2. CONTENT
• Introduction
• Function of immune system
• Component of immune system
• Classification of immunity
• Innate immunity
• Acquired immunity
• Humoral
• Cell mediated immunity
• Caries vaccine
• Immunology in pediatric dentistry
• Conclusion
• References
3. INTRODUCTION
The human body has the ability to resist almost all types of
organisms or toxins that tend to damage the tissues and organs.
This capability is called immunity.
Immune system must differentiate between individual’s own
cells and those of harmful invading organisms . Must not attack
commensal flora that inhabit the gut, skin, and other tissues to
the host’s benefit.
4. Functions of immune system
The immune system recognizes and responds to antigens. In order to protect the
individual effectively against disease, the following tasks need to be fulfilled:
Immunological recognition: presence of an infection must be detected.
Contain the infection and if possible eliminate it, via various immune effector
functions ( eg. antibodies, complement).
Immune regulation limits damage to the host by the immune response to
antigen. Failure of this regulation contributes to disease states including allergy
and autoimmune disease.
The adaptive immune system generates immunological memory – exposure
to an infectious agent produces an immune response that can persist, and
protect the host in a subsequent exposure.
6. The major types of pathogens confronting the immune
system, and some of the diseases they cause
7. Components of immune system
Immune responses are mediated by a variety of cells and by the soluble
molecules these cells secrete.
10. Innate immunity
• An additional element of immunity that results from general processes, rather than
from processes directed at specific disease organisms, is called innate immunity.
• Innate immune responses can start acting immediately on encounter with infectious
agents.
• Does not generate long-term protective immunological memory.
It includes the following aspects:
1.Phagocytosis of bacteria and other invaders by white blood cells and cells of
the tissue macrophage system.
2. Destruction of swallowed organisms by the acid secretions of the stomach and
the digestive enzymes.
3. Resistance of the skin to invasion by organisms.
4. Presence in the blood of certain chemicals and cells that attach to foreign
organisms or toxins and destroy them.
11. Some of these are
(1) lysozyme, a mucolytic polysaccharide that attacks bacteria and causes
them to dissolute;
(2) basic polypeptides, which react with and inactivate certain types of
gram-positive bacteria;
(3) the complement complex , a system of about 20 proteins that can be
activated in various ways to destroy bacteria; and
(4) natural killer lymphocytes that can recognize and destroy foreign cells,
tumor cells, and even some infected cells.
12. •After entering tissues, many pathogens are
recognized, ingested, and killed by phagocytes, as
part of the innate immune response .
(TLR-4 :-toll like receptor 4 also designated as
CD284=cluster of differentiation 284 is a key
activator of innate immune response and plays a
central role in fight
against bacterial infection.)
•Macrophages express receptors for many bacterial
components, including bacterial carbohydrate
(mannose and glucan), lipids (LPS) and other
pathogen-derived components (Pathogen
Associated Molecular Patterns, PAMPs)
•Binding of bacteria to macrophage receptors
stimulates phagocytosis and uptake of pathogens
13. Acquired immunity
• In addition to its generalized innate immunity, the human body has the
ability to develop extremely powerful specific immunity against individual
invading agents such as lethal bacteria, viruses, toxins, and even foreign
tissues from other animals.
• This ability is called acquired or adaptive immunity. Acquired immunity is
caused by a special immune system that forms antibodies and/or activated
lymphocytes that attack and destroy the specific invading organism or
toxin.
14. It is of 2 types active and passive
Active Immunity-
Active immunity is subdivided into two types : Natural and Artificial.
Natural- Through clinical or subclinical infection
Artificial- Induced by vaccination
It is the resistance developed by an individual as a result of contact with an
antigen. This contact may be in the form of natural infection or by vaccination. It
leads to stimulate the immune apparatus to form antibodies and/or the production
of immunologically active cells. Active immunity develops after a latent period
which is required for immune system to act but once developed, the active
immunity is long lasting.
15. • Two basic but closely allied types of acquired immunity occur in the body. In
one of these, the body develops circulating antibodies, which are globulin
molecules in the blood plasma capable of attacking the invading agent.
• This type of immunity is called humoral immunity or B-cell immunity
(because B lymphocytes produce the antibodies).
• The second type of acquired immunity is achieved through formation of large
numbers of activated T lymphocytes that are specifically crafted in the lymph
nodes to destroy the foreign agent.
• This type of immunity is called cell-mediated immunity or T-cell immunity
(because the activated lymphocytes are T lymphocytes).
