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Good
morning
Role of immune system
in inflammation
Presented by
Dr.AyeshaGuided by
Mrs. Veena A Patil
Department of
periodontia.
Major Histocompatibility Complex
 Clusters of genes found in all mammals
 Its products play role in discriminating
self/non-self participants in both humoral
and cell mediated immunity.
MHC act as antigen presenting structures
In human MHC is found on chromosome 6
 Referrred to as HLA complex
 Defensins are small cationic proteins found in
vertebrates and invertebrates.
 They are active against bacteria,fungal and
many enveloped and non-enveloped viruses.
 Cells of the immune system contains these
peptides to assist in killing phagocytised
bacteria, for example-in neutrophil granulocytes
and almost all epithelial cells.
 Most defensins function by binding to the
microbial cell membrane and once
embedded,forming pore like membrane defects
that allow efflux of essential ions and nutrients.
 Definition : series of heat-labile serum proteins
 Site : serum and all tissue fluids except
urine and CSF
 Synthesis : in liver – appear in fetal circulation
 Function : Responsible for certain aspects of
immune response and
inflammatory response
 Activation : antigen-antibody complex or
endotoxin, capsule
series of proteins activated
sequentially
 Inactivation: inhibitors in plasma (short lived)
 Biological effects: either beneficial or harmful to
host
A) Classical pathway:
- Complement is activated by antigen –antibody
complex (IgM or IgG)
- Fc portion of the antibody form a binding site
for C1q
- The numerical sequence of the complement
factors in the classic pathway is:
C1q,r,s , C4, C2, C3, C5, C6, C7, C8, C9
 This pathway is initiated by:
 Bacterial endotoxin, polysaccharide capsule,
aggregates of IgE
and properdin.
 It starts at C3 then C5, C6, C7, C8, C9.
 The complement components C1, C4, C2 are
by-passed
 Antibodies are not required to initiate
activation of this
pathway.
 This pathway provides a means of non-specific
resistance
Classic Pathway Alternative pathway
Specific acquired immunity Non-specific innate immunity
Initiated by antibody Bacterial endotoxin, capsule
Interaction of all components C1, C4, C2 are by-passed
Properdin system not involved Properdin system is involved
Beneficial effects:
1) Cytolysis:
- activated complement proteins
polymerize on cell surfaces of bacteria or
erythrocyte to form pores in its membrane
(killing by osmotic lysis).
2) Opsonization:
- Binding of complement proteins
opsonin (C3b)
to surfaces of foreign organisms or
particles
- Phagocytic cells express specific
receptors for
opsonins, so promote phagocytosis
Inflammatory response :
Small fragments released during complement
activation have several inflammatory actions:
a) C5a is chemotactic and attract neutrophiles and
macrophages
b) C5a activate phagocytes and neutrophils
C) C3,C4 and C5 are anaphylatoxins
Cause degranulation of mast cells and release of
histamine and other inflammatory mediators
5-Enhancement of antibody
production:
- Binding of C3b to its receptors on
activated B cells
(CR2) greatly enhances antibody
production
- Patient who are deficient in C3b produce
much less antibody than normal
individuals and
more susceptible to pyogenic infection
Harmful effects:
- If complement activate systematically on
a large
scale (Gm –ve bacilli)
- If activated by an autoimmune
response to host cells
 Directed movement of leucocyte from blood.
 Defects in trans endothelial migration results
in aggressive periodontitis.
 8 steps before the process of chemotaxis
reflects the importance of transendothelial
migration in periodontal disease.
 Once leucocyte enters tissue-it must be able
to locate and migrate to the site of insult..
 Leucocytes ability to sense a chemical
gradient across in cell body and migrate in
the direction of increasing concentration.
 Receptors for chemotaxisbelong to G-protein
coupled family
 To migrate leucocytes assume an asymmetric
or polarized shape rather than rounded
morphology.
