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THE IMMUNE SYSTEM
- AN INTRODUCTION …
Waleed K.
MDS first year
Dept. Of Periodontics
INTRODUCTION …
 DerivesfromaLatinwordIMMUNISmeaning“to makesafe’’
 Immune response involvesrecognizingthepathogen orother foreignmaterialand
mounting areactionagainstitto eliminateit.
 Itisthe body’sdefenseagainstdiseasecausingorganisms,malfunctioningcells,and
foreignparticles
 Disordersoftheimmunesystemcanresultindiseases
A LITTLE HISTORY …
 Theearliestknownmention ofimmunitywasduringtheplagueofAthensin430BC
 LouisPastuerisknownforhisdevelopment ofvaccination
 Robert Koch wasawardeda nobelprizein1905,thatmicroorganismswereconfirmed asthe
causeofinfectiousdisease
 Viruseswereconfirmed ashumanpathogens in1901,withthediscoveryoftheyellowfevervirus
byWalterReed
 Immunology madeagreatadvancetowardsthe endofthe19thcentury,bytheworkofPaul
Ehrlich,whoproposed theside-chaintheorytoexplainthe specificityoftheantigen-antibody
reaction
 Hiscontributions totheunderstandingof humoralimmunitywererecognized bytheawardofa
Nobel Prizein1908,whichwasjointlyawardedtothefounderofcellularimmunology, Flie
Metchnikoff.
SOME DEFINITIONS ….
 IMMUNITY : it is the resistance to disease, specifically
infectious disease.
 IMMUNE RESPONSE : it is the coordinated reaction of cells
and molecules to infectious microbes .
 IMMUNOLOGY : it is the study of the immune system and its
responses to invading pathogens .
 IMMUNE SYSTEM : it is the collection of cells, tissues, and
molecules that mediate resistance to infections .
The physiologic function of the immune system is to prevent
infections and to eradicate established infections
WHAT IS THE IMPORTANCE OF THE IMMUNE
SYSTEM IN HEALTH AND DISEASE …
Role of the IMMUNE SYSTEM Implications
Defense against infections Deficient immunity results in increased
susceptibility to infections
Vaccination boosts immune defenses
and protects against infections
Immune system recognizes and
responds to tissue grafts and newly
introduced proteins
Immune responses are barriers to
transplantation and gene therapy
Defense against tumours Potential for immunotherapy of cancer
WHAT IS ACTIVE AND PASSIVE IMMUNITY ….
 Immunity induced in an individual by infection or
vaccination is called active immunity .
 Immunity conferred on an individual by transfer of
antibodies or lymphocytes from an actively
immunized individual is called passive immunity.
WHAT ARE THE TYPES OF IMMUNITY …
Host Defense
Mechanisms
Innate
Immunity
Adaptive
Immunity
WHAT IS INNATE IMMUNITY …
 It is also called as Natural or Native Immunity .
 It mediates the initial protection against infections .
 This type of host defense is always present in
healthy individuals , prepared to block the entry of
microbes and to rapidly eliminate microbes that do
succeed in entering host tissues .
HOW THE INNATE IMMUNITY WORKS…
The first line of defense in innate immunity is provided by
Epithelial Barriers and by SPECIALIZED CELLS and natural
antibiotics present in the epithelia, which function to block the
entry of microbes.
When the microbes breach the epithelia and enter the tissues or
circulation, they are attacked by Phagocytes , specialized
lymphocytes called Natural Killer Cells and several plasma
proteins , including the proteins of the Complement System.
All these agents recognize and react against microbes but do not
react against noninfectious foreign substances.
The innate immune response will be explained later in the presentation …
MECHANISMS OF INNATE IMMUNITY …
WHAT IS ADAPTIVE IMMUNITY …
 It is also called specific or acquired immunity.
 It is the type of host defense that is stimulated by
microbes that invade tissues, which means , it
adapts to the presence of microbial invaders.
 The adaptive immune system consists of
lymphocytes and their products, such as antibodies.
The adaptive immune response will be explained later in the
presentation …
MECHANISM OF ADAPTIVE IMMUNITY..
