11.1 Antibody Production Flashcards
What does it mean if the immune system can differentiate between self and non-self?
The immune system has the capacity to distinguish between body cells (‘self’) and foreign materials (‘non-self’)
What does the immune system attack? self or non-self?
non-self
It will react to the presence of foreign materials with an immune response that eliminates the intruding material from the body
What identifies cells as “self”?
All nucleated cells of the body possess unique and distinctive surface molecules that identify it as self
What are self markers called?
These self markers are called major histocompatibility complex molecules (MHC class I) and function as identification tags
WIll the immune system react to self markers?
no
The immune system will not normally react to cells bearing these genetically determined markers (self-tolerance)
What can be categorised, as non-self?
Any substance that is recognised as foreign and is capable of triggering an immune response is called an antigen (non self)
What recognises antigens and what do they do?
Antigens are recognised by lymphocytes which bind to and detect the characteristic shape of an exposed portion (epitope)
What do lymphocytes trigger?
Lymphocytes trigger antibody production (adaptive immunity) which specifically bind to epitopes via complementary paratopes
What are 3 antigenic determinants?
Surface markers present on foreign bodies in the blood and tissue – inluding bacterial, fungal, viral and parasitic markers
The self markers of cells from a different organism (this is why transplantation often results in graft rejection)
Even proteins from food may be rejected unless they are first broken down into component parts by the digestive system
Where are self-markers present?
Self markers (MHC class I) are present on the surface of all nucleated body cells and identify the cell as part of the organism
Do all organisms have the same self markers?
no
Different organisms have distinct self markers which prevent transplantation of tissues (unless a very close genetic match)
Do RBC have self markers, why?
they do not - Red blood cells are not nucleated and hence do not possess the same distinctive and unique self markers as all other body cells
Due to RBC not being nucleated, what can be done to blood cells?
This means that red blood cells can be transferred between individuals without automatically causing immune rejection
Despite not having self markers, what may they contain?
However, red blood cells do possess basic antigenic markers which limit the capacity for transfusion (the ABO blood system)
What type of antigenic markers may red blood cells possess?
Red blood cells may possess surface glycoproteins (A and B antigens) either independently (A or B) or in combination (AB)
Can red blood cells have no surface glycoproteins?
yes
Alternatively, red blood cells may possess neither surface glycoprotein (denoted as O)
Why are blood transfusions not compatible between blood groups?
As humans produce antibodies against foreign antigens, blood transfusions are not compatible between certain blood groups
What blood groups can AB blood RECEIVE transfusions from?
AB blood groups can receive blood from any other type (as they already possess both antigenic variants on their cells)
What blood groups can A blood NOT RECEIVE transfusions from?
A blood groups cannot receive B blood or AB blood (as the B isoantigen is foreign and will stimulate antibody production)
What blood groups can B blood NOT RECEIVE transfusions from?
B blood groups cannot receive A blood or AB blood (as the A isoantigen is foreign and will stimulate antibody production)
What blood groups can O blood RECEIVE transfusions from?
O blood groups can only receive transfusions from other O blood donor (both antigenic variants are foreign)
What results in positive or negative blood groups?
An additional glycoprotein (Rhesus factor) is either present or absent, resulting in positive and negative blood groups
What is a pathogen?
A pathogen is an agent that causes disease – either a microorganism (bacteria, protist, fungi or parasite), virus or prion
What is a disease?
A disease is any condition that disturbs the normal functioning of the body (i.e. the body can no longer maintain homeostasis)
What is an illness?
An illness is a deterioration in the normal state of health of an organism (a disease may cause an illness)
Are pathogens species-specific?
YES
Pathogens are generally species-specific in that their capacity to cause disease (pathogenesis) is limited to a particular species
What are examples of diseases that affect human hosts?
Polio, syphilis, measles and gonorrhoea are examples of diseases caused by pathogens that specifically affect human hosts
Can certain pathogens cross the species barrier?
YES
Certain pathogens may cross the species barrier and be able to infect and cause disease in a range of hosts
What are zoonotic diseases?
Diseases from animals that can be transmitted to humans are called zoonotic diseases (or zoonoses)
What are examples of zoonotic diseases?
