins identifying cells called?
Major Histocompatibility (complex MHC) proteins. Eg/ CD4 and CD8
What is the first line of defence?
Non-specific immune response eg/ respiratory system and skin
What are lymphocytes responsible for?
The production of antibodies which target specific antigens present on pathogens
What are T cells?
Mature in the thymus gland
- Cell mediated immunity
- Have receptor proteins that can detect antigens and form antigen-receptors complexes
What is the process of the cell-mediated immune response?
- Pathogens invade body cells or get taken in by phagocytes
- The phagocyte places antigens from the pathogen on its cell-surface membrane
- Receptors on a specific helper T cell fit exactly on its cell-surface membrane
- This attachment activates the T cell to divide rapidly by mitosis (clonal expansion) and form a clone of genetically identical cells
- The cloned T cells:
a) Develop into memory cells that enable a rapid response to future infections by the same pathogen
b) Stimulate phagocytes to engulf pathogens by phagocytosis
c) Stimulate B cells to divide and secrete their antibody
d) Activate cytotoxic T cells
How do cytotoxic T cells kill infected cells?
Kill abnormal cells and body cells that are infected by pathogens, by producing perforin (makes holes in the cell-surface membrane). Therefore cell membrane becomes freely permeable to all substances and dies as a result
What are B lymphocytes?
Known as B cells
- Humoral-mediated immunity (immunity using antibodies dissolved in tissue fluid or plasma)
- Display and secrete antibodies that can detect antigens and form antigen-antibody complexes
What is the process of humoral immune response?
- B cells with antibody complementary to antigen bind to it, takes up the antigen and presents it on their surface membrane
- The cells activate the B cell presenting the antigen
- Activated B cells divide by mitosis to form plasma cell clones
- Plasma cells secrete large amount of antibodies
- Antibody attaches to antigen on the pathogen and destroys them
- Some B cells develop into memory cells
What happens during the primary immune response?
- Happens when a new pathogen first invades
- Relatively few initial specific T and B cells
- Relatively few clones produced
- Symptoms of disease visible
- Once primary infection has been detected and responded to the person has become immune
What happens during the secondary immune response?
- Happens when the same pathogen infects a second time
- Memory cells are present and ready to respond to a second infection
- Much faster response to re-infection:
- Memory T cells divide into cytotoxic cells
- Memory B cells divide into plasma cells - Many more T and B cells produced, therefore much stronger response
- Pathogen destroyed before it can cause symptoms
What cells are responsible for the immediate defence of the body against infection?
Plasma cells - secrete antibodies usually into blood plasma. Antibodies then leads to destruction of antigen
What are memory cells?
- Some of the activated B and T helper cells differentiate into memory cells
- Remain in blood for a number of years
- Can have a life span of decades
What are antibodies?
- Quaternary structured protein (immunoglobin)
- Secreted by B lymphocytes e.g. plasma cells and produced in response to a specific antigen
- Binds specifically to antigens (monoclonal) forming an antigen-antibody complex
Describe and explain how the structure of an antibody relates to its function?
Primary structure of protein = sequence of amino acids in a polypeptide chain
- Determines the folds in the secondary structure as E groups interact
- Determines the specific shape of the tertiary structure and position of hydrogen, ionic and disulfide bonds
- Quaternary structure is comprised of 4 polypeptide chains
- Enables the specific shaped variable region (binding site) to form which is a complementary shape to a specific antigen
- Therefore, antigen-antibody complex forms
How do antibodies work to destroy pathogens?
- Binds to two pathogens at a time (at variable region/binding site) forming an antigen-antibody complex
- Enables antibodies to clump together (agglutination) making it easier for the phagocytes to locate them as they are less spread out within the body
- They then serve as markers that stimulate phagocytes to engulf the bacterial cells to which they are attached
What is a vaccination?
- Injection of antigens
- From attenuated (dead or weakened) pathogens
- Stimulates the formation of memory cells
- A vaccine can lead to symptoms because some of the pathogens might be alive / active / viable; therefore, the pathogen could reproduce and release toxins, which can kill cells
What are the uses of vaccines to provide protection for individuals against disease?
- Normal immune response but the important part is that memory cells are produced
- On reinfection / secondary exposure to the same antigen, the secondary response therefore
produces antibodies faster and at a higher concentration - Leading to the destruction of a pathogen/antigen (e.g. agglutination and phagocytosis) before it can cause harm / symptoms = immunity
What is the use of vaccines to provide protection for herd immunity?
- Large proportion but not 100% of population vaccinated against a disease – herd immunity
- Makes it more difficult for the pathogen to spread through the population because…
- More people are immune so fewer people in the population carry the pathogen / are infected
- Fewer susceptible so less likely that a susceptible / non- vaccinated individual will come into contact with an infected person and pass on the disease
Differences between active and passive immunity:
Active immunity
- Initial exposure to antigen e.g. vaccine or primary infection
- Memory cells involved
- Antibody is produced and secreted by (B) plasma cells
- Slow; takes time to develop
- Long term immunity→antibody can be produced in response to a specific antigen again
Passive immunity
- No exposure to antigen
- No memory cells involved
- Antibody introduced into body from another organism e.g. breast milk / across placenta from mother
- Fast acting
- Short term immunity (antibody broken down)
What are the ethical issues associated with the use of vaccines?
