CIE As Level Biology:Immunity

What is a phagocyte

Phagocytes are 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

What are phagocytes responsible for

They are responsible for removing dead cells and invasive microorganisms.They carry out what is known as a non-specific immune response

What are the two main types of phagocytes

Neutrophils
Macrophages

What is phagocytosis

the process of recognising and engulfing a pathogen

What are neutrophils

Neutrophils 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 storesHowever, they are short-lived cells

Mode of action of neutrophils

Chemicals released by pathogens, as well as chemicals released by the body cells under attack (eg. histamine), attract neutrophils to the site where the pathogens are located (this response to chemical stimuli is known as chemotaxis)
Neutrophils move towards pathogens (which may be covered in antibodies)
The antibodies are another trigger to stimulate neutrophils to attack the pathogens (neutrophils have receptor proteins on their surfaces that recognise antibody molecules and attach to them)
Once attached to a pathogen, the cell surface membrane of a neutrophil extends out and around the pathogen, engulfing it and trapping the pathogen within a phagocytic vacuole
This part of the process is known as endocytosis
The neutrophil then secretes digestive enzymes into the vacuole (the enzymes are released from lysosomes which fuse with the phagocytic vacuole)
These digestive enzymes destroy the pathogen
After killing and digesting the pathogens, the neutrophils die
Pus is a sign of dead neutrophils

What are macrophages

Macrophages are larger than neutrophils and are long-lived cells.Rather than remaining in the blood, they move into organs including the lungs, liver, spleen, kidney and lymph nodes,After being produced in the bone marrow, macrophages travel in the blood as monocytes, which then develop into macrophages once they leave the blood to settle in the various organs listed above

Mode of action of macrophages

Macrophages play a very important role in initiating an immune response,Although they still carry out phagocytosis in a similar way to neutrophils, they do not destroy pathogens completely
They cut the pathogens up so that they can display the antigens of the pathogens on their surface (through a structure called the major histocompatibility complex)
These displayed antigens (the cell is now called an antigen-presenting cell) can then be recognised by lymphocytes (another type of white blood cell)

What is a phagosome

The vacuole formed around a bacterium once it has been engulfed by a phagocyte is called a phagosome. A lysosome fuses with the membrane of the phagosome (to form a phagolysosome) and releases lysozymes (digestive enzymes) to digest the pathogen.

What is an antigen

Every cell in the human body has markers that identify it.Microorganisms (both pathogenic and non-pathogenic), such as bacteria and viruses, also have their own unique markers
These markers are called antigens (which are macromolecules) and they allow cell-to-cell recognition

Where are antigens found

Antigens are found on cell surface membranes, bacterial cell walls, or the surfaces of viruses.Some glycolipids and glycoproteins on the outer surface of cell surface membranes act as antigens

What are self antigens

Antigens are found on cell surface membranes, bacterial cell walls, or the surfaces of viruses.Some glycolipids and glycoproteins on the outer surface of cell surface membranes act as antigens

What are self antigens

Antigens produced by the organism's own body cells (those that the immune system does not recognise as foreign antigens) are known as self antigens Self antigens do not stimulate an immune response

What are non-self antigens

Antigens not produced by the organism's own body cells (those that the immune system recognises as being foreign eg. the antigens found on pathogenic bacteria and viruses or if a person receives a different blood type during a transfusion) are known as non-self antigens Non-self antigens stimulate an immune response

What are lymphocytes

Lymphocytes are another type of white blood cell,They play an important part in the specific immune response,They are smaller than phagocytes,They have a large nucleus that fills most of the cell,They are produced in the bone marrow before birth

Name the types of lymphocytes

B-lymphocytes
T-lymphocytes

What are B-lymphocytes

B-lymphocytes (B cells) remain in the bone marrow until they are mature and then spread through the body, concentrating in lymph nodes and the spleen.Millions of types of B-lymphocyte cells are produced within us because 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, At this stage, the antibody molecules do not leave the B-lymphocyte cell but remain in the cell surface membrane. Part of each antibody molecule forms a glycoprotein receptor that can combine specifically with one type of antigen

Primary Immune Response (Mode of action B-lymphocytes)

When an antigen enters the body for the first time, the small numbers of B-lymphocytes with receptors complementary to that antigen are stimulated to divide by mitosis.This is known as clonal selection
As these clones divide repeatedly by mitosis (the clonal expansion stage) the result is large numbers of identical B-lymphocytes being produced over a few weeks
During an immune response, these B-lymphocytes then form two types of cell:
Some of these B-lymphocytes become plasma cells that secrete lots of antibody molecules (specific to the antigen) into the blood, lymph or linings of the lungs and the gut
These plasma cells are short-lived (their numbers drop off after several weeks) but the antibodies they have secreted stay in the blood for a longer time
The other B-lymphocytes become memory cells that remain circulating in the blood for a long time
This response to a newly encountered antigen is relatively slow and is known as a primary immune response

What are T-lymphocytes

Immature T-lymphocytes leave the bone marrow to mature in the thymus.Mature T-lymphocytes have specific cell surface receptors called T cell receptors.These receptors have a similar structure to antibodies and are each specific to one antigen