WHAT ARE ANTIGENS …
 Microbes as well as noninfectious molecules
produce substances , which are specifically
recognized by the cells of adaptive immunity ,
namely the lymphocytes.
 These substances are called as ANTIGENS.
HOW ANTIGENS AFFECT ADAPTIVE
IMMUNE RESPONSE ….
 Adaptive immune responses are triggered only if
microbes or their antigens pass through epithelial
barriers .
 They are delivered to lymphoid organs where they
are recognized by lymphocytes.
HOW ADAPTIVE IMMUNE RESPONSE AND INNATE
IMMUNE RESPONSE DEPEND ON EACH OTHER …
 Adaptive immune response often uses the cells and
molecules of the innate immune system to eliminate
microbes .
 In turn , adaptive immunity functions to greatly enhance the
antimicrobial mechanisms of innate immunity .
 For example : Antibodies {ADAPTIVE IMMUNITY} bind to
microbes, and the coated microbes bind to and activate
Phagocytes {INNATE IMMUNITY} which ingest and destroy the
microbes.
WHAT ARE THE TYPES OF ADAPTIVE
IMMUNITY ….
ADAPTIVE
IMMUNITY
Humoral
Immunity
Cell- Mediated
Immunity
WHAT IS HUMORAL IMMUNITY …
 Humoral immunity is mediated by proteins called
ANTIBODIES , which are produced by B
LYMPHOCYTES .
HOW DO ANTIBODIES WORK …
 Antibodies are secreted into the circulation and mucosal
fluids, and they neutralize and eliminate microbes and
microbial toxins that are present outside the host cells
,like in the blood and in the lumens of gastrointestinal
and respiratory tracts
 They stop the microbes that are present at mucosal
surfaces and in the blood from gaining access to and
colonizing in the host cells and connective tissues.
 In other words, antibodies prevent infection from ever
getting established .
 But, antibodies cannot gain access to microbes that
live and divide inside infected cells .
WHAT IS CELL-MEDIATED IMMUNITY …
 Defense against intracellular microbes is by CELL
MEDIATED IMMUNITY and it is mediated by cells
called the T LYMPHOCYTES .
 T lymphocytes activate phagocytes to destroy
microbes that have been ingested by the
phagocytes into intracellular vesicles.
 Other T lymphocytes kill any type of host cells that
are harboring infectious microbes in the cytoplasm .
The CELL MEDIATED and HUMORAL immune
responses will be explained again later in the
presentation ….
WHAT IS THE DIFFERENCE BETWEEN THE CELL MEDIATED
AND HUMORAL IMMUNITY …
HUMORAL IMMUNITY CELL MEDIATED IMMUNITY
Antibodies produced by B
lymphocytes , recognize
extracellular microbial antigens .
T lymphocytes recognize antigens
produced by intracellular microbes.
Antibodies are able to recognize
many different types of
molecules such as proteins,
carbohydrates , lipids .
T cells recognize only protein antigens.
WHAT ARE THE PROPERTIES OF ADAPTIVE
IMMUNITY …
FEATURE FUNCTIONAL SIGNIFICANCE
Specificity Ensures distinct antigens elicit specific responses
Diversity Enables immune system to respond to a large variety of
antigens
Memory Leads to enhanced responses to repeated exposures to the
same antigens
Clonal expansion Increases numbers of antigen specific lymphocytes to keep
pace with microbes
Specialization Generates responses that are optimal for defense against
different types of microbes
Contraction and
Homeostasis
Allows immune system to respond to newly encountered
antigens
Nonreactivity to
self
Prevents injury to the host during responses to foreign
antigens
CLONAL SPECIFICITY …
WHAT ARE THE CELLS OF THE IMMUNE
SYSTEM …
 Lymphocytes
 Specialized cells that capture and display microbial
antigens , called ANTIGEN PRESENTING CELLS
 EFFECTOR CELLS , that eliminate the microbes.
WHAT ARE LYMPHOCYTES …
 Lymphocytes are the only cells that produce specific
receptors for antigens.
 Thus , they are the key mediators of adaptive immunity
.
 The types , as mentioned before ,
 B lymphocytes
 T lymphocytes
 Natural Killer cells
 All lymphocytes arise from stem cells in the bone
marrow
WHAT ARE B LYMPHOCYTES …
 B lymphocytes are the only cells capable of
producing antibodies .
