The Immune System – What Is It And How Does It Operate

Immunology, immune system
Image by Bruno /Germany from Pixabay

Immunology is the study of the host’s defense mechanisms which we call the immune system, against a range of foreign chemicals, bacteria, viruses and other materials that might cause harm.

Immunity is the ability of the host to protect itself in particular against foreign organisms.

The immune response is the phenomenon of using the immune system to mount a defense against these foreign materials. The immune system includes all these cells and tissues, and molecules.

A  Short History Of Immunology

Back in Ancient Greece, around 430 BC, the Peloponnesian War was raging. Thucydides examines the outcomes of a great plague. he noticed that those who recovered from the disease were able to nurse other who were sick without having the disease a second time. It was a good description of acquired immunity.

In the 1400s, the Chinese and Turks used dried crusts of smallpox as a ‘vaccine’ against the aforementioned disease. 

The first application of a vaccine is in 1798 when Gloucestershire born Edward Jenner uses cowpox as a vaccine to treat smallpox having noticed that milkmaids who had cowpox never caught smallpox. He tested the cowpox on an 8 year old boy by scratching him with the cowpox virus. he then exposed him to smallpox but the boy was unaffected. The term vaccine was derived from the latin word for a cow which is ‘vacca‘ (incidentally a 1st declension, feminine noun).

The Function Of The Immune System

Two immune systems operate:-

(1) The natural, non-adaptive or innate immune system relies on skin, saliva, tears, acids produced in the vagina for example and mucus. It is a common property of all living creatures. It is our first line of defense and of the immune response.

(2) The adaptive or acquired immune system operates at a cellular level. It involves specialist cells, specific biomolecules such as cytokines and antibodies. It also involves specialised mucosal lymphoid tissue.

It is part of the second line of defense and works in conjunction with the innate immune response especially if this one does not immediately work.

This system is highly specific and with this system comes a ‘memory’ too. It relies on mechanisms that adapt following infection and is ‘managed’ by T- and B-lymphocytes.

The two immune systems operate to protect us against malignant microorganisms including bacteria, yeasts and fungi and viruses which are all collectively known as pathogens. It also operates against much larger organisms such as  parasites including tapeworms, helminths (flukes) and malaria parasites.

They also have another function which is to eliminate damaged or malignant cells such as cancer and tumour cells.

Antigens And Antibodies

An antigen is a substance which is introduced into the body and stimulates the production of biomolecules called antibodies. More specifically, antigens are glycoproteins which reside on the cell surface membrane of a pathogen and stimulate or elicit an immune response. 

These antibodies are highly specific to the antigen and help the immune system to eradicate the foreign body.

Complete antigens are substances that induce antibody formation by themselves and react specifically with the antibodies. There are also incomplete antigens called haptens which are substances that are unable to induce antibody formation by themselves but become ‘immunogenic’ when they are bound to proteins. These proteins are called carrier proteins and occur in tow types, simple or complex.

Our First Line Of Defense In Immunology: The Innate Immune System

The first line of defense refers to the innate immune system. This includes the Itegumentary System such as the skin, mucous membranes and mucous itself. These all form a physical barrier which prevents access by microbes and pathogens. This is backed up by a ‘chemical’ system that is the innate immune system described next.  

Innate Immunity

The defining features of the innate immune system are the following:

  • It is present in all multi-cellular organisms whatever their level of sophistication.
  • The response is immediate.
  • It is sophisticated enough to recognise foreign or ‘non-self’ particles and discriminate these from the ‘self’ i.e. those parts, structures and biological molecules associated with the host which is the operator of the innate immune system.
  • The innate immunity system does not generate an immunological memory.
  • Any receptors of foreign material are germline encoded. That means the genetic material that encodes for receptors are present in cells of the egg, sperm and fertilised egg. It means these receptors are also inheritable whereby they pass on their genetic material to their offspring (progeny). 

Nonspecific host defenses which operate in the body do not rely on exposure to an antigen. They do not involve antibodies!

Skin secretions tend to have an acid pH which acts as a hurdle to bacterial growth. The sebum which comes from specialist cells in the skin also produces natural antimicrobials which are toxic chemicals to bacteria. A vaginal section for example is probably the most acidic secretion known outside of the acidic pH in the stomach. .

The stomach is lined with mucosae whose secretions will kill most pathogens. The mucosa produce and then release strong acid which is hydrochloric acid (HCl) along with an acidic protease enzyme called pepsin. Pepsin is highly active at low acidic pHs around pH 2.

Our tears or lachrimal fluid washes the external eye surface and contains another powerful protease amongst many called lysozyme which kills bacteria.

We also produce mucous (snot) which is a sticky thick viscous fluid in our nose and other parts that literally traps microorganisms. We use cilia in nasal cells to move these packets of fluid, which is one of the reasons we are compelled at times to clear our throat or blow our nose. Colloquially, we call that mucous snot!

The Second Line Of Defense In The Immune System

When a pathogen enters the body, a series of secondary nonspecific defenses are put in place. The skin would normally be our first line of defense because it is an effective barrier that acts passively by preventing foreign substances entering. If there is a cut, a pathogen might enter and stimulate an inflammatory response.

In the inflammatory response, the pathogen such as bacteria stimulates an increase in blood flow to the infected area. The blood vessels expand in that area and white blood cells leak from vessels to invade the infected tissue.

The white blood cells called phagocytes engulf and destroy the bacteria. 

