Immunity & Inflammation

inflammation, immunity, cells of immunity & inflammation, hypersensitivity reactions.

1. IMMUNITY & INFLAMMATION Guided By: Presented By: DR. K.S. STELIN (HOD) DR. MARIYAM MOMIN DR. PARUL ANEJA (READER) I YEAR PG DEPARTMENT OF PERIODONTOLOGY & ORAL IMPLANTOLOGY.

2. CONTENTS Inflammation Immunity Cells of immunity & inflammation Immunoglobulins Complement Chemical mediators of inflammation Immune responses Immune mechanisms References

3. INFLAMMATION Inflammation refers to tissue injury or irritation, initiated by the entry of pathogens or other irritants – Kumar V et.al. (2005). Inflammation is defined as a local response of living mammalian tissues to injury due to any agent. It is a body defense reaction in order to eliminate or limit the spread of injurious agent as well as to remove the consequent necrosed cells and tissues.

4. SIGNS OF INFLAMMATION 4 cardinal signs of inflammation by Celsus Rubor (redness) Tumor (swelling) Calor (heat) Dolor (pain) Redness Pain Swelling Warmth

5. 5 th sign was later introduced by Galen Functio laesa (loss of function) Rudolf Virchow

6. TYPES OF INFLAMMATION Features Acute inflammation Chronic inflammation Causative agent Pathogens, injured tissues Persistant acute inflammation due to non-degradable pathogens, persistant foreign bodies or autoimmune reactions. Major cells involved Mainly neutrophils Mononuclear cells (monocytes, macrophages, lymphocytes, plasma cells), fibroblasts. Primary mediators Vasoactive amines, ecosanoids IFN- ꙋ and other cytokines, growth factors, reactive oxygen species, hydrolytic enzymes. Onset Immediate Delayed Duration Few days Upto many months or years Outcomes Resolution, abscess formation, chronic inflammation. Tissue destruction, fibrosis, necrosis. Difference between acute and chronic inflammation

7. IMMUNITY Immunity refers to the resistance exhibited by the host towards injury caused by microorganisms and their products.

8. Types of immunity Immunity Active Immunity Natural Immunity Induced Immunity Innate Immunity Passive Immunity Artificial Natural Artificial Natural

9. Difference between Active & Passive immunity S.No . Feature Active immunity Passive immunity 1 Production Produced actively by immune system Received passively by host. The host’s immune system does not participate. 2 Induction Induced by infection or by contact with immunoglobulin Conferred by administration of ready-made antibodies 3 Duration Long lasting & effective Short lived & less effective 4 Effectiveness Effective only after a lag period Effective immediately 5 Immunological memory Present Absent 6 Uses For prophylaxis to increase body resistance For treatment of acute infections

10. CELLS OF IMMUNITY & INFLAMMATION MACROPHAGES Develop from blood monocytes, which emigrate into tissues from the blood and are triggered to develop as cytokines, other inflammatory mediators, bacterial products such as endotoxins. Macrophage

11. MAST CELLS Mast cells are the cells concerned with immunity and immediate inflammation. Inflammatory mediators of mast cells Mast cells possess cytoplasmic granules called as lysosomes which store the following mediators: TNF- α Heparin Histamine Leukotriene B4 Neutrophil chemotactic factor Eosinophilic chemotactic factor Slow releasing substances of anaphylaxis (SRS-A).

12. Role of mast cells in gingiva The cytoplasmic granules contain heparin and histamine. The physiologic role of heparin in mast cells does not appear to be clear. Greater number of mast cells are found in inflamed gingiva as compared to healthy gingiva. Mast cell histamine plays a role in the inflammatory reaction and they have shown to degranulate in response to antigen-antibody formation on their sueface .

13. NEUTROPHILS Synonym – Polymorpho nuclear leukocytes (PMNs) Neutrophils are the frontline soldiers in inflammation. They are the first line of defense cells in gingiva. Trans-endothelial migration. Neutrophil granules Primary granules/ azurophilic granules Secondary/ specific granules Tertiary granules.

14. Functions of neutrophils Destructive mechanism Emigration & chemotaxis Phagocytosis. Protective mechanism Magnify inflammation Activate kinin producing system Activate complement components via alternativa pathway Carry potent substances Responsible for destruction of collagen & other connective tissue substances including bone resorption .