Mode of T-lymphocytes

T-lymphocytes are activated when they encounter (and bind to) their specific antigen that is being presented by one of the host's cells (host cells being the human's own cells)
This antigen-presenting host cell might be a macrophage or a body cell that has been invaded by a pathogen and is displaying the antigen on its cell surface membrane
These activated T-lymphocytes (those that have receptors specific to the antigen) divide by mitosis to increase in number (similar to the clonal selection and clonal expansion of B-lymphocytes)
These T-lymphocytes differentiate into two main types of T cell:helper T cells,killer T cells

Helper T cells:release cytokines (hormone-like signals) that stimulate B-lymphocytes to divide and develop into antibody-secreting plasma cells. Some helper T cells secrete cytokines that stimulate macrophages to increase their rates of phagocytosis
Killer T cells:attach to the antigens on the cell surface membranes of infected cells and secrete toxic substances that kill the body cells, along with the pathogen inside

What are the types of imune response

Primary immune response (responding to a newly encountered antigen)
Secondary immune response (responding to a previously encountered antigen)

What is secondary immune response

If the same antigen is found in the body a second time, the memory cells recognise the antigen, divide very quickly and differentiate into plasma cells (to produce antibodies) and more memory cells
This response is very quick, meaning that the infection can be destroyed and removed before the pathogen population increases too much and symptoms of the disease develop
This response to a previously encountered pathogen is, relative to the primary immune response, extremely fast

T-lymphocytes also play a part in the secondary immune response.They differentiate into memory cells, producing two main types:Memory helper T cells,Memory killer T cells

Just like the memory cells formed from B-lymphocytes, these memory T cells remain in the body for a long time If the same antigen is found in the body a second time, these memory T cells become active very quickly

What are antibodies

Antibodies are globular glycoproteins called immunoglobulins.Antibodies have a quaternary structure (which is represented as Y-shaped), with two 'heavy' (long) polypeptide chains bonded by disulfide bonds to two 'light' (short) polypeptide chains

Antibodies are produced by B-lymphocytes.Antibodies bind to specific antigens that trigger the specific immune response. Every antigen has one antibody,Antigens include pathogens and their toxins, pollen, blood cell surface molecules and the surface proteins found on transplanted tissues.Antibodies are divided into five major classes (isotypes), each with a different role

Functions of antibodies

Antibodies can combine with viruses and toxins of pathogens (e.g. bacteria) to block them from entering or damaging cells
Antibodies can act as anti-toxins by binding to toxins produced by pathogens (e.g. the bacteria that cause diphtheria and tetanus) which neutralises them making them harmless
Antibodies can attach to bacteria making them readily identifiable to phagocytes, this is called opsonisation. Once identified, the phagocyte has receptor proteins for the heavy polypeptide chains of the antibodies, which enables phagocytosis to occur
Antibodies can attach to the flagella of bacteria making them less active, which makes it easier for phagocytes to do phagocytosis
Antibodies act as agglutinins causing pathogens carrying antigen-antibody complexes to clump together (agglutination). This reduces the chance that the pathogens will spread through the body and makes it possible for phagocytes to engulf a number of pathogens at one time
Antibodies (together with other molecules) can create holes in the cell walls of pathogens causing them to burst (lysis) when water is absorbed by osmosis

What are monoclonal antibodies

Monoclonal antibodies are artificially produced antibodies produced from a single B cell clone

Hybridoma method to form monoclonal antibodies

They are produced by injecting mice with an antigen that stimulates the production of antibody-producing plasma cells
Isolated plasma cells from the mice are fused with immortal tumour cells, which result in hybridoma cells
These hybrid cells are grown in a selective growth medium and screened for the production of the desired antibody
They are then cultured to produce large numbers of monoclonal antibodies
Monoclonal antibodies have multiple applications to include diagnostics, treating disease, food safety testing and pregnancy testing

What can monoclonal antibodies be used diagnostically for

Monoclonal antibodies can be used diagnostically for:
Pregnancy tests
Diagnosing HIV
Detecting the presence of pathogens such as Streptococcus bacteria
Distinguishing between Herpes I and Herpes II
Blood typing before transfusions and tissue typing before transplants
Detecting the presence of antibiotics in milk
Detecting cancer cells

How Monoclonal antibodies can also be used to locate the position of blood clots for patients thought to have deep vein thrombosis

This occurs by:Injecting a mouse with human fibrin (the main protein found in blood clots)
This activates the plasma cells to produce antibodies against fibrin
These cells are collected from the mouse spleen
The plasma cells are then fused with tumour cells forming hybridomas that produce antifibrin antibodies
To detect where the antibodies are binding to fibrin molecules, a radioactive chemical (producing gamma radiation) is attached to the antibodies making them radioactively labelled
A gamma-ray camera is used to detect where these radioactively labelled antibodies have attached to a fibrin molecule, hence indicating where blood clots can be found

