Download defence mechanism of gingiva

DEFENCE
MECHANISM OF
GINGIVA
The gingival tissue is constantly subjected to bacteria and their toxic and antigenic products.
Host defense mechanisms are called into play to fend off these bacteria and their products
and to destroy any, which succeed in entering the tissue. When the host responses are altered,
a variety of microorganisms although most of them are commensals become pathogenic.
Periodontal diseases result from an interaction between the microorganisms and the host
defense mechanism.
Defense mechanism can be classed as
1. Nonspecific mechanism
2. Mechanism specific to invading antigens, which stimulate the immune system.
Non-specific mechanism provides protection by means of
1. Gingival Epithelium

Barrier function

Role of epithelium in inflammation
1

High Rate of Tissue Turnover

Bacterial Balance.
2. Surface Fluid

Saliva

Gingival crevicular fluid
3. Phagocytosis by

Polymorphonuclear leukocytes

Monocytes
The inter-relationship between the host and oral microflora are very dynamic. In a healthy
state there is a balance between the host defenses and the indigenous microflora. The balance
may be broken by an abnormal growth of microorganisms or when there is a decrease in the
host defense.
Gingival epithelium
Barrier Function
An epithelial barrier is provided by the kertinized gingival epithelium, the epithelium
covering the lateral wall of the gingival sulcus and the junctional epithelium. This barrier
prevents bacteria and their products from entering the tissues. This is achieved by epithelial
cells, which are tightly attached to one another, keratinized to resist trauma in exposed areas
and presence of a permeability barrier.
The Role of epithelium in inflammation
In addition to barrier function, epithelium also plays important roles in initiating and
maintaining inflammatory and immune reactions. Keratinocytes react to direct damage by
secreting a wide range of inflammatory cytokines particularly interleukin-1. These cytokines

initiate an inflammatory reaction in the underlying C.T.

induce neutrophil and macrophage e...gration

play a role in cell turnover.
2
Langerhans cells found in gingival epithelium recognize antigens which have penetrated into
surface layers of the epithelium and act as antigen presenting cells to induce an immune
response.
High Rate of cell turnover
This is a defense mechanism. Sulcus and junctional epithelium display inordinately high level
of turnover and thus can accommodate considerable amounts of damage without long-term
deleterious consequences. The thickness is maintained by a balance between new cell
formation in the basal and spinous layers and the shedding of old cells at the surface.
Bacterial Balance
The mouth as a whole and various zones in the mouth including which has been called the
crevicular domain can be viewed as ecosystems in which a balance exists between different
species of microorganisms and between this flora and the tissues. Some species have been
proposed to be protective to the host by preventing the colonization of pathogenic
microorganisms for e.g. production of hydrogen peroxide by streptococcus sangius, which is
known to be lethal to Actinobacillus actinomycetemcomitans. Upset in bacterial balance is
most commonly seen after prolonged use of antibiotics, which suppress some types of
bacteria and allow others to flourish.
Surface Fluid
Salivary Host Defense Mechanisms
Saliva plays an important role in the prevention of periodontal disease but its actions are
limited to the clinical crowns and those parts of gingival exposed to it. These sites are said to
be in the salivary domain of host defense.
Antibacterial actions of Saliva:
-
A vehicle for swallowing bacteria
-
Inhibition of attachment of bacteria
-
Aggregation of bacteria is saliva
-
Killing of bacteria by lysozyme, lactoferrin and other factors.
3
-
Killing of bacteria by peroxides system
Major function of saliva is to act as a vehicle for swallowing bacteria. The microorganisms
multiply in the dorsum of the tongue and in plague and are displaced into the saliva by eating
and soft tissue movements. They are quickly eliminated by swallowing. Approximately half a
liter of saliva is secreted and swallowed each day (19ml/hr average rate of flow).
Secretory IgA in Saliva
The function of sIgA has been summed up by Sir Macfarlane Buunet as an “antiseptic paint”
for the mucosal surface.Oral microorganisms stimulate the system in the gut after being
swallowed and the activated lymphocytes then migrate to the salivary glands and secrete IgA.
This passes into the saliva in a special stable dimer form called Secretory IgA. IgA and J
chains are secreted by salivary gland plasma cells. Dimeric IgA is then complexed to
secretory component; synthesized by the epithelial cells of salivary acini and the assembled
secretory IgA is then transported into duct lumen and excreted into the mouth. The advantage
of sIgA is that it is more resistant to proteolytic degradation than other immunoglobulins.
When sIgA in saliva binds to bacteria their surface properties are changed and they attach
less well to teeth and epithelial cells, but better to salivary mucins and thus more likely to be
swallowed. The action of sIgA against existing plaque is hampered because the bacteria are
already adherent and protected by extracellular matrix. Secretory IgA cannot kill bacteria by
opsonization or complement activation because there are few neutrophils and minimal
complement activity in saliva.
In addition to its antimicrobial activity saliva, paradoxically, also contributes to plaque
formation. It is a rich culture medium for those microorganisms, which are adapted to live in
the mouth, and the initial colonizers of early plaque attach to teeth by salivary glycoproteins
and use glycoproteins, glucose, citrate, urea and other compounds in saliva as nutrients.
Salivary Peroxidase System
4
The system consists salivary enzyme peroxidase synthesized by salivary gland acini and
secreted into saliva; hydrogen peroxide generated at low concentration by bacteria,
neutrophils and other host cells. Thiocyanate ions secreted into saliva by ductal cells.
Peroxidase oxidise thiocyanate to hypothiocyanous acid which kills the bacteria in the
presence of H2O2 which is in low concentration, short lived and cannot be formed in
anaerobic environment.
Peroxidase
enzyme
SCN
+
H202
Thiocyanate Hydrogen peroxide
HOSCN
Hypothiocyanous acid
Lysozyme