Movements
of
phagocytic
cells
N-formyl
methionine
Chemotaxis
Ameboid
movement
LPS
endotoxin
Bacteria initiate RNA translation with
NFM. Phagocytic receptors reacts to this,
causing the cell to move toward source of
signal.LPS endotoxin in outer membrane of
gm –ve bacteria activates compliment
cascade producing chemotaxin C5a
 Oxidative process:
oxidation reduction potential at or above -
160mv.
Both variables suboptimal in gingival crevice.
Neutrophils can function under aerobic
condition
Non oxidative process:
Phagosome lysosome fusion phagolysome
Neutrophil contains
specific granules :for both
extracellular and intraphagolysomal
secretion.
Specific granules
lysozyme lactoferrin
Bactericidal bacteriostatic
Enzyme independent domain lactoferricin
Bactericidal & fungicidal
Activity.
azurophil granules------for
intraphagolysosomal secretion
Neutrophils provide the first line of
defense when a micro-organism enters
the junctional epithelium and then
connective tissue. A thorough
understanding of neutrophil function is
very important to understand the disease
process of periodontal disease.
role of immune system in inflammation

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role of immune system in inflammation

  • 2. Role of immune system in inflammation Presented by Dr.AyeshaGuided by Mrs. Veena A Patil Department of periodontia.
  • 3.
  • 4.
  • 5.
  • 6.
  • 7.
  • 8.
  • 9.
  • 10.
  • 11.
  • 12.
  • 13.
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  • 15.
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  • 18.
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  • 21.
  • 22.
  • 23.
  • 24. Major Histocompatibility Complex  Clusters of genes found in all mammals  Its products play role in discriminating self/non-self participants in both humoral and cell mediated immunity. MHC act as antigen presenting structures In human MHC is found on chromosome 6  Referrred to as HLA complex
  • 25.
  • 26.
  • 27.
  • 28.  Defensins are small cationic proteins found in vertebrates and invertebrates.  They are active against bacteria,fungal and many enveloped and non-enveloped viruses.  Cells of the immune system contains these peptides to assist in killing phagocytised bacteria, for example-in neutrophil granulocytes and almost all epithelial cells.  Most defensins function by binding to the microbial cell membrane and once embedded,forming pore like membrane defects that allow efflux of essential ions and nutrients.
  • 29.  Definition : series of heat-labile serum proteins  Site : serum and all tissue fluids except urine and CSF  Synthesis : in liver – appear in fetal circulation  Function : Responsible for certain aspects of immune response and inflammatory response  Activation : antigen-antibody complex or endotoxin, capsule series of proteins activated sequentially  Inactivation: inhibitors in plasma (short lived)  Biological effects: either beneficial or harmful to host
  • 30.
  • 31. A) Classical pathway: - Complement is activated by antigen –antibody complex (IgM or IgG) - Fc portion of the antibody form a binding site for C1q - The numerical sequence of the complement factors in the classic pathway is: C1q,r,s , C4, C2, C3, C5, C6, C7, C8, C9
  • 32.
  • 33.
  • 34.  This pathway is initiated by:  Bacterial endotoxin, polysaccharide capsule, aggregates of IgE and properdin.  It starts at C3 then C5, C6, C7, C8, C9.  The complement components C1, C4, C2 are by-passed  Antibodies are not required to initiate activation of this pathway.  This pathway provides a means of non-specific resistance
  • 35. Classic Pathway Alternative pathway Specific acquired immunity Non-specific innate immunity Initiated by antibody Bacterial endotoxin, capsule Interaction of all components C1, C4, C2 are by-passed Properdin system not involved Properdin system is involved
  • 36. Beneficial effects: 1) Cytolysis: - activated complement proteins polymerize on cell surfaces of bacteria or erythrocyte to form pores in its membrane (killing by osmotic lysis).
  • 37. 2) Opsonization: - Binding of complement proteins opsonin (C3b) to surfaces of foreign organisms or particles - Phagocytic cells express specific receptors for opsonins, so promote phagocytosis
  • 38.