Examples of zoonotic diseases include rabies (dogs), certain strains of influenza (e.g. bird flu) and the bubonic plague (rats)
In what 4 methods can disease transmission occur?
direct contact
contamination
airborne
vectors
How can diseases spread via direct contact?
the transfer of pathogens via physical association or the exchange of body fluids
How can diseases spread via contamination?
ingestion of pathogens growing on, or in, edible food sources
How can diseases spread via airborne?
certain pathogens can be transferred in the air via coughing and sneezing
How can diseases spread via vectors?
intermediary organisms that transfer pathogens without developing disease symptoms themselves
In what two ways will the body respond to foreign pathogens?
When the body is challenged by a foreign pathogen it will respond with both a non-specific and a specific immune reaction
How does the non-specific response work?
Non-specific immune cells called macrophages will engulf pathogens non-selectively and break them down internally
What do a proportion of macrophages display?
A proportion of macrophages (dendritic cells) will present the antigenic fragments of the pathogen to specific lymphocytes
What can T and B lymphocytes be labelled as?
specific
The body contains millions of different T lymphocytes and B lymphocytes that each recognise a single, specific antigen
- why do macrophages present antigenic fragments?
Antigenic fragments are presented to specific helper T lymphocytes (TH cells) that, when activated, releases cytokines
- what do cytokines stimulate?
The cytokines stimulate a specific B cell that produces antibodies to the antigen to divide and form clones (clonal selection)
- what do most of the clones develop into?
Most of the clones will develop into short-lived plasma cells that produce large quantities of specific antibody
- what will a small proportion of the clones develop into?
A small proportion of clones will differentiate into long-lived memory cells that function to provide long-term immunity
Do pathogens only contain one antigenic fragment? Why?
Pathogens typically contain multiple distinct antigenic fragments on their surface and hence a single pathogen is likely to stimulate several different T and B lymphocytes to produce a variety of specific antibodies (polyclonal activation)
What happens when a specific B lymphocyte is activated?
When a specific B lymphocyte is activated following antigen presentation, it divides into plasma cells and memory cells
What are plasma cells?
Plasma cells are short-lived and secrete high numbers of antibodies that are specific to a particular antigen
What do plasma cells secrete?
Plasma cells will secrete ~ 2,000 antibody molecules per second into the bloodstream for roughly 4 to 5 days
By what mechanisms can antibodies aid in the destruction of pathogens?
Precipitation
Agglutination
Neutralisation
Inflammation
Complement activatio
mnemonic : PANIC
What is precipitation?
Soluble pathogens become insoluble and precipitate
What is agglutination?
Cellular pathogens become clumped for easier removal
What is neutralisation?
Antibodies may occlude pathogenic regions (e.g. exotoxins)
What is inflammation?
Antibodies may trigger an inflammatory response within the body
What is complement activation?
Complement proteins perforate membranes (cell lysis)
collectively, how does the action of antibodies enhance the immune system?
Collectively, the action of antibodies enhance the immune system by aiding the detection and removal of pathogens by the phagocytic leukocytes of the innate immune system (macrophages)
What is the role of the constant region?
The constant region of antibodies can be recognised by macrophages, improving pathogen identification (opsonisation)
What can macrophages do due to opsonization?
The macrophages can now engulf and eliminate pathogens more efficiently, reducing disease symptoms
What does the adaptive immune system rely on?
The adaptive immune system relies on the clonal expansion of plasma cells to produce sufficiently large numbers of antibodies
Therefore what does the clonal expansion of plasma cells lead to?
This means there is a delay between the initial exposure to a pathogen and the production of large quantities of antibodies
What can pathogens do during the delay period?
If pathogens can reproduce rapidly during this delay period, they can impede normal body functioning and cause disease
What are memory cells?
Memory cells are produced to prevent this delay in subsequent exposures and hence prevent disease symptoms developing
- What initiates B lymphocyte memory cell formation?
When a B lymphocyte is activated and divides to form plasma cells, a small proportion will differentiate into memory cells
- How long can memory cells survive for?
Memory cells are long living and will survive in the body for many years, producing low levels of circulating antibodies
- What happens in the case of a second infection, due to memory cells?
If a second infection with the same pathogen occurs, memory cells will react more vigorously to produce antibodies faster
- What does this faster production of antibodies lead to?