enzyme secreted by mucous salivary gland

shows bactericidal activity by splitting the bond between N-acetyl glucosamine and N–
acetyl muracmic acid in the mucopeptide components of gram positive bacterial cell wall
and causing lysis.

Most of this enzyme is bound to salivary mucin thus inactive

Few oral organisms are susceptible because their cell wall structure is complex.

Lactoferrin

heat stable protein secreted by serous salivary glands

bacteriostatic activity

binds to iron depleting the environment of important growth factor for many
microorganisms.
5
Salivary Agglutin
A variety of salivary glycoproteins bind to oral bacterial adhesins and cause agglutination of
the bacteria, thus facilitating their removal e.g. sialic acid specific lectin interacts with
adhesins on the surface of Streptococcus. sangius.
Leukocytes
They originate from blood and migrate predominantly through crevice to the oral cavity.
Saliva represents part of graveyard for polymorphs; however, these cells might exhibit
phagocytosis, killing and release of lysozyme, hydrolases and superoxide.
Thus, saliva is critically important to prevent the excessive build of supragingival plague. It
prevents drying and provides lubrication. Salivary buffers like bicarbonate–carbonic acid
system maintains the physiologic hydrogen ion concentration at mucosal epithelial cell
surface and tooth surface.
Gingival Crevicular Fluid
Gingival Fluid that exudes from the gingival sulcus especially once the inflammation begins
is also an important protective mechanism.
Alfano 1974 has put forward the hypothesis that pre-inflammatory flow of gingival
crevicular fluid may be osmotically mediated. In a strictly healthy gingiva, a small amount of
subgingival plaque will give rise to limited quantities of macromolecular by-products which
will be removed by adsorbing to surface of desquamating epithelial cells or through
phagocytosis. When more macromolecules are present, they will diffuse intercellularly to the
basement membrane, which can be considered as a major limiting barrier. As the
macromolecular accumulate at the basement membrane, a standing osmotic gradient is
created and the flow of gingival fluid is generated. The osmotically modulated fluid is not an
inflammatory exudate. However, at various times, gingival fluid may progress from an initial
osmotically modulated to a secondary inflammatory exudate.
6
Pashley developed a model where gingival fluid production is modulated by the passage of
fluid from capillaries into the tissues and by removal of this interstitial fluid by lymphatic of
gingival. When the production of fluid from capillaries is greater than lymphatic uptake, fluid
will accumulate as edema or leave the area as gingival fluid.
The inflammatory exudate which flows into the crevice contains many blood components
and host defense mediators which may inhibit or kill plaque bacteria but which can also be
degraded by the plaque and used as nutrients.
The continual unidirectional flow of crevicular fluid has a protective effect, washing nonadherent bacteria and their products out of the crevice and reducing the diffusion of plaque
products into the tissues. Flow is generally greater in more advanced disease, reflecting the
increased volume of inflamed tissue, increased severity of inflammation and the greater
surface area of pockets through which the fluid flows.
Crevicular fluid also carries a steady supply of inflammatory mediators, protease inhibitors
that protect the tissue from damage and host defense agents such as complement and
antibody into the crevice.
Complement
The complement system comprises of nine major complement proteins which circulate in an
inactive form and which are activated in a cascade. When it is activated, a series of
biologically active fragments are formed by cleavage. Some of the fragments, for example
C3a and C5a potentate the inflammatory response and cause an increase in vascular
permeability. C5a is a potent chemotactic factor for PMNs and monocytes whilst C3b
facilitates phagocytosis by opsonization. Activation of the entire complement cascade can be
lead to lysis of bacteria in the presence of lysozyme.
Schenkein reviewed relationship between complement system and periodontal disease.
Several studies on GCF samples demonstrated that native C3 is found in much lower
7
concentration in GCF than in serum, but cleaved forms were present in higher concentration,
suggesting active cleavage in GCF. Other studies demonstrated native C3 was elevated
significantly in GCF after completion of successful treatment. Experimental gingivitis studies
