Cell recognition and the immune system - Chapter 5 Flashcards
What is immunity?
The body’s ability to identify and protect itself against disease
What is the immune system ?
The system in the body responsible for maintaining homeostasis by recognising harmful from non-harmful organsims and produces an appropriate response
What are pathogens ?
Viruses, bacteria or other living things that cause disease/ immune system
Defence mechanisms
What are the two types of defence mechanisms?
Specific + non -specific
What is a non-specific defence mechanism?
Does not distinguish between one type of pathogen and another responds to all pathogens in the same way + quickly
What is a specific defence mechanism ?
It does distinguish between different pathogens long lasting immunity and slow response
What are the 2 forms of non-specific defence mechanisms ?
- Barriers to entry to the bloodstream
- Phagocytosis
What are the barriers to entry task (body) ?
- skin : many dead cells, protective layer for the majority of the body surfaces
- saliva : antibacterial enzymes
- tears : antibacterial enzyme: lysozyme. tear ducts : flushes out things in enzymes
- mucus : linings traps dirt + microbes , nasal hair …
- stomach acid : low pH kills harmful microbes. Contains hydrochloric acid, helps to kill any pathogens in food/water
When you get a cut, how does the body respond ?
By clotting the blood to prevent/ reduce the entry of pathogens
What does blood clotting involve (and the definition )?
Involves platelets found in the bloodstream.
Platelets: tiny, short-lived fragments of cells, with no nucleus, formed in the bone marrow + released in the blood
What does tissue damage result in ?
Inflammation
When tissue is damaged, what type of cells are activated , and what do they release ?
Mast cells are activated, releasing the chemicals histamine + cytokines
What does histamine do?
~> Causes capillaries to dilute
~> this increases blood supply (to infected area)
~> causes area to feel hot + red
The increased temperature reduces the ability of pathogens to reproduce.
Histamine also makes blood vessel walls more permeable.
~> allows more blood plasma to leave blood + form tissue fluid, causes tissues to swell
What do cytokines do ?
Attract phagocytes to the damaged tissue .
~> Phagocytes invade tissue
~> Phagocytosis
What is the flow chart of response?
Tissue damage ~> inflammation ~> phagocyte ~> phagocytosis ~> pathogen destroyed
What are the steps of inflammation?
Damaged cells ~> histone ~> capillaries dilate ~> increased blood supply
~> chemokines ~> Attract phagocytes ~> Phagocytes invade tissue
~> Phagocytosis
What are inflammation side effects
Red, when touch it (your skin), it is hot
Why does your skin turn red when inflamed?
Due to increased blood flow because of phagocytes.
Chemokines attract the phagocyte
What is phagocytosis ?
Is a form of endocytosis in which a phagocyte ( type of white blood cell) engulfs + digests a pathogen
Where are phagocyte produced ?
In the bone marrow
They are distributed around the body in the blood
What are phagocytes responsible for?
Responsible for removing dead cells + invasive microorganisms.
They carry out a non-specific immune system
What are the phagocytosis stages ?
- Phagocyte (neutrophils) detects chemicals released by pathogen and moves towards it (chemotaxis)
- [There are many receptor binding points on the surface of the phagocytes]
The phagocyte attaches to the antigen on the pathogen via these receptors - Phagocyte engulfs pathogen to form a vesicle ( a phagosome)
- Lysosomes move to phagosome and fuses with it (forms phagolysosome and release their contents into it. )
- The lysozyme in the lysosome destroysthe pathogen (by hydrolysis of their cell walls)
- The breakdown products are absorbed and used by the phagocyte
- After killing and digesting the pathogens, the phagocytes (neutrophils) die
- Pus is an accumulation of a sign of dead neutrophils
what is a non - specific response ?
Phagocytosis
What are two specific responses, and what WBC is used ?
WBC used : lymphocyte
- Cell - mediated responses , involving T lymphocytes
- Humoural responses, involving B lymphocytes
What are lymphocytes , and where are they produced ?
Is a type of white cell, produced by stem cells in the bone marrow
Why are T lymphocytes called this? (Where do they mature ?)
They mature in the thymus gland. They are associated with cell -mediated immunity, that is immunity involving body cells
Why are B lymphocytes so called this ? (Where do they mature ?)
They mature in the bone marrow. They are associated with humoural immunity (immunity involving antibodies that are present in body fluids)
What is an antigen ?