 Thus , they are the cells which mediate humoral
immunity .
 All lymphocytes arise from stem cells in the bone
marrow , and B lymphocytes mature in the bone
marrow .
HOW DO B LYMPHOCYTES WORK …
 They express membrane forms of antibodies which
serve as receptors .
 These receptors recognize antigens and initiate
process of activation of cells.
 Soluble antigens and antigens on the surface of
microbes and other cells bind to these B
lymphocyte antigen receptors and elicit humoral
immune response .
HOW B LYMPHOCYTES WORK…
WHAT ARE T LYMPHOCYTES …
 T lymphocytes are the cells of cell-mediated
immunity .
 All lymphocytes arise from stem cells in the bone
marrow , but T lymphocytes mature in the Thymus .
 The important T lymphocytes are ,
 CD 4+ T cells
 CD 8+ T cells
HOW DO T LYMPHOCYTES WORK …
 Antigen receptors of most T lymphocytes only
recognize peptide fragments of protein antigens
that are bound to specialized peptide display
molecules
 These display molecules are called MAJOR
HISTOCOMPATIBILITY COMPLEX (MHC)
molecules .
 MHC molecules are present on the surface of
specialized cells called ANTIGEN PRESENTING
CELLS (APC’S).
WHAT IS THE FUNCTION OF CD4+T CELLS …
 CD 4+ T cells are also called as Helper T cells
 They help B lymphocytes to produce antibodies .
 They also help phagocytes to destroy ingested microbes .
 A special subset of helper cells , functions to prevent or
limit immune responses .
 These are called as regulatory T lymphocytes .
HOW HELPER T CELLS WORK …
WHAT ARE THE FUNCTION OF CD8+T CELLS …
 CD8+ T Cells are also called as Cytotoxic or
Cytolytic T lymphocytes .
 This is because they kill cells harboring intracellular
microbes .
HOW CTL’S WORK …
WHAT ARE NATURAL KILLER CELLS …
 Natural killer cells are the third class of lymphocytes
.
 These kill infected host cells
 But they do not express the clonal distribution
antigen receptors like B cells and T cells .
 They are a component of the innate immunity and
are capable of rapidly attacking infected cells.
HOW NATURAL KILLER CELLS WORK …
HOW DO LYMPHOCYTES DEVELOP …
 All lymphocytes develop from stem cells in the bone
marrow .
 The sites where mature lymphocytes are produced are
called the generative lymphoid organs like the bone
marrow or the thymus .
 Mature lymphocytes leave the generative lymphoid
organs and enter the circulation and the peripheral
lymphoid organs .
 In the peripheral lymphoid organs , they may encounter
antigen for which they express specific receptors.
 Normal adult has 1012 lymphocytes in the circulation
and lymphoid tissues .
RELATED TO DEVELOPMENT AGAIN, WHAT ARE THE
TISSUES OF THE IMMUNE SYSTEM …
 The tissues may be divided into ,
 Primary/ Central / Generative lymphoid organs , in which T and B
lymphocytes mature and become competent to respond to
antigens .
 Peripheral/ Secondary lymphoid organs , in which adaptive
immune responses to microbes are initiated
 Peripheral Lymph nodes consist of the lymph nodes , the
spleen , the mucosal and cutaneous immune systems .
 Within peripheral lymph nodes , B cells are concentrated in
the FOLLICLES, T cells are concentrated in the
PARACORTEX adjacent to the follicles .
 Follicles contain a central region called a GERMINAL
CENTRE , which play role in the production of antibodies .
DEVELOPMENT OF LYMPHOCYTES …
WHAT ARE ANTIGEN-PRESENTING CELLS …
 The common portals for entry of microbes are ,
 Skin
 Gastrointestinal tract
 Respiratory tract
 These portals contain specialized antigen-presenting
cells (APC’s) located in the epithelium that capture
antigens.
 It is then transported to the peripheral lymphoid tissues
and display them to the lymphocytes .
 For example, the dendritic cells.
 The Dendritic cells capture the protein antigens , of
microbes that enter through the epithelia and
transport antigens to regional lymph nodes.
