cells of immune system
DESCRIPTION
cells of immunity and inflammationTRANSCRIPT
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PRESENTED BY :
DR. VARTIKA SRIVASTAVA
CELLS OF IMMUNE SYSTEM
3CONTENT INTRODUCTION
CELLS OF IMMUNE SYSTEM
Lymphocytes ,B cells ,T cells , Natural killer cell
Dendritic Cells, Monocytes, Macrophages, Neutrophils, Eosinophils, Basophils , Mast Cells
TYPES OF IMMUNITY
INNATE & CELL MEDIATED IMMUNITY IN PERIODONTAL DISEASE
CLINICAL IMPLICATION OF IMMUNE RESPONSES
REFERENCES
4INTRODUCTION
The state of periodontal health or disease depends upon the interaction between the resident microbiota and the host response.
Periodontal pathogens trigger both inflammatory reaction and host immune response.
5What Is Immunity
The ability of the body to defend itself against specific invading agents such as bacteria, toxins, viruses, and foreign tissue is called immunity.
6 The immune system plays a key role in limiting
the infections to the gingival crevice.
The main function of the immune system is to defend the body against a wide variety of pathogenic infectious agents with vastly differing natures, i.e. viruses, bacteria, fungi, protozoa and parasitic worms.
7what is the importance of immunity?
8 The complexity of this task requires a
sophisticated repertoire of mechanisms for the recognition of, and defense of the body against, these pathogens.
This is achieved by an array of cells and molecules which they secrete which are dispersed through- out the body and collectively constitute the immune system
9 Most of the major cell types of the immune
system are derived from progenitors (stem cells) in the bone marrow.
Many of the mature cells circulate in the bloodstream and are dispersed throughout tissues of the body, while some also congregate in specialized lymphoid tissues.
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Furthermore, in order to generate effective immunity, the various cell types cooperate with each other by means of direct interactions between cell surface molecules and via the molecules that they secrete.
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Lymphocytes B cells T cells
Natural killer cell
Dendritic Cells Monocytes
Macrophages Neutrophils Eosinophils
Basophils Mast Cells
CELLS OF IMMUNITY
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15NEUTROPHIL
Comprise the majority of white blood cells (60–70%). They are also known as polymorphonuclear leucocytes
because of their multi lobed nuclei and are larger than most mononuclear blood cells.
Derived from myeloid progenitors in the bone marrow, granulocytes are released at a rate of seven million per minute, but are short-lived (2–3 days).
16 They contain azurophilic lysosomal granules
which, in addition to myeloperoxidase, lysozyme and acid hydrolases, contain other antimicrobial proteins (e.g. defensins and serprocidins).
They also possess secondary specific granules which contain the iron-binding protein lactoferrin as well as lytic enzymes
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The main function of neutrophils is the phagocytosis and intracellular digestion of particulate antigens (e.g. bacteria) and to produce reactive oxygen intermediates (ROI) with antimicrobial potential.
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In addition to producing classical effector molecules, such as ROI and cytokines , neutrophils can extrude extracellular fibrillary networks termed neutrophil extracellular traps (NETs)
These networks are composed mainly of DNA, but also contain proteins from neutrophil granules
20 NETs act as a mesh that traps microorganisms and, in turn, facilitates their interaction with neutrophil-derived effector molecules.
NETs have been shown to trap microorganisms — such as Escherichia coli, Staphylococcus aureus, Shigella flexneri, Salmonella enterica subspecies enterica serovar Typhimurium, Candida albicans and Leishmania amazonensis and promote the interaction of these pathogens with granule derived proteins and their subsequent disposal
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22DENDRITIC CELL
Dendritic cells are antigen-presenting cells (APCs) which play a critical role in the regulation of the adaptive immune response.
DCs were first described by Ralph Steinman nearly forty years ago.
He found a population of striking dendritic-shaped cells in the spleen.
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Dendritic cells are so called because, when they are mature, their cytoplasm extends into transient spiny dendrites and sheet-like veils.
This provides a large surface area for their main function of antigen presentation to T lymphocytes.
24 All dendritic cells are derived from bone
marrow stem cells, but appear to be heterogeneous, with various precursors (including monocytes) differentiating into dendritic cells when stimulated by appropriate combinations of cytokines.
Immature dendritic cells are found in tissues throughout the body and are very efficient at capturing and processing antigens.
