cell recognition and immune system

each type of cell has specific molecules on its surface that identify it. these molecules include proteins and enable the immune system to identify:

• pathogens

• cells from other organisms of the same species

• abnormal body cells

• toxins

immune system

organs/systems of the body that provide resistance to pathogens and toxins

lymphatic system

- lymph fluid, nodes (glands), vessels
- the lymphatic system:
→ acts as a one-way drainage system transporting fluid from body tissues into the blood circulation
→ contains white blood cells called lymphocytes, which fight infection
→ gets rid of waste products produced by cells

what are the two common types of SCID (Severe Combined Immunodeficiency)

1. X-linked (inherited on X chromosome, affecting males only)

2. ADA deficiency (low levels of ADA enzyme → less T and B cells)

treatment for SCID (Severe Combined Immunodeficiency)

bone marrow transplant

types of pathogens

viruses, bacteria, fungi, protists, prions

mechanisms of disease

damaging cells produce toxins and disrupt cell function

cell surface receptors

• every cell has specific surface molecules

• they are large proteins with highly specific tertiary structures

• receptors found on your own body cells are recognised as “self” receptors

antigens

• a foreign protein that stimulates an immune response or the production of antibodies

• proteins found on: pathogens, toxins including those produced by pathogens, abnormal body cells such as cancer cells, non-self material e.g. cells from another human

the effect of antigen variability on disease prevention

inhibits to control some infectious diseases

pathogen

an infectious agent that causes disease or illness in a host

what are the two mechanisms of disease that pathogens utilise?

1. releases toxins

2. kills cells

self receptors/proteins

• proteins on your own cells

• have a specific tertiary structure

tissue rejection

- immune system recognises tissue as non-self
- it attempts to destroy the transplant
- to minimise tissue rejection:
→ donor tissues are matched closely with the recipient-proteins that are similar in tertiary structure - best matches come from genetically close relatives
→ immunosuppressant drugs administered to reduce the immune response

antibodies (immunoglobulins)

- a protein specific to an antigen, and is produced by B plasma cells
- Y shaped
- quaternary structure cuz made up of 4 polypeptide chains (2 heavy, 2 light)
- variable and constant regions
- disulfide bonds → very strong → joins the polypeptide chains together
- every mammal is able to make millions of different antibodies, each with a different pair of binding sites specific for an antigen
- antigen binding sites → must have complementary shape to antigens they’re binding to

antibodies: variable region

slightly different in structure compared to constant region → different sequence of amino acids → different tertiary structure

reasons for antigen-antibody complex

1. agglutination of cells - easier for phagocytes to locate

2. markers that stimulate phagocytes to engulf the bacterial cells

3. neutralised toxins

antigen-antibody complex

• antigens and antibodies are able to bind together

• the variable region on the antibody has a specific amino acid sequence

• the tertiary structure of the binding site is complementary to specific antigens

• this forms an antigen-antibody complex

antigen-antibody complexes lead to:

the pathogens being marked for attack by phagocytes or complement proteins

white blood cells

• phagocytes (e.g. neutrophils, monocytes, macrophages, etc.)

• lymphocytes (B & T)

non-specific response

1. physical and chemical barriers

2. phagocytosis

what are the two types of defence mechanisms?

1. non-specific

2. specific

physical barriers

skin

chemical barriers

• hydrochloric acid (found in stomach)

• mucus (found in airways)

• enzymes in your tears

phagocytosis

1. several receptors on phagocytes that recognise chemical products of pathogens or abnormal cells
2. phagocytes move along a concentration gradient
3. phagocyte engulfs pathogen forming phagosome
4. lysosomes fuse with phagosome containing antibodies
5. lysozyme enzymes hydrolyse the pathogen
6. the soluble products are absorbed into the cytoplasm
7. pathogens’ antigens presented on cell membrane (APC)

APC

antigen presenting cell

specific response

1. cell-mediated response → T lymphocytes

2. humoral response → B lymphocytes

main types of T cell

• helper

• cytotoxic

• memory

T cells

• mature in the thymus gland

• cell mediated immunity

• T cells recognise foreign material such as:

  • phagocytic antigen presenting cells

  • body cells invaded by viruses presenting viral antigens

  • transplanted cells

  • cancer cells presenting antigens on their cell surface membrane

cell mediated immunity

immunity involving body cells only

cell-mediated response (T cells)

