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Immunity is the resistance exhibited by the host towards injury caused by micro-
organisms and their products. Protection against the infectious diseases is only one
arm of the immune response, since the main purpose is the reaction of the body
against foreign antigen.
Immune cells and the responses they generate. There are 2 types of immunity:
1. INNATE - this is also called the NATURAL IMMUNITY since it is present even at
birth. This response will not increase upon repeated exposure to the antigen.
It is composed of skin, mucous membranes, secretions (saliva, tears),
phagocytic cells and NK cells. Innate immunity also allows elimination of
foreign substance like a bacteria, without previous exposure. It is enhanced
by natural antibodies or natural cytotoxic cells like macrophages, neutrophils,
eosinophils and NK cells. It is nonspecific since it is effective against a wide
range of infectious agents.
Factors which affect innate immunity: Age (infants are affected more by
infections since they have an immature immune system); Sex(death rate is
higher in males, but there is no marked differences in susceptibility between
males and females);Hormonal influence (there is decreased resistance to
infection in DM);Nutrition (poor nutrition leads to increased susceptibility to
infections).
The intact skin and mucous membranes of the body give avery good
protecton against pathogens. The skin is a resistant barrier because of
its outer cornified layer consisting mostly of keratin which micro-
organisms cannot digest. Also, the dry condition of the skin plus the
high concentration of salt in the sweat is lethal.
Basic polypeptides like spermine and spermidine can kill tubercle bacilli and
staphylococci.
C. COMPLEMENT
These are about 30 proteins found in the serum in their inactive forms, but
can be activated to form an enzyme cascade with the following end result:
Opsonization
Cellular activation
Cell lysis
There are two pathways: the classical and the alternative pathway
The final result for both pathways is the formation of the membrane attack
complex, which is formed from the reactions among C5, C6, C7, C8 and C9.
D.CELLS
Phagocytes are cells which engulf micro-organisms as they enter tissues, fluids or
the bloodstream. Mononuclear phagocytes in the blood are called monocytes,
macrophages in tissues, histiocytes in connective tissue, mesangial cells in the
kidney, osteoclasts in bone, microglia in the brain, and sinus-lining macrophages in
the spleen, lymph node and thymus.
Phagocytes are:
Actively phagocytic
Products of injured tissues, blood factors, leukotrienes and histamine from mast
cells and neutrophils, bacterial products
Chemotaxis
The foreign particle is engulf by the cell membrane and internalized as an ENDSOME
or PHAGOSOME
NATURAL KILLER CELLS recognize changes in virus-infected cells and destroy them
by an extracellular mechanism. This is present even without prior exposure to the
infectious agent. It is performed by cell large granular lymphocytes, and by cells
with T cell markers. Its activity is enhanced by Interferon. They have also been
implicated in the host defense against cancer cells.
E.TEMPERATURE
Pyrexia which follows many infections can also be a source of control. It is mediated
by interleukin-1, which is produced by macrophages. It is also known as the
endogenous pyrogen.
F.INFLAMMATION
This is the reaction of the body to injury, such as invasion by a infectious agent,
exposure to a toxix chemical, or physical trauma. The five signs are redness, heat,
swelling, pain and loss of function.
Vasodilatation
Cellular infiltration.
Eosinophils
Monocytes
Platelets
Chemotaxis
ACQUIRED IMMUNITY develops late in fetal life, and development continues into
childhood. Continued exposure to the antigen stimulates acquired immunity. The
response is specific to an individual antigen because of the antigen-specific
recognition by surface antibody on B cells and by T-cell receptors on T cells.
There are two types of acquired immunity: active and passive. Active immunity is
induced after contact with foreign antigen, such as micro organisms and their
products. This contact may be subclinical or clinical infection.
The response is just to some parts of the antigen, or individual chemical groups, and
not to the entire antigen itself. This is termed the specificity to antigenic
determinants or to epitopes. Thus ,since a micro-organism may have several
epitopes, more than one antibody will react with that particular organism.
2. Haptens, molecules that are able to react with antibodies, but are unable to
stimulate their production directly; low molecular weight; become active only
when attached to carriers, which are large molecules
A substance that act an as antigen in one species may not necessarily produce a
reaction in another species.
Antigens, in general, must have a molecular weight of more than 5000. However,
even lower molecular weight substances like glucagon , can function as an antigen
with they are combined with an adjuvant, which in turn, causes additional stimulus
to the immune response.
Aspirin, penicillin and formaldehyde may also act as antigens although they have
low molecular weight.
ANTIGENIC DETERMINANTS
The lymphocytes have receptors on their surface that function as the recognition
unit:
Surface-bound immunoglobulin on B cells
The part of the lymphocyte that attaches to the epitopes is called a PARATOPE.
