3.2.4 Cell recognition and the immune system

Question 1

Define the following: Immunity. Disease, Pathogen (give examples)

Answer 1

Immunity: to be better prepared for a second infection from the same pathogen and can kill it before it can cause any harm, quicker response

Diease: Collection of symptoms

Pathogen: any organism that can produce disease e.g viruses, baceteria, (bacterial) fungi etc

Question 2

How do pathogens cause disease?

Answer 2

Bacteria and Fungi: 1)Damaging cells by releasing digestive enzymes/digesting cells

2)Damaging cells by releasing toxins (less oxygen, more harmful the toxins)

Viruses: Invade host cells and insert their DNA triggering the host cell to make millions of more viruses- stops cell doing its job

Question 3

What is an Antigen?

Answer 3

“Antibody generating molecule”- causes body to make anitobdies to combat it

Anything that the immune system wil recognise as Non-self or foreign.

Antigens are substances (usually proteins) on the surface of cells, viruses, fungi, or bacteria. Nonliving substances such as toxins, chemicals, drugs, and foreign particles (such as a splinter) can also be antigens. The immune system recognizes and destroys, or tries to destroy, substances that contain antigens

Question 4

Non specific response- first line of defense is…

Answer 4

barriers to infection: Any part of the body exposed to the environment:

skin- impermeable, secrete acidic oils, only way in is cuts, have peptides called defensins that prevent bacteria and fungi

Eyes- tears have lysozyme enzyme- digests bacteria cell wall, also washes away pathogens. Enzymes in lacrimal eye-fluid

Digestive system- acidic, destroys pathogens

Lungs- cilia and mucus

G/U Tracts- mucus and acids

All have epithelial cells- line surface of body

Question 5

Non-specific part 2- Process of Phagocytosis- Phagocytes and Macrophages, NK Cells- waht can they do and how

Answer 5

Phagocytes- Neutrophils (most abundant- die after eating bacteria) and
Macrophages- derived from monocyte white blood cells that moved out of blood to occupy tissues. Some are free, some are fixed, attached to fibers of specific organs. Uses cytoplasmic extensions to snare pathogens.
They carry out phagocytosis- (draw diagram)

1)phagocyte attracted to pathogen by chemical pathogen products of the pathogen. It moves towards the (e.g.. bacterium) pathogen along a concentration gradient

2)The phagocyte has several receptors on its
cell-surface membrane that attach to chemicals
on the surface of the pathogen

3) Lysosomes within the phagocyte migrate
towards the phagosome formed by engulfing the bacterium

4) The lysosomes release their lysozymes into
the phagosome, where they hydrolysed the bacterium

5) The hydrolysis products of the bacterium are
absorbed by the phagocytes

6) Removed by exocytosis

NK Cells- unique in that they can kill own body cells if they become cancerous. Can tell as healthy human cells all have protein MHC1 on surface- defective cells stop producing this. NK cell pierces cell with enzyme to trigger apoptosis, cell dies.

Question 6

Non specific- recognising pathogens- Inflammation

Answer 6

Histamine released by specialised mast cells, triggers dilation of blood vessels and permeability of capillary walls.
Increases temp to increase cell’s metabolic rate so it heals faster.
Increased permeabilility causes capillary cells to release protein rich fluids which cause swelling- leaked protein helps clot blood and form scabs.

Phagocytes, macrophages and natural killer cells that fight infection are attracted to the site of infection. (Chemotaxis)

Question 7

Specific Immune Responses: Intro to Lymphocytes

Answer 7

Lymphocytes carry out a targeted (specific) attack on the pathogen:

T-Lymphocytes (T-cells): mature in the Thymus

B-Lymphocytes (B-cells): mature in the Bone marrow

What makes the T and B-cells specific to a pathogen?

Complimentary receptor protein on surface

T-cells respond to antigens presented on the surface of our own cells (antigen presenting cells APCs e.g macrophages - caused by phagocytes exchanging antigen on its surface with bacteria it digests.

B-Cells respond to free antigens found in our blood plasma and tissue fluid.

Use mitosis to make identical daughter cells, clones

Question 8

Specific Response: Cell Mediated Response

Answer 8

l Pathogens invade body cells or are taken in by phagocytes.