- complementary helper T cells to antigen on a phagocyte
- attachment activates T cell to divide rapidly by mitosis and form a clone of MANY genetically identical T cells
→ becomes a memory cell that circulates in the blood and tissue fluid in readiness to respond to a future infection by the same pathogen
→ this helper T cell stimulates a specific B cell
→ B cells divide by mitosis
→ stimulates phagocytosis by phagocytes
→ activates cytotoxic T cells to kill infected cells by making holes in their cell-surface membranes

cytotoxic T cells

• kill abnormal cells and body cells infected by pathogens

• produce perforin protein that creates pores in the cell-surface membrane

• the cell is now permeable to all substances → cell dies because water leaves and therefore no metabolic reactions can take place

what is the action of T cells most effective against?

viruses as they replicate inside host cells

B cells

• mature in the bone marrow

• humoral immunity (involves antibodies in the blood/tissue fluid)

• many different B cells, each producing their own specific antibody that responds to and is complementary to a specific antigen

the humoral response

1. helper T cell binds to APC, activated helper T cell stimulates specific B cells to divide by mitosis

2. clones of identical B cells produced - clonal expansion

3. clones only produce the specific antibody for that particular foreign antigen

4. results in plasma and memory cells

5. endocytosis of antigen into B cell, presented on surface

6. T helper cell binds to processed antigen, stimulates B cells to divide by mitosis, clonal selection

7. each clone produces 1 specific antibody - monoclonal antibodies

B-plasma cells

• produce and secrete identical and specific antibodies that are complementary to the antigen (monoclonal antibodies)

• short lived

• primary immune response

B-memory cells

• circulate in the blood and tissue fluid to provide long-term immunity

• do not produce antibodies, but can divide rapidly

• involved in secondary immune response

monoclonal antibody

antibodies with the same tertiary structure, cloned from the same B plasma cell

once antibodies bind to complementary antigens they:

1. are markers and attach to phagocytes

2. cause agglutination

3. neutralise any toxins released by pathogen

secondary response

• memory cells circulate in the blood/tissue fluid, when they encounter the same antigen again, they divide rapidly to produce more memory and plasma cells

• the many memory cells that have been created detect antigens quicker, and are stimulated

• memory cells divide by mitosis to form more plasma and memory cells, even more antibodies

• much stronger and quicker response, and can destroy the pathogen before it can cause any harm

primary immune response

• the first time you are exposed to a new pathogen: phagocytes detect foreign antigens, ingest them, present them, activate T cells, which then activate B cells (plasma and memory)

• after the pathogen has be defeated, plasma cells and antibodies die, they don’t remain in blood

antigen variability

• some viruses have many strains (e.g. influenza)

• antigens produced and presented on their surface are constantly changing

• so when a new strain is encountered, a primary immune response occurs

about monoclonal antibodies

• each antigen will induce a different B cell to divide by mitosis

• each of these clones produce one type of antibody (clonal selection)

• monoclonal antibodies have a number of useful functions

passive immunity

• when we do not encounter the antigen, but get ready made antibodies for it

• e.g. injected, cross the placenta from mother to baby, babies ingest antibodies from breast milk

limitation of passive immunity

no memory cells, so no long-lasting immunity

strength of passive immunity

immediate protection

active immunity

produced by stimulating the production of antibodies by the individuals’ own immune system

• natural active immunity

• artificial active immunity

natural active immunity

become infected, body produced its own antibodies

artificial active immunity

vaccination/immunisation → an immune response is created, but no symptoms occur

strength of active immunity

long-lasting immunity

limitation of active immunity

takes time to develop immunity

vaccination

- the introduction of disease antigens into the body (via injection or orally)
- after first treatment, antibodies and memory cells against the antigen are made (primary response)
- after second treatment, large numbers of B and memory cells are made (secondary immune response)
- these memory cells can react rapidly, if the patient is infected again with that particular pathogen (with the same antigen)

vaccines are made harmless by:

1. killing the pathogen, but leaving the antigens unaffected

2. using bacterial toxins (antigens) to produce less harmful toxoids

3. weakening the pathogen (attenuated), leaving antigens unaffected

4. using genetically engineered eukaryotic cells to produce a microbial protein/antigen

successful vaccines

• must be economically available to immunise most of the vulnerable population

• few side-effects (this could discourage people from getting the vaccine)

• low amount of doses

• ability to produce, store and transport (requires hygienic conditions, refrigerated transport)

• training staff to administer the vaccine properly

• must be possible to vaccinate majority of the population to produce herd immunity

herd immunity

- a large proportion of the population are vaccinated to prevent the spread of a pathogen
- vaccination should be carried out at one time to achieve herd immunity - so for a certain period there are very few individuals with the disease and transmission of the pathogen is less likely

who cannot always be vaccinated?