Foreign protein on the surface of an organism that stimulates on immune system
When do antigens become a problem, and how can we solve this?
F a problem during blood transports + organ systems
What is a self-antigen ?
A molecule found on the surface of your cells to which you do not respond.
It has a specific shape ; self recognition.
BUT it will cause a response if introduced into another human
What is a non- self antigen ?
A molecule found on cells entering your body that are not yours. E,g, bacteria, viruses or another oerson’s cells. This will produce an immune destined (you don’t need to respond )
What are antibodies ?
Protein made by B lymphocytes in response to the presence of a specific antigen (when non-self material has invaded the body)
Describe and explain the role of antibodies in stimulating phagocytosis
Bind to antigen, antibodies cause agglutination/ attract phagocytes
What do antibodies consist of (chains) , and what are they ?
Consists of 4 polypeptide chains :
A pair of heavy chains (long)
A pair of light chains (short)
What are the chains held together by ?
Disulphide bridges
What is the role of the disulphide bridge in forming the quaternary structure of an antibody ?
Joins two (different) polypeptides
What does the 2 antigen binding sites mean to the antibody ?
That one antibody molecule binds to 2 identical antigen molecules
Explain the antigen- antibody complex
When antigens bind, we call this an antigen-antibody complex.
The tertiary structure of the antigen-binding site is complementary to the structure of the antigen.
Simple terms:
The antigen fits perfectly into the antigen-binding site, meaning that antibodies are highly specific for the antigen they bind to
What is the hinge region, and what does it allow?
Where the heaving chain and light chain bend (in the middle of it).
It is flexible, allowing the distance between the two antigen binding sites to vary
What happens when antibodies are flexible + can bind to multiple antigens to clump together ?
This makes it easier for phagocytes to locate + destroy the pathogens
What is the constant region (in an antibody) ?
Where both antibodies have a region which is the same
Constant region has the same structure for every antibody, no matter which B lymphocyte produced it
What are variable regions ?
Where the ends of the antibody molecules are differeng
What do variable regions form , and what does this mean ?
The antigen - binding sites [ the shape of the variable regions are different for the antibodies produced by different B lymphocytes],
meaning antibodies produced by B lymphocytes will bind to different antigens
What are the 4 main functions in an antibody ?
- act as opsonins, tagging foreign bodies for phagocytosis
(helps phagocytes - make tracking + ingesting pathogens easier) - causes agglutination : antibodies can stick pathogens together (in clumps) preventing them from spreading around the body (makes it easier for the phagocyte to locate them as they are less spread-out within the body )
- by sticking pathogens such as viruses, antibodies prevent them from invading host cells
- Antibodies can stick to bacterial toxins, preventing the toxins from harming body cells
What are monoclonal antibodies ?
Antibodies with the same tertiary structure
What is the experiment that produces monoclonal antibodies ? (Mouse experiment)
- inject a mouse with an antigen, then lymphocytes will produce antibodies against the antigen
- then collect the lymphocytes from the mouse
- so in the next stage, we fuse our lymphocytes with a tumour (cancer) cell
- cell produced : hybridoma -> they produce antibodies + divide by mitosis
- next stage : select a single hybridoma cell producing the antibody that we want
- Allows this hybridoma cell to divide by mitosis, forming a clone of identical hybridoma cells
- antibodies produced are all identical
- then they collected + purified
What is a problem with lymphocytes in the monoclonal antibodies experiment ?
They do not divide by mitosis
Why is the benefit of using cancer cells in the monoclonal antibodies experiment ?
Cancer cells are very good at dividing by mitosis
What are monoclonal antibodies uses ?
1) For cancer treatment : targets cancer cells
2) immunoassay: e.g drug + pregnancy tests [calculating the amount of substance in a mixture]
3) medical diagnosis
What are ethical issues of monoclonal antibodies ?
- production : use of mice
- genetic engineering : human genes inserted into mice to produce human antibodies
- some deaths associated with multiple sclerosis treatment
- safety issues of testing new drugs …. informed decisions
Cell mediated response immunity
What are lymphocytes ?
They are white blood cells involved in the specific immune system
What type of lymphocytes are involved in cell - mediated response ?
T lymphocytes (T cells)
Where are lymphocytes made?
Bone marrow
Where do T cells mature ?