2 The phagocyte (e.g macrophage) places antigens from the pathogen on its CSM after engulfing- is a PAPC so has MCH2 bind to antigen protein- all cells in body except red blood cells have MCH1

3 Receptors on a specific helper T cell (TH cell) fit exactly onto these antigens.

4 This attachment activates the helper T cells to divide rapidly by mitosis and form a clone of genetically identical cells.

5 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 (Tc cells)- kill infected BODY cells
d cause inflammation

Question 9

Specific response: Humoral Response

Answer 9

Produces antibodies that are complementary to the antigen. They destroy the pathogen and their toxins. Called Humoral because it is triggered by antigens in the body’s “humour” (body fluids). Allows body to achieve immunity by encountering pathogens randomly or on purpose

1 The surface antigens of an invading pathogen are taken up by a B cell.

2 The B cell processes the antigens by endocytosis and presents them on its surface.

3 Helper T cells (activated in Cell Mediated Response) attach to the processed antigens on the B cell thereby activating the B cell.

4 The B cell is now activated to divide by mitosis to give a clone of plasma (lots of RER- antibody factory) cells.

5 The cloned plasma cells produce and secrete the specific antibody that exactly fits the antigen on the pathogen’s surface.

6 The antibody attaches to antigens on the pathogen and destroys them (see Topic 5.5).

7 Some B cells develop into memory cells. These can respond to future infections by the same pathogen by dividing rapidly and developing into plasma cells that produce antibodies. This is the secondary immune response.

Question 10

T-helper cells role

Answer 10

Are essential to trigger B Cells to mature into plasma cells and Memory B Cells

Activate Cytotoxic T Cells

Activate phagocytes e.g macrophages

Cause inflammation

Question 11

How do antibodies destroy pathogens?

Answer 11

Neutralisation- blocks viral bonding sites

Agglutination of antigen-binding particles e.g microbes- in experiment form precipitate

Precipitation- of soluble antigens

All of above enhance PHAGOCYTOSIS- easier for macrophage to engulf

Complement Fixation (activating complement)- punches hole in foreign cell, leads to CELL LYSIS

Question 12

Why is it possible that we have such a variety of antibodies? Describe structure

Answer 12

Proteins with specific binding sites synthesised by B cells
Proteins occur in almost an infinite number of forms!

Made of 4 polypeptide chains
One pair are long – ‘heavy chain’ One pair are short – ‘light chain’

Has a variable region – antigen binding site (different in different antibodies) forms antibody-antigen complex

Constant region (has receptor binding site) binds to receptors on cells such as B cells

Cloned B Cells will only make antibodies with the same shape variable region – they are genetically identical.

Question 13

Antibody- antigen complex, Agglutination

Answer 13

Antibodies react to an antigen that is presented on a cell by binding to them

Each antibody has 2 identical binding sites

The antibody binding sites are complementary to a specific antigen and form an antigen-antibody complex

This prepares the pathogen for destruction (does not destroy it directly)

Eg. If pathogen is a bacteria Causes agglutination (clumps of bacteria form) 🡪 easier for phagocytes to locate them
Serve as markers to stimulate phagocytes to engulf the cells
Poss bc have two sites- same antigen on two diff pathogens

Question 14

Polyclonal antibodies

Answer 14

Pathogens are likely to have hundreds of different antigens on their surface

What does this result in? Each antigen induces different B cells to multiply and clone – producing different antibodies
These are known as polyclonal antibodies

Question 15

Monoclonal antibodies what are they, uses, how produced

Answer 15

What do you think monoclonal antibodies are?

They are produced by isolating a single type of antibody that is needed and cloning it outside the body

Why would this be useful?

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

Medical diagnosis

Pregnancy testing

Question 16

Production of monoclonal antibodies process- draw a diagram too

Answer 16

It is now possible to produce large quantities of a single antibody outside the body. A procedure was developed by Cesar Milstein and Georges Kohler in 1975.