reveal the same changes are detected during gingivitis phase, which return to baseline after
plaque control. These findings imply that activation of complement pathways is due to
bacterial load.
Lysosomal enzymes released by phagocytic cells, proteases found by bacteria, lysozyme
hyaluronidase and collagenase are also found in crevicular fluid.
Phagocytosis
Certain cells in the bloodstream and in the tissues are capable of engulfing and digesting
foreign material. Initially, potential pathogens encounter plasma factors such as complement
within crevicular or extra-cellular fluids. The result is initiations of inflammatory processes.
If complement is not successful in controlling the pathogen, the host defense turns to
neutrophils. Neutrophils within gingival crevice provide the first cellular host mechanism to
control bacteria. If they are unsuccessful, monocytes are recruited which infiltrate connective
tissue, develop into tissue macroplages and either digests the antigen completely or present
partially digested antigen in association with MHC molecules to lymphocytes.
Neutrophils
Emigration and Chemotaxis
As in inflamed tissues the blood flow is slowed by fluid exudation, leucocytes attach to the
inside of vessel walls and emigrate out in the tissues by passing between endothelial cell
junctions. The cells move to the site of inflammation by chemotaxis, a process of cellular
locomotion directed by a gradient of soluble chemical messengers. The messengers are
known as chemotaxins and include compounds such as complement fragments leukotriene,
bacterial products and factors released by damaged tissues.
8
After migrating to the site of infection, neutrophils recognize and bind to invading
microorganisms using receptors on their surface. They can recognize microorganisms
directly by binding to their cell wall, but the process is much more effective if opsonins such
as complement and specific antibody are bound to the bacterium. The receptors trigger the
neutrophil to ingest the bacterium into a vacuole within the cell and activate the neulrophils
killing mechanism.
2O2 + NADPH
2O2- + 2H+
NADPH 2O2_+ NADP+ + H+
Oxidase
H2O2 + O2
H2O2 + H+ Myeloperoxidase
Chloride Ion
HOCL + H2O
2O2-  Superoxide anion
H2O2  Hydrogen peroxide
HOCL  Hypochlorous acid
Bacterial Killing
It involves two basic microbicidal systems

O2 dependent

O2 independent.
In O2 dependent mechanism there is a respiratory burst resulting in production of O2 derived
free radicals that can kill bacteria and fungi. If oxygen is readily available there is sharp
increase in O2 consumption by the phagocyte. This system is triggered by NADPH oxidase,
enzyme situated on the membrane of phagocytic vacuole. The enzyme traps oxygen and
converts it to O2 metabolite that can kill bacteria.
Two molecules of free radicals interact spontaneously to produce H2O2, which is another
metabolite.
9
While O2 and H2O2 are weakly baderocidal in the presence of myeloperoxidase, H2O2
oxidizes Cl- to HOCL. This is called H2O2–halide-myeloperoxidase system and it is
neutrophils major weapon against microbes.
Oxygen independent mechanism involves deguanulalion with release of contents of granules
like cationic proteins, lysozyme, lactoferrin, lysosmal proteases such as elastase and
collagenase, cathepsin D, cathepsin G, gelatinase.
Neutrophils in the crevice form a layer on the surface of the plaque, but cannot phagocytose
the adherent bacteria, which are embedded in plaque matrix. They therefore secrete enzyme
H2O2 and hypochlorous acid externally killing bacteria without phagocytosis. This
mechanism also solubilizes the plaque matrix, so that the plaque and bacteria can be washed
from the crevice by crevicular fluid. Neutrophils are inhibited by microbial factors such as
endotoxins, formyl peptides and toxins, and by host factors such as degraded antibody,
complement, and protease inhibitous in the crevicular fluid, which inhibit phagacytosis by
blocking the cells surface receptors. The low O2 concentration and redox poletial in deep
pockets also inhibit neutrophil function.
In cyclic neutropenia, increased lymphocyte production is observed. But it is associated with
destructive periodontal disease, thus neutrophil is considered protective with respect to
periodontal pathogenesis. Even in localized juvenile periodontitis as well as rapidly
progressive periodontitis case, phagocytic activity of neutrophils is clearly diminished
confirming the protective role of neutrophils.
Macrophages
They develop from blood monocytes and are triggered to develop into mature macrophages
by cytokines and other mediators, endotoxin etc.
Functions

