3.2.4 - Cell recognition and the immune system Flashcards
Topic 2
Antigen
Any substance/part of an organism/molecule/ protein that is recognised as foreign by the immune system and stimulates an immune response
How are cells identified by the immune system?
- Each type of cell has specific molecules on its surface (cell-surface membrane / cell wall) that identify it
- Often proteins → have a specific tertiary structure (or glycoproteins / glycolipids)
What type of cells and molecules can the immune system identify?
- Pathogens (disease causing microorganisms) eg. viruses, fungi, bacteria
- Cells from other organisms of the same species (eg. organ transplants)
- Abnormal body cells eg. tumour cells or virus-infected cells
- Toxins (poisons) released by some bacteria
When does phagocytosis occur?
When the body’s first line of defence (physical/chemical barriers to entry) fail
2 types of white blood cell
- Phagocyte
- Lymphocyte
Phagocytes…
- Ingest and destroy pathogens by process of phagocytosis before they can cause harm
- Defence against pathogens that manage to enter the body
Describe the process of phagocytosis
1) Phagocyte attracted by chemical products of pathogens / recognises (foreign) antigens on pathogen so,
- Phagocyte moves towards an increasing concentration of the chemical products via chemotaxis
2) Phagocyte engulfs pathogen by surrounding it with its cell-surface membrane
to form a vesicle/phagosome
3) Pathogen contained in vesicle / phagosome
4) Lysosomes within the phagocyte migrate towards the phagosome and fuse with it
5) Lysosomes release their lysozymes (hydrolytic enzymes) into the phagosome and destroy pathogen by hydrolysing its cell wall
6) The hydrolysis products of the pathogen (soluble) are absorbed into the cytoplasm of the phagocyte
Pathogen
(Micro)organism that causes disease / harm to body
What does phagocytosis lead to?
- Phagocytosis leads to presentation of antigens where antigens are displayed on the phagocyte cell-surface
membrane, stimulating the specific immune response (cellular and humoral response)
Phagocytes also act as…
Antigen presenting cells
Immune responses can be…
1) Specific
2) Non-specific
Describe non-specific immune responses
- Non-specific immune responses occur whatever the infection
> Eg: phagocytosis + physical barriers
Describe specific immune responses
- Specific immune responses depend on a type of white blood cell called a lymphocyte
- 2 types of lymphocytes:
1) B lymphocytes (B cells)
2) T lymphocytes (T cells)
> each produce different immune responses
What are lymphocytes produced by?
Stem cells
B lymphocytes (B cells)
- Mature in bone marrow
- associated with humoral immunity
> involves antibodies that are present in body fluids
T lymphocytes (T cells)
- Mature in thymus gland
- associated with cell-mediated immunity
> involves body cells
What do T lymphocytes respond to/recognise
- T lymphocytes recognise (antigens on surface of) antigen presenting cells / an organisms own cells that have been infected by non-self material
How do T lymphocytes recognise an organism’s own cells that have been infected by non-self material
1) Phagocytes that have engulfed and hydrolysed a pathogen present some of that pathogen’s antigens on their own cell-surface membrane
2) Body cells invaded by a virus present some of the viral antigens on their own cell surface membrane
What can B lymphocytes respond to?
- Cells from other individuals of the same species
- Pathogens in the blood
Why can B lymphocytes respond to cells from other individuals of the same species?
- These cells are genetically different and have different antigens on their cell-surface membrane
Antigen-presenting cells
Cells that display foreign antigens on their cell surface membrane
Describe how T lymphocytes respond to an infection
1) Pathogens invade body cells or are engulfed by phagocytosis
2) Invaded body cells present some of the foreign antigens on their cell surface membrane
3) Specific helper T cells with complementary receptors (on cell surface) bind to antigen on
antigen-presenting cell
4) This attachment activates the T cell to divide by mitosis and form a clone of genetically identical cells = clonal expansion
5) The cloned T cells can:
a) stimulate specific B cells to divide and secrete their antibody
b) stimulate cytotoxic T cells to kill infected cells / tumour cells (by producing perforin)
c) stimulate phagocytes to engulf pathogens by phagocytosis
Describe how cytotoxic T cells kill abnormal cells and body cells infected by pathogens
- The produce the protein perforin that makes holes in the cell surface membrane of the cells
- These holes make the cell surface membrane freely permeable to all substances and so the cell dies
Why is the action of cytotoxic T cells (Tc Cells) most effective against viruses?