- Tested on animals before use on humans → animals have a central nervous system so feel pain (some animal based substances are also used to produce vaccines)
- Tested on humans → volunteers may put themselves at unnecessary risk of contracting the disease because they think they’re fully protected e.g. HIV vaccine so have unprotected sex →vaccine might not work
- Can have side effects
- Expensive – less money spent on research and treatments of other diseases
Antigenic variability is often an explanation for why…
New vaccines against a disease need to be developed more frequently e.g. influenza
Vaccines against a disease may be hard to develop or can’t be developed in the first place e.g. HIV
May experience a disease more than once e.g. common cold
Explain the effect of antigen variability on disease
- Change in antigen shape (due to a genetic mutation)
- Not recognised by B memory cell → no plasma cells / antibodies
- Not immune
- Must re-undergo primary immune response → slower / releases lower concentration of antibodies
- Disease symptoms felt
Explain the effect of antigen variability on disease prevention
- Change in antigen shape (due to a genetic mutation)
- Existing antibodies with a specific shape unable to bind to changed antigens / form antigen-antibody complex
- Immune system i.e. memory cells won’t recognise different antigens (strain)
What makes a successful vaccination programme?
Produce suitable vaccine:
- Effective – make memory cells
- No major side effects → side effects discourage individuals from being vaccinated
- Low cost / economically viable
- Easily produced / transported / stored / administered
- Provides herd immunity
What are monoclonal antibodies?
Antibody produced from a single group of genetically identical B cells specific to one type of antigen
Why are they all identical in structure?
- They have the same primary structure as they are coded for by the same genes
- So have the same secondary and tertiary structures as a result
Why are monoclonal antibodies useful in medicine?
Only bind to specific target molecules / antigens because…
Antibodies have a specific tertiary structure (binding site / variable region) that’s complementary to a specific antigen which can bind/fit to the antibody
How are monoclonal antibodies produced?
- The specific antigen binds to the receptor on the B-cell
- A helper T-cell sends out a chemical signal to activate the B-cell which then releases specific antibodies
- Thus by using the same plasma cells, identical antibodies will be produced
How are monoclonal antibodies used in cancer treatment?
- Each different type of body cell has a different type of surface antigen.
- Only cancer cells have unique antigens called tumour markers
- Monoclonal antibodies can be produced to bind to these tumour markers.
- Anti cancer drugs can be attached to the antibodies
- Thus the drugs will only be released where antibody binding occurs i.e. at cancer cells
- This importantly reduces side effects because the drugs will only accumulate at specific cells
How do pregnancy tests work?
- The placenta in a pregnant woman produces a hormone called hCG (human chorionic gonadotropin). This can be found in the mother’s urine
- Monoclonal antibodies are immobilised in coloured beads on a test strip
- When urine is applied, any hCG will bind to the antibodies to form antigen-antibody complexes
What are the ethical uses of monoclonal antibodies:
- Production of monoclonal antibodies involves the use of mice. Used to produce antibodies and tumour cells. Involves deliberately inducing cancer in mice.
- There have been some deaths associated with their use in treatment of multiple sclerosis
- Testing for the safety of new drugs presents certain dangers
What is the use of antibodies in the ELISA (enzyme linked immunosorbent assay) test?
Can determine if a patient has
a) Antibodies to a certain antigen
b) Antigen to a certain antibody
- Used to diagnose diseases or allergies (e.g. HIV / Lactose intolerance)
Why do you use controls when performing the ELISA test?
- Controls enable a comparison with the test
To show that: - Only the enzyme and nothing else causes colour change
- Washing is effective and all unbound antibody is washed away
Explain why the secondary and detection antibody must be washed away?
- Enzyme attached to antibody reacts with substrate turning the solution a different colour; indicates a positive result
- Not washed out → enzymes will react with the substrate
- Therefore give a positive result even if no antigen present (false positive)
What is the structure of HIV?
Glycoprotein
RNA
Capsid
Matrix
Lipid membrane
Reverse transcriptase
Describe the process of the replication of HIV
- HIV enters the blood and attaches to CD4 proteins on helper T cells
- The protein capsid fuses with cell surface membrane and injects the viral enzymes and RNA into the cell
- HIV reverse transcriptase converts viral RNA into DNA which is then inserted into the helper T cells DNA
- The HIV DNA produces mRNA from the cell enzymes which codes for new HIV
- The mRNA moves out of the nuclear pores and uses the cell’s protein synthesis mechanism to create new HIV viruses
- The new HIV particles leave the cell with a piece of the cell membrane which they use as a lipid envelope.
How does HIV cause AIDS?
- The HIV virus targets helper T cells
- HIV causes AIDS by killing or interfering with the normal function of helper T cells
- So the immune system cannot stimulate B cells, cytotoxic T cells or memory cells
- The body becomes susceptible to other infections and cancers
- HIV doesn’t kill directly, instead those infected are unable to respond effectively to other pathogens, which will eventually lead to death
Why antibiotics are ineffective against viruses?
- Antibiotics can’t enter human cells - but viruses exists in its host cell (they are acellular)
- Viruses don’t have own metabolic reactions eg/ribosomes (use of the host cell’s) which antibiotics target
- If we did use them…. acts as a selection pressure + gene mutation = resistant strain of bacteria via natural selection -> reducing effectiveness of antibiotics
Describe how when a vaccine is given to a person, it leads to the production of antibodies against a disease-causing organism.
- Vaccine contains attenuated antigen from pathogen
- Antigen presenting cell presents its antigen on its cell-surface/T cell with complementary binds to it, takes up the antigen
- T cells stimulate B cells with complementary antibody on its surface
- Activated B cells secrete large amounts of anitbodies
- B cells also divide by mitosis to form plasma cell clones
