Introduction

Biologicals is a Wide and varied subject to talk about, from the starting of its manufacturing, intermediate steps of manufacturing quality controls to final product. This discussion will obstruct the comprehension of the readers, and what is interesting for us is that they have a plain knowledge.

Biologicals can be defined as complex substances obtained through proteins, cells and others, produced using biotechnology involving life beings and their derivated for its creation, product modification or processes for specific uses.

These products can not be copied, its quality is related to many factors linked with the production process making them difficult to replicate.

History

On the group of the biologicals, there are the vaccines. Its name comes from the Latin vacca that jeans cow, because these animals were involved in the invention process of the first vaccines against human smallpox by the doctor Edward Jenner in England around the year 1796.

This process was made without knowledge of the existent of micro-organisms, immune system and the process of infection and contagion.

Louis Pasteur, called father of bacteriology achieved advances in the knowledge related to micro-organisms and also with the development of some vaccines and introduced attenuation methods, it is, weakness of the infectious agent (whose nature was still not known).

During XIX century there were constant advances about the knowledge of infectious agents (virus and bacteria), about the human body working. Particularly, the physiology of the immune system was described by Dr. Erlich (Nobel 1908). After that, it was discovered that some diseases were caused not by the bacteria itself but its toxins.

It is to say that the evolution theory presented by the english naturalist Charles R. Darwin in its work “The origin of species by means of natural selection” leads to think that evolution of species was accompanied by development of immune system according to complexity degree of adaptation medium, aquatic, terrestrial, aerial or by facing to different microbian agents of the environment to be able to survive in time until our days.

It was between the 30’s and the 60’s when several vaccines were developed.  Though, their limitations were acknowledged and were gradually improved.

From the 50’s, new methods of cellular culture were developed concurrently with research in the  understanding of microbial agents.

The advance in the knowledge of the immune system lead to the development of vaccines,together with their use in different animal species and in the defence mechanisms at phylogenetic scale according if mammals, birds or aquatic animals.

To reach an immunitary response of the organism it is necessary to be an antigen.

What is an antigen?

Is all that substances that can be recognised by the adaptative immune system, own or foreign. The antigens are usually proteins or polysaccharides. This includes parts of bacteria (capsule, cellular wall, flagels, fimbrias and toxins), virus, parasites or other micro-organisms. Lipids and nucleic acids are antigens only when combined with proteins or polysaccharides.

Protides or proteins are biopolymers, it is, are formed of a large number of simple structural repetitive units. These units are amino acids linked by peptidic bonds. Each antigen is defined by its antibody who interact by spacial complementarity.

What is an antibody?

Antibodies (also known as immune globulins, shortened as IG), are glycoproteins of the type gamma globulin. Can be found in the soluble form in blood or other body fluids of vertebrate and act as lymphocytes B receptors and are used by the immune system to identify and neutralize strange elements as bacteria, virus and parasites.

Immune system has capacity to project body against specific agents as bacteria, virus and toxins or own cells that have become strange. Because of this it is necessary to know the microbial agents involved in the development of different pathologies in each country, to include these agents in the vaccines to avoid disqualify our vaccine when in a moment they do not reduce the effect of the vaccine.

Lymphocytes B, are the responsible for the antibodies production after the first exposition to an strange agent. Antibodies are molecules that recognize the infectious agent and alert the immune cells to destroy it.

The role of antibodies is to recognize and destroy the strange agents and to achieve this target have to make several works at the same time as agglutinate the toxic agents, break cells, neutralise the agent or to opsonise, what means make the agent more susceptible to phagocytosis by the responsible cells to destroy the agent as the neutrophylles or the macrophages.

Lymphocytes T, act forming the “sensibilised cells” with reactive places on their membranes. T cells are attached to invasor agents and help to their removal. With these and other strategies, the immune system allow to fight against the presence and invasion of pathogen agents, however the system need previously to know how to recognise the agents that generates the disease (virus and bacteria)

Vaccines act by simulating the pathogen attack but without risk so the individual learns to recognise the infectious agent.

Immune system

To understand more about the immunitary system of the animals, it is necessary to differentiate between vertebrates and invertebrate.

Invertebrate (shrimps)

The have an innate defence mechanism consisting in the participation of cellular components (cells with phagocyte capability) carried by haemocytes, and of other soluble and humoral components taht will be involved in activation and liberation of molecules stored in haemocyte that can be anticoagulant, aglutinines, phenoloxydase enzymes, antimicrobian peptides and more.

Vertebrate

They have an adaptative or acquired immune system distinguished by the ability to recognize in an specific way an antigen (lymphocytes T and B present a wide diversity of specific receptors in the surphace of its membrane to recognize Wide diversity of antigenic structures), allow to remind previous expositions to the antigen (immune response maturation) Aspect to take into account when using a vaccine when a unique dose can not be enough for the organism to give an appropriate response to the infectious agent.

There are 7 classes of vertebrated according to the order (from less to more) grade of defence mechanism development, so we have:

1 Fishes without mandibles ( as lamprey)

2. Gristly fishes (shark)

3. Bone fishes (trout)

4. Amphibians:

Urodela (salamander)

Anura (frogs)

5. Reptiles:

Anapside (turtles)

Euriapside (snakes)

Archosaure (cocodriles)

6. Birds

7. Mammals

Vertebrate are the only animals having acquired or specific immune system; to generalize is difficult because of the large diversity of animals except some fishes without mandibles, the rest of animals starting at the cartilaginous fishes as sharks have lymphocytes T and B and can produce antibodies.

Organs generating immunity

Limphoid organs 

Presence of lymphocytes T and B in vertebrate is linked to the presence of lymphoid organs used in the production or differentiation of these cells. Although lymphoid tissues and organs are found in all vertebrate, these are highly evoluted from cartilaginous fishes to the mammals that have them with a higher complexity grade.

Thymus and spleen as primary lymphoid organ for lymphocytes T is found from the sharks and is maintained in all phylogenetic scale except in non mandible fishes.

Bone marrow is the primary lymphoid organ of B lymphocites in mainly all vertebrate but it didn’t appear until they were adapted to the land life. In this way, fishes don’t have bone marrow while amphibians have rests of lymphoid tissue in bones, being the marrow totally functional in amphibians (anure), reptiles, birds and mammals.

Kidney behaves as primary lymphoid organ of fishes and some amphibians, supplying the lack of bone marrow and lymphoid nodules in these animals.

In the case of birds, the primary lymphoid organ for B cells is Fabricio sack, and in sheep and swine, where more than the bone marrow Peyer plates in intestine have be involved.

Lymphatic ganglions are art of the haematopoietic tissue and appear as lymphoid organised structures in the phylogenetic scale constituted by primary follicles for B cells, rounded by T lymphocytes. They appear well defined in amphibians and can be found in the rest of vertebrate but with some differences between them and act against infections destroying micro organisms and toxins.

Only in birds and mammals (hot blood homoeothermic animals), appear germinal centres or secondary lymphoid follicles.

Vertebrate animals are the only animals capable to produce specific antibodies against a big quantity of pathogens. Referring to the number and types of immune globulins that can be found in them, it is shown a evolution to a higher quantity and complexity of the classes.