In the thymus
What is the cell mediated response (definition) ?
Is the response involving T cells + body cells
Why are cell-mediated response specific ?
Because T cells respond to antigens on the surface of cells
What is an antigen presenting cell (APC) ?
Any cell that presents a non-self antigen on their surface
What are some examples of APC?
- infected body cells will present the viral antigens on their surface
- a macrophage which has engulfed + destroyed a pathogen will present the antigens on their surface
- cells of a transplanted organ will have different shaped antigens on their surface compared to your self-cell antigens
- cancer cells will have abnormal shaped self-cell antigens
What does APC trigger ?
The cell mediated response
What does cell meditated mean ?
The antigen attached to the cell
Why are T cell responses described as ‘cell-mediated’ ?
Because T cells only respond to antigens which are presented on APC, and not antigens attached from cells within body fluids . E.g the blood
What are the steps in the cell mediated response ?
- Once the pathogen has been engulfed + destroyed by a phagocyte, the antigens are positioned on the cell surface, APC (on plasma membrane ? )
- Helper T cells have receptors on their surface which can attach to the antigens on APC
- Once attached, this activated the helper T cells to divide by mitosis to replicate + make large number of cloned
- Cloned helper T cells can differentiate into different cells
What different types of cells can cloned T helper cells differentiate into ?
- some remain as helper T cells + stimulate B cells to divide (cytokines),
- Some stimulate macrophages to perform more phagocytosis (vis cytokines)
- some become memory cells far that shaped antigen
- some become cytotoxic T cells (killer T cells), they kill infected cells
How do Killer T cells destroy and how do they work ?
They destroy abnormal or infected cells
They work by producing a protein, perforin, which embeds in the cell surface membrane and makes a pore (holes) so that any substances can enter or leave the cell
What is a consequence of killer T cells?
The cell becomes freely permeable to all substance + eventually died
What do killer T cells cause ?
Cell death
What are killer T cells most common in?
Most common in viral infections because viruses infect body cells , viruses replicate within body cells, causing dying infected cells
Humoral response to immunity
Where are B lymphocytes made , and where do they mature ?
In the bone marrow
What is the humoral response?
The Humoral response is the response involving B cells + antibodies.
Antibodies are soluble + transport in bodily fluids in blood.
‘Humour’ is and old term for bodily fluids, so Humoral response
What is the Humoral response steps (B-cell activation) ?
[10 million different B cells, which have antibodies on their surface are complementary to 10 million different antigens ]
- At some point, a pathogen will encounter the B cell with the correct antibodies binding to the antigen on the pathogens surface.
Now the B cell attaches to the pathogen and the pathogen is engulfed. - The pathogen is digested and the antigens are presented on the surface of the B cell.
B cell now acts as an APC. - Antigens in the blood collide with their complementary antibody on a B cell. The B cell takes in the antigen by endocytosis + presents it on its cell -surface membrane
- When this B cell collides with a helper T cell receptor, this activates the B cell to go through clonal expansion + differentiation (clonal selection )
- B cells undergo mitosis to make large numbers of cells, they differentiate into plasma cells or memory B cells
What do plasma cells make ?
Antibodies
How are B memory cells associated with plasma cells and antibodies (how do they make them) ?
B memory cells can divide rapidly into plasma cells when re-infected with the same pathogen to make large numbers of antibodies rapidly
How long can memory B cells live for vs plasma cells ?
Memory B cells can live for decades in your body, whereas plasma cells are short lived
What do memory B cells not make, but what do they make instead?
They do not make antibodies, they divide by mitosis + make plasma cells rapidly if they collide with an antigen they have previously encountered
What does memory B cells result in ?
Active immunity : memory B cells make plasma cells, which results in large numbers of antibodies produced so rapidly that the pathogen is destroyed before any symptoms can occur
What happens in primary immune response ( in the primary + secondary immune response graph ) ?
Plasma cells make antibodies, life span is short
What happens in secondary immune response ( in the primary + secondary immune response graph ) ?
Memory cells produce plasma cells, producing antibodies -> faster rate
What is the pathway of specific immune response ?
1) pathogens eaten by phagocyte
2) displays antigen of pathogen on surface
3) helper T cell recognises antigen, stimulating further phagocytosis
4) this activates B cell ( producing memory and plasma cells, plasma cells producing antibodies)
This also activates cytotoxic T cells (killer T cells)
What does infection with a pathogen trigger ?
