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Chapter: Biochemistry: Immunology

Natural Immunity

The non specific immunity present from birth is known as innate immunity or natural immunity.

Natural Immunity


The non specific immunity present from birth is known as innate immunity or natural immunity. It protects the body against any foreign invaders and does not show any specificity. It is also functionally matured in a new born. It does not become more efficient after subsequent exposures to same organism.


 Components (Cell types) involved in immunity


The cells of the immune system include leukocytes, which are also known as white blood cells (WBC). They developed from the bone marrow stem cells and give rise to two families of white blood cells namely the Myeloid cells (named after bone marrow) and the Lymphoid cells, which take their name from the lymphatic system. Myeloid cells include Basophils, Eosinophils and Neutrophils.


The monocytes give rise to macrophageswhen enter into the tissue spacefrom blood circulation. Similarly, Basophilare transformed to mast cells. Thelymphoid cells include T and B lymphocytes which get their maturation in different lymphoid organs. B-cell maturation begins in the liver (fetal) and continues within thebone marrow as maturation progresses (adult) and T cells complete their maturationin the thymus.


Mechanisms involved in Natural immunity Skin barrier


The skin covers and protects the body as a barrier to prevent invading pathogens. Intact skin prevents the penetration of most pathogens, by secreting lactic acid and fatty acids which lower the skin pH.


Mechanical barriers


Mucous membranes form the external layer where body is not covered with skin and it plays an important role in the prevention of pathogen entrance by traping them. Movement of the mucociliary process in the upper respiratory tract, the cilia in the eyelids act as escalators to remove the pathogens.




Sweat has antibacterial substances and tears contain lysozyme. Mucous secretion in nose prevents the dust and microorganism entry into the respiratory tract. Saliva contains lysozyme, thiocyante and lactoferrin. The HCl acid secreted in the stomach kills the microbes.




The ingestion (endocytosis) and killing of microorganisms by specialized cells called as phagocytes. Phagocytes are polymorphonuclear leukocytes (eg.Neutrophils) and mononuclear cells (Monocytes and Macrophages). Opsonization -The process by which microbes are coated by a molecule called opsonin which aids attachment of microbes to the phagocytic cells which facilitates phagocytosis. Neutrophils constitutively express ligands and receptors (L-selectin) which interact with reciprocal receptors and ligands on endothelial cells (P- and E-selectin).The endothelial cells are located in the innermost layer of the blood vessels. These interactions help the neutrophils to marginate and roll along the endothelium. Neutrophil responds and move towards a group of molecules called chemo-attractants (chemical mediators) and this process is called chemotaxis (chemical attraction). The phagocytes make its way through intact capillary walls and into the surrounding tissue by a process called diapedesis (emigration of phagocytes into tissues). Chemo-attractants include complement protein C5a, bacterial products, cytokines, lipid mediators from injured tissue. The various stages of Phagocytosis given below.


Stages of Phagocytosis (Fig. 10.1)


Opsonization (process by which microbes are coated by a molecule called opsonin). Attachment to the pathogen (so that pathogen movement can be restricted).


·              Formation of Pseudopodia (hand like projections).


·              Encircling of pathogen by pseudopodia leads to the formation of Phagosome.


·              Fusion of Phagosome with lysozyme vesicle leads to the formation of phagolysosome.

Killing of Pathogen.


Killing by phagocytes


Neutrophil are able to kill the pathogen as they posses certain chemicals in the form of granules and also the lysozyme enzyme. Neutrophil invasion to an inflammed area is consider as the second line of defence. Neutrophil has three types of granules namely Primary granules( contain serine proteases, lysozyme and phospholipase A2) Secondary granules ( include perforrin, elastase and collagenase) and Tertiarygranules ( contain gelatinase). Apart from these granules the phagocytes alsoposses a variety of oxygen dependent killing mechanisms. Phagocytes produce a respiratory burst, which produces superoxides and hydrogen peroxide. Neutrophils contain an enzyme called as myeloperoxidase, which can convert superoxide into hypochlorite ion which has a strong bactericidal activity.


Reticulo endothelial system (RES)


A diffuse system of cells that includes monocytes and macrophages, which are phagocytic in nature. The role of macrophage is consider as first order defence mechanism, as it engulf and kill more pathogens efficiently. Macrophages also takes part in antigen presentation. Apart from this, RES also involved in removing aged RBCs, denatured protein, steroids,dyes and drugs.


The macrophages derive the name according to their location.


Liver - Kupffer cells

Brain          Microglial cells

Kidney Mesangial cells

Spleen Splenic macrophages

Peritoneum Peritoneal macrophages.

Alveoli Alveolar macrophages.




A localized protective reaction produced in tissue response to any irritation, injury or infection is called as inflammation. This is characterized by pain, redness, swelling, and sometimes loss of function. Usually, the name of the tissue, organ and the region which develops inflammation is suffixed with ‘itis’ for example conjunctivitis, gastritis and pharyngitis respectively. The inflammatory response helps to mobilize the nonspecific defense forces to the tissue space where pathogen is present. The damaged cells release chemical mediators such as histamine from the mast cells, which dilate the near by blood vessels. The complement system gets activated and attracts phagocytes. The plasma leaking from the dilated blood vessel contains clotting system of proteins. They get activated due to the tissue damage and this process leads to “walling off” the area and this helps to prevent spreading of the infectious material. 


Natural Killer Cells


Among the immune cells, natural killer cells (NK cells) are the most aggressive. They are first line of defense against infected and cancerous cells. They are lymphocytes (Large granular lymphocytes, LGL) with no immunological memory and are part of the innate immune system. It attaches to the target and releases a lethal burst of chemicals called as perforins that penetrate the cell wall. Fluids begin to leak in and out and eventually the cell explodes.




Interferons are proteins produced by body cells when they are invaded by viruses, is released into the bloodstream or intercellular fluid, in order to induce healthy cells to manufacture an enzyme that block viral replication.


Complement System


It is a group of proenzymes. They circulate in serum in inactive form. The complement system is the part of innate immune system plays an important defense against microorganisms, especially gram-negative bacteria. The complement system consists of a set of over twenty serum proteins which are getting activated as follows.

The complement cascade consists of two separate pathways that converge in a final common pathway (Fig.2). The pathways include the classic pathway (C1qrs, C2, C4), the alternative pathway (C3, factor B, properdin) and these two pathways converge at the component C3. The terminal complement pathway consists of all proteins activated after C3. The most notable are C5-C9 group of proteins collectively

known as the membrane attack complex (MAC). The MAC exerts powerful killing activity by creating perforations in cellular membranes. Activated C3b opsonizes bacteria and C5a function as chemotactic agent.


Antigen presenting cells (APC)


B cell,dendritic cells (lymphnodes), Langerhans cells (from skin) and macrophages are called as antigen presenting cells. All these cells, process the antigen and express the antigen over the surface of its cell membrane along with a molecule called as Major Histo Compatibility Complex (MHC) class II molecule.


Major Histocompatability complex


A set of cell surface glycoproteins are called as the Major Histocompatibility Complex or MHC molecules. Generally, they take part in differentiating self and non self antigens and the presentation of processed foreign antigen to activate the T cells. There are two classes of MHC proteins, MHC class I and MHC class II. MHC class I molecule is expressed on the cell surface of all nucleated cells of the body. MHC class I molecules with processed antigen are expressed on the surface of the infected cells, which present the processed antigen to cytotoxic T cells (CD8). MHC class II molecule are expressed on APC cell surface which present the processed antigen to Helper T cells (CD4 cells).


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