• babies / very young children

• those who are ill or a have compromised immune system

diseases can be extremely difficult to eradicate (even with vaccines)

• fails to induce immunity for those with defective immune systems

• may develop the disease immediately after having the vaccine (haven’t had enough time to create antibodies and memory cells)

• pathogen may mutate - antigenic variability

• difficult to develop a vaccine for pathogens with multiple strains (e.g. cold virus)

• pathogens conceal themselves from the immune system

• individuals may object to vaccines (religion, ethical or medical reasons)

ethics of vaccines

vaccines save millions of lives, however:

• involve the use of animals

• side effects can cause long term harm

human immunodeficiency virus (HIV)

• can lead to AIDS

• is a retrovirus because it has RNA in it

• affects and invades T helper cells

• you can use antiretrovirals

structure of HIV

• lipid envelope

• attachment proteins

• capsid (protein layer)

• 2 RNA strands and enzymes

• reverse transcriptase enzyme catalyses the production of DNA from RNA

• retrovirus

transmission of HIV

• when the body fluids of a HIV positive individual mix with a HIV negative individual

• sexual intercourse (bodily fluids)

• blood transfusions

• intravenous drug users

• infected mother to baby via childbirth, breast milk or placenta

how to prevent transmission of HIV from mother to baby

• caesarean

• antiretroviral drugs are taken throughout pregnancy

• antiretroviral drugs are given to babies for up to 4 weeks after birth

• babies are bottle-fed with formula milk instead of breastfed

reverse transcription

• to make amino acids viruses will want to go through protein synthesis

• however, since they don’t contain DNA, viruses convert RNA back to DNA using the enzyme reverse transcriptase

• the DNA is then inserted into T cells

HIV life cycle

HIV enters the bloodstream and circulates; virus enters the cell by endocytosis; HIV proteins bind to CD4 proteins found primarily on helper T cells; capsid fuses with the cell-surface membrane, RNA and enzymes enter; HIV reverse transcriptase (occurs outside nucleus): viral RNA → DNA; viral DNA inserted into helper T cell’s DNA, helper T cell undergoes transcription; HIV DNA is made into mRNA using the T cells enzymes; protein synthesis creates a new virus particle (RNA and viral proteins); new HIV particles leave the cell, taking some of the cell-surface membrane with it to form the lipid envelope; (replication of HIV often goes into dormancy, years later it can lead to AIDS)

virion

the complete ineffective form of a virus outside a host cell

how is HIV replicated?

1. attachment proteins attach to receptors on T helper cells

2. nucleic acid/RNA enters cell

3. reverse transcriptase converts RNA to DNA

4. viral protein produced

5. virus particles assembled and released from cell

how is HIV replicated once inside the T cell?

1. RNA converted into DNA using reverse transcriptase

2. DNA inserted into helper T cell DNA

3. DNA transcribed into HIV mRNA

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

what is a vaccine?

a substance that contains antigens and stimulates production of antibodies

how do vaccines protect us against pathogens?

1. antigen binds to surface receptor on a specific T cell

2. T cell stimulates a specific B cell to divide by mitosis/produce clones (plasma and memory cells)

3. B plasma cells release antibodies

4. some B cells become memory cells

5. memory cells produce larger amount of plasma cells/antibodies faster when the antigen is encountered again

testing for HIV

enzyme-linked monoclonal antibodies to show a colour change which indicates the presence of the HIV antigen

why are antibiotics ineffective against HIV?

- antibiotics like penicillin inhibit enzyme required to form the murein cell walls on bacterial cells
- this weakens cell walls so they cannot withstand pressure (to prevent osmotic lysis)
- water enters via osmosis, causing the cell to burst and the bacterium dies
- viruses lack their own metabolic pathways as they use the host cell, so it’s difficult to target a pathway to distrupt
- viruses do not have a murein cell wall to target
- viruses are often found inside host cells, where antibiotics cannot reach them
- viruses also can have antigenic variability

herceptin

monoclonal antibody used to treat breast cancer

what are the advantages of direct monoclonal antibody therapy over radiotherapy and chemotherapy?