They phagocytes and kill bacteria
10

They remove damaged host tissue during infection.

They trap and present antigens to lymphocytes for the induction of responses.

They produce cytokines IL–1, TNF, PG
They do cause some bystander damage
Although not regarded as primary infection cells, endothelial cells, fibroblasts and epithelial
cells are essential for an effective inflammatory response.
Mediators: The link between inflammation, immunity and tissue damage
Plaque elicits simultaneous inflammatory and immunologic response. The linkage between
these processes with result in integrated host responses are formed by soluble chemical
messengers. These mediators have some basic common features–they are short lived, potent
and subject to rapid inactivation by cells or local and circulating inhibitors. Mediators of
rapidly acting responses are usually stored in most cells or generated from inactive
circulating precursors while mediators of more chronic reactions are synthesized by
neutrophils, macrophages and lymphocytes.
Mediators of vascular permeability
Soluble chemical messengers mediate changes like dilatation of gingival blood vessels,
increased blood flow and a continual outflow of inflammatory exudate into the tissues.
Mast cells store histamine and release it into tissues when triggered by the complement
fragments C3a and C5a, IL-1 and other factors derived from endothelium, neutrophils and
lymphocytes. Histamine causes a rapid but short-lived vasodilatation and increased
permeability of small vessels.
Bradykinin is a small peptide, which causes a long lined vasodilatation and increased
vascular permeability. It is released from a circulating protein called kininogen by many
stimuli present in inflammation including endotoxin. Together with C2-kinin it helps to
mediate continued exudation of crevicular fluid flow.
11
Prostaglandins and leukotriens are lipid mediators, which are continually synthesized by
cells. They are produced from arachidonic acid in the plasma membranes of cells of capillary
dilatation and endothelial permeability. They are produced by neutrophils, macrophages and
most cells, but smaller amounts are sources of IL-1 and TNF synthesized by lymphocytes,
fibroblasts, keratinocytes and osteoblasts. PGE 2 is a relatively long-lived and potent
mediator of bone resporption. Nonsteroidal anti-inflammatory drugs inhibit synthesis of PGs.
Complement cascade generates C3a and C5a that cause histamine release by mast cells and
also C2 kinin that cause vascular dilatation and increased permeability.
Cytokines and interleukins
Cytokines are soluble proteins secreted by cells that transmit signal to neighboring cells to
regulate their growth, differentiation and function. It includes the interleukins that
communicate between leukocytes, interferons and colony stimulating factors with mediate
immunological and inflammatory processes.
Interleukin1 & TNF
They are the most important mediators for chronic inflammation induced by bacteria,
bacterial antigens and endotoxins.
Sources of IL1 and TNF are mcrophages, endothelial cells, lymphocytes, fibroblasts and
keratinocytes.
Effects
1. It increases emigration of inflammatory cells into the tissues
2. Activates neutrophils and monocytes and their antibacterial activity.
3. It increases secretion of PG, leukotrienes and further mediatiors.
4. Causes fibroblast and endothelial cell proliferation
5. It is essential for antigen presentation and an effective immune response.
12
Interleukin 8, interleuken and colony stimulating factors:
Sources are the following cells-macrophages, lymphocytes, fibroblasts, endothelial cells
when activated by IL1, TNF, endotoxins.
Effects
It causes increased chemotaxis, granule enzyme secretion, toxin production and also release
of further mediators including PG, IL-1 & TNF
Interferon Ÿ
Secreted by T lymphocytes that acts on macrophages, increases their anti-bacterial activity,
secretion of PGs, complement components, toxins enzymes and cytokines including IL-1 and
TNF.
IL-6
Secreted by macrophages, causes polyclonal B cell activation and stimulates keratinocyte
proliferation
Specific Protective Mechanisms
The adaptive immune system is brought about by the action of an array of cells, which takes
up, process, present and react to foreign proteins known as antigens. Antigen presenting cells
such as macrophages roam the body ingesting the antigen they find and fragmenting it into
antigenic peptides. Within the cell, these species of peptide are bound to the major
histocompatibility complex (MHC) molecules and displayed on the surface of the cell. T
lymphocytes have antigenic surface receptors that recognize the specific peptide–MHC
combinations. The T lymphocytes are activated by that process and divide to produce
memory and effector cells. The effector cells produce lymphokines that mobilize other
components of immune system. One set of cells that respond these signals are B-lymphocytes
that also have specific receptor molecules on their surface but unlike T lymphocytes can
recognize parts of whole antigen in solution. When activated they differentiate into plasma
13
cells that secrete specific antibodies. By binding to antigen, antibodies can neutralize them or
precipitate their destruction by activating complement cascades or enabling phagocytic cells
to destroy them.
Possible mechanism of action of antibodies
Binding to bacteria
-
Opsonizing for phagocytosis
-
Activating neutrophil enzyme secretion
-
Coating bacteria and inhibiting attachment
-
Activating complement and thus enhancing opsonization
-
Directly inhibiting bacterial metabolism
Binding to soluble factors
-
neutralizing toxins
-
inhibiting enzymes
Development of Immune cells
They derive from stem cells in the bone marrow. One group of these cells T lymphocytes is
dependent on the thymus gland for its development and B lymphocyte development takes
place in the bone marrow.
Cells destined to become T lymphocytes migrate early in foetal life to the thymus where they
divide and differentiate. They give rise to successive bands of cells, which migrate to the
