SPECIFIC HOST RESISTANCE &THE PRACTICAL ASPECTS OF IMMUNITY

ADELABU O.A

OUTLINE•Definition of key words

•Antibodies

•Immunity &its types

•Immune response

•Antigens

•Immunization

•vaccination

Specific host resistance: Ability of an organism(host) to recognize and defend itself against specific pathogens or antigens(foreign).

PRACTICAL ASPECTS OF IMMUNITY

Specific host resistance• is triggered when a pathogen evades the innate

immune system and generates a threshold level of antigen and generates "stranger" or "danger" signals activating dendritic cells.

The major functions of the acquired immune system include:

• the recognition of specific "non-self" antigens in the presence of "self", during the process of antigen presentation.

• the generation of responses that are tailored to maximally eliminate specific pathogens or pathogen-infected cells.

• the development of immunological memory, in which each pathogen is "remembered" by a signature antibodies or T cell receptors, this is also known as the "anamnestic response". These memory cells can be called upon to quickly eliminate a pathogen should subsequent infections occur.

specificity• T cells compare non-self antigens to HLA

(human leukocyte antigens) molecules• Antigens can be proteins, polysaccharides or

glycoproteins components of pathogens• An antigen announces its foreignness by

means of intricate and characteristic shapes called epitopes, which protrude from its surface. Most antigens, even the simplest microbes, carry several different kinds of epitopes on their surface; some may carry several hundred. However, some epitopes will be more effective than others at stimulating an immune response.

Specific host resistance

• its remarkable ability to distinguish between the body’s own cells, recognized as “self,” and foreign cells, or “nonself.”

• The body’s immune defenses normally coexist peacefully with cells that carry distinctive “self” marker molecules. But when immune defenders encounter foreign cells or organisms carrying markers that say “nonself,” they quickly launch an attack.

• Anything that can trigger this immune response is called an antigen

Antibodies Proteins that recognize and bind to a

particular antigen with very high specificity. Made in response to exposure to the

antigen. One virus or microbe may have several

antigenic determinant sites, to which different antibodies may bind.

Each antibody has at least two identical sites that bind antigen: Antigen binding sites.

Valence of an antibody: Number of antigen binding sites. Most are bivalent.

Belong to a group of serum proteins called immunoglobulins (Igs).

ANTIBODY STRUCTURE

Immunoglobulin Classes

I. IgG Structure: Monomer Placental Transfer: Yes Known Functions: Enhances phagocytosis,

neutralizes toxins and viruses, protects fetus and newborn.

II. IgM Structure: Pentamer Known Functions: First antibodies produced

during an infection. Effective against microbes and agglutinating antigens.

Immunoglobulin ClassesIII. IgA Structure: Dimer Known Functions: Localized protection of mucosal

surfaces. Provides immunity to infant digestive tract.

IV. IgD Structure: Monomer Known Functions: In serum function is unknown. On B

cell surface, initiate immune response.

V. IgM Structure: Pentamer Known Functions: First antibodies produced during an

infection. Effective against microbes and agglutinating antigens.

Monoclonal antibodiesA substance, usually a protein, which can be

synthesised in the laboratory in pure form by a single clone of cells.

Detect only one epitope on the antigen.Polyclonal antibodiesThe immune response to an antigen

generally involves the activation of multiple B-cells all of which target a specific epitope on that antigen.

Recognise multiple epitopes on any one antigen

Specific immunity• Occurs as the result of prior exposure to an

infectious agent or its antigens. It is sub-divided into natural and artificial immunity.

• Natural immunity – occurs through contact with a disease causing agent, where the contact was not deliberate.

• Artificial immunity – is produced by deliberate exposure to an antigen, as in vaccination.

Natural immunity Passive(maternal) – is acquired by the

neonate by transplacental transfer of immunoglobulins or from ingestion of colostrum.

Active(infection) – follows an exposure to an antigen; where adaptive immunity occurs.