25 Mature DCs are defined by key morphological features and by the presence or absence of various molecules on the cell surface.
The key morphological characteristic of DCs is the presence of numerous membrane processes that extend out from the main cell body (similar to dendrites on neurons).
26 An additional morphological feature of DCs is that they contain abundant intracellular structures relating to antigen processing including endosomes, lysosomes, and Birbeck granules of Langerhans cells of the epidermis.
27 Recently, subsets of DC were recognized based on
their function in immune responses. DC1 cells, also called myeloid DCs, express different Toll-like receptors (TLR)-2, -3, -4, and -7.
After encountering different natural ligands or pathogens for these TLRs in the blood, DC1 cells become activated and mature into antigen-presenting cells (APC) that can secrete Th-1 or Th-2 cytokines and prime naive T cells for a proper immune response.
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29What is the function of dendritic cells?
The function of DCs falls broadly into three categories, each of which involve antigen presentation.
30• The first category of DCs function is antigen presentation and activation of T cells.
• The second category of DC function is not as well established, but it has been suggested that a different class of DCs exist with the function of inducing and maintaining immune tolerance.
• The third category of DCs, known as follicular DCs, appear to work to maintain immune memory in tandem with B cells.
31EOSINOPHIL
The granulocytes whose granules stain with acidic dyes are called eosinophils.
They comprise 2–5% of white
blood cells and have bilobed nuclei.
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In contrast to the phagocytosis and intracellular digestion normally displayed by neutrophils, eosinophils secrete their granule contents for extracellular digestion of infectious pathogens which are too large to be engulfed.
Eosinophils also produce cytokines, prostaglandins and leucotrienes, and enzymes which can inhibit the inflammatory products of mast cells
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Eosinophils have Fc receptors for IgG and IgE antibodies and for C3b, enabling them to bind to opsonized targets.
They then secrete their antibiotic granule contents (including major basic protein and eosinophil cationic protein) and reactive oxygen species to bring about damage to the target.
34Monocytes and Macrophages
Monocytes, which constitute 5–10% of mononuclear leucocytes in the blood, differentiate into macrophages when they migrate into tissues.
Monocytes are larger than most lymphocytes and have a kidney-shaped nucleus: they possess azurophilic lysosomal granules containing lysozyme, acidhydrolases and myeloperoxidase.
35
The blood monocytes arise from myeloid progenitors in the bone marrow.
Macrophages can be resident in tissues for prolonged periods of time where they take on various morphologies, and are known by different names, depending on their tissues of residence, e.g. Kupffer cells in the liver, mesangial cells in the kidney and microglial cells in the brain.
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Phagocytic activity increases when there is tissue damage and inflammation, which releases substances that attract macrophages.
Activated macrophages migrate more vigorously in response to chemotactic factors and should enter sites of inflammation.
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The activity of mononuclear phagocytes against cancer cells in humans is less well understood than the phagocytosis of microorganisms.
Phagocytes are thought to suppress the growth of spontaneously arising tumors.
40 The ability of these cells to control malignant
cells may not involve phagocytosis but may be related to secreted cellular products such as lysosomal enzymes, oxygen metabolites, proteinases, and TNFα
The proteolytic enzymes present on the surface
membrane of monocytes also may play a role in tumor rejection
41Basophils
Basophilic granulocytes (basophils) derive their name from the affinity of their cytoplasmic granules for certain basic dyes.
They constitute less than 1% of white blood cells.
Basophils are of hematopoietic origin.
Typically mature in the bone marrow and then circulate in the peripheral blood, from where they can then be recruited into the tissues
42Basophils have a short life-span of several days.
Interleukin-3 (IL-3) promotes the production and survival of human basophils in vitro and can induce basophili in vivo.
Mediators stored preformed in the cytoplasmic granules of basophils include chondroitin sulphates, proteases and histamine
Chondroitin sulphates probably contribute to the storage of histamine and neutral proteases, and basophils are the source of most of the histamine found in normal human blood.
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A mast cell (also known as a mastocyte or a labrocyte) is a resident granulocyte of several types of tissues that contains many granules rich in histamine and heparin.
The mast cell is very similar in both appearance and function to the basophil. However, they are not the same, as they arise from different cell lines.
Mast cells were first described by Paul Ehrlich in 1878.
