Fundamentals of Microbiology

5.1.2 General or Non specific host immune defense mechanisms

These general or nonspecific defense mechanisms can be grouped into four major categories:

1. General 2. Physical 3. Chemical and 4. Biological barriers

General barriers

These include many direct factors like nutrition, fever, age, genetic factors and many indirect factors like personal hygiene and living conditions.

Physical barriers

Physical barriers are the first line of host defense against infection. These include skin and mucous membranes. The intact skin forms a very effective mechanical barrier to parasitic invasion. Similarly mucous secretions of the respiratory, digestive and urino-genital systems form a protective covering that resists penetration and traps many microorganisms.

Chemical barriers

Mammalian hosts produce several chemicals that include, gastric juices, salivary glycoproteins, lysozyme, oleic acid on the skin, urea etc. Body fluids (tissue extracts, blood, lymph etc.) contain chemicals such as antibodies and complements, fibronectin, hormones, beta-lysin and other polypeptides, interferons and bacteriocins.

The pH level of many body systems limits the entry or propagation of microorganisms with body. For eg. Stomach pH 1 to 2 ( Gastric acid = HCl + enzymes + mucus). Vaginal pH 4.4 to 4.6 inhibits disease causing microbes. Enzymes esp. Lysozyme (which can degrade the cell wall of bacteria) present in tears, sweat, saliva and mucus kills invading pathogens. Iron – binding proteins like lactoferrin and transferrin present in the body bind iron, thereby making iron not available for pathogens.

Some blood cells produce interferons (glycoproteins) which make host cells unsuitable for viral replication. Blood contains a family of glycoprotein molecules called complement that helps in removal of invading pathogens

Microbial and Biological barriers

Normal microbiota consists of microorganisms that are associated with particular body tissues. The normal microbiota prevents other microorganisms from colonizing the areas where they grow by producing antimicrobial substances, reducing oxygen concentrations and competing for available nutrients.

Once an organism has breached (overcome) the first line of defense, it encounters the host’s second line of defense. This involves cells derived from bone marrow cells. Most of these are phagocytes. Normal microbiota are also involved in the general defense. Inflammation is one of the defensive reactions to a tissue injury where the major events that occur are increased blood supply, increased capillary permeability, leukocyte migration and phagocytosis.

Specific immunity

If the non specific defenses are breached specific immunity comes into protect the host. The specific immune response system consists of certain cells (Lymphocytes) that can recognize foreign molecules (antigens) and respond to them by forming specialized protein (antibodies) that target the antigens with other components of the immune system, thus offering protection to the host.

Phagocytosis

Several leukocytes (white blood cells) protect the body against infection by the process of phagocytosis. The different types of leukocytes include granulocytes and agranulocytes. Granunolocytes include basophils, eosinophils and neutrophils and agranulocytes include monocytes and lymphocytes.

The immune Response

Specific host defense is the next line of defense against microbial infections. This immune response recognizes any substance that is foreign to the body and acts to eliminate the specific substance out of the body.

Antigen

An antigen is any macromolecule that activates the immune system. Antigens include all proteins, most polysaccharides, nucleoproteins, lipids (glycolipids and lipoproteins) etc. The two essential properties of an antigen are its: Immunogenicity (ability to stimulate the immune system) and its specific reactivity (ability to react with the specific effector molecules of the immune system). Effector molecule of the immune system refers to the antibody. An antigen can elicit the formation of an antibody and react with the antibody to form antigen-antibody complex or immune complex.

The antigen molecule consists of a reactive portion called the epitope or antigenic determinant that reacts chemically with the antibody molecule to form the complex.

A bacterial cell can have numerous antigens on its surface. The antigens on the cell of Salmonella are called ‘O’ antigen and those on the flagella are called ‘H’ antigens. ‘O’ antigens are also called somatic antigens.

Some molecules called haptens have antigenic determinants that are too small to elicit the formation of antibodies, but can complex with a larger molecule (carrier) and thereby become an antigen.

Antibody

Antibodies or immunoglobulins are glycoproteins that are synthesised in response to specific antigens and react with those antigens. They are secreted into lymph and then drain into the blood. The major concentrations of antibodies in the body are the serum of blood.

Antibodies are glycoprotien substances produced by ‘B’ lymphoid cells in response to stimulation with an immunogen. They possess the ability to react in vitro and in vivo specifically and selectively with the antigenic determinants or epitopes. Antibody molecules are immunoglobulins found in the blood and body fluids. Immunoglobulins (antibodies) constitute approximately 1 to 2% of the total serum proteins in healthy individuals.

Structure of antibody

Each immunoglobulin is composed of four peptide chains, two identical large or heavy (H) chains and two identical light (L) chains. There are 5 different types of immunoglobulin based on the amino acid contents, sequence and size of the heavy chains. The ‘H’ chains are the

gamma for Ig G

alpha for Ig A

mu for Ig M

delta for Ig D and

epsilon for Ig E

The L chains exist either as kappa or lamda chains called ‘L’ chain allotypes. They have nearly identical structures but are antigenically distinct.

Functionally antibodies have two protein fragments namely Fc and Fab fragments. The Fc enables the immunoglobulin to bind to complement or host cells. Fab contains the antigen binding sites of the immunoglobulin. Each four-peptide unit of an immunoglobulin can react with two copies of the antigenic determinant site. The ‘H’ & ‘L’ chains have both variable and constant regions (domains). The variable domain provides the specificity of an immunoglobulin for its antigen.