16. Humoral (antibody mediated)
ANTIBODY & ANTIGEN -
• Antibody is a glycoprotein which is produced in response to a
particular antigen.
• Antigen is a foreign substance that induces a immune response,
thereby stimulating the production of antibody.
17. Formation of Antibody:
• Upon entry of a foreign antigen, macrophages in lymphoid tissue
phagocytize the antigen and then present it to adjacent B
lymphocytes.
• In addition, the antigen is presented to T cells at the same time,
and activated T-helper cells are formed. These helper cells also
contribute to extreme activation of the B lymphocytes.
• The B lymphocytes specific for the antigen immediately enlarge
and take on the appearance of lymphoblasts. Some of the
lymphoblasts further differentiate to form plasmablasts, which
are precursors of plasma cells.
• The mature plasma cell then produces gamma globulin
antibodies at an extremely rapid rate—about 2000 molecules per
second for each plasma cell. In turn, the antibodies are secreted
into the lymph and carried to the circulating blood.
18. Formation of “Memory” Cells Enhances the Antibody Response
to Subsequent Antigen Exposure.
• A few of the lymphoblasts formed by activation of a clone of
B lymphocytes do not go on to form plasma cells but instead
form moderate numbers of new B lymphocytes similar to
those of the original clone.
• In other words, the B-cell population of the specifically
activated clone becomes greatly enhanced, and the new B
lymphocytes are added to the original lymphocytes of the
same clone.
• They also circulate throughout the body to populate all the
lymphoid tissue; immunologically, however, they remain
dormant until activated once again by a new quantity of the
same antigen.
• These lymphocytes are called memory cells.
19. Nature of the Antibodies
Antibodies are gamma globulins called immunoglobulins (Ig)
that have molecular weights between 160,000 and 970,000 and
constitute about 20 percent of all the plasma proteins.
All the immunoglobulins are composed of combinations of light
and heavy polypeptide chains.
Their are five classes of immunoglobulins,
1. IgG
2. IgA
3. IgM
4. IgD and
5. IgE
20. IgG
1. Serum anti-bodies representation is 71%.
2. Weight present in blood 0.8-1.6 gm/dL (avg. 1.3gm/dL)
3. Molecular weight 1,60,000
4. Antibodies of secondary immune response, because get
stimulated by natural infection or artificial immunization with
viruses or bacteria, therefore, produce major antiviral,
antibacterial and antitoxin activity in serum.
5. These antibodies are distributed equally between blood and
tissue fluids.
6. They cross the placenta from mother to foetus by active
transport e.g. antibodies of Rh blood group system and are
found in milk, saliva, nasal and bronchial secretion.
7. They can serve as opsonin and promote chemostatic activity of
WBC's
21. IgA
1. Serum anti-bodies representation is 22%.
2. 140-420 mg/dL avg. 250 mg/dL
3. 1,70,000
4. Occur in plasma and are also secreted in tears, saliva, intestinal
juices, respiratory secretions and colostrum.
5. They can't cross the placenta.
6. Lyse bacteria in the presence of lysozyme, which also occurs in
the secretions containing IgA, there by protect mucous surfaces
i.e. provide localized protection.
22. IgM
1. Serum anti-bodies representation is 7%.
2. 50-200 mg/dL avg. 120 mg/dL
3. 1,00,000
4. Because of their large size they are predominantly intravascular
and produced in primary immune response.
5. Each IgM molecule possesses at least 5 identical combing sites,
therefore, these antibodies can adhere to surfaces of cells with
large numbers of similar antigenic sites.
6. Activate complement system, promote phagocytosis and cause
cell lysis by digesting holes in the cell membrane at the site of
antibody attachment.
7. More effective than IgG antibodies in lysing cells.
23. IgE : Reagins
1. Serum anti-bodies representation is in traces.
2. 0.03 mg/dL
3. 1,85,000
4. Heat labile, skin sensitizing antibodies, therefore, also called
reagins.
5. When specific antigen is brought into contact with IgE-coated
mast cells or blood basophils; these cells undergo degranulation
with release of chemical mediators and E.C.F.(Eosiniphil
chemotactic Factor)-A. Thus play important role in allergies,
parasitic infestations and anaphylactic type of immediate
hypersensitivity disorders.
24. IgD
1. Serum anti-bodies representation is in traces.
2. 3 mg/dL
3. 1,50,000
4. Present on the surface of B-lymphocytes with IgM, therefore,
involved in antigen recognition.