15. Mechanism of phagocytosis

16. Oxidative mechanism of phagocytosis

17. NEUTROPHIL DISORDERS Neutrophil disorders associated with periodontal diseases Diabetes mellitus Cyclic neutropenia Down’s syndrome Chediak – Higashi syndrome Papillon lefevre syndrome Drug induced agranulocytosis

18. Periodontal diseases associated with neutrophil disorders Refractory periodontitis (RP) Pre-pubertal periodontitis (PPP) Localized juvenile periodontitis (LJP) Rapidly progressive periodontitis (RPP) Acute necrotizing ulcerative gingivitis (ANUG) Neutrophil defects associated with aggressive periodontitis Abnormalities in adherence – LAD-1 & LAD-2 Abnormalities in chemotaxis – Chediak -Higashi syndrome Abnormalities in phagocytosis & intercellular killing.

19. LYMPHOCYTES

20. IMMUNOGLOBULINS Synonym – Antibodies Definition - Immunoglobulin is a glycoprotein composed of heavy & light peptide chains; functions as antibody in serum and secretions – PLR. Types of immunoglobulins & its functions S.No . Immunoglobulin Function 1 IgA Mucosal defense 2 IgD Activates B cells 3 IgM Acts as agglutinins & activates complement 4 IgG4 & IgE Acts against parasites & anti-inflammation 5 IgG1, IgG2, IgG3 Acts as opsonin & complement activation.

21. COMPLEMENT Complement is an interacting network of about 30 membrane associated cell receptors and soluble serum glycoprotein – Carranza Activation path Sequence of activation Classical pathway C1, C2, C3, C4, C5, C6, C7, C8 & C9. Alternative pathway C3, C5, C6, C7, C8 & C9. Pathways of activation of complement

22. Effects of complement S.No . Component Activity 1 C1 & C9 Cytolytic & cytotoxic damage to cells 2 C2 & C3a Kinin activity 3 C3 & C4 Promotion of clot lysis 4 C3 & C5 Promotion of phagocytosis 5 C5a Lysosomal enzyme releasing from leukocytes 6 C6 Enhancement of blood clotting 7 C5 & C6 Inactivation of bacterial lipopolysaccharides from endotoxin 8 C3a, C5a & C567 Chemotactic activity for leukocytes 9 C3a & C5a Histamine release from mast cells & increase vascular permeability.

23. CHEMICAL MEDIATORS OF INFLAMMATION

24. Cell derived mediators Histamine – main actions are vasodilatation & increase permeability. Serotonin (5-HT) – actions are similar to histamine. Prostaglandins (PGE) Production of PGE-2 Tissue destruction in PGE-2

25. Effects of PGE Vascular dilatation & erythema Increased vascular permeability Induction of platelet aggregation by cyclic endoperoxides Chemotaxis of PMNs & macrophages Cytotoxicity of fibroblasts. PGE-2 is associated with inflammation & attachment loss . PGE-2 is elevated in gingivitis & periodontitis . PGE-2 appears to be partly responsible for the bone loss associated with periodontitis .. Analysis of PGE-2 in GCF may eventually be considered as a diagnostic marker for future bone loss. Inhibition of lymphocyte transformation & cytotoxicity . Inhibition of antibody secretion with high concentration of prostaglandins . Inhibition of IgE mediated release of mediators from mast cells & basophils. PGE in inflammation PGE in immunity PGE in periodontal diseases

26. Effects of prostaglandins S.No . Acts on Effects 1 Osteoblasts To inhibit bone formation 2 Osteoclasts To induce bone resorption 3 Fibroblasts To produce MMP which degrade soft connective tissue component 4 Monocyte / macrophages Increases the production of inflammatory cytokines in response to bacterial endotoxins 5 Blood vessels To dilate the vessels & increase the inflammatory fluid at the site, resulting stasis 6 Collagen synthesis Inhibition of bone formation by inhibition of collagen synthesis.