1) A mouse is exposed to the non-self material against which an antibody is required
2) The B cells in the mouse produce a mixture of antibodies that are extracted from the spleen
3) The extracted antibodies are mixed with cells that divide readily outside the body eg. Cancer cells
4) Detergent is added to the mixture to break down the cell-surface membranes and enable them to fuse together. The fused cells are called hybridoma cells
5) The hybridoma cells are separated and each single cell is cultured to form clones.
6) Each clone is tested to see if it produces the required antibody
7) That clone is grown on a large scale and monoclonal antibodies are extracted from the growth medium. These are called monoclonal antibodies
8) The mouse cells need to be modified to make them like human cells = humanisation

Question 17

What is the purpose of adding detergent to the mixture of B cells and tumour cells?

When the detergent is added to the cells the mixture is gently agitated – why?

Why are cells from cancer tumours used to fuse with the B cells?

Some B cells and tumour cells fuse together. Suggest which other cells might also fuse together?

Why is it necessary to carry out ‘humanisation’ of the monoclonal antibodies?

Answer 17

To break down the cell-surface membranes allowing B cells and tumour cells to fuse

To ensure the B cells and tumour cells repeatedly come into physical contact – essential if they are to fuse

Because B cells are short lived and don’t divide outside the body. Tumour cells are long lived and divide outside the body. Using both leads to long lived B cells that can grow outside the body

B cells with B cells, and tumour cells with tumour cells

Monoclonal antibodies from mouse tissue will be recognised as foreign and will be destroyed by human antibodies if not ‘humanised’

Question 18

Uses of monoclonal antibodies

Answer 18

Targeting Medication

Medical Diagnosis

Pregnancy Testing

Question 19

Targeting Medication- why useful, what it can treat, two types, advantages of them, what they are, examples, draw diagrams!

Answer 19

(to specific cell types by attaching a therapeutic drug to an antibody)

Monoclonal antibodies can be used to target specific substances and specific cells

When might this be useful? Monoclonal antibodies can be used to treat cancer

Direct monoclonal antibody therapy

• MC ABs prod that are spec to ANs on cancer cell
• ABs given to patient + attach to receptors on cancer cells
• Block the chemical signals that stim their uncontr growth e.g Hereceptin in breats cancer

Indirect

• Attach radioactive/ cytotoxic drug to AB
• When the antibody attaches to the cancer cell, it kills it

Question 20

Pregnancy tests- gen explanation, steps, hormone name etc

Answer 20

When a woman is pregnant the placenta produces the hormone human chorionic gonadatrophin (hCG) which is found in the urine

The test strip contains monoclonal antibodies linked to coloured particles

If hCG is present it binds to the antibodies and forms a hCG-antibody-colour complex

This moves along the strip and is then trapped by a different antibody creating a coloured line

1) First MOBILE MC AB, comp to hCG, has coloured dye attached
2) Another AB- comp to hCG-AB-complex- is immobilised, has dye attached, if pregnant, complex attaches and line appears
3) Third IMMOBILISED AB, comp to AB first AB to ensure test isn’t faulty

Question 21

Medical Diagnosis- ELISA test, draw diagram, write steps (abbreviate)

Answer 21

1) Apply the sample to a surface to which all the antigens will bind
2) Wash the surface to remove unattached antigens
3) Add the specific antibody to the antigen we are detecting and leave to bind
4) Wash the surface remove unattached ABs
5) Add a second antibody with an enzyme attached to it- complementary to first one so if first one binds, second one does too (2nd ab binds with the first ab) (an-ab complex)
6) Add the colourless substrate of the enzyme (changes to a coloured product in presence of the enzyme)

How can we quantify the amount of antigen present?
Amount is relevant to intensity of colour
Could use a colorimeter to quantify

Question 22

Ethical use of monoclonal antibodies

Answer 22

The production of monoclonal antibodies involves mice

• Mice used to produce antibodies and tumour cells
• Production of tumour cells involves directly inducing cancer in mice
• There are specific guidelines drawn up on their use however people still have reservations about using them

Monoclonal antibodies have been used to treat many diseases and saved lives however there have still been many deaths associated with their use
-Important patients have full knowledge of their risks and benefits of the drugs (informed consent)

Testing for safety of new drugs presents some dangers
-March 2006, six healthy volunteers took part in the trial of a new monoclonal antibody (TGN1412). Within minutes they suffered multiple organ failure, probably as a result of T cells overproducing chemicals that stimulate an immune response or attacking the body tissues. All the volunteers survived, but it raises issues about the conduct of drug trials.