25. Specificity of Antibodies-
•Each antibody is specific for a
particular antigen;
• This characteristic is caused by its
unique structural organization of amino
acids in the variable portions of both the
light and heavy chains.
• The amino acid organization has a
different steric shape for each antigen
specificity, so when an antigen comes in
contact with it, multiple prosthetic
groups of the antigen fit as a mirror
image with those of the antibody, thus
allowing rapid and tight bonding
between the antibody and the antigen.
26. Mechanisms of Action of Antibodies:
Antibodies act mainly in two ways to protect the body against
invading agents:
(1) by direct attack on the invader and
(2) by activation of the “complement system” that then has
multiple means of its own for destroying the invader.
27. Direct Action of Antibodies on
Invading Agents:
Figure shows antibodies (designated
by the red Y-shaped bars) reacting with
antigens (designated by the shaded
objects).
28. • Because of the bivalent nature of the antibodies and the
multiple antigen sites on most invading agents, the antibodies
can inactivate the invading agent in one of several ways, as
follows:
1. Agglutination, in which multiple large particles with antigens on
their surfaces, such as bacteria or red cells, are bound together into
a clump.
2. Precipitation, in which the molecular complex of soluble
antigen (such as tetanus toxin) and antibody becomes so large that
it is rendered insoluble and precipitates.
3. Neutralization, in which the antibodies cover the toxic sites of
the antigenic agent.
29. 4. Lysis, in which some potent antibodies are occasionally
capable of directly attacking membranes of cellular agents
and thereby cause rupture of the agent.
• These direct actions of antibodies often are not strong
enough to play a major role in protecting the body against
the invader.
• Most of the protection comes through the amplifying
effects of the complement system.
30. COMPLEMENT SYSTEM FOR ANTIBODY ACTION
“Complement” is a collective term that describes a system of
about 20 proteins, many of which are enzyme precursors.
The principal actors in this system are 11 proteins designated
C1 through C9, B, and D. All these are present normally among
the plasma proteins in the blood, as well as among the proteins
that leak out of the capillaries into the tissue spaces.
The enzyme precursors are normally inactive, but they can be
activated by the so-called classical pathway.
31. Classical Pathway:
The classical pathway is initiated by an antigen-antibody reaction.
That is, when an antibody binds with an antigen, a specific reactive
site on the “constant” portion of the antibody becomes uncovered,
or “activated,” and this in turn binds directly with the C1 molecule
of the complement system, setting into motion a “cascade” of
sequential reactions.
32. The C1 enzymes that are formed then activate successively
increasing quantities of enzymes in the later stages of the system so
that from a small beginning, an extremely large “amplified”
reaction occurs.
Multiple end products are formed, and several of these cause
important effects that help to prevent damage to the body’s tissues
caused by the invading organism or toxin. Among the more
important effects are the following:
1. Opsonization and phagocytosis: One of the products of the
complement cascade, C3b, strongly activates phagocytosis by both
neutrophils and macrophages, causing these cells to engulf the
bacteria to which the antigen-antibody complexes are attached.
This process is called opsonization.
33. 2. Agglutination: The complement
products also change the surfaces of the
invading organisms, causing them to
adhere to one another, thus promoting
agglutination.
3. Chemotaxis: Fragment C5a initiates
chemotaxis of neutrophils and
macrophages, thus causing large numbers
of these phagocytes to migrate into the
tissue area adjacent to the antigenic agent.
4.Activation of mast cells and basophil:
Fragments C3a, C4a, and C5a activate
mast cells and basophils, causing them to
release histamine, heparin, and several
other substances into the local fluids
34. 5. Neutralization of viruses. The complement enzymes and other complement products
can attack the structures of some viruses and thereby render them nonvirulent.
6.Lysis. One of the most important of all the products of the complement cascade is the
lytic complex, which is a combination of multiple complement factors and is
designated C5b6789. This has a direct effect of rupturing the cell membranes of
bacteria or other invading organisms
7. Inflammatory effects. In addition to inflammatory effects caused by activation of
the mast cells and basophils, several other complement products contribute to local
inflammation.
35. Cell mediated immunity
• Release of Activated T Cells from Lymphoid Tissue and Formation of Memory
Cells.
• Upon exposure to the proper antigen, as presented by adjacent macrophages,
the T lymphocytes of a specific lymphocyte clone proliferate and release large
numbers of activated, specifically reacting T cells in ways that parallel antibody
release by activated B cells.