Mast cell
44 Two types of mast cells are recognized,
A. connective tissue mast cell
B. mucosal mast cells.
Mast cells are present in most tissues characteristically surrounding blood vessels and nerves, and are especially prominent near the boundaries between the outside world and the internal milieu, such as the skin, mucosa of the lungs, and digestive tract, as well as the mouth, conjunctiva, and nose.
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Mast cells and basophils may have particularly important roles as effector cells in initiating and or amplifying IgE-dependent inflammatory reactions
Both cells play an important protective role as well, being intimately involved in wound healing and defense against pathogens
Role Of Basophil And Mast Cell
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47 Basophils appear in many specific kinds of inflammatory reactions, particularly those that cause allergic symptoms.
They contain anticoagulant heparin, which prevents blood from clotting too quickly.
They also contain the vasodilator histamine, which promotes blood flow to tissues.
They can be found in unusually high numbers at sites of ectoparasite infection.
48 Basophils have protein receptors on their cell surface that bind IgE, an immunoglobulin involved in macroparasite defense and allergy.
It is the bound IgE antibody that confers a selective response of these cells to environmental substances, for example, pollen proteins or helminth antigens.
Recent studies in mice suggest that basophils may also regulate the behavior of T cells and mediate the magnitude of the secondary immune response
49 Mast cells are important in immediate
inflammation.
It is best known for their role in allergy and anaphylaxis.
They possess receptors for complement components (C3a and C5a) as well as receptors for the Fc portion of the antibody molecules IgE and IgG .
50 The stimulation of these receptors can result in activation and secretion of vasoactive substances that increase vascular permeability and dilation, two important signs of anaphylaxis
Mast cells can synthesize, de novo, other inflammatory mediators, such as the slow-reacting substances of anaphylaxis (SRS- A), tumor necrosis factor-a (TNF-a), and leukotriene C4.
51
52CARRANZAS Clinical Periodontology-10th Edition.
Periodontics-grant,stern,listgarten-8th Edition.
Robbins And Cotran Pathologic Basis Of Disease - 7th and 8th Edition
Guyton - Textbook Of Medical Physiology 11th Ed - 2005
Cells Of The Immune System ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group ;Ian Todd , University Of Nottingham, Nottingham, UK
Neutrophils In The Activation And Regulation Of Innate And Adaptive Immunity Alberto Mantovani, Marco A. Cassatella, Claudio Costantini And Sébastien Jaillon NATURE REVIEWS IMMUNOLOGY VOLUME 11 AUGUST 2011
Mast Cells And Basophils In Acquired Immunity Jochen Wedemeyer And Stephen J Galli ; British Medical Bulletin 2000; 56 (No. 4): 936-955
Cells And Cellular Activities Of The Immune System: Granulocytes And Mononuclear Cells
REFERENCES
53
54What Is Azurophilic Granules ?
An azurophil is an object readily stained with an azure stain. Neutrophils in particular are known for containing azurophils
loaded with a wide variety of anti-microbial defensins that fuse with phagocytic vacuoles.
Azurophils may contain myeloperoxidase, phospholipase A2, Acid Hydrolases, Elastase, defensins, neutral serine proteases, bactericidal/permeability-increasing protein, lysozyme, cathepsin G, proteinase 3, and proteoglycans.
Azurophil granules are also known as "primary granules.
55CONTENTS
Cells of immune system
Lymphocytes ,B cells ,T cells , natural killer cell
Types of immunity
Innate & cell mediated immunity in periodontal disease
Clinical implication of immune responses
Conclusion
References
56LYMPHOCYTE
Lymphocytes are 20-40% of WBC, 99% of cells in lymph.
Only cells of immune system exhibit specific receptor for antigen .
Bridge between various parts of immune system Small, round 5-12 m diameter spherical densely
compact nucleus occupies almost entire cell & scanty cytoplasm.
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Lymphocytes includes three types of cells.
T-lymphocytes or T cells, which are derived from the thymus and play a role in cell-mediated immunity.
B-lymphocytes or B-cells which are derived from liver, spleen and bone marrow are the precursors of plasma cells and play a role in humoral immunity.
Natural killer (NK) and killer (K) cells.
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Development Of Cells
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Function Of Cells
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62T Cell
About 70% of human blood lymphocytes are T cells.
Those cells destined to be T cell which leave the bone marrow via the blood stream and move to the thymus.
There the T cell become able to differentiate between self and nonself antigens.
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The main functions of T lymphocytes are to exert effects on other cells, either regulating the activity of cells of the immune system or killing cells that are infected or malignant.
