topic 2B - immunity Flashcards
examples of our bodies defence mechanisms against pathogens:
-physical and chemical defences
-inflammation
-recognising ‘foreign’ cells
examples of physical defence mechanisms against pathogens:
-skin
-mucus membranes
-tears (containing the enzyme lysozyme, which destroys bacteria)
-saliva
what is an inflammatory response?
swelling and heating of the region invaded by the pathogen (non-specific)
what is a specific immune response?
recognising foreign antigens & targeting pathogens (involves the activation of B & T cells)
how is the body able to recognise foreign cells?
due to specific molecules found on the surface of cells
examples of molecules that help us recognise foreign cells:
-glycoproteins
-glycolipids
what do glycoproteins & glycolipids allow the body to recognise?
its own cells (‘self’) and foreign cells (‘non-self’):
-pathogens (organisms which can cause disease - viruses, bacteria)
-cells from other organisms of the same species
-abnormal body cells (cancerous)
-toxins
define antigens
a protein marker on a cells surface which stimulates an immune response
self antigens
antigens produced by the organism’s own body cells
do self antigens stimulate an immune response?
no
which cells stimulate an immune response?
non-self antigens
what is antigen variability?
the antigens on the surface of viruses change frequently due to genetic mutations
why is antigenic variability bad for mammals?
-lymphocytes and memory cells produce a specific immune response
-the surface receptors on lymphocytes and memory cells are complementary to only one antigen
-when the antigen on a pathogen changes, the lymphocytes and memory cells can no longer bind, there is no secondary immune response
-the host gets infected and suffers from the disease again
what are phagocytes?
-white blood cells that are produced continuously in the bone marrow
-they are stored in the bone marrow before being distributed around the body in the blood
function of phagocytosis:
removing dead cells and destroy pathogens (non-specific immune response)
what are the two main phagocytes?
-neutrophils
-macrophages
describe phagocytosis (simple)
the phagocyte engulfs the pathogen
the phagocyte forms a phagosome around the pathogen
the phagocyte releases lysosomes (contain hydrolytic enzymes) which digest the pathogen and destroy it
the pathogen is released
the process of recognising and engulfing a pathogen
what do all phagocytes carry out?
phagocytosis
neutrophil: key facts
-travel throughout the body and often leave the blood by squeezing through capillary walls to ‘patrol’ the body tissues
-during an infection, they are released in large numbers from their stores
-short-lived cells
how phagocytosis occurs with neutrophils
ENDOCYTOSIS:
1) chemicals released by pathogens, attract neutrophils to the site where the pathogens are located (chemotaxis)
2) neutrophils move towards pathogens and attach to them
3) once attached to a pathogen, the neutrophil engulfs it and traps the pathogen within a phagosome
4) a lysosome fuses with the membrane of the phagosome (to form a phagolysosome) and releases lysozymes to digest the pathogen
5) the lysozymes destroy the pathogen
6) after killing and digesting the pathogens, the neutrophils die
what are lysosomes?
membrane organelles that contain digestive enzymes (lysozymes)
what is a sign of dead neutrophils?
pus
macrophages: key facts
-larger than neutrophils
-long-lived cells
-after being produced in the bone marrow, macrophages travel in the blood as monocytes, then they develop into macrophages once they leave the blood & settle in organs
how phagocytosis occurs with macrophages
-they cut the pathogens up so that they can display the antigens of the pathogens on their surface
-the cell is now an antigen-presenting cell & can then be recognised by lymphocytes
what are lymphocytes a type of?
white blood cell
what do lymphocytes play an important part in?
the specific immune response
what size are lymphocytes compared to phagocytes?
smaller than phagocytes
what fills most of a lymphocyte cell?
a large nucleus
where are lymphocytes produced?
in the bone marrow before birth
what are the two types of lymphocytes?
t-lymphocytes (t cells)
b-lymphocytes (b cells)
what happens during the maturation of T lymphocytes: steps
1) after they have divided, immature t-lymphocytes leave the bone marrow to mature in the thymus
2) mature t-lymphocytes have specific surface receptors called t-cell receptors
3) these receptors have a similar structure to antibodies and are each specific to one antigen
when are t lymphocytes activated?
when they encounter (and bind to) their specific antigen that is being presented by one of the host’s cells (eg: a body cell that has been invaded by a pathogen)
what are the two types of t cell?