 The antigen-bearing dendritic cells display portions
of the antigens for recognition by T lymphocytes.
WHAT ARE ANTIGEN-PRESENTING CELLS – DENDRITIC
CELLS …
 If a microbe has invaded through the epithelium, it
may be phagocytosed by macrophages that live in
tissues and in various organs.
 Macrophages are also capable of presenting
protein antigens to T cells.
WHAT ARE ANTIGEN-PRESENTING CELLS –
MACROPHAGES …
WHAT ARE PROFESSIONAL APC’S …
 Specialized cells which display antigens to T cells
and provide additional activating signals are called
as Professional APC’s .
 The protypical professional APC’s are dendritic
cells .
 Macrophages may also serve the same function.
WHAT CELLS DISPLAY ANTIGENS TO B
LYMPHOCYTES ….
 B lymphocytes may recognise antigens of microbes
released or on surface of microbes .
 Macrophages lining lymphatic channels may
capture antigens and display them to B cells .
 A type of Dendritic cell called Follicular Dendritc
Cell (FDC) residing in the germinal centers of
lymphoid follicles in the peripheral lymphoid organs
.
 These may display antigens that stimulate the
differentiation of B cells in the follicles .
WHAT ARE EFFECTOR CELLS ….
 The cells that eliminate microbes are called effector
cells
 These consist of lymphocytes and other leukocytes.
 When naïve lymphocytes recognize microbial
antigens, the antigen specific lymphocytes
proliferate and differentiate into EFFECTOR CELLS
AND MEMORY CELLS .
 Naïve Lymphocytes express receptors for antigens but DO
NOT eliminate antigens .
 These cells reside in and circulate between peripheral
lymphoid organs and survive for several weeks or months,
waiting to find and respond to antigen .
 If they are not activated by antigens, naïve lymphocytes die
by the process of apoptosis and are replaced by new cells
that arise in generative lymphoid organs.
 This cycle of cell loss and replacement, maintains a stable
number of lymphocytes , and is called as homeostasis .
 Homeostasis will be explained in detail later in the
presentation…
WHAT HAPPENS TO NAÏVE LYMPHOCYTES...
HOW ARE EFFECTOR CELLS FORMED…
 Differentiation of Naïve lymphocytes into effector
cells and memory cells is initiated by antigen
recognition, ensuring that immune response
develops is specific for the antigen .
 Effector cells are the differentiated progeny of naïve
cells that have the ability to produce molecules that
function to eliminate antigens.
WHAT ARE MEMORY CELLS …
 Memory cells are generated from the progeny of
antigen-stimulated lymphocytes.
 Frequency of memory cells increases with age,
probably due to exposure to environmental
microbes.
 Memory cells are functionally inactive.
 They do not perform effector functions unless
stimulated by antigens .
 When memory cells encounter the same antigen that
induced their development , cells rapidly respond to
give rise to secondary immune responses.
WHAT ARE EFFECTOR CELLS FOR B AND T
LYMPHOCYTES ….
 Effector cells in B lymphocyte lineage are antibody
secreting cells called PLASMA CELLS.
 Helper T cells produce proteins called CYTOKINES
that activate B cells and macrophages.
 Cytotoxic T Lymphocytes have the machinery to kill
infected host cells.
SO TO SUMMARIZE , THE CELLS OF THE IMMUNE
SYSTEM …
SO, WHAT ACTUALLY DOES HAPPEN, WHEN A
MICROBE ATTACKS THE BODY ???
 This can be explained, by seeing an overview of the
immune responses ,
1. Overview of the Innate immune response
2. Overview of the Adaptive immune response
3. Overview of the cell-mediated immune response
4. Overview of the humoral immune response
5. Overview of the homeostasis process
OVERVIEW OF INNATE IMMUNE
RESPONSE …
 Principal barriers between the host and the
environment are epithelia of the skin ,
gastrointestinal tract and respiratory tract .
 When microbes enter through these routes , they
attempt to colonize the host .
 Epithelia serve as physical and functional barriers
to infections which prevent the entry of microbes
and interfere with their growth , by producing
natural antimicrobial agents .