• The principal difference is that instead of releasing antibodies, whole activated T
cells are formed and released into the lymph. These T cells then pass into the
circulation and are distributed throughout the body
• Also, T-lymphocyte memory cells are formed in the same way that B memory
cells are formed in the antibody system. That is, when a clone of T lymphocytes is
activated by an antigen, many of the newly formed lymphocytes are preserved in the
lymphoid tissue to become additional T lymphocytes of that specific clone
36. • Antigen-Presenting Cells, MHC Proteins, and Antigen
Receptors on the T Lymphocytes. T-cell responses are
extremely antigen specific, like the antibody responses
of B cells, and are at least as important as antibodies in
defending against infection.
• Although B lymphocytes recognize intact antigens, T
lymphocytes respond to antigens only when they are
bound to specific molecules called MHC proteins on
the surface of antigen-presenting cells in the
lymphoid tissues .
37. The three major types of antigen presenting cells are macrophages, B
lymphocytes, and dendritic cells. The dendritic cells, the most potent of the
antigen-presenting cells, are located throughout the body, and their only known
function is to present antigens to T cells
The MHC proteins are encoded by a large group of genes called the major
histocompatibility complex (MHC). The MHC proteins bind peptide fragments of
antigen proteins that are degraded inside antigen presenting cells and then
transport them to the cell surface.
38. • The antigens on the surface of antigen-presenting cells bind
with receptor molecules on the surfaces of T cells in the
same way that they bind with plasma protein antibodies.
These receptor molecules are composed of a variable unit
similar to the variable portion of the humoral antibody.
39. SEVERAL TYPES OF T CELLS AND THEIR DIFFERENT
FUNCTIONS
It has become clear that there are multiple types of T cells. They
are classified into three major groups:
(1)T-helper cells,
(2) Cytotoxic T cells, and
(3) Suppressor T cells.
The functions of each of these T cells are distinct.
40. T-Helper Cells
• The T-helper cells are by far the most numerous of the T cells,
usually constituting more than three quarters of all of them.
• As their name implies, they help in the functions of the immune
system, and they do so in many ways. In fact, they serve as the
major regulator of virtually all immune functions.
• They do this by forming a series of protein mediators, called
lymphokines, that act on other cells of the immune system, as
well as on bone marrow cells.
• Among the most important lymphokines secreted by the T-
helper cells are the following:
Interleukin-2
Interleukin-3
Interleukin-4
Interleukin-5
Interleukin-6
Granulocyte-monocyte colony-stimulating factor Interferon
42. Specific Regulatory Functions of the Lymphokines.
• In the absence of the lymphokines from the T-helper cells, the
remainder of the immune system is almost paralyzed.
• In fact, it is the T-helper cells that are inactivated or destroyed
by the human immunodeficiency virus (HIV) which leaves the
body almost totally unprotected against infectious disease,
therefore leading to the now well known debilitating and lethal
effects of Acquired Immuno Deficiency Syndrome (AIDS).
43. Stimulation of Growth and Proliferation of Cytotoxic T Cells
and Suppressor T Cells.
In the absence of T-helper cells, the clones for producing cytotoxic T cells and
suppressor T cells are activated only slightly by most antigens.
The lymphokine interleukin-2 has an especially strong stimulatory effect in
causing growth and proliferation of both cytotoxic and suppressor T cell
Stimulation of B-Cell Growth and Differentiation to Form
Plasma Cells and Antibodies.
The direct actions of antigens to cause B-cell growth, proliferation, formation of
plasma cells, and secretion of antibodies are also slight without the “help” of the
T-helper cells.
Almost all the interleukins participate in the B-cell response, but especially
interleukins 4, 5, and 6.
44. Activation of the Macrophage System.
The lymphokines also affect the macrophages. First, they slow or stop the
migration of the macrophages after they have been chemotactically attracted
into the inflamed tissue area, thus causing great accumulation of
macrophages.
Second, they activate the macrophages to cause far more efficient
phagocytosis, allowing them to attack and destroy increasing numbers of
invading bacteria or other tissue destroying agents.
Feedback Stimulatory Effect on the T-Helper Cells. Some of the
lymphokines, especially interleukin-2, have a direct positive feedback effect in
stimulating activation of the T-helper cells.
This acts as an amplifier by further enhancing the helper cell response, as well
as the entire immune response to an invading antigen.