The infected area also becomes red and swollen, and also painful during inflammation.

The pathogen can also stimulate the immune system to release chemicals that raise body temperature. This is a fever. Increased body temperature helps slow down or even stop the reproduction of the pathogen and in turn speeds up the overall immune response.

Organs Of The Immune System

There are two distinct groups of organs involved in the immune system. These are the primary and the secondary lymphoid organs.

The primary lymphoid organs include the bone marrow and thymus which are ‘maturation’ sites.

The secondary lymphoid organs include the spleen and lymph nodes. There are also two type of lymph tissue: MALT (mucosal associated lymph tissue) and GALT (gut associated lymph tissue).

Cytokines 

Cytokines are small peptides and proteins which are released by cells to attract others that are part of the immune system. They are a significant part of the weaponry of the body in organising the immune response. 

Classic examples include the interferons (IFNs) which are natural proteins produced by specific cells of the immune system in vertebrates. They are produced in response to a challenge by foreign substances such as parasites, viruses and tumour or cancer cells. It is said that interferons are more useful than antibodies.

The chemokines are similar types of peptides that attract macrophages to places of inflammation.

Phagocytes

Phagocytes are cells that exist as macrophages or as neutrophils. Both cells engulf and digest pathogens by fusion of the phagosome with lysosomes.

Lymphocytes

The immune system is composed of numerous different cells which include the lymphocytes. The lymphocytes are subdivided into T-lymphocytes, the B-lymphocytes or plasma cells and the natural killer lymphocytes. We also have the monocytes which are known as macrophages too.

Then there are the granulocytes which are divided into three groups – the neutrophils, eosinophils and finally the basophils.

The T and B cell lymphocytes are produced from stem cells that grow in the bone marrow. The mature in different lymphoid organs: the B cells mature in the bone marrow itself whilst the T calls mature in the thymus.

The Neutrophils

The neutrophils are granulocytes which are 10 to 14 microns in diameter. They are characterised by having a nucleus which is multilobed, from 1 to 6 lobes and are often described then as polymorphonuclear leucocytes. The young cells have a single horseshoe shaped nucleus which develops lobes as it gets older. The lobes are connected to each other by chromatin threads. The cytoplasm of these cells contain granules which are neutrally stained hence their name. They have a half-life in the blood circulation of 6 hours.

There are 4 different types of granules present in a neutrophil. The first is the primary or azurophilic granule. They have an extremely important role in destroying bacteria. They have fewer different types of enzymes than other neutrophils but what they produce is extremely potent and toxic to any bacteria. They produce myeloperoxidase which produces HOCl that works by free radical attack to kill bacteria. The lysosomal granules contain acid hydrolases that digest bacterial cell walls, elastase, protease itself and alpha-1 antitrypsin. They produce antimicrobial proteins such as cathepsin-G and the alpha and beta-defensins. Generally, they are also involved in tissue destruction during inflammation.

The Lymphocytes

 There are two types:-

  • B lymphocytes which look after humoral immunity.
  • T lymphocytes which do not produce antibodies but are part of the cell-mediated arm of immunity.

T Lymphocytes (T Cells)

The T cells or T lymphocytes are a type of white blood cell (WBC). All white blood cells are present to protect the body from infection. This is the main role of the T-cells in particular. A number of different types of T-cells are known which act in various ways where they identify, directly attack and destroy a range of different infectious agents. They are operate alongside other WBCs which have described here in this protection capacity.

We know of three types. One set are the helper T-lymphocytes (CD4+). These cells stimulate and activate B lymphocytes which divide and become phagocytes. These activated B lymphocytes will secrete antibodies that serve as marker proteins that enlist phagocytes to go on to kill microbes.

The second set are the cytolytic or cytotoxic T-lymphocytes (CD8+). These cells destroy abnormal cells  and infected cells containing microbes or microbial proteins using a protein called perforin.

The third set are the T memory cells which remain in the blood for many years and provide the long term protection.

B Lymphocytes

The B-lymphocytes (B-cells) are a type of white blood cell that produce the antibodies to attack bacteria and nullify toxins. The B- nomenclature comes from the word bursa which is derived directly from the latin 1st declension feminine noun for purse or provider of funds as in bursary. They develop from stem cells in the bone marrow to become these particular cells.

The B-cells are covered with thousands of B-cell receptors (BCRs) which can match with antigens. The can also be described as ‘cognate’ antigens because they are recognizable. As soon as the antigen binds to the receptor on the B-lymphocyte it triggers repeated division. These B-cells proliferate to become either memory B lymphocytes or effector B lymphocytes.

The effector B cells become known as plasma B-cells. Only when they have become these plasma cells will they start to secrete antibodies. The plasma cells can only live for a few days but they produce an enormous amount of antibodies.

The B memory cells which like the T memory cells will remain in the blood for ever virtually and provide the long term protection.

Immunoglobulins/Antibodies 

Antibodies are also immunoglobulins which are composed of two heavy chains and two light chains. The chains are bound together using disulphide links. The protease enzyme papain is used to cleave immunoglobulins at specific sites. 

The Cell Mediated Immune Response

The primary response is the production of specific clones of effector T cells and memory clones. These develop after several days following infection but do not limit the infection.

As you can see animals have two principal defense mechanisms: the innate system and the inflammatory response. These are two main lines of defence against attack by a range of organisms, against particles and various chemicals.

Revised: rewritten sections on B cells from March 25th, 2021.

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