ALLERGIES AND THE DEFENCE AGAINST DISEASES.

A couple of years ago, a major medical journal reported the tragic case of a teenage girl who died within 20 minutes of taking a health supplement containing ‘royal jelly’, the substance made by queen bees. Sudden death in young people usually makes headlines, particularly when it seems to be related to a trivial event such as taking a normally harmless food supplement. But similar deaths have also occurred as a result of a bee sting.

^Pixabay

The victims all have in common a very rare and severe allergy. Just as some of us suffer from hay fever in the summer because we react to pollen in the air, some people ‘over-react’ to the ‘foreign’ proteins produced by bees.

Normally, when someone is stung by a bee, the result is a painful red swelling that disappears again in a couple of days. In someone who is allergic to bee protein, the effects can be catastrophic. As soon as the poison gets into his or her bloodstream, many of the white cells release large amounts of histamine and other chemicals that cause severe inflammation.

Fluid builds up in the tissues and the smooth muscles contract. The whole body is affected and both blood volume and blood pressure quickly plummet. Sometimes, the airways in the lungs narrow so much that the affected person can no longer breathe. These symptoms, collectively known as Anaphylactic shock, can happen very quickly and can be fatal unless immediate treatment with adrenaline and antihistamines is available.

INTRODUCING IMMUNITY

We are surrounded by bacteria, viruses, fungi and other organisms that are capable of invading our bodies and causing disease. We are able to overcome infections by these pathogens (disease-causing organisms) because we have an immune system. This is a complex system involving many different cells and tissues that allows us to develop immunity – resistance to infections.

Common pathogens include bacteria, fungi, viruses and protoctists. This last group includes microscopic parasites such as Plasmodium, which causes malaria, and larger parasitic animals such as tapeworms. A pathogenic organism is able to:

• break through the physical barriers of the body and enter tissues or cells,

• resist the efforts of the immune system to destroy it, long enough to multiply inside the host’s body,

• get out of one host and into another,

• damage the host’s tissues – either directly, or indirectly by means of toxins (poisons) that it releases. Some bacterial exotoxins, such as the one produced by E. Coli O157, which has caused epidemics of gastroenteritis in the past few years are very powerful and can be fatal.

The easiest way to start understanding the immune system is to look first at its overall functions, rather than concentrating on the individual parts. The figure below summarises the main lines of defence that an organism comes up against when it tries to infect a healthy person.

^{An illustration by me showing the overview of the body's defences: non-specific responses are general responses to damage. They include inflammation and phagocytosis of debris. Specific responses are targeted against individual types of microorganism.}

We will look at each of these in more detail in the sections that follow. This article on the immune system will cover:

• The ability of the immune system to distinguish between invading organisms and the tissues of its own body. This concept of self and non-self is important in determining whether the immune system keeps the body healthy, or whether it is overcome by infection.

• Problems of the immune system. We will get to see how the body can react against its own tissues, causing autoimmune disease.

• How medicine today can manipulate the immune system to provide life-saving treatments such as vaccines, blood transfusions, organ and tissue transplants.

THE BODY’S BARRIERS TO INFECTION

One of the most obvious ways to avoid infection is to stop potential pathogens getting into the body in the first place. The four main strategies that the body uses are summarised below:

• Mechanical defence: Nasal hairs filter the air that is drawn into the upper airways. Cilia, which line the airways, sweep bacteria and other particles away from the lungs.

• Physical defence: The skin, made from stratified squamous epithelium, forms a tough, impermeable barrier that normally keeps bacteria and viruses. The mucous membranes that line the entry points to the body such as the nose, eyes, mouth, airways, genital openings and anus produce fluids and/or sticky mucus. These fluids trap out microorganisms and stop them attacking the cells underneath.