T cells have surface antigen receptors, but there is no secreted form of these equivalent to antibodies.
64 Furthermore, T cells cannot recognize antigens in
their native forms, but only when they are presented on the surface of antigen-presenting cells (APCs).
The antigen receptors of most T cells (ab T cells) are composed of two polypeptides called a and b chains, and they interact with peptides derived from the degradation (processing) of foreign antigenic proteins
65The T lymphocytes are associated with two types of immunological functions,
EFFECTORREGULATOR
Y
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The effector functions include activities such as killing of virally infected cells and tumors.
The regulatory function are represented by their ability to amplify or suppress through cytokines or other effector lymphocytes including B and T cells.
67 T cells receptor has two parts TCR and CD3.
CD3 is present on all T cells .
Presently two types of TCR are defined:TCR-1 & TCR-2
Both receptors are associated with a complex of a polypeptides making up the CD3 complex.
68 Thus a T cell is defined either by TCR-1 or TCR2
which is associated with CD3.
Approximately 95% of blood T cells express TCR-2.
TCR-2 bearing cells can be further divided into CD4+ T cells and CD8+ cells .
69HELPER T CELLS
Helper T cells are the major driving force and the main regulators of the immune defense.
Their primary task is to activate B cells and killer T cells.
However, the helper T cells themselves must be activated.
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This happens when a macrophage or dendritic cell, which has eaten an invader, travels to the nearest lymph node to present information about the captured pathogen.
The phagocyte displays an antigen fragment from the invader on its own surface, a process called antigen presentation.
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When the receptor of a helper T cell recognizes the antigen, the T cell is activated.
Once activated, helper T cells start to divide and to produce proteins that activate B and T cells as well as other immune cells.
72T-INDUCER CELLS :
Some T cells induce other T cells to become suppressor T cells and involve in regulation of the immune response.
These cells have common phenotypic characteristics.
Examples are Ly1a and Ly2 cells in mice.
73T-suppressor cells
Suppressor effector T cells bind antigen and release factor that inactivate T-helper cells.
T-suppressor cells can: Suppress delayed –type hypersensitivity
reactions, Prevent proliferation and antibody secretion by
antigen-binding B cells, Suppress antibody secretion by some types of
B cells.
74T-CYTOTOXIC CELLS :
These cells recognize certain histocompatibility antigens and are capable of killing foreign cells (i.e., virus) and altered self-cells (i.e. tumor antigens).
T-cytotoxic cells are important in the cytotoxicity of graft reactions and graft-versus-host reactions.
75 Cytolysis requires direct contact between the T-cytotoxic cell and the target cell, occurs as a result of antigen specific receptors on the T-cells.
76 T-CONTRASUPPRESSOR CELLS
These cells present the inactivation of T-helper and T-inducer cells by the action of suppressor effector T-cells.
They are antigen specific and may be important in immunologic memory.
77B cells
B lymphocytes represents 3 to 15% of circulating lymphoid cells and are primarily defined by surface immunoglobulins (Ig).
The B lymphocytes are common in areas of antibody production, such as the germinal centers of the lymph nodes and diffuse lymphoid tissue of mucosal systems.
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The main function of a B cell is to secrete soluble recognition molecules called antibodies which specifically bind to an antigen recognized by that B cell.
Throughout the life, bone marrow remains the major repository of stem cells for B lymphocytes.
79A B cell will only produce antibodies when it has been activated by binding antigen; this activation process also usually requires help from T cells. The activated B cell undergoes multiple divisions and some of the resulting cells differentiate into antibody-secreting cells.
These are known as plasma cells, and they possess copious rough endoplasmic reticulum involved in antibody synthesis.
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An important aspect of antigen recognition by B cells is that these lymphocytes, and the antibodies they produce, bind to antigens in their natural or native form, i.e. as they occur as constituents of pathogens
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82Natural Killer Cells
Natural killer (NK) cells constitute up to 15% of human blood lymphocytes.
Together with δ T cells and about 50% of CD8+ T cells they are known as large granular lymphocytes because, compared with most T and B lymphocytes, they have more cytoplasm and contain prominent granules.
83 In contrast to all T and B cells, NK cells do not
express antigen-specific receptors and do not possess the adaptive property of memory cell development; they are therefore considered to form part of the innate immune system.
Their main function is to kill infected cells and tumor cells by inducing apoptosis of their targets.