As antibodies are produced faster, the pathogen cannot reproduce in sufficient amounts to cause disease symptoms
- When can the individual be termed as, “immune”?
Hence, because pathogen exposure no longer causes the disease to occur, the individual is said to be immune
What is an allergen?
An allergen is an environmental substance that triggers an immune response despite not being intrinsically harmful
How can the immune response (in response to an allergen) be termed?
This immune response tends to be localised to the region of exposure (e.g. airways and throat) as an allergic reaction
What is anaphylaxis?
A severe systemic allergic reaction is called anaphylaxis and can be fatal if left untreated
What does an allergic reaction require?
An allergic reaction requires a pre-sensitised immune state (i.e. prior exposure to the allergen)
- What happens when a specific B cell encounters an allergen?
When a specific B cell first encounters the allergen, it differentiates into plasma cells and makes large quantities of antibody (IgE)
- What happens to the IgE antibodies? (immunoglobulin E)
The IgE antibodies attach to mast cells, effectively ‘priming’ them towards the allergen
- What happens upon re-exposure to the allergen?
Upon re-exposure to the allergen, the IgE-primed mast cells release large amounts of histamine which causes inflammation
How can an inflammatory response be triggered? (allergen)
The release of histamine from IgE-primed mast cells causes an inflammatory response that results in allergic symptoms
What does inflammation improve?
Inflammation improves leukocytes mobility to infected regions by triggering vasodilation and increasing capillary permeability
What is vasodilation?
Vasodilation is the widening of blood vessels to improve the circulation of blood to targeted regions
What does vasodilation cause in terms of immune response?
Vasodilation causes redness (as vessel expansion moves blood closer to the skin) and heat (which is transported in blood)
What is capillary permeability?
Capillary permeability describes the capacity for leukocytes to leave the bloodstream and migrate into the body tissue
What does increased permeability lead to?
Increased permeability leads to swelling (more fluid leaks from the blood) and pain (swelling causes compression of nerves)
What are typical symptoms of an allergic response?
Redness, heat, swelling and localised pain are all typical symptoms of an allergic response
What are monoclonal antibodies?
Monoclonal antibodies are antibodies artificially derived from a single B cell clone (i.e. identical specific antibodies)
- What is injected to start monoclonal antibody production?
An animal (typically a mouse) is injected with an antigen and produces antigen-specific plasma cells
- What is removed and what are they fused with?
The plasma cells are removed and fused (hybridised) with tumor cells capable of endless divisions (immortal cell line)
- What is the resulting hybridoma cell capable of?
The resulting hybridoma cell is capable of synthesising large quantities of monoclonal antibody
What can monoclonal antibodies be used for?
Monoclonal antibodies can be used for both the therapeutic treatment and clinical detection of disease
What is an example of a therapeutic use of monoclonal antibodies?
An example of therapeutic use involves the use of antibodies in the treatment of rabies
What is an example of a diagnostic use of monoclonal antibodies?
An example of diagnostic use involves the use of antibodies in the detection of pregnancy
What can monoclonal antibodies be used to provide protection for?
Monoclonal antibodies are commonly used to provide immune protection for individuals who contract harmful diseases
How can monoclonal antibodies be used to treat rabies?
Because the rabies virus can potentially be fatal, injecting purified antibodies functions as an effective emergency treatment
How can monoclonal antibodies be used to treat cancer?
Monoclonal antibodies can be used to target cancer cells that the body’s own immune cells fail to recognise as harmful
What are therapeutic monoclonal antibodies named according to?
Therapeutic monoclonal antibodies are named according to the source organism from which the antibodies were derived
What is a downside of mice antibodies?
Mice antibodies (‘-omab’) are easier to synthesise than human antibodies but are less likely to be tolerated by the patient
What can monoclonal antibodies be used to test for?
Monoclonal antibodies can be used to test for pregnancy via the presence of human chorionic gonadotrophin (hCG) in urine
What is hCG and how can it be used to test for pregnancy?
hCG is a hormone produced by women during foetal development and thus its presence in urine is indicative of pregnancy
What process do pregnancy tests use?
Pregnancy tests use a process called ELISA (enzyme-linked immunosorbent assay) to identify a substance via a colour change
- How do monoclonal antibodies change the colour of the dye of a pregnancy test?
