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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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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