How many times are monoclonal antibodies used

Generally monoclonal antibodies are used only once

Therapeutic uses of monoclonal antibodies

Treatment for the rabies virus, (which can be potentially fatal), by injecting purified antibodies
The prevention of transplanted organ rejection, achieved by intervening with the T cells involved in the rejection process
Autoimmune therapies for allergic asthma and rheumatoid arthritis; here monoclonal antibodies are able to bind and deactivate factors involved in the inflammatory response
Treatment for diseases caused by the overproduction or inappropriate production of B-cells (eg. leukaemia, multiple sclerosis and myasthenia gravis); the antibody (rituximab) binds to cell surface receptor proteins on B-cells (not plasma cells) and causes the death of the cells
Prevention of blood clotting following angioplasty procedures; here monoclonal antibodies bind to receptors on the platelet surface thereby inhibiting fibrinogen from binding and subsequent clotting from ensuing
Targeted treatment of breast cancer; Herceptin (trastuzumab) is a monoclonal antibody used to treat breast cancer, it recognises receptor proteins on the surface of cancer cells and binds to them allowing the immune system to identify and destroy them
Treatment of melanoma (a type of skin cancer); the antibody (ipilimumab) binds to a protein produced by T-cells (whose role is to reduce the immune response) which results in the immune system remain active against the cancer cells

Problems of using monoclonal antibodies

Using monoclonal antibodies as a treatment requires multiple administrations and this can cause problems.Initially the monoclonal antibodies were produced by mice, rabbits or other laboratory animals (as these were easier to produce), however this triggered an immune response when they were introduced to humans

Active Immunity

Active immunity is acquired when an antigen enters the body triggering a specific immune response (antibodies are produced).Active immunity is naturally acquired through exposure to microbes or artificially acquired through vaccinations.The body produces memory cells, along with plasma cells, in both types of active immunity giving the person long-term immunity In active immunity, during the primary response to a pathogen (natural) or to a vaccination (passive), the antibody concentration in the blood takes one to two weeks to increase. If the body is invaded by the same pathogen again or by the pathogen that the person was vaccinated against then, during the secondary response, the antibody concentration in the blood takes a much shorter period of time to increase and is higher than after the vaccination or first infection

Passive Immunity

Passive immunity is acquired without an immune response. Antibodies are not produced by the infected person,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 antibodie sDepending on the disease a person is infected with (eg. tetanus) they may not have time to actively acquire the immunity, that is, there is no time for active immunity. So passive immunity occurs either artificially or naturally Artificial passive immunity occurs when people are given an injection / transfusion of the antibodies. In the case of tetanus this is an antitoxin. The antibodies were collected from people whose immune system had been triggered by a vaccination to produce tetanus antibodies Natural passive immunity occurs when:
Foetuses receive antibodies across the placenta from their mothers
Babies receive the initial breast milk from mothers (the colostrum) which delivers a certain isotype of antibody (IgA)

What is a vaccine

A vaccine is a suspension of antigens that are intentionally put into the body to induce artificial active immunity. A specific immune response where antibodies are released by plasma cells

Two types of vaccines

Live attenuated vaccine
Inactivated vaccine

Problems with vaccines

People can have a poor response (eg. they are malnourished and cannot produce the antibodies - proteins or their immune system may be defective)
A live pathogen may be transmitted (e.g. through faeces) to others in the population (ideally enough number of people are vaccinated at the same time to give herd immunity)
Antigenic variation - the variation (due to major changes) in the antigens of pathogens causes the vaccines to not trigger an immune response or diseases caused by eukaryotes (eg. malaria) have too many antigens on their cell surface membranes making it difficult to produce vaccines that would prompt the immune system quickly enough
Antigenic concealment - this occurs when the pathogen 'hides' from the immune system by living inside cells or when the pathogen coats their bodies in host proteins or by parasitising immune cells such as macrophages and T cells (eg. HIV) or by remaining in parts of the body that are difficult for vaccines to reach (eg. Vibrio cholerae - cholera, remains in the small intestine)

Live attenuated vaccine

Live attenuated vaccines contain whole pathogens (e.g. bacteria and viruses) that have been 'weakened'
These weakened pathogens multiply slowly allowing for the body to recognise the antigens and trigger the primary immune response (plasma cells to produce antibodies)
These vaccines tend to produce a stronger and longer-lasting immune response
They can be unsuitable for people with weak immune systems as the pathogen may divide before sufficient antibodies can be produced
An example of this type of vaccine is the MMR (Measles, Mumps and Rubella)

Inactivated vaccine

Inactivated vaccines contain whole pathogens that have been killed ('whole killed') or small parts ('subunit') of the pathogens (eg. proteins or sugars or harmless forms of the toxins - toxoids). As inactivated vaccines do not contain living pathogens they cannot cause disease, even for those with weak immune systems. However these vaccines do not trigger a strong or long-lasting immune response like the live attenuated vaccines. Repeated doses and / or booster doses are often required. Some people may have allergic reactions or local reactions (eg. sore arm) to inactivated vaccines as adjuvants (eg. aluminium salts) may be conjugated (joined) to the subunit of the pathogen to strengthen and lengthen the immune response. An example of a whole killed vaccine is polio vaccine. An example of a toxoid subunit vaccine (where inactivated versions of the toxins produced by pathogens are used) is Diphtheria