-helper t cells
-cytotoxic t cells (killer t cells)
when will t cells bind to an antigen?
if it is present on the surface of an antigen-presenting cell
what is an antigen presenting cell?
one of the host’s cells that has been invaded by a pathogen and is displaying the antigen on its cell surface membrane
how do t-lymphocytes increase in number?
they divide by mitosis
what do t-helper cells do?
assist other white blood cells in the immune response
what do t-helper release & what is the effect of the released products?
they release cytokines (hormone-like signals) which stimulate:
-the maturation of B-lymphocytes into plasma cells
-the production of memory b cells
-the activation of cytotoxic t cells (destroy pathogenic cells)
where do b cells stay while immature and move when mature?
b-lymphocytes remain in the bone marrow until they are mature and then spread through the body, concentrating in lymph nodes and the spleen
how many b cells are produced throughout life and why?
-millions of types of B-lymphocyte cells are produced within us
-as they mature, the genes coding for antibodies are changed to code for different antibodies
-once mature, each type of B-lymphocyte cell can make one type of antibody molecule
b lymphocytes and antigens
part of each antibody molecule forms a glycoprotein receptor that can bind specifically with one type of antigen
define clonal selection
the process of matching the antigens on an APC with the receptors on B and T lymphocytes (the correct antibodies) and then activating the lymphocytes with a T-helper cell
define clonal expansion
cell division of the activated B or T lymphocyte after clonal selection
which two cells do b cells divide into?
-plasma cells
-memory cells
what do plasma cells do?
secrete lots of antibody molecules (specific to the antigen)
into the blood, lymph or linings of the lungs/gut
lives of plasma cells
-short-lived (their numbers drop off after several weeks)
-the antibodies they have secreted stay in the blood for a longer time
what do b cells remaining in the blood become?
memory cells:
-provide long-term immunity against specific pathogens
-they have a much longer lifespan than plasma cells
-rapidly divide into plasma cells if the body is re-infected by the same pathogen
what are antibodies?
proteins that bind to antigens as a part of the immune response
what structure do antibodies have?
a quaternary structure (which is represented as Y-shape)
components of antibodies
-two ‘heavy’ polypeptide chains bonded by disulfide bonds to two ‘light’ polypeptide chains
-constant region
-variable region
the variable region of an antibody
-different for each antibody.
-where the antibody attaches to the antigen to form an antigen-antibody complex
-the antigen binding site is at the end of the variable region
why do the antigen-binding sites vary greatly?
to give the antibody its specificity for binding to antigens, the sites are specific to the epitope
what is the epitope?
the part of the antigen that binds to the antibody
what is the hinge region of an antibody and what does it do?
-where the disulfide bonds join the heavy chains)
-gives flexibility to the antibody molecule -allows the antigen-binding site to be placed at different angles when binding to antigens
do all antigens have a hinge region?
no
an antigen and its antibody have…
complementary molecular shapes, this means that their molecular structures fit into each other
what happens when an antibody collides (randomly) with a foreign cell that possesses non-self antigens with a complementary shape?
it binds with one of the antigens & forms an antigen-antibody complex
→ leads to agglutination or phagocytosis
how many antigen-binding sites do antibodies usually have?
at least two antigen-binding sites
how many foreign cells can an antibody bind to at once?
more than one
agglutination
when an antibody binds to more than one foreign cell at a time, causing groups of the same pathogens to become clumped together
what does the binding of antibodies to antigens do?
-neutralises the pathogen
OR
-acts like a marker to attract phagocytes to engulf and destroy the pathogens
what do memory cells for the basis of ?
immunological memory
define immunological memory
the ability of the immune system to quickly recognise an antigen that the body has previously encountered and initiate a corresponding (specific) immune response
how long do memory cells usually last?
many years and often a lifetime
what are the two types of immune responses?