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85 Since they lack antigen receptors, NK cells do not recognize specific antigens on the surface of a target cell.
Instead, they detect molecular changes in the surface of a cell which are indicative of that cell being abnormal and therefore a potential threat to the body.
They kill cells with reduced expression of MHC class I molecules, as can result from viral infection or malignant transformation.
86 NK cells express surface ligands for MHC class
I known as killer inhibitory receptors (KIRs) because their binding to MHC class I on the surface of a potential target cell inhibits the cytotoxic activity of the NK cell.
This prevents NK cells from killing normal tissue cells with normal levels of MHC class I expression
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89TYPES OF IMMUNITY
Natural / Innate Immunity
Acquired
/ Adaptive Immunity
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91Acquired Or Adaptive Immunity
Specific Resistance that an individual acquires during
his life time May be weak / absent on first exposure Increases with subsequent exposures to same
specific pathogen
92 Acquired immunities are of two types:
ACTIVE PASSIVE
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Active immunity is the resistance developed by an individual as a result of an antigenic stimulus.
Involves the synthesis of antibodies and/or the
production of immunologically active cells.
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Passive immunity is the resistance that is transmitted to a recipient in a readymade form as passive immunity.
Preformed antibodies are administered
95There are two types of effecter mechanisms that mediate specific immune response:
Humoral Immunity
• Immune responses are those mediated by a cell product of the lymphoid tissues referred to as antibody.
• Associated with the fluid phase of blood (plasma or serum.
Cell Mediated Immunity
• Immune reactions reside in cells of the lymphoid system,
• Are mediated by specifically sensitized lymphocytes themselves
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97NATURAL OR INNATE (NON SPECIFIC)
First line of defense against invasion by microbes.
Inborn resistance . First time a pathogen is encountered. Does not require prior exposure . Not modified significantly by repeated
exposures. Eg: phagocytosis by leukocytes, natural killer
cells, tissue secretion and complement.
98Mechanism involved in innate immunity are :
Epithelial surfaces : Intact skin and mucous membrane Protection against invasion by microorganism.
Eg: mucosa of respiratory tract, mucopolysaccharides capable of neutralizing the bacterial products. The mouth is constantly bathed in saliva, contain
antibodies, iga, t-helper and suppressor cell, macrophages.
99Antibacterial substance in blood and tissues :
The complement system possess bactericidal activity . Destroys pathogenic bacteria invading the blood and
tissues. Substances possessing antibacterial property include:
a) Beta lysine – active against anthrax, and related bacteria
b) Basic polypeptides such leukins.
c) Acidic substances such as lactic acid found in muscle tissue, has anti bacterial action.
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Cellular factor in innate immunity :
Inflammation : Tissue injury and irritation by the entry of
pathogens or other irritation
Causes inflammation, which is an important non-specific mechanism of defence.
Help in the initial defense.
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Fever : Rise in temperature following infection is a
natural defense mechanism.
Help not merely to accelerate physiological
processes but many in some cases.
Actually destroy the infecting pathogens.
103Acute phase proteins :
Infection or injury leads to a sudden increase in plasma concentration of certain proteins, collectively called acute phase proteins.
Include c-reactive protein, mannose binding protein, alpha 1-acid glycoprotein, serum amyloid p component and many others.
Believed to enhance host resistance, Prevent tissue injury . Promote repair of inflammatory lesions.
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Innate Mechanisms Of Defence Against Periodontal Disease
Salivary secretions are protective
Exerts a major influences on plaque
Mechanically cleanse the exposed oral surfaces
By buffering acids produced by bacteria
By controlling bacterial activity
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Morphology And Physiology Of The Dento-gingival Region Contributing To Gingival
Defense :
High turnover rate of the junctional epithelium.
The constant renewal of these epithelial cells.
The ability of junction epithelium to produce attachment to the tooth - counteract subgingival plaque growth.
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Intercellular material, by the epithelial cells may prevent the penetration of bacteria into the epithelium.
The loose arrangement of the junctional epithelial cells, facilitates the transport of phagocytic cells and antimicrobial substances from the vascular system into this region.
107 In 1971 Lange and Schroeder demonstrated
that the epithelial cells in the base region of the sulcus contain lysosomes and cells also showed phagocytic activity toward bacteria.