Artificial immunityPassive(antibody transfer) – the transfer of

antibodies from a donor in which they were produced to a recipient for temporary immunity.

Active(immunization) – stimulation with specific antigen to induce an immune response.

Humoral immunity – is mediated by secreted antibiotics, where the protection provided by cell mediated immunity involves T-lymphocytes alone.

Passive – antibodies are transferred between individuals, the T-cells come from another organism.

Active – organisms generates its own antibiotics, the T-cells are stimulated.

Figure 1: Divisions of immunity

Types of immunityInnate(non-specific) immunityIt is the basic resistance to disease that a

species possesses, it is the first line of defense against infection

Adaptive (acquired) immunityIs the adaptive immune system, also

known as specific immune system that is composed of highly specialized, systemic cells and processes that eliminate or prevent pathogenic growth.

Adaptive(acquired) immunityPassive immunity – is the protection by

products produced by an animal or human and transferred to another human, usually by injection, it is effective but it doesn’t last long(few week or months).

Active immunity – is the protection that is produced by the person’s own immune system, is usually permanent.

Immune Response• Immune response is the reaction of the body’s

cells and fluids to the presence of a substance unknown to the body and its components

• The immune system recognizes and destroys substances that contain antigens, in this way the body is protected from possibly harmful substances

• Antigens are substances(usually proteins) on the cell surface or non living substances such as toxins, drugs and foreign particles

• HLA antigens is a group of antigens that the immune system sees as normal and usually doesn’t react against them. HLA are proteins of the body’s cells.

Primary and Secondary Response

• Primary immune response is what happens when the body is first exposed to a pathogen or an unwanted substance, the T-helper is triggered.

• Secondary response is triggered on subsequent infections, the body being invaded keeps memory B and T cells and has antibodies for the antigen.

B cells and T cells

• B cells also called B lymphocytes are produced and mature in the bone marrow

• B cells are essential components of Adaptive immunity and play a large role in the humoral immune response

• B cells make antibodies against antigens, perform the role of APCs and develop into memory B cells after activation by antigen interaction

• On the other hand, the precursors of T cells leave the bone marrow and mature in the thymus

• T cells play a central role in cell-mediated immunity

• T cells have a special receptor on their cell surface called T cell receptors (TCR)

Antigens and Immunogens

• All immunogens are antigens but not all antigens are immunogens

• Immunogen is any agent capable of inducing an immune response, it activates the immune system cascade

• While antigen is any agent that binds to components of the immune response-lymphocytes and their receptors- antibodies and the TCR

Immunization

• Immunization, or immunisation, is the process by which an individual's immune system becomes fortified against an agent.

• When this system is exposed to molecules that are foreign to the body, called non-self, it will orchestrate an immune response, and it will also develop the ability to quickly respond to a subsequent encounter because of immunological memory.

Cont…• The most important elements of the immune

system that are improved by immunization are the T cells, B cells, and the antibodies .

•  Memory B cells and memory T cells are responsible for a swift response to a second encounter with a foreign molecule.

• Immunizations are less risky and an easier way to become immune to a particular disease than risking a milder form of the disease itself. They are important for both adults and children in that they can protect us from the many diseases out there

Immunological memory

Active immunization• Active immunization is the induction of immunity after

exposure to an antigen. Antibodies are created by the recipient and may be stored permanently.

• Active immunization can occur naturally when a microbe or other antigen is received by a person who has not yet come into contact with the microbe and has no pre-made antibodies for defence. The immune system will eventually create antibodies for the microbe, but this is a slow process and, if the microbe is deadly, there may not be enough time for the antibodies to begin being used.

Artificial active immunization

• It is when the microbe is injected into the person before they are able to take it in naturally.

• The microbe is treated, so that it will not harm the infected person. Depending on the type of disease, this technique also works with dead microbes, parts of the microbe, or treated toxins from the microbe.

Passive immunization• it is when pre-synthesized elements of

the immune system are transferred to a person so that the body does not need to produce these elements itself.