27. CYTOKINES Cytokines are the small protein messengers released by the cells which affect the division, differentiation & function of other cells, which may be of the same or different types. All these biologically active substances lymphokines , monokines & interleukins are collectively known as cytokines. Cytokines Produced by Lymphokines Lymphocytes Monokines Monocytes & macrophages Interleukins Lymphocytes, monocytes, keratinocytes, macrophages, fibroblast , platelets. Production of cytokines

28. Cytokines in periodontal diseases S.No , Action Cytokines 1 Pro-inflammatory IL-1, IL-6, IL-8, TNF- & IFN- 2 Anti-inflammatory IL-4, IL-10, IL-13 & TGF- 3 Scarring IL-6 & TGF- 4 Anti-scarring IL-10 5 Angiogenic IL-8 & angiogenins 6 Anti- angiogenic IL-10 S.No , Action Cytokines 1 Pro-inflammatory 2 Anti-inflammatory 3 Scarring 4 Anti-scarring IL-10 5 Angiogenic IL-8 & angiogenins 6 Anti- angiogenic IL-10

29. Nitric oxide – causes vasodilatation, antiplatelet activating agent & microbicidal action. Plasma derived mediators Anaphylatoxins Complement peptides C3a,C4a, C5a which can cause smooth muscle contraction, incease vascular permeability & histamine release from mast cells. Thrombin It is a serine protease that converts soluble fibrinogen into insoluble fibrin. Plasmin It is a proteolytic enzyme that acts to break down fibrin clots, leave complement protein C3 & activate factor XII. Bradykinin It is a short-lived, vasoactive peptide that is able to induce vasodilation, increase vascular permeability, cause smooth muscle contraction & induce pain.

30. Immune Responses The specific reactivity induced in a host following an antigen stimulus is called as immune response. Types Humoral immunity Cell mediated immunity

31. IMMUNE MMECHANISMS

32. Anaphylactic reaction

33. Cytotoxic reaction

34. Arthu’s reaction

35. Cell mediated immunity

36. Pathogenic immune reactions S.No . Type Immune reactions Mechanism Example 1 Type I Anaphylactic Antigen reacts with cells sensitized by IgE antibodies & release mediator Food allergies Urticaria Hay fever 2 Type II Cytotoxic Antibody reacts with cell associated antigen usually, but not always, kills cells with the help of complement or phagocytic cells. Transfusion reactions Autoimmune reactions 3 Type III Arthu’s reaction Antibody reacts with antigen in tissue spaces or blood stream to cause vasculitis requires complement. Serum sickness Arthu’s reaction 4 Type IV Delayed hypersensitivity Lymphocytes reacts with antigen. Tuberculin reaction Contact dermatitis Allograft rejection.

37. Comparison of different types of hypersensitivity S.No . Characteristics Type I Type II Type III Type IV 1 Antibody IgE IgG , IgM IgG , IgM None 2 Antigen Exogeous Cell surface Soluble Tissues & organs 3 Response time 15-30 minutes Minutes - hours 3-8 hours 48-72 hours 4 Appearance Wheal & flare Lysis & necrosis Erythema, edema & necrosis Erythema & induration 5 Histology Basophils & eosinophils Antibody & complement Complement & neutrophils Monocytes & lymphocytes 6 Transferred with Antibody Antibody Antibody T-cells 7 Examples Hay fever Allergic asthama Erythroblastosis fetalis Good pasture’s nephritis SLE Farmer’s lung disease Poison ivy Granuloma Tuberculin test

38. Impact of micro- oraganisms on immunity & inflammation S.No . Microbes & products Impact on inflammation & immunity 1 Microbes Are antigenic Activate complement Activate neutrophils & macrophages 2 Proteins & peptides Are antigenic Chemotactic for neutrophils & macrophages 3 Lipopolysaccharides Are antigenic Activate complement Damage host cells & alveolar bone resorption 4 Polysaccharide plaque matrix Are antigenic Polyclonal B-cell activator 5 Enzymes Are antigenic Degrade antibody Damage host cell Degrade connective tissue matrix Activate & degrade complement.

39. Influence of host response on periodontal diseases S.No . Aspect of disease Host factors 1 Bacterial colonization Subgingivally antibody & complement in GCF inhibits adherence & coaggregation of bacteria & potentially reduces their numbers by lysis . 2 Bacterial invasion Antibody – complement mediates lysis reduces bacterial counts. Neutrophils as a consequence of chemotaxis , phagocytosis & lysis reduces bacterial counts. 3 Tissue destruction By antibody mediated hypersensitivity & cell mediated immune responses. Activation of tissue destructio factors such as collagenase. 4 Healing & fibrosis Lymphocytes & macrophages produce chemotactic factors for fibroblasts, fibroblast activationg factor.

40. References Carranza’s Clinical Periodontology- 10th Edition. Essentials of Periodontology – ( Sahitya Reddy S) Textbook of Periodontics – Shalu Bathla (2 nd Edition).

41. Thank You.