To eliminate ned for humanisation of AB, transgenic mice can be used. In this case, a human gene is placed in the mice so they can produce human antibodies rather than mouse antibodies. Raises Qs abt ethics of genetic engineering

Question 23

What is an APC?

Answer 23

Any cell that presents a non-self antigen on its surface e.g

Infected body cells will present the viral antigens on their surface

A macrophage which has engulfed and destroyed a pathogen will present the antigens on their surface

Cells of a transported organ will have different shaped antigens on their surface compared to your own cells

Cancer cells will have abnormal shaped self-cell antigens

Question 24

Clonal selection

Answer 24

The immune system contains millions of slightly different T and B cells. Why are they different?

1) The antigen “selects” or determines which B and T cells are triggered to reproduce.
2) This results in 1000s of genetically identical B and T cells (Clones).

Question 25

What is immunity? Immunity vs Resistance, what diff ways can we acquire immunity

Answer 25

Can be born immune but not long-lasting

Immunity = an acquired characteristic of your immune system that can not be inherited - IS can destroy pathogen b4 you display symptoms

Resistance = a genetic characteristic that can be passed on to your offspring.

Question 26

Look at graph
1) Why lag period? 2) What are two diffs in secondary response 3)Why can the body respond much quicker after the second exposure to an antigen? 4)Why can’t the body respond quickly to antigen B?

Answer 26

1) Takes time for phagocytes, usually first neutrophils, to come into contact with pathogen and alert lymphacytes- google
2) Steeper gradient, rate of production of abs quicker, more abs produced, no lag period
3) Memory cells
4) First response

Question 27

Why doesn’t the body develop long term immunity against the flu? (Diff strains of pathogen)Explain drift/shift, give examples, name of term where infectious disease that has jumped from a non-human animal to humans

Answer 27

Antigen proteins change – antigenic variability, so ABs no longer complementary, back to primary response, no longer immune

Antigenic drift – mutation of DNA (frequent small changes)- v quick in viruses + bacteria bcuz reproduce v quickly

Antigenic shift – mixing of DNA between different strains (rare large changes leading to epidemics)- bc v+b can share (swap info) e.g Wuhan Bat Covid +Human Covid in same cell- ZOONOSIS

Question 28

What’s the difference between: 1) passive immunity 2) active immunity
1) natural immunity 2) artificial immunity - give examples for AA,PA,PN,AN

Why is protection in babies temporary?

So, what do we need to inject if we want to achieve artificial active immunity?

Answer 28

Passive- ABs not produced by self- e.g babies get ABs from placenta and breastmilk
Active- ABs produced by sel, pri+sec response.

Natural- always naturally existing e.g babies
Artificial- body is given immunity to a disease by intentional exposure to small quantities of it, modern

AA- Vacinations
PA- Injected w/ABs
PN- Babies
AN- when you get a disease naturally, making ABs for it, recovering

Obtained ABs don’t live long + cant produce effector or mem cells so baby’s immune system won’t remember antigen

Vaccinations to achieve artificial active immunity…

Introduce the antigen to the person’s body without causing the disease.
The body will make memory cells against the antigen

Question 29

Diff types of vaccinations, most to least effective (how is pathogen weakened), pros and cons if possible

Answer 29

Attenuated Pathogen: weakened live pathogen- weakend by radiation, heating high, cooling over again
V effective, strong response
Can become disease, too strong for people with weak immune system, difficult to make

Dead pathogen: whole cell

Subunit Vaccine: mixture of correct antigens
No poss. of causing disease
Needs ALL Ans, weaker response

Toxoid: altered toxin made harmless e.g Tetnis

Question 30

How does the Oxford vaccine work

Answer 30

Is a genetically modified common cold virus that used to infect chimpanzees

Injects viral RNA into cell, coated in lipid, goes through PL bilayer

Cell then starts to produce coronavirus spike protein

Immune system produces ABs and T killer cells activated to destroy infected cells

Memory cells remain so if disease actually encountered, quick response

Question 31

Herd Immunity- definition, steps

Answer 31

“the indirect protection from infection of susceptible members of a population, which is brought about by the presence of immune individuals.”

There is a critical percentage of a population that need vaccination to prevent the spread of disease.