• direct treatment of cancer, less side effects

• smaller doses

monoclonal antibodies can be used to treat symptoms in therapies or to test for and diagnose conditions - monoclonal antibodies and therapeutic drugs → direct monoclonal antibody therapy

- specific antigens on the surface of cancer cells
- complementary monoclonal antibodies can be given to a patient, antigen-antibody complexes formed
- growth factors bind to antigen on surface of cancer cells and sends signals to the cancer cell telling it to divide, this leads to uncontrollable division and tumours form
- monoclonal antibodies are made with complementary shape to binding site to block growth factor
- cancer cell can no longer replicate at an uncontrolled rate

indirect monoclonal antibody therapy

• antibodies can be tagged with radioactive or cytotoxic drug

• antigen-antibody complex formed

• once bound, the drug will destroy the cancer cell

advantage of indirect monoclonal antibody therapy

no need for chemotherapy which kills healthy cells as well as cancer cells

medican diagnosis - monoclonal antibodies can be used to rapidly diagnose:

influenza, chlamydia, cancers, etc.

medical diagnosis e.g. prostate cancer

• sufferers have high levels of Prostate Specific Antigen (PSA) in the blood

• monoclonal antibodies can be used to obtain a measure of the level of PSA in a sample of blood

• this can give an early indication of the possibility of prostate cancer

ELISA - Enzyme Linked Immunosorbant Assay

• tests for the presence of proteins (i.e. antigens)

• uses monoclonal antibodies, antigens, enzymes and substrates to test and diagnose patients

• test for pregnancy, HIV, Hepatitis, etc.

ELISA - e.g. HIV medical diagnosis

1. HIV antigen is attached to a plate

2. sample of patients blood added (if they have HIV, their blood will contain antibodies for this antigen)

3. antibodies bind to antigens forming complexes

4. plate is washed to remove any unbound antibodies

5. an enzyme-labelled antibody is added that will bind to the antigen-antibody complex

6. plate is washed again to remove unbound labelled antibodies

7. colourless substrate added

8. enzyme hydrolyses substrate, which changes colour indicating a positive result

antibodies can detect pregnancy

• antibodies are specific to bind with hCG with coloured markers are fixed onto a strip

• the antibody-antigen complex will move along the strip, until trapped by another antibody

• this creates the coloured lines to indicate pregnancy or no pregnancy

• pregnant women produce high levels of the hormone human chorionic gondatropin (hCG) in their urine

why is the top row of immobilised antibodies necessary in a pregnancy test?

prevents a false negative result, and shows that the antibody has moved up the strip / has not bound to hCG hormone

ethics of monoclonal antibodies

1. production of antibodies and cancer cells involves the use of mice that have been induced to produce tumours.
2. while they have been successful in the treatment of a lot of diseases, the use of monoclonal antibodies have been linked with the deaths of MS sufferers.
3. monoclonal antibodies are derived from mice
→ pros: mice are not killed, allows production of medicines, allows quick diagnosis + treatment because mice have quick immune response, mice are cheap to keep
→ cons: harmful to mice, might go against some religions or morals

lymphocyte apoptosis

- in the foetus, lymphocytes constantly collide with other cells
- the foetus is protected from the outside world by mother and placenta
- lymphocytes collide almost exclusively with the body’s self cells
- some lymphocyte have receptors that fit the body’s cells, these lymphocytes die or are suppressed
- the only remaining lymphocytes are those that would fit foreign material
- in adults lymphocytes initially only encounter self-antigens
- any lymphocytes showing an immune response to self-antigens undergo programmed cell death (apoptosis) before they can differentiate into mature lymphocytes

explain why the solution used to dilute the blood had to have the same water potential as the blood

• to prevent too much water entering RBCs via osmosis, causing the cells to burst

• to prevent to much water leaving RBCs via osmosis, causing them to shrivel up and die

ineffective vaccines

• pathogens may have multiple strains (e.g. cold virus)

• pathogens may mutate - antigenic variability

• pathogens conceal themselves from the immune system (capsule)

• may develop the disease immediately after having the vaccine (haven’t had enough time to create antibodies and memory cells)

AIDS

• when HIV replicates, T cell numbers decline

• helper T cells are destroyed leading to: no activation of cytotoxic T cells and B cells, and no antibodies

• memory cells can become infected and destroyed

• the body no longer responds to infections or cancerous cells

• HIV does not directly cause death, but these secondary infections do

The diagram shows the structure of HIV. Name structures A and B.

A - attachment protein

B - capsid

give three types of cell, other than pathogens, that can stimulate an immune response

1. cells from other organisms
2. abnormal cells
3. cells infected by virus

Give one example of using monoclonal antibodies in a medical treatment.

blocks receptors on cells

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

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.

1. bind to antigen
2. antibodies cause agglutination

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

1. phagosome fuses with lysosome
2. virus destroyed by lysozymes
3. antigens from virus are displayed on the cell membrane

what is an antibody?

a protein specific to an antigen produced by B cells

Describe the difference between active and passive immunity.

1. active involves memory cells, passive doesn’t
2. active involves production of antibody by memory cells
3. passive involves antibody introduced into body from outside
4. active long term, because antibody produced in response to antigen
5. passive short term, because antibody given is broken down
6. active can take time to develop, passive fast acting