OVERVIEW OF INNATE IMMUNE
RESPONSE …(CONTD.)
 When microbes cross the epithelia, they encounter
defense mechanisms of the innate immunity .
 Phagocytes , including neutrophils and
macrophages, ingest microbes into vesicles and
destroy them by producing microbicidal substances
in these vesicles.
 Macrophages and dendritic cells also secrete
soluble proteins called CYTOKINES which
stimulate inflammation and lymphocyte responses.
OVERVIEW OF INNATE IMMUNE
RESPONSE …(CONTD.)
 Natural killer cells kill virus infected cells and produce
macrophage activating cytokine interferon –γ(IFN–γ)
 Many plasma proteins, including proteins of the
COMPLEMENT system are activated by microbes, and
their products , either kill microbes, or coat (opsonize)
them for phagocytosis by macrophages and neutrophils .
 Innate immunity stimulate adaptive immunity , by
providing signals that are essential for initiating
responses of antigen- specific T and B lymphocytes.
OVERVIEW OF ADAPTIVE IMMUNE RESPONSE
…
 Adaptive immune response uses three main
strategies to combat microbes,
 Secreted antibodies bind to extracellular microbes,
block their ability to infect host cells , and promote their
ingestion and subsequent destruction by phagocytes.
 Phagocytes ingest microbes and kill them , helper T
cells enhance the microbicidal abilities of the
phagocytes
 Cytotoxic T lymphocytes destroy cells infected by
microbes that are inaccessible to antibodies.
 Microbes that enter through the epithelia, and their
protein antigens , are captured by dendritic cells
that are resident in these epithelia , and cell-bound
antigens are transported to draining lymph nodes .
 Protein antigens are processed in the dendritic cells
to generate peptides that are displayed on the
surface of the APC’s bound to MHC molecules.
 Naïve T cells recognize the peptide MHC
complexes and this is how T cell responses are
mediated.
OVERVIEW OF ADAPTIVE IMMUNE RESPONSE
… (CONTD.)
 Protein antigens also are recognized by B lymphocytes in
the lymphoid follicles of the peripheral lymphoid organs.
 Polysaccharides and other nonprotein antigens are
captured in the lymphoid organs and are recognized by B
lymphocytes , but not T cells.
 As part of Innate immune response , Dendritic cells which
present antigen to Naïve T cells , are activated to express
molecules called COSTIMULATORS , and to secrete
CYTOKINES, both are needed , alongwith the antigen , to
stimulate proliferation and differentiation of T lymphocytes .
OVERVIEW OF ADAPTIVE IMMUNE RESPONSE
… (CONTD.)
 The innate immunity response to some microbes
and polysaccharide antigens, also results in
activation of complement, generating cleavage
products of complement proteins ,that enhance the
proliferation and differentiation of B lymphocytes .
 Antigen and molecules produced during innate
immune responses function cooperatively to
activate antigen-specific lymphocytes.
 This ensures that adaptive immune response is
induced by microbes and not by harmless
substances .
OVERVIEW OF ADAPTIVE IMMUNE RESPONSE
… (CONTD.)
HOW IS CELL MEDIATED OR ADAPTIVE IMMUNE
RESPONSE INITIATED ….
 As previously mentioned …
 Antibodies produced by B lymphocytes recognize
EXTRACELLULAR microbial antigens , BUT , T
lymphocytes recognize antigens produced by
INTRACELLULAR microbes.
 Antibodies are able to recognize MANY different
types of molecules such as proteins, carbohydrates
, lipids , BUT , T cells recognize ONLY protein
antigens .
OVERVIEW OF CELL MEDIATED IMMUNE RESPONSE
…
 When naïve T cells are activated by antigen and
costimulators in lymphoid organs, they secrete
cytokine growth factors , and respond to other
cytokines secreted by APC’s .
 The combination of Antigen , Cytokines , and
Costimulators, stimulates the proliferation of T cells
and their differentiation into effector Tcells.
 Naïve CD 4+ T cells become Helper T cells, while
CD 8+ T cells become CTL’s .
 These are generated in the lymphoid organs , and
then migrate back into the blood, and then into any
site where the antigen (microbe) is present .