45. Cytotoxic T Cells Are “Killer”
Cells
The cytotoxic T cell is a direct-attack cell
that is capable of killing microorganisms
and, at times, even some of the body’s
own cells.
For this reason, these cells are called
killer cells. The receptor proteins on the
surfaces of the cytotoxic cells cause them
to bind tightly to the organisms or cells
that contain the appropriate binding-
specific antigen. Then they kill the
attacked cell
After binding, the cytotoxic T cell secretes hole-forming proteins, called
perforins, that literally punch round holes in the membrane of the attacked cell.
Then fluid flows rapidly into the cell from the interstitial space. In addition, the
cytotoxic T cell releases cytotoxic substances directly into the attacked cell.
46. Almost immediately, the attacked cell becomes greatly swollen, and it usually
dissolves shortly thereafter. Of special importance is that these cytotoxic killer
cells can pull away from the victim cells after they have punched holes and
delivered cytotoxic substances and then move on to kill more cells.
Indeed, some of these cells persist for months in the tissues.
Suppressor T Cells
• Much less is known about the suppressor T cells than about the others, but they
are capable of suppressing the functions of both cytotoxic and T-helper cells.
• These suppressor functions are believed to prevent the cytotoxic cells from
causing excessive immune reactions that might be damaging to the body’s own
tissues.
• For this reason, the suppressor cells are classified, along with the T-helper
cells, as regulatory T cells.
48. IMMUNIZATION BY INJECTION OF ANTIGENS
• Immunization has been used for many years to produce acquired immunity against
specific diseases. A person can be immunized by injecting dead organisms that are
no longer capable of causing disease but that still have some of their chemical
antigens.
• This type of immunization is used to protect against typhoid fever, whooping cough,
diphtheria, and many other types of bacterial diseases.
• Immunity can be achieved against toxins that have been treated with chemicals so
that their toxic nature has been destroyed even though their antigens for causing
immunity are still intact.
• This procedure is used in immunizing against tetanus, botulism, and other similar
toxic diseases.
• And, finally, a person can be immunized by being infected with live organisms that
have been “attenuated.” That is, these organisms either have been grown in special
culture media or have been passed through a series of animals until they have
mutated enough that they will not cause disease but do still carry specific antigens
required for immunization.
51. • In order to replace previous methods of curing dental caries
which was “to drill and fill”, measures have been taken to
prevent dental caries, among which one is to immunize the
population against the disease through dental caries vaccine.
• This approach to the prevention of dental caries should not be
regarded as being in competition with other methods such as
use of water fluoridation, topical fluorides in the form of mouth
rinses, sealants, topical varnish, antimicrobial
chemotherapeutics, or good dietary habits.
• Immunization with combination of all other techniques which
have been mentioned, may contribute towards an even greater
reduction of the prevalence of the disease.
Caries vaccine
52. Our defense system
Saliva has a buffering action against acid produced as a result of metabolism of
carbohydrates by microorganisms. Buffering is produced with the help of
carbonates, phosphates, peptides and proteins.
Antimicrobial: Mucin, lactoferrin, lysozyme, histidine rich proteins and sialo
peroxidase have antimicrobial action.
Innate and humoral immunity: Viral activity is checked by immunoglobulins (IgA
and IgG) Peptides- Such as cystatins and defensins are histidine rich polypeptide.
Indigenous Microbiota: Act against any external pathogen as in the case of
Pseudomonas aeurogenosa attempt for biofilm formation is prohibited by oral
microflora.
53. Oral Mucosa
1. Continuous exfoliation of oral mucosal epithelium prevents the growth of
microbes.
2. Human β-defensins1(H β-D1) and human β-defensins2 (H β-D2) from epithelial
cells along with chemokines attract monocytes and neutrophils activating the innate
immune system.
3. Acquired immune system includes immunoglobulins, Langerhans cells and
intraepithelial lymphocytes.
4. Stratum granulosum secretes membrane coating granules which has its role in
inhibiting microbial deposition.
5. Intraepithelial dendritic Langerhans cells are antigen presenting cells which present
the antigen complexed with the MHC Class II to helper T cells.
54. Mechanism of Vaccine Action
The saliva contains 1-3% of antibodies primarily of which are IgA.
But IgM and IgG are some antibodies also present in gingival crevicular fluid.
There are certain cellular immunological agents like lymphocytes, macrophages and
neutrophils that are also associated with immunological response. Some of the possible
ways antibodies control microbial growth are:
1. The salivary agglutinin may interact with bacterial surface receptors and inhibit
their colonization.