2. May be assembled from residues far apart in the sequence, but are
brought together in close proximity due to folding of the
molecule(CONFORMATIONAL EPITOPES)
For example, Forssman antigen is found in RBC and pneumococci and salmonella. It
is thus termed a HETEROPHILE ANTIGEN. The antibodies then clump the rbc, thus
they are called ISOHAEMAGGLUTININS.
IMMUNOGLOBULINS
19TH CENTURY, von Behring and Kitasato in Berlin discovered that the serum of an
appropriately immunized animals contained specific neutralizing substances. They
were called ANTIBODIES OR IMUNOGLOBULINS.
1. Glycoprotein
2. Present in the serum and body fluids
4. Reactive with, and are specific, to the antigen that induced their formation
ANTIBODY STRUCTURE
All antibodies have the same basic structure: 2 light chains and 2 heavy chains.
The two light chains are one of two types: either a Kappa or a Lambda. The
molecular weight is about 25000. They are composed of 2 areas, which are called
DOMAINS, and these are approximately 110 amino acids. One end of the chain is
constant, and is identical in all members of the isotype. This is termed the CL
region.
The other end shows sequence variation, and is called the VL region.
The heavy chains determine the isotype, and have a molecular weight of 50000 to
70000. They also have two domains which show sequence variation ( VH); while the
other domain is similar for all isotypes (CH).
The tertiary structure of the VL and VH regions determines the shape of the antigen-
combining site or paratope.
The two chains are held together by disulfide bridges and non-covalent interactions.
Since the two light and two heavy chains are identical, there will be two binding
sites for the antigen (2 paratopes ) at the amino- terminal or N- terminal.
The carboxyl – terminal or C-terminal at the other end of the antibody will be the
same for all the members of the isotype. It is responsible for the biological
properties of the isotype.
There is an area in heavy chains which is called the HINGE REGION. Enzymes may
break up the antibody, dividing them into Fab and Fc region.
The Fc (fragment crystallizable) is similar for all the antibodies of the same isotype.
The differences from the other isotypes define the biological activity of the antibody.
The variability in the amino acid sequence in the variable domains of the light and
heavy chains is not found over their entire length, but restricted to short segments
only. These segments show variation, thus are called HYPERVARIABLE REGIONS.
These are the areas that come in direct contact with the antigen.
5 CLASSES OR ISOTYPES
1. IgA
2. IgM
3. IgD
4. IgG
5. IgE
IgG
This is the major immunoglobulin of the serum, as well as the CSF and the lymph,
making up almost 75%. It has a molecular weight of 150,000 in humans. It is also
the major antibody of the secondary response, and is an important defense against
bacteria and viruses.
It is the only antibody to cross the placenta, so it is the highest antibody in the
newborn, protecting it in the first 4-6 months of life.
2. Acts as an opsonin
IgA
IgM
This is the antibody produced during the immune response, especially to bacteria
and viruses. Due to its large size, this isotype is mainly confined to the
intravascular pool. The presence of IgM in the newborn may indicate intrauterine
infection such as Syphillis, Rubella, HIV infection and Toxoplasmosis.
IgD
IgE
This is present in very low levels in the blood; found on the surface of mast cells and
basophils, which possess a receptor specific for the Fc part of the immunoglobulin.
It is also called the REAGINIC ANTIBODY since it is associated with allergic response
and immediate hypersensitivity reaction.
Functions:
Bence Jones protein is found in multiple myeloma. It can be identified in the urine
by its characteristic property of coagulation when heated to 50C, but redissolving at
70C.
This is a collection of highly polymorphic genes encoding the proteins that regulate
an immune response. These genes include the class I and class II cell surface
proteins, and the class III which encode for the complement proteins. In humans,
the MHC is called HUMAN LEUKOCYTE ANTIGENS (HLA). And are found on the short
arm of chromosome 6.
The HLA proteins are present on the cell surfaces that enable the T cells to
recognize and bind antigenic peptides(immune recognition).
HLA CLASS II ANTIGENS are proteins expressed on more restricted set of cells,
including the antigen-presenting cells (Langerhans cells, activated macrophages)B
cells, and thymic epithelial cells involved in T-cell maturation. They are necessary
for antigen recognition by Th cells. In humans, the class II genes include HLA-DR,
HLA-DQ and HLA-DP. Class II proteins are found on cells that interact directly with
the Th cells, including B cells, monocyte-macrophages, langerhans cells, dendritic
cells and thymic epithelium. The proteins made by extracellular bacteria or
parasites or injected vaccines will also be displayed on HLA class II proteins.
HLA CLASS III ANTIGENS. Class III genes encode for the complement components or
regulators of serum complement component complex.
Many diseases are associated with an increased frequency of the HLA antigens.
Ankylosing spondylitis (HLA-B27), rheumatoid arthritis (HLA-DR4), and IDDM (HLA-
DR3 and HLA-DR4).
Tissue typing for organ transplantation involves matching the HLA Class I and HLA
Class II antigens.