- B lymphocytes to produce antibodies, they specifically target antigens on the pathogen
- T lymphocytes to become activated :
T cells produce cytokines (which stimulate B cells)
T cells also stimulate killer T cells, and T cells form memory cells
Vaccination
What is active immunity ?
Immune system has created the antibodies due to exposure to the pathogen
(B + T cells were activated, and antibodies were produced + memory cells were formed )
What are the two types of active immunity ?
- Natural active immunity
- Artificial active immunity
What is natural active immunity ?
Being infected with a pathogen [ + creation of the bodies own antibodies + memory cells ]
What is artificial active immunity ?
Vaccination [ is a medical procedure, not a natural process ]
Following the introduction of a weakened version of the pathogen or antibodies via a vaccine ~> herd immunity
What is passive immunity ?
The immune system is not activated. The pathogen doesn’t enter the body [plasma cells and memory cells are not made ]
Antibodies are introduced into the body
What is natural passive immunity ? (2 examples)
In babies:
1. New born babies cannot make antibodies effectively as their immune system is not fully developed. Instead, the baby in the foetus receives antibodies from the mother through the placenta.
Provides protection for the first few months of life.
- In first few days baby is born, the mother’s breast milk is very rich in antibodies : milk + colostrum. The antibodies in colostrum pass from the baby’s digestive system into the baby’s bloodstream. So, because the baby has received antibodies from its mother, the baby has some immunity to pathogens.
What is artificial passive immunity ?
If antibodies are needed immediately, then they can give ready-made antibodies
What is a vaccines?
They are small amounts of weakened/ dead pathogens or antigens, which are introduced in the mouth or by injection.
What do vaccines stimulate ?
The immune system, activating T + B cells
What are vaccines used to prevent ?
Epidemics + pandemics
What is an epidemic ? (And an example )
When an infectious disease spreads rapidly in a population either in a specific location e,g, city or across a whole country.
E.g. New Zealand : measles
What is a pandemic ? (And an example)
When an infectious disease spreads rapidly across several countries, a continent or whole world.
E.g. COVID pandemic
How do vaccines work?
Usually given via the mouth or as an injection into the bloodstream
What do vaccines contain ?
They contain antigens from the pathogens that we want to protect the body against
Other than antigens, what other things to vaccines contain (4 points) ?
- Some vaccines contain a weakened strain of a virus/bacteria, so can affect the patient (but is easily fought off by the immune system )
- Other vaccines contain bacterial cells (which have been killed). [In this case, the pathogen cannot cause an infection, but the antigens can trigger an immune response ]
- Other vaccines only contain antigen molecules. These antigens may be extracted from the pathogen or manufactured using genetic engineering
- Some vaccines provide protection against a bacterial toxin.
[In this case, the vaccine contains toxin molecules which have been modified, making the toxin harmless, but still allow them to act as an antigen.]
Once the vaccine enters the body, what does this stimulate ?
A primary response
~> leads to production of antibodies + memory B cells
~> T cells also activated
If the person later comes into contact with the pathogen, then what is triggered ?
The secondary immune response
What makes a vaccination programme successful ?
- Availability of vaccine : cost + quantity
- lack of side- effects
- production, storage + transport of vaccine
- Administration of vaccine- staff availability
- Herd immunity must be possible
What is herd immunity ?
If enough of the population are vaccinated, the pathogen cannot spread easily amongst the population (providing protection for those who are not vaccinated. E.g. those who are too ill to have a vaccine, or have lowered immunity unable, or those who are too young. )
When does herd immunity only work ?
If a high enough percentage of people have been vaccinated
Why does a pathogen’s DNA change the shape of an antigen ?
It can mutate frequently
What is antigenic variability?
The mechanism that pathogens use to alter their surface proteins to evade the host immune response.
E.g. the influenza virus mutates regularly + changes its surface antigens
Due to antigenic variability, what do people need to be ?
Revaccinated every year with an updated influenza virus
Why is there no effective vaccine for common cold ?
The common cold is caused by a virus (but over a hundred types of the cold virus). Each of these types of the common cold virus has different surface antigens, so this is why there is no effective vaccine for common cold.
Why is disease not eradicated (gotten rid of ) ?