1) Disease will quickly spread through a susceptible population
2) If majority of population are immune than susceptible individuals become protected

(Different diseases require different critical percentages to prevent its spread. )

Question 32

Why vaccination may not eliminate a disease?

Answer 32

• People with defective immune systems- vaccination fails to induce immunity in certain individuals
• Individuals may develop the disease- immediately after vaccination but before their immunity levels are high enough to prevent it. These individuals may harbour the pathogen and reinfect others.
• Antigenic variability- (antigens change, no longer recognised by immune system, vaccine ineffective) e.g influenza virus, changes antigens frequently. Immunity is therefore short-lived and individuals may develop repeated bouts of influenza during their lifetime
• Too many varieties of pathogen- almost impossible to develop a vaccine that is effective against them all. For example, there are over 100 varieties of the common cold virus and new ones are constantly evolving.
• Hiding- Certain pathogens ‘hide’ from the body’s immune system. either by concealing themselves inside cells, or by living in places out of reach, such as within the intestines, for example, the cholera pathogen.
• Individuals may have objections- religious, ethical or medical reasons. For example, unfounded concerns over the measles. mumps and rubella (MMR) triple vaccine has led a number of parents to opt for separate vaccinations for their children, or to avoid vaccination altogether.

Question 33

The ethics of using vaccines raises the following questions…

Answer 33

• The production or existing vaccines, and the developmem of new ones, often involves the use of animals. How acceptable is this?
• Vaccines have side-effects that may sometimes cause long-term harm. How can the risk of side-effects be balanced against the risk of developing a disease that causes even greater harm?
• On whom should vaccines be tested? How should such trials be carried out? To what extent should individuals be asked to accept risk in the interests of the public health?
• ls it acceptable to trial a new vaccine with unknown health risks only in a country where the targeted disease is common, on the basis that the population there has most to gain if it proves successful?
• To be fully effective the majority, and preferably all, of the population should be vaccinated. Is it right, in the interests of everyone’s health, that vaccination should be compulsory? If so, should this be at any time, or just when there is a potential epidemic? Can people opt out? If so, on what grounds: religious belief, medical circumstances, personal belief?
• Should expensive vaccination programmes continue when a disease is almost eradicated, even though this might mean less money for the treatment of other diseases?
• How can any individual health risks from vaccination be balanced against the advantages of controlling a disease for the benefit or the population at large?

Question 34

How do cytotoxic T-cells work? Most effective against…

Answer 34

Bind to antigen combo MHC + releases perforin to puncture holes in CSM- CSM freely permeable to all granzymes which trigger apoptosis- cell dies

Viruses because viruses replicate inside cells. As viruses use living cells in which to replicate, this sacrifice of body cells prevents viruses multiplying and infecting more cells.

Question 35

Virus structure and structure of HIV

Answer 35

RNA or DNA
Protein “coat” called the capsid
Some may have a lipid membrane
They don’t: respire, excrete, eat, grow, move, or are sensitive to their environment.
They need a host cell to reproduce.

HIV- Core- made up of RNA, enzyme reverse transcriptase- both need for viral replication
Capsid- outer protein coat
Lipid envelope (instead of CSM) - Made of host-cell membrane
Protein attachments- how HIV able to attach to host’s helper T-cells

Question 36

HIV Replication

Answer 36

• Following infection HIV enters the bloodstream and circulates around the body.
• A protein on the IIIV readily binds to a protein called CD4. While this protein occurs on a number of different cells, HIV most frequently attaches to helper T cells (see Topic 5.3).
• The protein capsid fuses with the cell-surface membrane. The RNA and enzymes of HIV enter the helper T cell.
• The HIV reverse transcriptase converts virus’ RNA to DNA
• The newly made DNA is moved into the helper T cell’s nucleus where it is inserted into the cell’s DNA.
• The HIV DNA in the nucleus creates m essenger RNA (mRNA), using the cell’s enzymes. This mRNA contains the instructions for making new viral proteins and the RNA how to go into the new HIV.
• The mRNA passes our of the nucleus through a nuclear pore and uses the cell’s protein synthesis mechanisms to make HIV particles.
• The HIV particles break away from the helper T cell with a piece of its cell-surface membrane surrounding them which forms their lipid envelope.