 Effector T cells are reactivated by antigens at sites
of infection and perform the functions that are
responsible for elimination of the microbes.
 Helper T cells produce cytokines and express cell
surface molecules that bind to receptors on B cells
and macrophages and promote antibody production
, or macrophage killing of ingested microbes.
 Helper T cells also function to activate neutrophils,
which then phagocytose and destroy microbes.
OVERVIEW OF CELL MEDIATED IMMUNE RESPONSE
…(CONTD.)
 CTL’s directly kill cells harboring microbes in the
cytoplasm .
 These microbes may be viruses that infect many
cell types .
 It may also be bacteria , which are ingested by
macrophages, but are not phagocytosed.
 Thus, CTL’s eliminate the reservoirs of infection
itself .
OVERVIEW OF CELL MEDIATED IMMUNE
RESPONSE …(CONTD.)
OVERVIEW OF HUMORAL IMMUNE RESPONSE
…
 On activation , B lymphocytes proliferate and
differentiate into plasma cells that secrete different
classes of antibodies with distinct functions.
 Many polysaccharide and lipid antigens have
multiple antigenic determinats, that are able to
engage to many antigen receptor molecules , on
each B cell and initiate the process of B cell
activation.
 But , globular protein antigens are not able to bind
to many antigen receptors, and B cells requires
help from the Helper T cells .
 The B cells ingest protein antigens , and degrade
them , and display peptides bound to MHC
molecules for recognition by Helper T cells .
 The Helper T cells express cytokines and cell
surface proteins, which together activate the B cells
.
 Each B cell secretes antibodies , which first
recognizes the antigen .
 Polysaccharides and lipids stimulate secretion of a
class of antibody called IMMUNOGLOBULIN M
or IgM .
OVERVIEW OF HUMORAL IMMUNE RESPONSE
… (CONTD.)
 Protein antigens stimulate helper T cells, which
induce the production of antibodies of different
classes ( IgG, IgA , and IgE ).
 This production of different antibodies , is called as
HEAVY CHAIN CLASS ISOTYPE SWITCHING .
 It provides plasticity in the antibody response,
which enables antibodies to function more
efficiently .
OVERVIEW OF HUMORAL IMMUNE RESPONSE
… (CONTD.)
 Helper T cells also stimulate production of
antibodies with higher and higher affinity for the
antigen .
 This is called as AFFINITY MATURATION , and it
improves the quatlity of the humoral immune
response
OVERVIEW OF HUMORAL IMMUNE RESPONSE
… (CONTD.)
 Antibodies bind to microbes and prevent them from
infecting cells , thus neutralizing the microbes.
 Antibodies coat or opsonize microbes , and make
them a target for phagocytosis , as phagocytes like
neutrophils and macrophages express receptors for
the antibodies.
 Antibodies also activate a system of serum
proteases called Complement, and complement
products promote phagocytosis and destruction of
microbes.
OVERVIEW OF HUMORAL IMMUNE RESPONSE
… (CONTD.)
SO , TO SUMMARIZE , THE DIFFERENT PHASES IN
ADAPTIVE IMMUNE RESPONSE…
IN SUMMARY , THE HUMORAL AND CELL MEDIATED
IMMUNE RESPONSE ….
OVERVIEW OF HOMEOSTASIS …
 After the microbe is eliminated, a majority of effector
lymphocytes die by apoptosis.
 It returns the immune system to its basal resting state.
 This return to a stable state is called as homeostasis.
 It happens as microbes provide essential stimuli for
lymphocyte survival and activation and effector cells are
short lived.
 When the stimuli are eliminated, the activated
lymphocytes are also eliminated.
 Initial activation of lymphocytes generates long lived
memory cells, which may survive years after infection
.
 Memory cells,as already explained , are expanded
pool of antigen-specific lymphocytes .
 They respond faster and more effectively against the
antigen than do naïve cells.
 This property of generation of memory cells is
important for vaccines to work .
OVERVIEW OF HOMEOSTASIS …(CONTD.)
SO FINALLY , WHY IS IMMUNITY IMPORTANT TO
PERIODONTICS ???
 Although periodontal disease is caused by bacterial
infection, the resulting tissue damage is due to the
immune response .