  • 39. Inflammatory response : Small fragments released during complement activation have several inflammatory actions: a) C5a is chemotactic and attract neutrophiles and macrophages b) C5a activate phagocytes and neutrophils C) C3,C4 and C5 are anaphylatoxins Cause degranulation of mast cells and release of histamine and other inflammatory mediators
  • 40. 5-Enhancement of antibody production: - Binding of C3b to its receptors on activated B cells (CR2) greatly enhances antibody production - Patient who are deficient in C3b produce much less antibody than normal individuals and more susceptible to pyogenic infection
  • 41. Harmful effects: - If complement activate systematically on a large scale (Gm –ve bacilli) - If activated by an autoimmune response to host cells
  • 42.
  • 43.
  • 44.  Directed movement of leucocyte from blood.  Defects in trans endothelial migration results in aggressive periodontitis.  8 steps before the process of chemotaxis reflects the importance of transendothelial migration in periodontal disease.
  • 45.
  • 46.  Once leucocyte enters tissue-it must be able to locate and migrate to the site of insult..  Leucocytes ability to sense a chemical gradient across in cell body and migrate in the direction of increasing concentration.  Receptors for chemotaxisbelong to G-protein coupled family  To migrate leucocytes assume an asymmetric or polarized shape rather than rounded morphology.
  • 47. Movements of phagocytic cells N-formyl methionine Chemotaxis Ameboid movement LPS endotoxin Bacteria initiate RNA translation with NFM. Phagocytic receptors reacts to this, causing the cell to move toward source of signal.LPS endotoxin in outer membrane of gm –ve bacteria activates compliment cascade producing chemotaxin C5a
  • 48.
  • 49.
  • 50.  Oxidative process: oxidation reduction potential at or above - 160mv. Both variables suboptimal in gingival crevice. Neutrophils can function under aerobic condition Non oxidative process: Phagosome lysosome fusion phagolysome Neutrophil contains specific granules :for both extracellular and intraphagolysomal secretion.
  • 51. Specific granules lysozyme lactoferrin Bactericidal bacteriostatic Enzyme independent domain lactoferricin Bactericidal & fungicidal Activity. azurophil granules------for intraphagolysosomal secretion
  • 52.
  • 53.
  • 54.
  • 55.
  • 56.
  • 57.
  • 58.
  • 59.
  • 60.
  • 61.
  • 62.
  • 63.
  • 64.
  • 65.
  • 66. Neutrophils provide the first line of defense when a micro-organism enters the junctional epithelium and then connective tissue. A thorough understanding of neutrophil function is very important to understand the disease process of periodontal disease.

Editor's Notes

  1. the quality or state of being immune; especially :a condition of being able to resist a particular disease especially through preventing development of a pathogenic microorganism or by counteracting the effects of its products
  2. Is a network designed for the homeostasis of large molecules oligomers and cells based on specific recognition mechanisms.
  3. he innate immune system, also known as the non-specific immune system or in-born immunity system,[1] is an important subsystem of the overall immune system that comprises the cells and mechanisms that defend the host from infection by other organisms. The cells of the innate system recognize and respond to pathogens in a generic way, but, unlike the adaptive immune system, the system does not provide long-lasting immunity to the host.[2] Innate immune systems provide immediate defense against infection, and are found in all classes
  4. The adaptive immune system, also known as the acquired immune system or, more rarely, as the specific immune system, is a subsystem of the overall immune system that is composed of highly specialized, systemic cells and processes that eliminate pathogens or prevent their growth.
  5. When the microbe comes in contact with the b cell,igs present on the bcell binds with the microbe and microbe is neutralised and is phagocytosed. Cell mediated microbe is presented by antigen presenting cells.