-primary immune response
-secondary immune response
define primary immune response
responding to a newly encountered antigen (relatively slow, individual experiences symptoms of the disease)
define secondary immune response
responding to a previously encountered antigen (quicker, pathogens are destroyed before any symptoms appear)
steps of a primary immune response
1) the production of antibodies is slow after the first exposure to the pathogen
2) the concentration of antibodies increases slowly
3) this is because there are very few B cells that are specific to the pathogen’s antigens
4) it takes time for the B cells to divide into plasma cells to produce the correct antibody, so the individual experiences symptoms of the disease
5) during this process, some B cells divide into memory cells to make the individual immune to this disease
steps of a secondary immune response
1) memory cells remember the pathogens antigens from the previous encounter
2) memory cells quickly divide into plasma cells
3) they produce antibodies and more memory cells
4) these plasma cells secrete larger numbers of antibodies to quickly destroy the pathogen before the individual experiences any symptoms
what two sections are defence mechanisms split into?
-specific
-non- specific
what is a non specific response & longevity?
(+ examples)
-mechanisms that do not distinguish between pathogens, but respond to all of them in the same way.
-these mechanisms act immediately
( physical barriers, phagocytosis)
what is a specific response & longevity?
-mechanisms that distinguish between different pathogens
-the response is less rapid but provides long lasting immunity
define cell mediated response
an immune response that does not involve antibodies, primarily driven by t cells
define humoral response
produces antigen-specific antibodies and is primarily driven by b cells
what are vaccines?
-antigens are injected that cause your body to produce memory cells against a particular pathogen, without the pathogen causing disease
-this means you become immune without getting any symptoms
the two types of vaccines:
1) dead
2) attenuated (weakened)
how are vaccines administered?
by injection (into vein/muscle) or orally
disadvantages of taking a vaccine orally
it could be broken down by enzymes in the gut or the molecules of the vaccine may be too large to be absorbed into the blood
how can vaccinations produce long term immunity?
-they cause memory cells to be created
-the immune system remembers the antigen when reencountered and produces antibodies to it faster
benefits of vaccines:
1) highly effective with one vaccination giving a lifetime’s protection (less effective ones will require booster)
2) generally harmless as they do not cause the disease they protect against
disadvantages of vaccines
1) people can have a poor response (eg. they are malnourished and cannot produce the antibodies / their immune system may be defective)
2) antigenic variation – the variation in the antigens of pathogens causes the vaccines to not trigger an immune response/diseases caused by eukaryotes have too many antigens on their cell surface membranes making it difficult to produce vaccines that would prompt the immune system quickly enough
3) antigenic concealement - occurs when the pathogen ‘hides’ from the immune system by living inside cells / when the pathogen coats their bodies in host proteins / by parasitising immune cells / remaining in parts of the body that are difficult for vaccines to reach
what are attenuated vaccines?
vaccines that contain whole pathogens that have been ‘weakened’
how do attenuated vaccines work?
benefits of attenuated vaccines
tend to produce a stronger and longer-lasting immune response
disadvantages of attenuated vaccines
-can be unsuitable for people with weak immune systems, the pathogen may divide before sufficient antibodies can be produced
examples of attenuated vaccines
MMR
what is a dead/inactivated vaccine?