Free monoclonal antibodies specific to hCG are conjugated to an enzyme that changes the colour of a dye
- What happens to the second set of monoclonal antibodies?
A second set of monoclonal antibodies specific to hCG are immobilised to the dye substrate
- What will happen if hCG is present in the urine?
If hCG is present in urine, it will interact with both sets of monoclonal antibody (forming an antibody ‘sandwich’)
- What happens if both antibody sets are bound to hCG?
When both sets of antibody are bound to hCG, the enzyme is brought into physicial proximity with the dye, changing its colour
- What will a third set of monoclonal antibodies do?
A third set of monoclonal antibodies will bind any unattached enzyme-linked antibodies, functioning as a control
What do vaccinations induce?
Vaccinations induce long-term immunity to specific pathogenic infections by stimulating the production of memory cells
What is a vaccine?
A vaccine is a weakened or attenuated form of the pathogen that contains antigens but is incapable of triggering disease
What may antigenic components of a vaccine be conjugated to?
The antigenic determinants in a vaccine may be conjugated to an adjuvant, which functions to boost the immune response
How does the body respond to a vaccine?
The body responds to an injected vaccine by initiating a primary immune response, which results in memory cells being made
After vaccination, what happens when the body is exposed to an actual pathogen?
When exposed to the actual pathogen, the memory cells trigger a more potent secondary immune response
What do vaccinations ultimately result in?
As a consequence of this more potent immune response, disease symptoms do not develop (individual is immune to pathogen)
How long do vaccinations allow an individual to be immune for?
The length of time a person is immune to infection following a vaccination depends on how long the memory cells survive for
Due to the varying lifespans of memory cells, what may be required?
Memory cells may not survive a lifetime and individuals may subsequently require a booster shot to maintain immunity
Why are vaccination programs implemented?
Vaccinations programmes are implemented to reduce the outbreak of particular infectious diseases within populations
What is an epidemic?
An epidemic is a substantially increased occurrence of a particular infection within a given region
What is a pandemic?
A pandemic is an epidemic that has spread across a large geographical area (like a continent)
Apart from immunity to an individual, what does vaccination provide?
Vaccination confers immunity to vaccinated individuals but also indirectly protects non-vaccinated individuals via herd immunity
What is herd immunity?
Herd immunity is when individuals who are not immune to a pathogen are protected from exposure by the large amounts of immune individuals within the community
What was smallpox and what is its significance?
Smallpox was the first infectious disease of humans to have been eradicated via vaccination
When is a disease considered to be eliminated?
When a disease stops circulating in a region it is considered eliminated – if it is eliminated worldwide, it is considered eradicated
When was smallpox targeted for eradication?
Smallpox was targeted for eradication in 1967 by the World Health Organisation (WHO), via a global vaccination programme
When was the last case of smallpox and when was it declared eradicated?
The last known case of smallpox in a civilian was registered in 1977 and it was officially declared eradicated by WHO in 1980
Give 4 reasons why the eradication of smallpox was successful.
Smallpox was easily identifiable due to overt clinical symptoms, which helped to limit potential transmission
Transmission only occurred via direct contact and there were no animal vectors or reservoirs to sustain the infectious agent
The infection period was short-lived (3 – 4 weeks) and the virus was stable and didn’t mutate into alternate strains
There was global cooperation and immunity was long-term so repeated booster shots were unnecessary
What have vaccination programs led to? How may they differ?
Vaccination programmes have lead to a reduction in the incidence of infectious diseases in a number of regions
Different nations will implement different vaccination practices depending on the regional pathogenic threats
What is epidemiology?
Epidemiology is the study of the patterns, causes and effects of health and disease conditions in a defined population
What is epidemiology used for
It can be used to compare the incidence of a disease over time (prior and following vaccination programme implementation)
It can be used to compare the incidence of a disease in different regions (both with and without vaccination programmes)
What 3 factors may influence disease rates?
Populations have increased year on year, which would be likely to increase the risk of potential outbreaks
Improvements to health care services, public sanitation and medical breakthroughs will also influence disease rates
Different regions may experience different levels of exposure to particular infections (due to climate and vector presence)