- Detective immune system of individuals
- Different varieties of pathogens. E.g. cold virus
- Pathogen mutates frequently
- Some pathogens conceal themselves in other cells
- Some people avoid vaccines - religious grounds
What is HIV, and what does it cause ?
Human immunodeficiency Virus
It is an RNA virus , a virus that causes AIDS
What are the types of organelles in HIV?
-RNA
-Capsid (protein capsid)
- reverse transcriptase (enzyme)
- Matrix proteins - helps to maintain the structure of the virus
- lipid envelope
- attachment proteins - allow HIV to attach to its host cell
What is the replication of HIV?
[Once a person is infected, HIV particles circulate in the bloodstream]
-The attachment protein on HIV attaches to a molecule : CD4, via receptors on helper T cell
- [ Once HIV attaches to CD4, the HIV lipid envelope fuses with the cell membrane ]
- [The protein capsid passes into the cell, then fuses with the helper T cell membrane ] , enabling RNA + enzymes from HIV to enter
- The reverse transcriptase enzyme converts the viral RNA into DNA , why its called retrovirus
- [The DNA now moves into the cell nucleus and integrates with the host DNA ]
- Here the mRNA is transcribed, and the helper T cell starts to create viral proteins to make new viral particles
- The virus particles assemble and then bud from the helper T cell, and are released from the cell, causing a lipid envelope to form
Once HIV becomes active +replicates, what does this lead to ?
The death of helper T cells
What does the death of helper T cells result in ?
As the number of helper T cells decreases, the patient’s immune system can no longer function effectively.
Without enough helper T cells, antibody production by B cells + cell -mediated immune response becomes less effective, causing the patient to have AIDS
How does HIV cause AIDS, and what are they more vulnerable to ?
Kills or interferes with the normal function of helper T cells.
Patient with AIDS are more vulnerable to tuberculosis + higher risk of developing cancer
Why can antibiotics not be used to treat viral infections ?
They kill bacteria : target bacterial cell structures
E.g. penicillin prevents cross-linking of peptidoglycon molecules in bacterial cell wall. Causing bacterial cell to burst when water enters by osmosis
Why can viruses not be treated using antibiotics?
They don’t have any cellular structure, so take advantage of the metabolic process of their host cell
How do we treat viral diseases?
Using antiviral drugs.
-antiviral drugs against HIV inhibit key enzymes in the HIV replication cycle
e.g. reverse transcriptase
What is a consequence of having insufficient helper T cells?
Cannot stimulate B cells to make antibodies, killer T cells to kill cells + memory cells can be destroyed
Therefore, the body cannot produce an adequate immune response and is open to secondary disease
What is an ELISA test ?
Used to see if a patient has only antibodies to a certain antigen
What happens in an ELISA test?
A coloured product is formed when enzyme reacts with certain substrate, causing solution in reaction vessel to change colour.
If colour change occurs, shows that the antigen or antibody of interest is present in the sample being tested.
What are ELISA tests carried out using and why?
Plastic plates - has a number of small wells : allows us to analyse a number of samples in one go
What are the steps in an ELISA test?
1) First HIV antigens are bound to the bottom of the reaction vessel [material on bottom of vessel is designed so that antigen molecules stick]
2) Wash well several times, removing any antigen molecules that did not stick
3) A blood plasma sample is taken from the patient + added to the reaction vessel
4) Any HIV- specific antibodies present in the blood plasma now bind to the HIV antigens : primary antibodies
5) Any other antibodies present in the blood plasma are unbound and washed out
6) Now add a 2nd antibody (secondary antibodies) has on enzyme attached to it, add to the blood vessel
7) These secondary antibodies specifically bind to the first antibody. The reaction vessel is washed out again to remove any unbound secondary antibodies (if not washed out, would give a positive result) .
8) Finally, a solution is added that contains a substrate for the enzyme. Substrate is normally a colourless molecule the enzyme converts the substrate into a product molecule which is coloured, causing the solution in the reaction vessel to change colour.
~> Indicates patient has HIV - specific antibodies in the blood
What does the intensity of the colour produced in the ELISA test depend on ?
Depends on the number of enzyme molecules, which in turn depends on the number of antigen molecules present
What makes the ELISA test a quantitative test ?
The intensity of the colour can be used to determine the amount of antigen, making the ELISA test a quantitative test