In this section you’ll learn about immunology and the Defence Against Infectious Disease.
We are surrounded by microbes in the air, on the ground and all other surfaces, and in our food and
water. So if we are constantly being bombarded with potentially infectious and deadly microorganisms Why are we able to combat them and survive?
The reason we are still alive is because humans (and all other animals) have a very elegant and powerful defence mechanism known as – The Immune System.
The Immune System
The parts of the immune system are spread all over the body. They include: -
The lymph and blood vessels. These transport pathogens and leukocytes all over the body.
The lymph nodes. These contain millions of phagocyte and lymphocyte cells, which identify and remove pathogens from lymph.
The spleen. This also contains millions of phagocyte and lymphocyte cells, which identify and remove pathogens from blood.
The thymus. This is where blood stem cells are differentiated into T-lymphocytes.
The cells of the immune system.
The cells of the immune system are the white blood cells (or leukocytes).
Leukocytes are derived from stem cells, which are produced in huge numbers in the bone marrow (the soft centre of large bones). These stem cells differentiate to form dozens of different kinds of leukocytes, which fall into four categories: -
Phagocytes - for phagocytosis. e.g. Macrophages, Neutrophils & Monocytes.
Granulocytes - for inflammation. e.g. Mast cells, Eosinophils & Basophils.
T Lymphocytes - for cell-mediated immunity. e.g. Helper T-cells, Killer T-cells & Memory T-cells.
B Lymphocytes - for antibody-mediated immunity. e.g. B-cells Plasma B-cells Memory B-cells.
Download and Complete this diagram showing the 4 categories of white blood cells (Leukocytes)
Phagocytes and granulocytes are a part of the Non-Specific Immune System whilst T and B lymphocytes are a part of the Specific Immune System.
The phagocytes and the granulocytes form the non-specific immune system, which kills pathogens
quickly and indiscriminately. Although effective, the non-specific immune system does not "learn
from experience", so it does not lead to immunity to a disease.
The B and T lymphocytes form the specific immune system, which is a more complex and sophisticated series of events that not only kill invading pathogens, but also remember the pathogen's features. Thus, that pathogen can be killed quickly on subsequent infections. While all animals have a non-specific immune system, only vertebrates have a specific immune system, which leads us to believe the specific immune response is a evolutionary adaptation conferring and survival advantage.
The key difference of the specific immune system is that it is capable of recognising foreign
cells as distinct from its own cells, an ability called self/non-self recognition, Which is achieved by making use of antigens.
A Level Biology - T-Cells and Antigens
So, What are antigens?
An antigen is a large molecule (protein, glycoprotein, lipoprotein or polysaccharide) on the outer
surface of a cell. All living cells have these antigens as part of their cell membrane or cell wall.
Remember the basic structure of a virus? Well, the capsid proteins of viruses and even individual protein molecules can be classed as antigens.
What is the purpose of an antigen?
An antigens purpose is for cell communication. Cells from different individuals have different antigens, Whereas all the cells of the same individual have the same antigens.
Antigens are genetically controlled, so close relative have more similar antigens than unrelated individuals.
Blood groups are an example of antigens on red blood cells (but remember, all cells have them).
What are Lymphocytes?
There are two kinds of lymphocyte – B-lymphocytes (or just B-cells) and T-lymphocytes (or just T-cells).
B-cells are called that because they mature from stem cells in the Bone marrow.
T-cells are called that because they mature from stem cells in the Thymus.
B-cells make antibodies.
An antibody (also called an immunoglobulin) is a protein molecule that can bind specifically to an antigen.
Antibodies all have a similar structure composed of 4 polypeptide chains (2 heavy chains and 2 light chains) joined together by strong disulphide bonds to form a Y-shaped structure. The stem of the Y is called the constant region because in all immunoglobulins it has the same amino acid sequence, and therefore same structure.
The ends of the arms of the Y are called the variable regions of the molecule because different immunoglobulin molecules have different amino acid structure and therefore different structures.
These variable regions are where the antigens bind to form a highly specific antigen-antibody complex, much like an enzyme-substrate-complex.
A Level Biology - The Immune System: Antibody Structure and Function
Each B-cell has around 100000 membrane-bound antibody molecules on its surface and can also secrete soluble antibodies into its surroundings. Every human has around 100000000 different types of B cell, each making antibodies with slightly different variable regions. Between them, these antibodies can therefore bind specifically to 100000000 different antigens, so there will be an antibody to match almost every conceivable antigen that might enter the body.
T-cells have receptor molecules on their surfaces which are very similar, but not identical, to antibodies.
These receptors also bind specifically to antigens to form antigen-receptor complexes.
Each T-cell has around 100000 receptor proteins, and again there are about 100000000 different types of T-cell, each with slightly different receptor molecules, so they can also specifically bind to any conceivable antigen.
T-cells do not secrete soluble proteins.
The B and T cells are exposed to so many "self" antigens on every normal cell they come across, that they quickly "learn" to recognise them very early in life. From then on self antigens are ignored, but any non-self antigens are recognised and stimulate an immune response…
The immune Response.
Three Lines of Defence: Humans have three lines of defence against invading pathogens: -
1. Physical Barriers – the skin and associated chemicals stop microbes entering the body.
2. The non-specific immune system – phagocytes quickly destroy microbes that pass the first line of defence
3. The specific immune system – lymphocytes kill any microbes that pass the second line of defence, and remain on guard for future attacks.
The First Line of Defence – Physical Barriers
The body has many mechanism to try to stop microbes entering the body, particularly the bloodstream.
