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Summary 11 Immunity
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EVERYTHING you need to know about "Immunity" for A-level biology CIE
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Immunity09 March 2021 11:39
Our External Defence System
• We have quite a few methods of defending ourselves against disease
• If we are healthy, we have physical, chemical and cellular defences that prevent pathogens from entering our
bodies
• The epithelia, which cover our airways are an effective barrier to pathogens
• The HCl in our stomach kills many pathogens that we ingest with our food and drink
• Blood clotting prevents the entry of pathogens as well as the loss of blood
Our Internal Defence System
• If pathogens do enter our blood stream, we put into action a second line of defence, the white blood cells
• White blood cells recognise pathogens because they possess distinctive, large molecules on their cell surfaces
• These may be proteins, glycoproteins, lipids, and polysaccharides, as well as the waste material that some
pathogens produce
• Any molecule which the white blood cells recognise as foreign is called an antigen
White Blood Cells (Leucocytes)
• There are two types of white blood cell, phagocytes and lymphocytes
• Phagocytes patrol the body and engulf any cell that possesses non-self antigens
• Lymphocytes produce antibodies in response to specific antigens
• The response of lymphocytes to the presence of a foreign antigen is called the immune response
• In some cases, special lymphocytes don't produce antibodies, but directly kill our own cells which have been
infected by pathogens
Phagocytes
• Phagocytes are produced throughout our lives in the bone marrow
• They are stored there before being distributed around the body
• They are scavengers and non-specific in that they will attempt to engulf any foreign or 'non-self' microorganism
• They also remove any of our dead cells
• Two types are neutrophils and macrophages
Neutrophils:
- Neutrophils are a kind of phagocyte and form about 60% of all the white blood cells patrolling the body
- They are able to leave the capillaries by squeezing through the walls so they can patrol the tissues
- They are released in large numbers during an infection, but don't live long (about two days)
Macrophages:
- Also phagocytes, but larger than neutrophils
- Tend to be found in organs such as the lungs, liver and spleen, kidney and lymph nodes rather than remaining in
the blood
- They are made in bone marrow and travel in the blood as monocytes which settle in the organs and become
macrophages
- Macrophages remove foreign matter from the organs in which they reside
- They are long-lived and play a crucial role in initiating the immune response as they don't destroy pathogens
completely, but cut them up and display their antigens to the lymphocytes
Phagocytosis
• If pathogens invade the body and cause an infection, some of the cells under attack respond by releasing
histamines
• These attract passing neutrophils to the site (chemotaxis)
• The neutrophils destroy the pathogens by phagocytosis
• The pathogens may already be covered by antibodies from the lymphocytes which the neutrophils are able to
recognise
• The cell surface membrane of the neutrophil engulfs the pathogen in a vesicle by endocytosis
• This fuses with a lysosome, which releases digestive enzymes, destroying the pathogen
Lymphocytes
• Lymphocytes are smaller than phagocytes
• Their nucleus fills up most of the cell
• Lymphocytes are produced before birth in the bone marrow
• There are two types:
- B lymphocytes (B cells), which remain in the bone marrow until they are mature and then spread throughout
the body, concentrating in the lymph nodes and spleen
- T-lymphocytes (T cells), which leave the bone marrow and mature in the thymus (a gland in the chest which
shrinks after puberty)
• Only mature lymphocytes can take part in the immune response
• As they mature, many different types of B and T cell develop
• Each type is specific to one antigen, so there are probably many millions of different types
• As a result of their speciality, the immune system has the ability to respond to almost any pathogen which enters
the system
• When mature, the cells circulate between the blood and the lymph ensuring they cover the whole body and so can
come into contact with pathogens and with one another
B Lymphocytes:
- As each B cell matures, it develops the ability to make antibodies against a particular antigen
- Each cell then divides to give a small number of clones that are able to make the same type of antibody
- The antibodies do not leave the cells at this stage, but stay embedded in the cell surface membrane
- At this point, they form a glycoprotein receptor which can combine specifically with one type of antigen
T Lymphocytes:
- Mature T cells have specific T cell receptors on their cell surface membranes
- These are similar in structure to antibodies and each is specific to one antigen, so like B cells, T cells are highly
specific to a particular pathogen
- T cells are activated when they encounter this antigen on the surface of the host (our own) cells
- This may either be a macrophage which has engulfed the pathogen or it may be a body cell which has been
invaded by a pathogen and is displaying some of its antigens as a 'help' signal
- Helper T Cells
- When these are activated, they release chemicals called cytokines which stimulate appropriate B cells to divide,
develop into plasma cells and secrete antibodies
- Some helper T cells make macrophages work more vigorously as a result of cytokine release
- Killer T Cells
- These search the body for cells that have become invaded by pathogens and are displaying foreign antigens
from the pathogen
, develop into plasma cells and secrete antibodies
- Some helper T cells make macrophages work more vigorously as a result of cytokine release
- Killer T Cells
- These search the body for cells that have become invaded by pathogens and are displaying foreign antigens
from the pathogen