-contain whole pathogens that have been killed or subunit’s of the pathogens
-do not contain living pathogens they cannot cause disease
benefits of dead vaccines
they cannot cause disease, even for those with weak immune systems
disadvantages of dead vaccines
-do not trigger a strong or long-lasting immune response
-booster doses are often required
-some people may have allergic reactions or local reactions to inactivated vaccines as adjuvants may be joined to the subunit of the pathogen to strengthen and lengthen the immune response
examples of dead vaccines
whole → polio vaccine
subunit → diphtheria
what is herd immunity?
when a sufficiently large proportion of the population has been vaccinated which makes it difficult for a pathogen to spread within that population
why is herd immunity important?
it allows for the individuals who are unable to be vaccinated (e.g. children and those with weak immune systems) to be protected from the disease
how does herd immunity vary?
the proportion of the population that needs to be vaccinated in order to achieve herd immunity is different for each disease
issues with eradicating disease:
-some pathogens are complicated and so a successful vaccine has not been developed
-a diseases that could be eradicated where a vaccine does exist, hasn’t been eliminated because too few in the community have been vaccinated
-unstable political situations
-lack of public health facilities
what is active immunity?
antigen enters the body triggering a specific immune response (antibodies are produced)
how can active immunity be acquired?
-through exposure to microbes
-artificially acquired through vaccinations
during the primary response to a pathogen how long does the antibody concentration in the blood take to increase?
one to two weeks
what is passive immunity?
acquired without an immune response. antibodies are not produced by the infected person
passive immunity & secondary immune responses
as the person’s immune system has not been activated then there are no memory cells that can produce antibodies in a secondary response, if a person is reinfected they would need another infusion of antibodies
when does artificial passive immunity occur?
when people are given an injection / transfusion of the antibodies
when does natural passive immunity occur?
when:
-foetuses receive antibodies across the placenta from their mothers
-babies receive the initial breast milk from mothers which delivers a certain isotype of antibody
how is HIV spread? (+ examples)
by direct exchange of body fluids:
-sexual intercourse
-blood donation
-sharing of needles by drug users
-from mother to child across the placenta
-mixing of blood between mother and child during birth
-from mother to child through breast milk
components of HIV
-two RNA strands
-proteins (including the enzyme reverse transcriptase)
-capsid
-viral envelope consisting of a lipid bilayer and glycoproteins
-attachment proteins
when viruses enter the bloodstream they…
infect t helper cells
how does HIV avoid being recognised and destroyed by lymphocytes?
by repeatedly changing its protein coat
HIV replication steps:
1) hiv attaches to receptors on
t-lymphocytes
2) hiv injects it’s genetic material into the lymphocyte, which becomes a host
3) reverse transcriptase enzymes produce a DNA copy of the viral RNA, the DNA copy is inserted into the chromosomes of the cell
4) each time the cell divides it copies the viral DNA
5) the infected cells remain normal as the viral DNA is inactive
what happens after years when viral DNA within the host cells becomes active?
-it takes control of the helper t cell so more HIV particles are produced &
the helper t cell dies
-thousands of new HIV particles are released which canto infect other helper t cells
-gradually the virus reduces the number of t helper cells in the immune system
-b cells are no longer activated, no antibodies are produced
-this decreases the body’s ability to fight off infections
symptoms of AIDS
-mild flu-like symptoms after HIV infection
when are people said to have AIDS?
when they can no longer produce antibodies and fight off infections
what are opportunistic diseases?
diseases that would usually cause very minor issues in healthy individuals that cause an individual with advanced AIDS to die
treatment of AIDS
antiretrovirals that slowing the spread of the virus within the body / delay the development of AIDS in those with HIV
what are antibiotics used for?
-to kill bacteria or limit bacterial growth
what are antibiotics ineffective against?
viruses
HIV vs AIDS
-HIV is a virus
-AIDS is the disease caused by HIV
uses of monoclonal antibodies:
-pregnancy tests
-diagnosing HIV
-detecting the presence of pathogens
-detecting the presence of antibiotics in milk
-detecting cancer cells
how many times are monoclonal
antibodies used?
generally only once
how monoclonal antibodies are used to detect HIV: (steps)
1) the hiv antigen is attached to a test plate
2) the blood sample being tested is passed over the test plate. if hiv antibodies are present they bind to the antigen. the plate is then washed
3) a monoclonal antibody is then passed over the plate. its antigen is the hiv antibody and it will bind to it if it is present. the monoclonal antibody is attached to an enzyme
4) the bound monoclonal antibody is proportional to the bound hiv antibody. a dye called chromogen is passed over the plate. the enzyme catalyses a colour change in the dye. the more intense the colour on the plate, the more hiv antibody present in the test blood sample
therapeutic uses of monoclonal antibodies
-treatment for the rabies virus
-the prevention of transplanted organ rejection
-autoimmune therapies
-prevention of blood clotting
-targeted treatment of breast cancer
-prevention of blood clotting
-treatment of melanoma
what does a colour change show?