The skin is a tough, impenetrable barrier (which is why we use it to make leather shoes). The
outer layer, the epidermis, is 20-30 cells thick (about as thick as a sheet of paper) and its cells are
toughened by the protein keratin. The next layer, the dermis, is 20-40 times thicker and provides
the main structure for the skin as well as all the receptor cells, blood vessels and hairs. Cells are
constantly being lost from the surface of the skin (to form dust) and are replaced by new cells
from further down.
Sweat and tears, secreted by glands in the skin, contain lysozyme enzymes, which destroy (lyse)
bacteria growing on the surface of the skin by digesting their peptidoglycan cell walls.
The digestive tract is a potential entry route for pathogens, but it is protected by concentrated acid
in the stomach, which denatures microbial enzymes and cell surface proteins, as well as protease
enzymes. Saliva also contains lysozymes.
The respiratory tract is another potential entry route, but it is protected by sticky mucus secreted
by glands in the bronchi and bronchioles, which traps microbes and other particles in inhaled air
before they can reach the delicate alveoli. Mucus contains lysozymes, and cilia constantly sweep
the mucus upwards to the throat, where it is swallowed so that the microbes are killed by the
The human body is home to billions of bacterial cells called variously the natural microbiota, the
normal flora, the commensal flora (because they have a non-harmful or commensal relationship
with their host) or even the "friendly bacteria". There are more bacteria cells in a human than
there are human cells. These commensal bacteria colonise the skin, mouth, lower digestive tract,
respiratory tract and vagina, and they help prevent infection by out-competing pathogenic microbes
for food and space.
The Second Line of Defence – The Non-Specific Immune System
The second line of defence is the non-specific immune system, a host of quick, non-specific methods of killing microbes that have passed the first line of defence and entered the body. Some of the main methods are: -
Phagocytosis. Phagocytes are large, irregularly-shaped leukocyte cells that remove bacteria, viruses, cellular debris and dust particles. The phagocytes are constantly changing shape, and they flow over microbes, surrounding and ingesting them through the process of phagocytosis to form a phagosome. The phagosome then fuses with lysosomes - small vesicle containing lysozymes, which are released into the phagosome, killing and digesting the microbe. Different phagocyte cells work in different locations: neutrophils circulate in the blood, while macrophages are found in lymph, tissue fluid, lungs and other spaces, where they kill microbes before they enter the blood.
A Level Biology - Phagocytosis
Complement System. This comprises more than 20 different proteins, which kill microbes by
making pores in their cell membranes and can also inhibit viral reproduction inside cells. They are
also involved in activating other parts of the immune system.
Inflammation. This is a localised response to an injury or infection. The granulocyte cells and the
affected cells release chemicals, including histamines and prostaglandins, which stimulate: vasodilation to increase the flow of blood to the area (so the area turns red); capillary leakage so that
phagocytes and granulocytes can enter the local tissue fluid (so the area swells); sensory neurone
impulses (so the area is tender or painful); blood clotting to seal a wound (so a scab is formed).
The dead pathogens and phagocytes, together with excess tissue fluid, are release as pus. The
chemicals also help to stimulate the specific immune response (see below).
Fever. This is caused by pyrogen chemicals, which include some of the inflammation chemicals
as well as bacterial endotoxins. These stimulate the hypothalamus of the brain to increase the
body's temperature from 37°C up to 39°C. This helps the immune system and inhibits growth of
some pathogenic bacteria.
The Third Line of Defence – The Specific Immune System.
1. Antigen Presentation
Infection is started when cells with non-self antigens enter the blood of tissue fluid. The antigens
can be from a variety of sources:
a virus capsid protein or envelope protein.
on the surface of a bacterial cell.a toxin released from a bacterium.
on a macrophage that has ingested a pathogen.
on the surface of cells of a transplanted organ.
on a cancerous cell
on a cell infected with a virus so that it has viral proteins on its surface
Macrophages are the most important antigen-presenting cells because they are the most numerous.
They constantly inspect the surface of every cell they come into contact with in the blood, spleen,
lymph nodes, tissue fluid and alveolar spaces. If the antigens are not recognised as self antigens,
then the macrophage ingests the antigen and its cell by phagocytosis. Some of the antigens pass to
the surface of the macrophage, which thus becomes an antigen-presenting cell. This amplifies the number of antigens. The macrophage also secretes cytokine chemicals (also called lymphokines or
interleukins) to stimulate the lymphocytes.
2. Clonal Selection
At birth we have less than 100 copies of each type of B or T lymphocyte. Whenever a particular antigen enters the body it comes into contact with all the various cells in the blood and lymph,
including the lymphocytes. Sooner or later the antigen will encounter a lymphocyte with a matching
receptor molecule, to which it can bind tightly. As soon as a match is found, the binding of the antigen to the receptor stimulates the lymphocyte to divide repeatedly by mitosis, making an army of about 1000000 identical cloned B and T lymphocyte cells. This is called clonal selection, because only the selected cell is cloned. This army of clones can now destroy the infecting microbe…
3. T-Cells and Cell-Mediated Immunity
The T-lymphocytes differentiate into cells with different functions.
Cytoxic T-cells (or killer T-cells) bind to antigens on infecting cells and kill the cells by releasing
perforin proteins. These insert into the cell membrane of the other cell, where they make a pore,
which allows water to diffuse in so that the cell bursts.
Helper T-cells bind to antigens on infecting cells and secrete chemicals called cytokines. These
stimulate all the other white blood cells (phagocytes, granulocytes and B lymphocytes) and speed
up the immune response. The AIDS virus HIV destroys these helper T-cells, and the immune
system doesn't work nearly as well without them.
Memory T-cells remain the blood for many decades after the infection. This means that the same
antigen will be identified much more quickly in a subsequent infection, when the memory T-cells
will quickly divide to form cytoxic T-cells and helper T-cells.
A Level Biology -
The Role of T-Cells in the Immune System Response