Endodontic immunology

II- Specific Immune response:

*Activation of cells of specific immune response (T- and B- cells) requires
antigen presenting cells + antigen + lymphoid system interaction at infection
site or at lymphoid tissue (Lymph node draining site of infection).
*Antigen presenting cells (APC) phagocytose antigen and process antigen by
its partial degradation exposing its epitope. The epitope is re-excreted on
APC surface with one of major histocompitability complex (MHC) that
stimulates differentiation of certain lymphocyte either B- or T- cells or one of
their subgroups.
e.g. If MHC class II is presented on APC it stimulates T-helper cells
activation. If MHC class I is presented on APC it stimulates T-cytotoxic cells
activation.

Types of specific immune response:

1. Cell mediated: T- Cells differentiating to T H-helper, TC- cytotoxic, TS-

suppressor and TD that produce lymphokines.

a) T H-helper enhances immune response. TH cells are the maestro of the

immune system.
It secretes factors which help other cells to perform their function:
1. Factors which stimulate B cells. (Th2 activation)
2. Factors which stimulate macrophages. (Th1 activation)
3. Factors which stimulate Tc.
4. Release lymphokines (Cytokine).
5. Stimulate Clone of Memory T cells.
b) TS-suppressor suppresses immune response.
c) TC-cytotoxic has cytotoxic effect on infected host cells and produces
lymphokines.
d) TD-depressor (regulatory) produces lymphokines which affect
macrophages, Antigen and alter inflammatory reaction.

Example of produced Lymphokines:

i. Lymphotoxin: has direct lethal effect on bacterial cells.
ii. Macrophage activating factor: activates macrophage.
iii. Migration inhibiting factor: holds macrophage in area of response.
iv. Osteoclast activating factor: causes bone resorption in periapical
lesions.

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v. Eosinophil chemotactic factor of anaphylaxis: calls eosinophils to area
of inflammation.

2. Antibody mediated (humoral mediated): B- Cells differentiating to

plasma cell that synthesize immunoglobulins.
Humoral response requires B-cells + APC-Ag complex + Thelper to
differentiate into plasma cells producing Immunoglobulins (Antibodies)

Immunoglobulins produced are of five types Ig G, M, A, D, E.

a) IgM is a pentamer. It is the first Ig made by fetus and B cells. It appears in
primary immune response. It has short life. It is present in colostrum and
mother milk to protect newly born. It fixes complement, cause
agglutination and cytolytic.
b) IgG is a major serum Ig 75%. It is a monomer. It appears in secondary
immune response. It is the only Placental transfer Ig. It fixes complement,
causes opsonization to enhance phagocytosis, Antitoxin and antibody
dependent cellular cytotoxicity.
c) IgA is found in serum (monomeric) and body secretion (dimeric): Tears,
saliva, gastric and pulmonary secretions.It is a major secretory Ig on
Mucous surfaces to give Local Immunity by coating bacteria or viruses
preventing their adherence to mucosal cells. It does not fix complement
(unless aggregated).
d) IgD is present in very small amount in serum (monomer). It is found on
B cell surface. It may function as Antigen receptor.
e) IgE is the least common serum Ig (monomer). It binds to basophils and
mast cells (complexed with Ag binding) causing allergic and
hypersensitivity reactions (type I)

Immunoglobulins Functions:
1. Specifically bind and agglutinate or precipitate antigen, allow its
phagocytosis
2. With complement enhance inflammation to destroy antigen
3. Ig M and G circulating 80-85% of serum Ig
4. Ig A maintains stable relation between host and normal flora and has a
protective function
But If canals left open, this increases sIgA which activate rests of
mallassez in periapical tissues by epithelium growth factor present in
saliva, that might cause periapical cyst

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Inflammatory mediators of vascular system in inflammation and
immune response
They are chemical mediators that exist in non specific immune response as
histamine, kinins, PGs, LTs, complement. Others exist in specific immune
response as immunoglobulins and cytokines.

1. Histamine
2. Kinin
3. Arachedonic acid derivatives (PGs & LTs)
4. Complement system

1. Histamine
-It is the most important vasoactive amine that causes vasodilatation.
-It is the first mediator to act, but becomes rapidly inactivated (has a
transient action).
-It is released from mast cell degranulation. When mast cell attaches to
endothelium, it releases histamine that causes vasodilatation, contraction of
endotheliel cells and increase intracelluler gaps for substances to pass.
-It increases in periapical lesion and inflammed pulp.
-Agents that release histamine are mechanical trauma, UV radiation,
bacterial toxin, components of complement, proteolytic enzymes from cells,
peptides from PNLs, allergens.

2. Kinins
-It is a cascade starting from activation of Hagman factor XII (a component
of blood clotting system)
-It releases bradykinin
-It is important in delayed phase of vascular permeability, vasodilataion and
pain.

3. Prostaglandins (PG) and leukoterines (LT)

- They are produced from long chain fatty acids in all tissues, derived from
arachedonic acid, synthesized within seconds in response to stimulus.
-Most cells produce them but in inflammation mainly from PNLs and
macrophages
-Their main functions are:

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 1. They are responsible for delayed prolonged phase of vascular
permeability
2. PG plays role in inflammation and pain in inflammed pulp
3. PG cause bone resorption
4. There is a correlation between increased LTB4 and PNLs and
symptomatic acute periapical lesion.

4. Complement
-They are inactive complement proteins in circulation.
-Complement Activation is either by:
a) Classical pathway initiated by antigen – antibody complex which
activates C1 then C4 followed by C2 then C3 forming C3b
b) Alternative pathway initiated by bacterial products (toxins) or
aggregated immunoglobulins which activate C3 leading to binding of
C3b to cell surface
-Complement Cascade C3b activates C5 to C5b which binds to C6, C7,
C8 and C9 to form the “membrane attack unite “C5b6789” which causes
cell lysis.
-Complement Action:
i) Inflammation: C3a and C5a induce local vascular permeability and
attract phagocytes.
ii) Lysis of foreign cells: the membrane attack complex (C5b6789)
creates pores in cell membranes disrupting their integrity
iii) Opsonization: C3b binds to bacterial cells and serves as an Opsonin.
Opsonization signals phagocytes to engulf materials including
bacterial cells.

Role of immune system in inflammatory process:

1. Protective mechanism.
2. Augment and enhance inflammation.
3. Self destructive (allergy and hypersensitivity).
In dental practice, 2 types of Hypersensitivity are important:
a. Immediate: within seconds or minutes
By interaction with specific IgE (humoral immunity)
as anaphylaxis due to local anasthesia
b. Delayed: takes days
By Cell Mediated Immunity by previous sensitization by
Antigen
as contact dermatitis due to allergy from latex gloves