lining epithelia of body orifices and later to the lymphoid organs. The first cells going to the
epithelia develop T-cell receptor (TCR) with gamma-delta chains where as the later ones
going to the lymphoid organs develop TCRs with alpha-beta chains and develop into helper
(T4) and killer (T8) lymphocytes. As they develop, they make and express either CD4 or
CD8 receptors.
CD4 cells react with Class II MHC and become T4 helper cells and CD8 cells react with
Class I MHC and become T8 killer cells. They are first tested to whether they detect antigens
14
presented by other cells. Cells that react with self-MHC survive and those that do not
undergo apoptosis. They also die if they react with large amounts of self-antigen. The
surviving T lymphocytes migrate to lymphoid organs and these are the cells that can
recognize both foreign peptides and self-MHC.
B-lymphocytes develop under the influence of stromal cells, which produce factors needed
for their growth and development. They develop IL-7 receptors, which are stimulated by IL-7
from stromal cells. Then-they progressively develops and expresses specific antibody
receptors. They form the heavy chain first, then add the light chain and ultimately express the
complete specific Ig receptor. They produce addition Ig alpha and beta chains, which
associate with the Ig molecule to produce the complete receptor. If the developing Blymphocytes react with large amounts of self-antigens then they are signaled to undergo
programmed death (apoptosis), The clones that survive this process migrate to the lymphoid
organs.
Immune Response and Function
Antigens are first taken up by antigen presenting cells. These include macrophages
throughout the body, follicular dendritic cells in lymphoid organs and dendritic and
langerhans cells throughout mucosal surfaces. All these cells carry the CD4 surface marker
Antigens: usually in the form of infecting organisms are phagocytosed by these cells and
broken down with in phagolysosomes into their constituent peptides. A class II MHC
molecule made in the endoplasmic reticulum is transported to the vesicle. A covering protein
chain keeps the molecule inactive until it reaches the antigenic peptide with in its processing
vesicle. In this vesicle, the chain falls away, enabling the MHC molecule to bind to any
antigenic peptide there. The complex then moves to the cell surface where it is presented so
that it can be detected by T & B cells with the appropriate specific antigen receptor.
Antigenic peptides held in the groove of class II MHC molecule are recognized by T4 helper
lymphocytes carrying CD4 marker and appropriate TCR. The binding of the antigen to
15
receptor interacts with biochemical message system in T4 cell which will tell the cell to
divide, grow, differentiate and produce its products. The lymphocyte must also receive a
second message at the same time for these events to occur, otherwise it is programmed to die.
A molecule known as B7 serves this purpose and is presented at the same time by antigen
presenting cells and reacts with a CD28 receptor on the T helper cell. B7 is only produced by
infected cells and thus protects against stimulation by auto-antigens.
During this process IL-1 is also produced by macrophage and reacts with its receptor on T4
cell. This activates the appropriate genes in T4 cell to produce IL-2 and IL-2 receptors.
Stimulation by IL-2 and other cytokines causes cell division and results in the production of a
clone of memory T4 cells and effector T4 cells. The effector T4 helper lymphocytes
produces helper lymphokines with stimulate T4, T8 and B-lymphocytes reacting to same
antigen.
T4 Immunity Controlling Interacellular Parasites.
Effector T4 lymphocytes produces lymphokines that activate macrophages containing the
antigens to destroy the material within their vesicles. The T4 cells consists of two subsets of
cells and one secretes predominantly Il-2 and interferon (IFNY) and the other IL-2, IL-4, IL5, IL-6 and IL-10.
IFNY induces macrophage to produce TNF and chemicals such as nitric oxide and toxic
forms of O2, which lead to microbial destruction in the phagosome. The other response
activates B lymphocytes.
Humoral Immunity
The antibody receptor on the surface of a B lymphocyte can recognize foreign antigens in the
blood stream and binds to it. The antigen is taken into the cell and placed with a vesicle
inside the cell. Class II MHC molecules made in the Endoplasmic reticulum are delivered to
the vesicle. It is then presented on the cell surface where it is detected by the appropriate
clone of T4 helper lymphocytes.
16
The TCR and CD4 bind to antigen and MHC respectively B cells also need a second signal
from T-helper cells. This comes from the production and presentation of CD4O by the helper
cell, which binds to CD4O receptor on B cell. The T4 cell produces helper lymphokines,
which then switch on the signal system that results in division and differentiation to plasma
cells and antibody production. Thse helper lymphokines include IlL-2, IL-4, IL-5, IL-6 and
INFY
When differentiation of B-lymphocytes begins they cease to display their Ab receptor
molecule and prepare for Ab production. Ab produced by the cell are the same as those that
are presented by the cell as antigen receptor. Different kinds of Ab are made each with the
same specificity by a different variation of the Ab molecule, by altering the so-called
constant part of the heavy chain by gener re-arrangement.
All Ab molecules have the same basic structure with 2 specific antigens–combining sites and
a single receptor-binding site. There are 5 types of Ab molecule, each made by a separate
group of plasma cells.
IgM and IgG are found in blood and inflammatory exudates. IgG is most abundant and is a
single Ig molecule with 2 receptor area for C3 and Ig gamma receptors on macrophages and
polymorphs IgM is a polymer of 5Ig molecules with the same receptors as IgG. IgA is a
dimer and has a secretory piece added between 2 molecules. IgE binds to receptors on mast
cells and barophils and causes a release of mediator.
IgG:

Antitoxin

Opsonin

Complement activation

Neutralizes virus in blood
IgM:

Opsonin
17

Bacterial agglutination
IgA:

Prevents viral attachment

Neutralizes virus on mucous membrane

Prevents bacterial adherence on mucous membrane

Antitoxin
IgE:

Degranulates mast cells

Promotes inflammation

Lethal to parasites

Attaches to macrophages and may bind parasites.
IgD:

Possible role in B cell function.
T8 immunity controlling viral infection
Class I MHC molecules are manufactured by practically all cells in their ER and they bind to
peptides that originate from proteins in cytosolic compartment of the cell.
Viruses infect this area of the cell and some of the viral proteins are broken down to peptides.
They are pumped by a transport system to ER. There, the class I MHC molecules are
synthesized as long chains of aminoacids that shape themselves around antigenic peptide to
form complete molecules. This signals for it to be transported to the surface in a vesicle to be
displayed on the surface. Here it can be detected by a killer T8 lymphocyte with expresser
CD8 protein. Again two stimuli are needed to activate the cell, one from class I MHC and
antigen and other from B7 that is synthesized and expressed by the body cell when it presents
a foreign peptide. This links to CD28 receptor on T8 cell.
When activated killer T8 lymphocyte acts directly and indirectly to kill the infected cells they
secrete perforin and other proteins that disrupt the cellular membrane and may release
18
molecules that promote apoptosis. They also release IFNY and TNF, which limit viral
multiplication inside a cell and attract phagocytes that can destroy cells.
Overall, the host defenses are extremely successful in preventing infection around the teeth, a
potential weak point in the epithelial covering of the body. They are also successful in
preventing destructive periodontal disease in the majority of the population despite the
difficulty of dealing with a large mass of bacteria outside the body. The price of successful
host defense is a small degree of tissue damage caused in part by bacteria and their products
and in part by the inflammatory and immnologic response, which they elicit. This is
acceptable considering the effectiveness of the host defense in preventing overt infection
consequently pockets do not form and periodontal diseases do not occur.
19