 The first response triggered by bacterial infection is
the innate immune response.
 Bacteria are taken up by macrophages, causing
the macrophage to release cytokines.
 The cytokines cause the inflammation associated
with periodontal disease.
 Cytokines cause the blood vessels to dilate and
become permeable, leading to increased local
blood flow, thus causing inflammation.
 The inflammation attracts neutrophils and more
macrophages.
 Studies have shown that polymorphonuclear
neutrophils (PMN) are the most abundant immune
cells found in areas of periodontal disease.
 Interleukin-8 (IL-8) is a chemoattractant for
neutrophils, therefore increased levels of IL-8 are
found in gingival cells.
 The increase PMN and IL-8 are likely contributors
to the inflammatory response
WHY IS IMMUNITY IMPORTANT TO
PERIODONTICS …(CONTD.)
 The adaptive immune response is initiated by
dendritic cells which act as antigen presenting cells
(APC) to stimulate naive T cells.
 Porphyromonas gingivalis, one of the many
bacteria involved in periodontal disease, is able to
sensitize and activate dendritic cells .
 Once dendritic cells are activated and presenting
bacterial peptide, they travel to the nearest lymph
node in order to activate T cells.
 A major source of bone loss has been attributed to
the presence of CD4+ T cells and the cytokines
they secrete .
WHY IS IMMUNITY IMPORTANT TO
PERIODONTICS …(CONTD.)
 T cells activate B cells to secrete antibodies.
 The epithelial cells of patients with periodontitis
contain high levels of IgA and IgG, while IgM is
found in deeper tissues .
 The antibodies are able to aid in the fight of
infection through neutralization, opsonization,
and/or complement activation .
 The latter two scenarios utilize the abundance of
neutrophils and macrophages in order to
phagocytize the bacteria.
WHY IS IMMUNITY IMPORTANT TO
PERIODONTICS …(CONTD.)
 The bacteria that cause periodontal disease have
adapted in a couple of different ways to increase
their effectiveness.
 The first adaptation is displayed by Porphyromonas
gingivalis; they cause apoptosis of lymphocytes,
thereby increasing the spread of infection and
leading to greater pathogenesis .
 The second adaptation by periodontal causing
bacteria is the production of superantigens .
 Superantigens are able to activate a large subset
of T cells by binding to MHC class II molecules on
the T cell receptor .
WHY IS IMMUNITY IMPORTANT TO
PERIODONTICS …(CONTD.)
 Research has been conducted that associates
periodontal disease with cardiovascular disease,
premature births, and other problems.
 A possibility is that the cytokines and other
inflammatory mediators, produced during
periodontal disease could reach levels where they
begin affecting the cardiovascular system and/or
placental tissues.
 The mouth may serve as a "bacterial reservoir" for
the lungs, possibly resulting in bacterial pneumonia
.
 But , Research is currently being done to further
substantiate the above mentioned associations.
WHY IS IMMUNITY IMPORTANT TO
PERIODONTICS …(CONTD.)
 BasicImmunology ,Functions anddisordersoftheImmuneSystem,AbdulK.
AbbasandAndrewH.Lichtman
 CellularandMolecularImmunology ,AbdulK. AbbasandAndrewLichtman
 TheWorldWideWeb
Thank You for your patience and time …
Have a good day ….

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The Immune System-An introduction.pptx

  • 1. THE IMMUNE SYSTEM - AN INTRODUCTION … Waleed K. MDS first year Dept. Of Periodontics
  • 2. INTRODUCTION …  DerivesfromaLatinwordIMMUNISmeaning“to makesafe’’  Immune response involvesrecognizingthepathogen orother foreignmaterialand mounting areactionagainstitto eliminateit.  Itisthe body’sdefenseagainstdiseasecausingorganisms,malfunctioningcells,and foreignparticles  Disordersoftheimmunesystemcanresultindiseases
  • 3. A LITTLE HISTORY …  Theearliestknownmention ofimmunitywasduringtheplagueofAthensin430BC  LouisPastuerisknownforhisdevelopment ofvaccination  Robert Koch wasawardeda nobelprizein1905,thatmicroorganismswereconfirmed asthe causeofinfectiousdisease  Viruseswereconfirmed ashumanpathogens in1901,withthediscoveryoftheyellowfevervirus byWalterReed  Immunology madeagreatadvancetowardsthe endofthe19thcentury,bytheworkofPaul Ehrlich,whoproposed theside-chaintheorytoexplainthe specificityoftheantigen-antibody reaction  Hiscontributions totheunderstandingof humoralimmunitywererecognized bytheawardofa Nobel Prizein1908,whichwasjointlyawardedtothefounderofcellularimmunology, Flie Metchnikoff.