- Viruses replicate inside body cells and present their viral antigens on these cell surface membranes
- Body cells are sacrificed to prevent virus multiplying/infecting more cells
Describe the response of B lymphocytes to a foreign antigen (the humoral
response)
- Clonal selection:
- Specific B lymphocyte with complementary receptor (antibody on cell surface) binds to antigen
○ This is then stimulated by helper T cells (which releases cytokines)
○ So divides (rapidly) by mitosis to form clones (clonal expansion) - Some differentiate into B plasma cells → secrete large amounts of (monoclonal) antibody
- Some differentiate into B memory cells → remain in blood for secondary immune response
In each clone of B cells produced, cells develop into either..
1) Plasma cells
> secrete antibodies which lead to destruction of antigens
> only survive a few days
> plasma cells are responsible for immediate defence of the body against infection
- primary immune response
2) Memory cells
> responsible for secondary immune response
> live longer
> circulate blood + tissue fluid
How do memory cells respond to an encounter with the same antigen later on?
- They divide rapidly by mitosis and develop into plasma cells + more memory cells
> so antiodies can be secreted quicker and at a geater volume than primary response
> They provide long term immunity against the original infection - responsible for secondary immune response
Secondary immune responses are…
Faster than primary immune responses
Antibodies
- Proteins with specific binding sites that are complementary to, and so bind to specific antigens forming antigen-antibody complexes
- They are secreted by plasma cells/produced by B cells
Structure of antibodies
- Made up of 4 polypeptide chains
> so they are quaternary structure/ globular proteins
> these consist of 2 long chains ‘heavy’ and 2 short chains ‘light’ - Each antibody has 2 specific antigen binding sites
- Antibodies have a constant region tha binds to receptors (eg: on B cells)
Describe the binding sites on antibodies
- The binding site is the variable region of an antibody.
> binding sites are different on different antibodies - Each binding site consists of a sequence of amino acids that form a specific 3D shape that binds to a specific antigen
How do antibodies prepare antigens for destruction?
1) Agglutination
> agglutination of antigens forms clumps of them
> makes it easier for phagocytes to locate and engulf the antigens - as they are less spread out in the body
2) Opsonisation
> serve as markers that stimulate phagocytes to engulf the antigens to which they are attached
3) Neutralisation
> anti-toxins
> neutralise toxins released from pathogens
Explain how antibodies lead to the destruction of antigens
- Specific antibodies bind to complementary antigens on pathogens forming an antigen-antibody complex
○ Specific tertiary structure so binding site / variable region binds to complementary antigen - Each antibody binds to 2 pathogens at a time causing agglutination (clumping) of pathogens
- Antibodies attract phagocytes
- Phagocytes bind to the antibodies and phagocytose many pathogens at once
Monoclonal antibodies
- Antibodies produced from genetically identical / cloned B lymphocytes / plasma cells
- have the same tertiary structure
Explain the differences between the primary & secondary immune response
- Primary - first exposure to antigen
○ Antibodies produced slowly & at a lower concentration
○ Takes time for specific B plasma cells to be
stimulated to produce specific antibodies
○ Memory cells produced - Secondary - second exposure to antigen
○ Antibodies produced faster & at a higher concentration
○ B memory cells rapidly undergo mitosis to
produce many plasma cells which produce
specific antibodies
Vaccine
Injection of antigens from attenuated (dead or weakened) pathogens which triggers an immune respobse
● Stimulating formation of memory cells
Explain how vaccines provide protection to individuals against disease
- Vaccines contain antigens from dead/weakened/attenuated pathogens
- Specific B lymphocyte with complementary receptor binds to antigen
- Specific T helper cell binds to antigen-presenting cell and stimulates B cell
- B lymphocyte divides by mitosis to form clones
> Some differentiate into B plasma cells which release antibodies
> Some differentiate into B memory cells - On secondary exposure to antigen, B memory cells rapidly divide by mitosis to produce B plasma cells
> These release antibodies faster and at a higher concentration - Antibodies destroy pathogens
Explain how vaccines provide protections for populations against disease
● Herd immunity - large proportion of population vaccinated, reducing spread of pathogen
○ Large proportion of population immune so do not become ill from infection
○ Fewer infected people to pass pathogen on / unvaccinated people (eg: those unfit for vaccination) less likely to come in contact
with someone with disease
Describe the differences between active and passive immunity
- In active immunity, there is an Initial exposure to antigen eg.