• Currently, antibodies can be used for passive immunization. This method of immunization begins to work very quickly, but it is short lasting, because the antibodies are naturally broken down, and if there are no B cells to produce more antibodies, they will disappear.

Artificial passive immunization

It is a short-term immunization which is achieved by the transfer of human (or animal) antibodies specific for a pathogen to non-immune human or animal. It is used when there is a high risk of infection and the body has no sufficient time to develop its own immune response

Vaccination • it is the administration of antigenic material

(a vaccine) to stimulate an individual's immune system to develop adaptive immunity to a pathogen.

• Vaccines can prevent or ameliorate morbidity from infection. The active agent of a vaccine may be intact but inactivated (non-infective) or attenuated (with reduced infectivity) forms of the causative pathogens, or purified components of the pathogen that have been found to be highly immunogenic (e.g., outer coat proteins of a virus).

Early tissue and Cell Culture in vaccine Development

•In order to develop vaccines that could be mass-produced, researchers first had to grow the viruses or bacteria with which to develop those vaccines in large quantities and with great consistency.• Compared with bacteria, which can be grown in a laboratory environment when placed in a suitable growth medium, viruses cannot reproduce on their own and require living cells to infect. After a virus infects a cell, it uses the cell’s own components to produce more copies of itself. 

Types of vaccines Inactivated vaccine

– It consists of virus or bacteria that are grown In culture and then killed, using a method such as heat or formaldehyde. E.g Polio vaccine and Hepatitis A vaccine

– Although the virus or bacteria particles are destroyed and cannot replicate, the virus capsid proteins or bacterial wall are intact enough to be recognized and remembered by the immune system and evoke a response. When manufactured correctly, the vaccine is not infectious, but improper inactivation can result in intact and infectious particles.

 Attenuated vaccine– live virus or bacteria with very low virulence are

administered. They will replicate, but very slow. Since they do reproduce and continue to present antigen to the immune system beyond the initial vaccination, boosters may be required less often.

– These vaccines may be produced by passaging, for example, adapting a virus into different host cell cultures, such as in animals, or at suboptimal temperatures, allowing selection of less virulent strains, or by mutagenesis or targeted deletions in genes required for virulence.e.g Measles, mumps, rubella (MMR combined vaccine) Varicella (chickenpox), Influenza (nasal spray,Rotavirus vaccines

Types of vaccines

SUBUNIT AND CONJUGATE VACCINESBoth subunit and conjugate vaccines contain only pieces of the pathogens they protect against.Subunit vaccines use only part of a target pathogen to provoke a response from the immune system. This may be done by isolating a specific protein from a pathogen and presenting it as an antigen on its own. Examples are acellular pertussis vaccine and influenza vaccine ,Meningococcal,Pneumococcal,influenza(injection),Hepatitis B.

A preventative vaccine is administered to a person who is free of the targeted infection. By introducing a part of the virus or an inactive virus  into the body, the immune system reacts by producing antibodies. If, years later, the virus enters the organism, these antibodies will recognize and destroy it.examples influenza virus vaccine,Polio vaccines

A therapeutic vaccine is administered to a person afflicted with a chronic viral infection, against which naturally produced antibodies are ineffective. In other words, therapeutic vaccines aim to increase the activity of the body’s natural defenses. Examples Bacillus Calmette-Guérin (BCG) vaccine, Arcitumomab, Pankomab.

o An antigen is injected into a mouse, and after a few weeks its spleen is removed and plasma cells are extracted.

o The mouse's spleen cells are fused with myeloms cells to create hybrid cells called hybridoma cells. Each hybridoma cell indefinitely produces identical antibody, and the hybridoma cells are then screened using an antigen/antibody assay that will reveal which cells produce the desired antibody.

o The collection of selected hybridoma cells that produce the preferred antibody are re-screened multiple times until a pure line is isolated. These cells are grown in a culture and/or injected into into mice to induce tumors. The cells can also be frozen and saved for later use.

Production of monoclonal antibodies

ACTION OF MONOCLONAL ANTIBODIES