- They secrete toxic substances such as hydrogen peroxide, killing the body cells and the pathogens inside
Recognition of 'Self' Versus 'Non-Self'
• All cells are recognised by specific molecules that are embedded in the outermost surface of the cell
• These include things like the variable glycoproteins on the cell surface membrane
• These specific glycoproteins are also known as the major histocompatibility complex antigens, more commonly
known as MHC
• We have genes on our chromosome (number 6) that code for these antigens
• Each individual's MHC is therefore genetically determined (so inherited)
• As with all inherited features, variation occurs as a result of sexual reproduction
• Each of us therefore has a distinctive set of MHC antigens on the surfaces of most of our body cells
• Unless you have an identical twin, these MHC antigens are unique
• Lymphocytes have antigen receptors which recognise our own MHC antigens and can tell them apart from any
foreign antigens
• It is obviously critically important that our own body cells are not attacked by our immune system
• However, when making lymphocytes, every possible structure of antigen are made so the first step in maturation
of the lymphocytes is that those lymphocytes which are designed to recognise our own antigens are eliminated
• In the case of T cells, this occurs in the thymus
How it All Works
• When a neutrophil engulfs a pathogen, it destroys it completely
• Neutrophils are unspecific in their attack, they simply engulf anything ‘non-self’
• However a macrophage does not completely destroy the pathogen
• It keeps some of the cell surface antigens of the pathogen and places these in its own membrane
• It then leaves the circulation and moves to the areas where the lymphocytes are
• It is an antigen-presenting cell
• On arrival of this antigen presenting cell, B cells with surface receptors (antibodies) line up to ‘look at’ the antigen
to see if they are the one that has the complementary antibodies
• Those that do will bind to it
• The antigen is taken into the cytoplasm of the B cell by endocytosis before being expressed on the cell surface
membrane of the B cell
• Meanwhile T cells can only respond to antigens when they are presented on the cell surface membranes of other
cells
• T cells that have come in contact with the macrophages acting as antigen presenting cells and that recognise the
antigens become activated helper T lymphocytes
• Activated T cells now bind to B cells with the same antigen expressed on their membrane
• The B cell is activated by the T cell to become an activated B lymphocyte
Clonal Selection and Clonal Expansion
• Activated B cells now divide very rapidly by mitosis forming a mass of cloned cells, known as plasma cells
• These cells are full of RER, which start to mass-produce antibodies
• The antibodies are then released from the cells by exocytosis in huge numbers (at the rate of about 2000
molecules per second per cell)
• These antibodies pass into the blood stream and tissue fluid and overwhelm the pathogen
• The selection of the correct B cell is known as clonal selection and the rapid division of the chosen cell is clonal
expansion
Memory Cells
• After the antibodies have tackled the pathogens and the disease threat is over, the antibodies disappear from the
blood and tissue fluid
• So do most of the B and T cells responsible for their production
• However, certain of the specifically chosen lymphocytes are retained in the body as memory cells
• These are very long-lived cells, unlike the plasma cells
• They will be on stand-by in the event of a further infection by the same pathogen so that the response to infection
will be so much faster we won't feel any symptoms
Cell Mediated vs Humoral Response
• T killer cells carry out a cell mediated response, they do not secrete antibodies, but they tend to go to the site
required and do the job themselves
• B cells do not travel to the site of infection, rather they produce antibodies which travel in the body fluids and do
the work
• B cells are therefore described as carrying out a humoral response
Leukaemia
• All the white blood cells in the body originate from stem cells in the bone marrow
• There are two groups of these:
- Myeloid stem cells, which produce neutrophils, monocytes, and platelets
- Lymphoid stem cells, which produce lymphocytes (B and T)
• These stem cells divide rapidly to produce huge numbers of mature, differentiated blood cells that function in
various ways in the immune response
• Leukaemias are cancers of these stem cells
• The cells divide uncontrollably to give many cells that do not differentiate properly and disrupt the production of
normal blood cells, including red blood cells and platelets
• These malignant cells fill up the bone marrow and then flow out into the blood and the lymphatic system
• There are myeloid or lymphoblastic leukaemias depending on which of the stem cells is affected
• The immature white blood cells are produced very quickly and disrupt the normal balance of things in the blood
• The body does not have enough red blood cells or platelets
• This causes anaemia and increased risk of excessive bleeding
• The number of mature neutrophils and lymphocytes drop so people become immunosuppressed (more
susceptible to infection)
• There are acute and chronic forms of leukaemia
• Acute forms develop very quickly, have severe effects and need immediate treatment
• Chronic leukaemia may take many years to develop and changes in blood counts are usually monitored over time
so treatment can be given at a time when it is most likely to be effective
Antibodies
• All antibodies are globular glycoproteins with a quaternary structure
• They form the group of plasma proteins known as immunoglobulins
• The basic model of all antibodies is that they consist of two 'long' or 'heavy' chains and two 'short' or 'light' chains
which are connected by strong disulphide bridges (covalent bonds)
• Each molecule has two identical antigen binding sites which are formed by the ends of the light and heavy chains Hinge
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