that the antigen or antibody of interest is present in the tested sample
how can the quantity of an antigen or antibody be worked out?
from the intensity of the colour change
ethical issues associated with the use of vaccines
-use of animals
-human testing
-side-effects
-epidemics
vaccine ethics: use of animals
-all vaccines are tested on animals before they can move onto human-trials
-animal-based substances are sometimes used in the production of vaccines
vaccine ethics: human testing
-even at the human-trial stage, a vaccine carries a small risk
-volunteers may be at higher risk of contracting the disease if they think the trial vaccine will fully protect them but it actually doesn’t (e.g. they might have unprotected sex because they have had a trial HIV vaccine but they actually end up contracting the disease as a result)
-human volunteers are often paid to take part in vaccine trials, ethical issues can arise if these volunteers feel pressured into doing this (i.e. people who are struggling financially)
vaccine ethics: side effects
-some people refuse to take a particular vaccine due to the possibility of side effects, these people are often protected due to herd immunity, other people may think this is unfair
-some parents refuse to let their children be vaccinated - should a parent be allowed to put their child at risk?
vaccine ethics: epidemics
-when new pandemics occur there is often a struggle as to who should be vaccinated first
-there is also often a struggle between countries as to who receives the vaccines first and in what quantities
ethical issues associated with the use of monoclonal antibodies
-new monoclonal antibody therapies are often tested on animals before they can move onto human-trials
define monoclonal antibodies
identical copies of one type of antibody
what does ELISA stand for?
enzyme-linked immunosorbent assay
what are ELISA tests used to do?
to see if a patient has any antibodies to a certain antigen
two different types of ELISA tests
-direct
-indirect
direct ELISA test
use a single antibody that is complementary to the antigen being tested for
indirect ELISA tests
use two different antibodies
steps of ELISA test for HIV:
(indirect)
1) HIV antigens are bound to the bottom of the reaction vessel
2) a blood sample from the patient
is added
3) any HIV-specific antibodies (primary antibodies) in the blood bind to the HIV antigens
4) any unbound antibodies are washed out
5) secondary antibody with an enzyme attached to it is added to the reaction vessel / these secondary antibodies bind to the primary antibodies
6) the reaction vessel is washed out again to remove any unbound secondary antibodies (no primary antibodies = all of the secondary antibody will be washed out as it wouldn’t have bound)
7) a solution is added that contains a substrate that reacts with the enzyme attached to the secondary antibodies
8) if there are any secondary antibodies present, a coloured product is formed & the solution in the reaction vessel changes colour
(this indicates that the patient has HIV)
ELISA TESTING: prostate cancer
1) antibodies to PSA are both to the bottom of the reaction vessel
2) blood plasma sample is added & then washed out
3) secondary antibody (with an enzyme attached) is added, it only binds to primary antibody if PSA is present
4) substrate is added & the enzyme reacts with substrate forming a coloured product, the colour change means that PSA is present
why is it important to wash off unbound secondary antibodies?
this is important in avoiding false-positive test results, If they are not washed out, unbound secondary antibodies would give a positive result, even if there were no primary antibodies present to start with
indirect ELISA test:
(steps)
1) antigens from a patient sample are bound to the inside of a well in a well plate
2) a detection antibody (with an attached enzyme) that is complementary to the antigen of interest is added
3) If the antigen of interest is present, it will be immobilised on the inside surface of the well and the detection antibody will bind to it
4) the well is washed out to remove any unbound antibody
5) substrate solution is added
6) if the detection antibody is present, the enzyme reacts with the substrate to give a colour change