• Chemical defence: Fluids such as sweat, saliva and tears contain chemicals that create harsh environments for microorganisms. Sweat
Contains lactic acid and the enzyme lysozyme, both of which slow down bacterial growth. Stomach acid kills many microorganisms that manage to get that far. When we are injured, blood clots at the injury site, sealing the breach to prevent entry of bacteria.

• Biological defence: Normally, a vast number of non-pathogenic bacteria live on the skin and mucous membranes. These do not harm the body but they out-compete pathogenic bacteria, preventing them from gaining a foothold from which to launch a full-scale infection.

BLOOD CELLS AND DEFENCE AGAINST DISEASE

BLOOD CLOTTING

Whenever blood vessels break, blood leaks out and clots. We can see this happening when we cut ourselves, but blood can also clot deep inside the body. Clotting enables the body to avoid blood loss and, at the surface, to prevent infection. It is important that blood clots only when it should, because when a blood clot, and
a thrombus, blocks a vital blood vessel, it can cause a fatal heart attack or stroke.

Let's be reminded that the process of thrombosis causes blood to clot inside vessels. The clot itself –a thrombus– can be fatal if it prevents blood from reaching vital tissues such as heart muscle. A coronary thrombosis is a common cause of heart attack while a thrombosis in the brain can cause a stroke.

The illustration below outlines the major steps involved in the control of blood clotting.

^{An illustration drawn by me.}

When blood vessels are injured or burst, a cascade reaction is initiated. The activation of one molecule leads to the activation of many more. In the final steps of the process, an inactive enzyme, prothrombin, is converted to active thrombin. This form of the enzyme converts soluble fibrinogen into insoluble fibrin. The fibrin fibres form the mesh that traps red blood cells and forms a clot.

If any of the factors in the cascade are missing, the blood cannot clot. This occurs in the condition haemophilia, a sex-linked genetic disease in which the sufferer (usually a male) cannot make factor VIII.

CLASSIFICATION OF WHITE CELLS

^{Blood smear from a normal healthy adult

Wikimedia, Keith Chambers • CC BY-SA 3.0}

The figure above is a blood smear showing some white cells leucocytes along with many red blood cells. The red cells outnumber the white by about 700 to 1. White cells are made in the bone marrow and are found throughout the body. They can move and are able to squeeze between cells, passing freely in and out of the circulation. Individual types of white cell are classified according to their appearance, origin or function as shown in the table below.

A table showing the different types of white cell.
Neutrophils, eosinophils and basophils have a granular cytoplasm and are therefore called granulocytes. The other types are called agranulocytes.

Cell type	How to recognise them	Relative abundance	Function
Neutrophils	Lobed nucleus	57	Phagocytosis
Lymphocytes	Large round nucleus; little cytoplasm	33	Specific immunity;B cells make antibodies, T cells involved in cell-mediated immunity
Monocytes	Large, kidney-shaped nucleus	6	Phagocytosis; monocytes develop into macrophages: general ‘rubbish collecting’ cells
Eosinophils	Stain red with eosin	3.5	associated with allergy
Basophils	Stain with basic dye	0.5	release chemicals such as histamine that are responsible for inflammation

THE NON-SPECIFIC IMMUNE RESPONSE

When the body is damaged by cuts, scratches or burns, or is attacked by a pathogenic organism that manages to breach its defences, it produces a non-specific immune response. It is called a non-specific response because it occurs in response to tissue damage itself, not to the cause of the damage.

INFLAMMATION

Inflammation is a rapid reaction to tissue damage. Whether it is in response to a cut, insect bite or a heavy blow such as a sport injury, the classic signs of inflammation are always the same:

• Redness– blood vessels dilate, increasing blood flow to the area.

• Heat – also caused by the extra blood flow.

• Swelling – extra blood forces more tissue fluid into damaged tissues.

• Pain –swollen tissues press on receptors and nerves. Also, chemicals produced by cells in the area stimulate the nerves.