  6. Dendritic cells capture microbial antigens from tissues and transport antigens to lymph nodes, during this process dendritic cells mature and express high levels of MHC molecules and co stimulators. T cell recognise MHC associated antigens displYED ON DENDRITIC CELLS. T cells are activated to differentiate into effector and memory cells which migrate to sites of ifection and serve various functions in cell mediated immunity.
  7. There are 2 types of T cells Th cells and CTLS. microbial antigen on apcs presented Th cells which then bring about activation of cytokines.these cytokines then bring about activation of macrohages…to kill the microbe, then bring about inflammation and also activates T and b lymphocytes. In ctls infected cell itself presents the microbial antigen to ctls,infected cell and ctls bind together thus the infected cell is killed.
  8. Mhc I helps in identifing self and non self antigens. Mhc II present on apcs Helps in immunity against intra cellular infection. Helps in extra cellular infection. Prsent on dendriic cells,macrophages,B-cells.
  9. The reaction sequence divided into three stages: 1) Recognition stage: - C1q act as the recognition element - It binds to Fc portion of IgM or IgG - The activated C1 molecule can cleave many C4 molecules. 2) Activation stage: The complement components C4, C2, C3, C5, C6, C7, C8, C9 participate in that order 3) Membrane attack stage: Complement components C5, C6, C7, C8, C9 participate where cell membrane damage and cell lysis occur
  10. 1.rolling-leucocytes use l-selectin to interact with vascular adressins..on the luminal surface of endothelial cells----rolling of the leucocyte along the luminal surface. 2.Local insult triggers release of IL-1,TNF-@ FROM MAST CELLS, 3.Signalling endothelium- mast cells initiate neutrophil recruitment against bacteria and responding to C3a nd C5a. 4.IL-1beta,TNF-@,C5a& liposacchrides can stimulate endothelial cells to express P-selesctin,E-selectin on their luminal surfaces.
  11. 5. Signal for rolling arrest: Stimulated endothelium releases chemokines-----functions as signal for rolling arrest 6.Strong adhesion (arrested rolling): interaction of chemokine,IL-8 with leucocyte receptor CXCR2 shed L-selectin and upregulate integrin leucocyte function associted antigen. Lfa-1 binds ICAM-2 expressed constitutely by endothelium. Results in rolling arrest. 8 basement membrane degration:.Leucocytes accumulate between between bsement membrane & endothelial cells. secretion of proteases to degrade the basement membrane. Leucocytes posses several proteases urokinase plasminogen activator receptor.
  12. Selectins- transmembrane molecules expressed on surface of leucocytes and activated endothlial cells. L----leucocytes. P--platelets and endothelial cells. E------activated on endothelium.
  13. Process by which cells ingest particles of a size visible to light microscope. Phagosome delimited strucuture after phagocytosis.
  14. The three phases of the T-cell immune response (expansion, contraction and memory) are indicated. Antigen-specific T cells clonally expand during the first phase in the presence of antigen. Soon after the virus is cleared, the contraction phase ensues and the number of antigen-specific T cells decreases due to apoptosis. After the contraction phase, the number of virus-specific T cells stabilizes and can be maintained for great lengths of time (the memory phase). Note that, typically, the magnitude of the CD4+ T-cell response is lower than that of the CD8+ T-cell response, and the contraction phase can be less pronounced than that of CD8+ T cells. The number of memory CD4+ T cells might decline slowly over time, as reported recently2
  15. 2) B cells obtain help from T cells in the antibody response by acting as antigen-specific antigen presenting cells. As a result of helper T cell recognition of antigen on the B cell surface, the T cell becomes activated and in turn activates the B cell. T cell help has two components: lymphokines which act as growth and differentiation factors for B cells, and additional signals which require cell contact and enable B cells to respond to lymphokines.
  16. Subsetof t helper cells. In response to stimuli mainly cytokines present at the time of antigen recognition, naïve T cells differentiate into population of effector cells,that produce distinct sets of cytokines and perform different functions. These are capable of converting from one to another.