2. It may also inactivate surface glucosyltransferase which would further reduce the
extracellular glucans resulting in reduction in plaque formation.
3. The salivary glands produce secretory antibody IgA by direct immunization of gut
associated lymphoid tissue (GALT). Since these antibodies has direct access to
tooth surface they prevent S. mutans to adhere to the enamel surface or it may
inhibit activity of glucosyltransferase (GTF) and may prevent formation of
dextran.
55. Antigenic determinants of S. Mutans Adhesins:
Purified from two major microorganisms- S. mutans and S. sorbinus.
Glucosyltransferases: 3 types are available
Water-soluble glucan synthesizing enzymes: GTFS
Water insoluble and water-soluble glucan synthesizing enzymes: GTF-S-I.
Glucan synthesizing enzyme: GTF-I.
Genes encoding the 3 forms are: GTF-C - GTF-S: GTF-I: GTF-B - GTF-SI:
GTF-D .
Glucan Binding Protein (GBP): 3 distinct proteins with glucan binding activity
are released: GBP-A, GBP-B and GBP-C. Adhering of glucan to S. mutans
becomes easy with these proteins.
It makes the dental biofilm porous, thus contributing the nutrients for bacterial
metabolism.
Dextranase, an enzyme of Dextran (major constituent of early dental plaque and
prevents colonization of organism at early stage), removes it and thus bacteria can
invade plaque at an early stage.
56. Routes of Administration
Two important routes of administrations through Common Mucosal Immune Pathway
are:-
1. Systemic route
2. Active gingiva-salivary route
Common Mucosal Immune System: This method is preferred for the induction of
sectretory IgA antibodies.
Following methods are used:
Oral Route: Relied on oral induction of immunity in the GALT. Oral feeding, gastric
intubation, or in vaccine containing capsules or liposomes are best way of application
for antigen. Lehner T. in his study showed that oral immunization with S. mutans did
not induce significant secretory IgA in monkeys depicting limited immunological
memory in secretory IgA responses and this may limit the value of oral immunization.
57. Intranasal Route: Nasal route administration procedure is preferred to induce
immunity to bacterial antigens to avoid colonization and aggregation of
microorganisms. Katz J et al. in his study showed that intranasal immunization of rats
with S. mutans antigen I/II combined with the B subunit of cholera toxin-induced a
protective salivary immune response along with a reduction in S. mutans accumulation
and dental caries
Minor Salivary Gland: Considered one of the best routes, takes less time and has
broad ducts providing retrograde passage to bacteria and its products.
Tonsillar: A study showed that formalin-killed cells of S. sobrinus in rabbits by
tonsillar administration reduced the carious sites in rabbits. Repeated application can
induce IgA antibodies in both major and minor salivary glands
Rectal: The lower intestinal tract has highest concentration of lymphoid follicles and
thus it is known as inductive location for immune responses.
Systemic Route: IgG, IgM and IgA antibodies find their way into oral cavity via GCF
and thus protect against dental caries. However, Protection against caries was
associated predominantly with increased serum IgG antibodies.
58. Passive immunization
1. Monoclonal antibodies: These antibodies to S. mutans cell surface Ag I/II have
been examined. Topical application where S. mutans are more in number found to be
more affected and showed massive reduction.
2. Bovine milk: Systemic immunization of cows with a vaccine using whole S. mutans
has led to the bovine milk - containing polyclonal IgG antibodies. This was then added
to the diet of a rat model. This brought a drop in the caries level.
3. Egg-yolk antibodies: Due to presence of formalin killed whole cells and cell
associated GTFs reduction in caries was appreciated.
4. Transgenic plants: It is the first plant derived vaccine which is genetically
modified. Being tasteless and colourless can be directly applied onto the teeth.
59. IMMUNOLOGY IN PEDIATRIC DENTISTRY
• On a more mundane level, the pedodontist deals with the immune system daily
when inquiring about allergies and rheumatic fever in the medical history. Oral
immunology affects pediatric dentistry when considering ulcerative lesions of the
oral mucosa, junvenile periodontitis, and research areas such as caries vaccination.
• Every practitioner should have a working knowledge of immunology and its
implications in oral medicine.
60. Allergy
The evalution of the child patient for atopic immune reactions is one of the most
important, yet potentially difficult, tasks facing the pediatric health care practitioner.
