Download Immun System/PART 2 The immune adaptive defense system

Immun System/PART 2
The immune adaptive defense system-specific response
Introduction
Is made up of cells derived from the bone marrow and located in
the circulating blood, lymph vessels, lymph nodes, tonsils, spleen
and peyers patches. The lymphoid cells distribute more or less
randomly throughout the C.T or the site of inflammation
There are TWO distinct types of adaptive immunity
1- humoral immunity
2- cellular immunity
carried out by the B-lymphocyte, these cells when exposed to
antigen give rise to mature plasma cells which able to produce
one type of immunoglobuline either IgA,IgG,IgM,IgE,IgD
depending on type of antigen.
humoral immunity:
carried out by the B-lymphocyte, these cells when exposed to
antigen give rise to mature plasma cells which able to produce
one type of immunoglobuline either IgA,IgG,IgM,IgE,IgD
depending on type of antigen.
1- cellular immunity
carried out by the T-lymphocyte, these cells when exposed to
antigen will get differentiated into lymphoblast and give rise to
several enzymes and mediators.
The antigenic molecules are taken up by macrophege to be
represented to the reactive lymphocytes,
There are two types of antigen representation either in T-or Blymphocyte
IF this Ag in T-lymphocytes-dependent-antigen, whithin1-2
days the T-cell begin to undergo BLASTOGENESIS, this
response give rise to a large population of antigen-sensitive
cell.some of these cells become memory lymphocytes(small size
circulating lymphocytes)these cells able to recognize the Ag to
which it is previosly sensitive, then capture the Ag by its wall
receptors, then differentiated into lymphoblast(large size cell)
which give rise to apopulation of active lymphocytes,
immunologically named as helper cytotoxic suppressor which
carrying on their surface aspecific antigen receptors
recognition sites, all these cells ineract by their cellular activity
or by releasing enzymes, immunologically active biochemical
elements in collaboration with macrophages to neutralize or
kill and destroy the recognized Ag.
IF this Ag in B -lymphocytes-dependent-antigen, the Blymphocytes will transform into plasma cell and form clones of
mature antibody-producing cells, each clone produces and
secretes one type of immunoglobulins(Ig).
The secreted antibodies(immunoglobulins)have in general the
following activity:
1- toxins and other noxious antigens are inactivated and
neutralize by specific antibodies to form the immune-complex
which is ingested by macrophages.
2- specific antibody combines with antigen of bacterial surface
to form an immune-complex which activate the complement
system and leads to bacteriolysis.
3- immune-complex activate the phagocytosis of neutrophils
and microphages
4- antibodies are able to neutralize viruses.
5- activating the complement system.
The humoral immunity is effective against bacterial invasions
and its soluble elements able to build up specific antibodies and
anti specific type of bacteria.
The cellular system is effective against viral,fungal,and some
bacterial infections, this system functioning throughout direct
cell interaction resulting in cytotolysis and through the release
of cytokines
The lymphokines (lymphocyte cytokines)
They are chemical products released by lymphocytes able to
transform B and T lymphocytes, produce and secret numerous
substances other than immunoglobulines responsible for
avariety of biologic activities which named as SOLUBLE
MEDIATORS.
Some of lymphokines considerd to be of specific importance in
inflammatory gingival and periodental diseases including
cytotoxic factors,chemotactic factors and osteoclast activating
factors, these cytokines acting on macrophages as follow:
(MAF),(MIF),(MCF)(MSF),(LF),(CF),(OAF)and (IF).
IMMUNOPATHOLOGY OF PERIODONTIUM
The epithelial surface is the first region of the periodontium
which comes into contact with and responds to bacteria attaching
and colonizing the dento-gingival region. Prevention of
attachment and colonization is important for the host defenses
and this is achieved through multiple innate mechanisms which
include
1-the washing effect of the saliva and gingival reticular fluid
(GCF),
2- the constituents of these fluids such as antibodies and
proteases,
3- complement, 4-salivary antibacterial agents and lactoferrin
and
5-other salivary proteins which are detrimental to bacterial
growth and can be bactericidal.
In periodontal lesions, the balance between synthesis and
degradation is disrupted.
Even during early gingivitis many of the collagen fibers in the
overt gingiva are broken down, to make space for the infiltrating
inflammatory cells. This process changes a firm, pink gingiva
into a swollen, loose and reddish tissue which has lost its
integrity.
When this condition becomes chronic, progression of the lesion
into deeper periodontal structures may occur and then the
collagen fibers of the periodontal ligament are broken down,
together with the supporting alveolar bone. This occurs via an
MMP-mediated extracellular digestion.