vaccine or primary infection - Whereas in passive immunity there is no exposure to an antigen (but rather an antibody)
- In active immunity memory cells are involved
- Whereas in passive immunity memory cells are not involved
- In active immunity antibodies are produced and secreted by B plasma cells
- Whereas in passive immunity Antibody introduced from another organism eg: breast milk / across placenta from mother
- Active immunity is slower / takes longer to develop
-Whereas passive immunity is faster acting - Active immunity is Long term immunity as antibody can be produced
in response to a specific antigen again - Whereas passive immunity is Short term immunity as antibody given will break down / hydrolysed (by endo/exo/dipeptidases)
Explain the effect of antigen variability on disease and disease prevention
● Antigens on pathogens change shape / tertiary structure due to gene mutations (creating new strains)
● So organism is no longer immune (from vaccine or prior infection)
○ B memory cell receptors cannot bind to / recognise changed antigen on secondary exposure
○ Specific antibodies not complementary / cannot bind to changed antigen
Describe the structure of a HIV particle (out to in)
- Attachment protein
- Lipid envelope
- Matrix
- Capsid (outer coating of protein)
- Reverse transcriptase
- RNA
Describe the replication of HIV in helper T cells
- HIV attachment proteins attach to receptors on helper T cell
- Lipid envelope fuses with cell-surface membrane, releasing capsid into cell
- Capsid uncoats, releasing RNA and reverse transcriptase into the helper T cell
- Reverse transcriptase converts viral RNA to DNA
- Viral DNA inserted / incorporated into helper T cell DNA (may remain latent)
- Viral protein / capsid / enzymes are produced
a) DNA transcribed into HIV mRNA
b) HIV mRNA translated into new HIV proteins - Virus particles assembled and released from cell (via budding)
Explain how HIV causes the symptoms of acquired immune deficiency
syndrome (AIDS)
● HIV infects and kills helper T cells (host cell) as it multiplies rapidly
○ So T helper cells can’t stimulate cytotoxic T cells, B cells and phagocytes
○ So B plasma cells can’t release as many antibodies for agglutination & destruction of pathogens
● Immune system deteriorates → more susceptible to (opportunistic) infections
● Pathogens reproduce, release toxins and damage cells
Explain why antibiotics are ineffective against viruses
Viruses do not have structures / processes that antibiotics inhibit:
● Viruses do not have metabolic processes (eg. do not make protein) / ribosomes
● Viruses do not have bacterial enzymes / murein cell wall
> Viruses also hide in cells, antibiotics can’t reach
Explain how monoclonal antibodies can be used in medical treatments
- Monoclonal antibody has a specific tertiary structure / binding site / variable region
> Complementary to receptor / protein / antigen found only on a specific cell type (eg. cancer cell)
> Therapeutic drug can be attached to antibody
> Antibody binds to specific cell, forming antigen-antibody complex, delivering drug
> Some monoclonal antibodies are also designed to block antigens / receptors on cells
Explain how monoclonal antibodies can be used in medical diagnosis
● Monoclonal antibody has a specific tertiary structure / binding site / variable region
● Complementary to specific receptor / protein / antigen associated with diagnosis
● Dye / stain / fluorescent marker attached to antibody
● Antibody binds to receptor / protein / antigen, forming antigen-antibody complex
Explain the use of antibodies in the ELISA (enzyme-linked immunosorbent
assay) test to detect antigens
Example method 1 (direct ELISA):
- Attach sample with potential antigens to well
- Add complementary monoclonal antibodies with enzymes attached → bind to antigens if present
- Wash well → remove unbound antibodies (to prevent false positive)
- Add substrate → enzymes create products that cause a colour change (positive result)
Explain the use of antibodies in the ELISA (enzyme-linked immunosorbent
assay) test to detect antigens
Example method 2 (sandwich ELISA):
- Attach specific monoclonal antibodies to well
- Add sample with potential antigens, then wash well
- Add complementary monoclonal antibodies with enzymes attached → bind to antigens if present