Epidermal cell, mainly keratinocytes, to a lesser extent melanocytes and Langerhan cells, release a variety of regulatory proteins (cytokines) which may assist local defense by recruitment and enhancement of phagocyte functions. (E.g- IL-3, TGF-alfa and beta, TNF-alpha etc.,)
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Functions Of Innate Immune Mechanisms In Periodontal Diseases
Various factors and cells make up the innate immune system.
Include complement, acute-phase proteins, and interferons.
The complement system appears to be down-regulated in patients with periodontal diseases.
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The decrease in complement function results from both bacterial and host actions and may increase the susceptibility of the host to periodontal disease.
Neutrophils have a primary role in the immunopathogenesis of at least some forms of periodontal disease.
The basic paradigm shift is that in some cases, PMNs do not exhibit a decrease in function, but rather they become hyperactive and are primed for actions that result in tissue breakdown. ease.
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Functions Of Adaptive Immunity In Periodontal Diseases
T lymphocytes, B lymphocytes/plasma cells, and macrophages.
The mechanisms of innate and adaptive immunity are extensive, overlapping, and redundant.
If the functions of innate immunity, do not abate the initial infection, an inflammatory infiltrate becomes localized to the connective tissue of the affected area.
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This infiltrate is composed mainly of lymphocytes and macrophages, with some neutrophils, and reflects an adaptive immune response.
Lymphocytes, macrophages, and other immune cells produce cytokines that drive the immune response to clear the infection.
The early inflammatory infiltrate is dominated by lymphocytes; Predominantly, T cells.
T cells have two basic subpopulations: CD4 or helper T cells, and CD8, which are suppressor/cytotoxic T cells.
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B cells predominates at the expense of T cells when gingivitis progresses to a periodontitis.
There is a decreased CD4/CD8 ratio
And an increase in memory T cells.
B cells mature and differentiate into plasma cells, which ultimately produce antibodies
113 Antibody titers and disease severity commonly
express a positive relationship – that is, patients with higher titers have severe disease, especially in patients with chronic periodontitis or localized aggressive periodontitis.
Antibody titers decrease after resolution of periodontal disease
114
Immune Responses As Markers Of Susceptibility Of Periodontal Diseases
IgG3 and IgG1 to A. actinomycetemcomitans were significantly elevated in localized juvenile periodontitis and rapidly progressive periodontitis patients, while IgG2 was similar among the disease groups.
Only the rapidly progressive periodontitis patients had IgG4 to A. actinomycetemcomitans.
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Rapidly progressive periodontitis and adult periodontitis patient had elevated IgG2, IgG1 and IgG4 to P. gingivalis.
Patients with rapidly progressive periodontitis had elevated IgG1 to P. intermedia.
IgG2 was the primary response to C. rectus in the localized juvenile periodontitis and adult periodontitis.
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Serum IgG2 levels were elevated in localized juvenile periodontitis patients compared with healthy controls.
The IgG2 antibody levels to A. actinomycetem comitans were similar among adult periodontitis and generalized juvenile periodontitis patients and healthy controls.
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CONCLUSION
Pathogenesis of periodontal destruction involves a complex interplay between bacterial pathogens and the host tissues.
In order to generate effective immunity, the various cell types cooperate with each other by means of direct interactions between cell surface molecules and via the molecules that they secrete.
Recent investigation have revealed that not all strains of a specific microbial species are equal in their capacity to cause disease, and not all host are equal in their susceptibility to diseases.
The challenge for future is to be able to better identify the more virulent bacterial strain and the more susceptible host.
118
119CARRANZAS Clinical Periodontology-10th Edition.
Periodontics-grant,stern,listgarten-8th Edition.
Robbins And Cotran Pathologic Basis Of Disease - 7th and 8th Edition
Guyton - Textbook Of Medical Physiology 11th Ed - 2005
Cells Of The Immune System ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 ;Ian Todd , University Of Nottingham, Nottingham, UK
Neutrophils In The Activation And Regulation Of Innate And Adaptive Immunity Alberto Mantovani, Marco A. Cassatella, NATURE REVIEWS IMMUNOLOGY VOLUME 11 AUGUST 2011
Mast Cells And Basophils In Acquired Immunity Jochen Wedemeyer And Stephen J Galli ; British Medical Bulletin 2000; 56 (No. 4): 936-955
Cells And Cellular Activities Of The Immune System: Granulocytes And Mononuclear Cells
Molecular Biology of the Cell. 4th edition.
REFERENCES