(1)producing and/or releasing cytokines and other molecules that kill the microbes
(2) releasing other molecules (such as IL-1) capable of inducing or enhancing the
inflammatory reaction.
(3)The epithelium can also respond by increasing expression of surface molecules such
as cell adhesion molecules which can function with cytokines and chemoattractants to
bring leukocytes to the region.
Molecules in saliva such as lactoferrin have several detrimental effects on bacteria,
which include;
1-the binding and restriction of iron in the environment that prevents microbial
growth.
2-In addition, lactoferrin is also highly cidal for bacteria.
Molecules present in the GCF include complement, which can kill bacteria directly or
together with antibodies, and can bring PMNs to the region (via chemotaxis).
The presence of PMNs may be further detrimental to the bacteria.
In the classical description of inflammation an area is presented which appears
macroscopically red, swollen, hot and painful, and with possible loss of function in
specific sites.
*Redness and heat are due to vasodilatation and increased blood flow.
*Swelling is a result of increased vascular permeability and leakage of plasma proteins
which create an osmotic potential that draws fluid into the inflamed tissues. Related to
the vascular changes there is an accumulation of inflammatory cells infiltrating the
lesion.
* Pain is rarely experienced in periodontal disease, particularly in the early stages, but
could theoretically occur due to stimulation of afferent nerves by chemical mediators
of inflammation (necrotizing ulcerative gingivitis where rapid tissue destruction is
typical) and pressure from vastly increased tissue tension (typical of periodontal
abscesses).
* Impairment of function: an oral example of impaired function is the reduced
opening or trismus of the mandible sometimes associated with pericoronitis in the third
molar region. A periodontal example of loss of function would be the reduced
masticatory efficiency of mobile teeth following advanced tissue destruction in
periodontitis.
Proteinases (proteases)
Periodontal disease results in tissue degradation, and thus proteases, both host and
microbial, are central to
the destructive processes. Proteinases, or proteases, cleave proteins by hydrolyzing
peptide bonds .
A- Endopeptidases cleave bonds in their substrate within the polypeptide chain,
B- exopeptidases cleave their substrate near the end of the polypeptide chain
Endopeptidase activity, including collagenase, elastaselike
and trypsin-like, as well as serine and cysteine proteinases, has also been detected in
homogenates of gingival tissue
proteinase inhibitors would serve as modulators of protease function in the area and
would dampen the inflammatory process.
All the host derived endopeptidases known to be released into the gingival crevice can
be inhibited by the combined function of alpha-2 macroglobulin (A2-M) and alpha-1
antitrypsin (Al-AT).
In
gingival tissue there are also possibilities that potent proteinases from
microorganisms such as P. gingiva/is (Arg-1 protease or gingipain) are capable of
degrading these inhibitors.
Matrix metalloproteinases (MMP) are responsible for remodeling and degradation of
matrix components. MMPs also degrade interstitial and basement membrane
collagens, fibronectin, elastin, laminin, and the proteoglycan core protein.
MMPs are made in a proenzyme form, and activation is extra cellular. One of the
MMPs receiving much attention is the neutrophil (PMN) collagenase which is found
in higher concentrations in inflamed gingival specimens than in clinically healthy
gingivae
Cytokines
Cytokines are soluble proteins, secreted by cells, which act as messenger molecules
that transmit signals to other cells. They have numerous actions which include
initiation and maintenance of immune and inflammatory responses and regulation
of growth and differentiation of cells
The interleukins are important members of the cytokine group and are primarily
involved in communication between leukocytes and
other cells
Note; The term chemokine is used to describe these molecules and is an abridged
form of the term "chemotactic cytokine".
Interleukin 1( IL-1) can act on the fibroblasts to promote cellular matrix repair or
destruction.
interleukin 8 (IL-8), which has powerful chemotactic functions for leukocytes
particulary for neutrophils but also for lymphocytes and macrophages.
The polymorphonuclear leukocytes PMN
-is the predominant leukocyte within the gingival crevice/pocket in both health and
disease.
-PMNs from the circulation are attracted to the area via chemotactic stimuli elicited
from microorganisms
-PMNs are, however, also present in clinically healthy gingiva and are recruited to
this tissue in response to chemotactic factors in the gingival crevice region.
-PMN numbers increase in the gingival crevice with the development of gingivitis
and more PMNs are found in periodontitis compared to gingivitis sites.
Note; PMNs in the gingival crevice form the first line of defense against periodontal
pathogens.