- Wash well → remove unbound antibodies (to prevent false positive)
- Add substrate → enzymes create products that cause a colour change (positive result)
Explain the use of antibodies in the ELISA test to detect antibodies
Example method (indirect ELISA):
- Attach specific antigens to well
- Add sample with potential antibodies, wash well
- Add complementary monoclonal antibodies
with enzymes attached → bind to antibodies if
present - Wash well → remove unbound antibodies
- Add substrate → enzymes create products that
cause a colour change (positive result)
Suggest the purpose of a control well in the ELISA test
● Compare to test to show only enzyme causes colour change
● Compare to test to show all unbound antibodies have been washed away
Suggest why failure to thoroughly wash the well can result in a false positive
in the ELISA test
● Antibody with enzyme remains / not washed out
● So substrate converted into colour product
Discuss some general ethical issues associated with the use of vaccines and monoclonal antibodies
● Pre-clinical testing on / use of animals - potential stress / harm / mistreatment
○ But animals not killed & helps produce new drugs to reduce human suffering
● Clinical trials on humans - potential harm / side-effects
● Vaccines - may continue high risk activities and still develop / pass on pathogen
● Use of drug - potentially dangerous side effects
Suggest some points to consider when evaluating methodology relating to
the use of vaccines and monoclonal antibodies
● Was the sample size large enough to be representative?
● Were participants diverse in terms of age, sex, ethnicity and health status?
● Were placebo / control groups used for comparison?
● Was the duration of the study long enough to show long-term effects?
● Was the trial double-blind (neither doctor / patient knew who was given drug or placebo) to reduce bias?
Suggest some points to consider when evaluating evidence and data
relating to the use of vaccines and monoclonal antibodies
● What side effects were observed, and how frequently did they occur?
● Was a statistical test used to see if there was a significant difference between start & final results?
● Was the standard deviation of final results large, showing some people did not benefit?
● Did standard deviations of start & final results overlap, showing there may not be a significant difference?
● What dosage was optimum? Does increasing dose increase effectiveness enough to justify extra cost?
● Was the cost of production & distribution low enough?
Describe the role of macrophages in stimulating B lymphocytes
antigen in membrane presented to lymphocytes/produces cytokines
techniques the scientists may have used when analysing viral DNA to determine that the viruses were closely related.
* The polymerase chain reaction
* Genetic/DNA fingerprinting
* (Gel) electrophoresis
* DNA/genome sequencing;
Changes to the protein coat of the influenza virus cause antigenic variability. Explain how antigenic variability has caused some people to become infected more than once with influenza viruses.
- memory B / T cells do not recognise (new antigens);
antibodies previously produced are not effective - as shape not complementary to new antigen;
An antigen in a vaccine leads to the production of antibodies. Describe the part played by B lymphocytes in this process. (4)
1 macrophages present antigens to B lymphocytes;
2 antigen binds to / is complementary to receptors on B lymphocyte;
3 binds to a specific lymphocyte;
4 lymphocytes become competent / sensitised;
5 (B) lymphocytes divide by mitosis / (B) lymphocytes cloned;
6 plasma cells secrete antibodies;
Hepatitis B vaccine contains a viral antigen produced by genetically modified bacteria. Describe how the isolated gene that codes for a protein in the virus’s coat could be transferred to the bacterial cells. (3)
1 restriction enzyme / endonuclease;
2 to cut plasmid / to form sticky ends in plasmid;
3 (use) ligase(to join) gene to plasmid;
4 culture bacteria with (in medium containing) plasmids
5 to allow uptake of plasmids / transformation;
6 use of cold shock / chemical treatment (to enhance uptake) / heat
shock;
What makes a good antigen
- different shape to body proteins
- on the surface of cell/pathogen