Inflammation is triggered by damaged cells. Ruptured cells and some white cells (mast cells and basophils) release ‘alarm’ chemicals such as histamine. These substances dilate blood vessels and the increased blood flow leads to the classic signs of inflammation. The alarm chemicals also attract white cells that remove bacteria and debris by phagocytosis.

Why inflammation is useful

Inflammation prevents the spread of infection and speeds up the healing process. It also provides a way of telling the rest of the immune system what is going on. When microorganisms are phagocytosed, fragments of their cells (particularly molecules that were originally on their surface) are processed by the phagocytes. Some of these surface molecules, which we call antigens, allow the specific immune system to recognise and remember the type of microorganism that has tried to invade the body.

Antigens stimulate the specific immune system to produce cells and chemicals that bind specifically to that antigen, and to no others. I'll discuss more about specific immunity in my next post.

Phagocytosis

Neutrophils are the commonest type of white cell. Together with monocytes, they are known as phagocytes because of their ability to ‘eat’ pathogens by phagocytosis. In this process, the white cell engulfs the pathogen, takes it into a vacuole inside its cytoplasm and then digests it with lytic enzymes.

^{Scanning electron micrograph of a neutrophil phagocytosing anthrax bacilli (orange)

Volker Brinkmann • CC BY 2.5}

Phagocytosis involves the following steps:

• The membrane of the neutrophil extends and surrounds the bacterium.

• The bacterium ends up inside the cell cytoplasm, contained within a vacuole.

• Lysosomes that contain digestive enzymes and free radicals fuse with the vacuole that has the bacterium inside.

• The bacterium is digested into fragments within the vacuole.

• Part of the vacuole buds off, taking some of the bacterial fragments with it.

• The fragments then attach to proteins of the major histocompatibility complex (MHC).

• When the vacuole fuses with the cell membrane, the bacterial fragments, bound to MHC proteins become part of the cell membrane and stick out from the surface of the neutrophil.

• The antigens of the bacterium are 'presented' on the outside of the neutrophil. They can now be 'seen' better by other cells of the immune
System, enhancing the immune response against the bacteria.

The MHC comprises a group of genes in the human genome. It is important in the development of immunity. The proteins coded for by the genes are expressed on the outer surface of all body cells and are commonly called 'self antigens'. These allow our immune system to tell what is self and what is not.

An antigen is a molecule or part of a molecule, for example, protein, that is detected by the specific immune system as 'foreign': not part of the host's body. The immune system responds to an antigen by producing a very specific protein, antibody, which reacts with that antigen, and that antigen only.

MHC proteins are attached to antigens from invading bacteria, viruses and parasites to stimulate the cell-mediated immune response proteins from the MHC.

Autoimmune disease: when the body attacks its own tissues

In people who have an autoimmune disease, the mechanism that enables the immune system to tell what is self and what is non-self breaks down. T and B cells (types of lymphocytes) begin to attack the body’s own cells and tissues. This is the underlying cause of multiple sclerosis, insulin-dependent diabetes, myasthenia gravis and rheumatoid arthritis.

510px-Antibody.svg.png

^{An illustration that shows how antigens induce the immune system response by interacting with an antibody that matches the antigen's molecular structure.

Fvasconcellos 19:03, 6 May 2007 (UTC) • Public domain}

In multiple sclerosis, T cells attack the myelin sheath around nerves. This severely limits nerve function, resulting in loss of movement and sometimes in blindness.

In insulin-dependent diabetes, the body makes antibodies that destroy the B cells in the Islets of Langerhans in the pancreas. This means that the pancreas becomes unable to produce insulin and the affected person can no longer control their blood glucose.

In myasthenia gravis, the body makes antibodies that attack the motor end plates, the specialised synapses that connect motor nerves to muscles. If the motor end plates become damaged, the muscles cannot contract.

Finally, the first symptom of this disease, which affects one in 30 000 people (mainly female), is rapid tiring during exertion. The muscles become progressively more unresponsive and the affected person can have difficulty breathing.

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