A child's medical history may be vague in references to drug or environmental
hypersensitivity.
An adolescent may deny any adverse reaction to a previously prescribed medication
but develop an allergic reaction. Allergy to one drug may preclude the use of an entire
group of substances.
62. 1. The antibody type which initiates the histamine releasing
immediate atopic reaction is IgE.
• Molecule dimers of IgE adhere to mast cells and basophils
causing degranulation and subsequent increase in extracellular
levels of vasodilators such as histamine, slow-reacting
substance - A, and the kinins.
• Clinical symptoms are cutaneous wheal and flare, edema,
rhinorrhea, tearing, possible respiratory embarrassment, and
hypotension . Antihistamines are the most effective treatment
in mild cases.
• Active therapy of allergy may include induction of IgG
antibody synthesis by multiple injections of minute quantities
of the allergen. This is done in the hope that circulating IgG
will block the secretion of IgE and its sequelae.
63. 2. Angioneurotic edema- is a localized immediate hypersensitivity
characterized by swelling of the lips, skin, tongue, and eyes.
• Airway obstruction is not uncommon. At times, the salivary glands
and/or distal extremities also may be involved. The etiology is
presumed to be histamine release. Treatment is dictated by the
severity of the individual case.
• There is a hereditary form of angioneurotic edema transmitted as
an autosomal dominant trait.
• Previously, patients with serious or frequent occurrences of
hereditary angioneurotic edema were treated with antifibrinolytic
agents such as epsilon-aminocaproic acid, but recently the
synthetic androgen, danazol has been shown to be highly effective.
64. • Patients not on chronic drug therapy can undergo dental treatment
following preoperative infusion of fresh frozen plasma. If an
unsuspected severe episode occurs, the most important emergency
steps are airway maintenance, i.e., tracheostomy, and fluid therapy
• A family history is of crucial importance in preventing episodes
secondary to dental treatment. Laboratory tests such as the
complement decay rate and C-4 levels are helpful in confirming the
diagnosis.
65. • Anaphylaxis is a generalized histamine release secondary to a
severe, acute allergic reaction. The patient might have had
previous exposure to the antigen and probably will give a
positive history of a previous milder allergic response. Most
often, the allergy is caused by penicillin or insect stings.
• Death resulting from untreated anaphylaxis will occur in 3-15
minutes. The initial signs are agitation, sneezing, coughing,
itching, and stridor. These will be followed by hypovolemic
shock and hypoxia. Convulsions and incontinence precede total
cardiovascular and respiratory collapse.
66. Treatment of an anaphylactic reaction in the dental requires
prompt, efficient action.
• Starting an intravenous infusion is desirable, but usually
impractical considering the time element and the circulatory
collapse. Therefore, pharmacologic intervention should be
intramuscular.
• The first step is injection of 0.5 cc 1:1,000 epinephrine
intramuscular. This should be repeated every five minutes as
needed.
• Next, an antihistamine (i.e., 50 mg diphenhydramine) is
injected to prevent laryngeal edema and prolonged histamine
release. At this point, while waiting for transportation to the
hospital, 100% oxygen should be administered and, if possible,
an IV line started.
67. Steroids then can be administered intravenously 100 mg every one to two hours as
needed for hypotension. Infusion of an electrolyte solution will help to reduce the
patient's hypovolemia.
Urticaria may persist following recovery.
Erythema multiforme is a delayed hypersensitivity reaction which usually
involves orofacial signs of contact dermatitis.
The allergen is usually a pharmaceutical compound or bacteria. The long period
between exposure and clinical manifestations decreases with each exposure and may
be as short as a few hours.
Features of contact dermatitis reactions include pruritis at the site, erythema, and
bullae. Allergens include ester type local anesthetics, preservatives such as
methylparaben, items containing para-aminobenzoic acid (PABA), acrylic monomer,
and many other dental materials.
68. Some drugs that frequently are allergenic are penicillin, streptomycin, sulfonamides,
barbiturates, aspirin, dilantin, and tetracycline. Oral reactions to drug compounds, stomatitis
medicamentosa, encompass many presenting forms from erythema to purpura and
angioneurotic edema.
69. Primary Immunodeficiencies
There is a wide variety of congenital immune-system abnormalities with which the
pediatric dentist must be familiar.
For a child with a deficient immune mechanism, every infection is potentially fatal.
Therefore, each requires the most careful diagnostic and clinical care. Major
presentations of immuno-deficiencies are:
(1) increased frequency of infections,
(2) unusually severe infection,
(3) prolonged duration of infection,
(4) unexpected complication or manifestation, and
(5) infection with a minor pathogen .
For example, a child with an acute pulpitis or dentoalveolar abscess rapidly could
develop an acute osteomyelitis. In chronic mucocutaneous candidiasis, the oral thrush
is unresponsive to treatment.
70. Screening tests include complete blood count (noting leukocyte morphology),
immunoglobulin levels, Schick test, isoagglutinin (anti-A, anti-B) titers, spleen scan,
cultures, sedimentation rate, and radiography.
Pedodontists and orthodontists should note that cephalometric radiographs can be
useful. Patients with antibody deficiencies will have decreased adenoidal tissue on
lateral skull and facial views .
71. Periodontitis
• The etiology of juvenile periodontitis has been debated and
remains highly speculative.
• The work of Lehner and coworkers has provided a cornerstone
for the implication of immune dysfunction in the pathogenesis
of periodontitis.
• Alteration of immunoglobulin levels also has been noted.
Cianciola and coworkers reported a depression of neutrophil
phagocytosis and chemotaxis in this disease.
• Some workers have suggested limiting the designation of
periodontitis to acute periodontal disease in pediatric patients
who are otherwise healthy.
72. Patients with one of these diseases are more prone to other such conditions. Rubin
and Cianciola outline a variety of immune system disorders which are
predisposing factors in periodontal disease.
The child with other syndromes should make the diagnostician weigh
periodontosis more heavily in the differential diagnosis
Autoimmunity
A wide variety of clinical entities currently are thought to have an autoimmune
pathogenesis. The antiself antibodies are produced by "forbidden" clones of
lymphocytes which overcome homeostatic immune-system regulation. Cellular
phenomena are also a part of autoimmune diseases.
Most autoimmune states occur predominantly in adults but those that manifest in
children can be severely debilitating and potentially fatal.
73. The patient first may present to a dental office since oral complications may be an early
sign.
Lupus erythematosis may present in adolescents in the systemic or discoid form. Both
forms frequently have orofacial involvement . Skin lesions usually precede those of the
mucous membrane.
74. • Oral manifestation of these diseases is gingival hemorrhage with
or without other mucosal lesions. Petechiae and ecchymosis may
occur on the palate. Connective tissue disorders of the salivary
glands may occur in children.
• Prepubertal Sjogren's syndrome has been reported. The
keratoconjunctival sicca may develop in a child with other
autoimmune disease.
• Treatment is usually palliative. Regular oral physiotherapy is
necessary to prevent rampant caries in patients with xerostomia.
Rheumatoid arthritis may occur in childhood with the typical
joint lesions. Temporomandibular joint symptoms may or may not
be present. Several autoimmune blood dyscrasias may occur in
childhood or adolescence; pernicious anemia, autoimmune
hemolytic anemia, and idiopathic thrombocytopenic purpura are
among them
75. Immunization
Pedodontists treating oral trauma must be aware of the child's
vaccination status, most notably tetanus. Infection by the anaerobe
Clostridium tetani has a 45-55% mortality in the United States but
is completely preventable by immunization and wound care.
Tetanus toxoid is used as a booster when the patient gives a history
of not being vaccinated for at least five years. Boosters produce
adequate antibody titers in less than one day.
In the case of infection, palliative care is rendered, including
debridement, antibiotics, antitoxin, and life support (i.e., intubation
and sedation). The human globulin tetanus antitoxin neutralizes
circulating clostridial neurotoxin but not that which is bound to the
motor endplate.
76. CONCLUSION
The immune system is a complex network of organs, cells and
proteins that defends the body against infection, whilst protecting the
body's own cells. The immune system keeps a record of every germ
(microbe) it has ever defeated so it can recognize and destroy the
microbe quickly if it enters the body again.
77. REFERENCES
1. Hall J E, Hall ME. Guyton and Hall textbook of medical physiology 13th
edition
2. Parkin J, Cohen B. An overview of the immune system. The Lancet.
2001 Jun 2;357(9270):1777-89.
3. Gupta C, Mankel H. Caries Vaccine: An Overview.
4. Donlon WC. Immunology in pediatric dentistry. Pediatric dentistry. 1983
Sep 1;5(3):195.
5. Chaturvedi M, Punj A. Human Oral Microflora. Int J Curr Adv Res.
2017;7(7):14065-70.
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