  • 4. SOME DEFINITIONS ….  IMMUNITY : it is the resistance to disease, specifically infectious disease.  IMMUNE RESPONSE : it is the coordinated reaction of cells and molecules to infectious microbes .  IMMUNOLOGY : it is the study of the immune system and its responses to invading pathogens .  IMMUNE SYSTEM : it is the collection of cells, tissues, and molecules that mediate resistance to infections . The physiologic function of the immune system is to prevent infections and to eradicate established infections
  • 5. WHAT IS THE IMPORTANCE OF THE IMMUNE SYSTEM IN HEALTH AND DISEASE … Role of the IMMUNE SYSTEM Implications Defense against infections Deficient immunity results in increased susceptibility to infections Vaccination boosts immune defenses and protects against infections Immune system recognizes and responds to tissue grafts and newly introduced proteins Immune responses are barriers to transplantation and gene therapy Defense against tumours Potential for immunotherapy of cancer
  • 6. WHAT IS ACTIVE AND PASSIVE IMMUNITY ….  Immunity induced in an individual by infection or vaccination is called active immunity .  Immunity conferred on an individual by transfer of antibodies or lymphocytes from an actively immunized individual is called passive immunity.
  • 7. WHAT ARE THE TYPES OF IMMUNITY … Host Defense Mechanisms Innate Immunity Adaptive Immunity
  • 8. WHAT IS INNATE IMMUNITY …  It is also called as Natural or Native Immunity .  It mediates the initial protection against infections .  This type of host defense is always present in healthy individuals , prepared to block the entry of microbes and to rapidly eliminate microbes that do succeed in entering host tissues .
  • 9. HOW THE INNATE IMMUNITY WORKS… The first line of defense in innate immunity is provided by Epithelial Barriers and by SPECIALIZED CELLS and natural antibiotics present in the epithelia, which function to block the entry of microbes. When the microbes breach the epithelia and enter the tissues or circulation, they are attacked by Phagocytes , specialized lymphocytes called Natural Killer Cells and several plasma proteins , including the proteins of the Complement System. All these agents recognize and react against microbes but do not react against noninfectious foreign substances. The innate immune response will be explained later in the presentation …
  • 10. MECHANISMS OF INNATE IMMUNITY …
  • 11. WHAT IS ADAPTIVE IMMUNITY …  It is also called specific or acquired immunity.  It is the type of host defense that is stimulated by microbes that invade tissues, which means , it adapts to the presence of microbial invaders.  The adaptive immune system consists of lymphocytes and their products, such as antibodies. The adaptive immune response will be explained later in the presentation …
  • 12. MECHANISM OF ADAPTIVE IMMUNITY..
  • 13. WHAT ARE ANTIGENS …  Microbes as well as noninfectious molecules produce substances , which are specifically recognized by the cells of adaptive immunity , namely the lymphocytes.  These substances are called as ANTIGENS.
  • 14. HOW ANTIGENS AFFECT ADAPTIVE IMMUNE RESPONSE ….  Adaptive immune responses are triggered only if microbes or their antigens pass through epithelial barriers .  They are delivered to lymphoid organs where they are recognized by lymphocytes.
  • 15. HOW ADAPTIVE IMMUNE RESPONSE AND INNATE IMMUNE RESPONSE DEPEND ON EACH OTHER …  Adaptive immune response often uses the cells and molecules of the innate immune system to eliminate microbes .  In turn , adaptive immunity functions to greatly enhance the antimicrobial mechanisms of innate immunity .  For example : Antibodies {ADAPTIVE IMMUNITY} bind to microbes, and the coated microbes bind to and activate Phagocytes {INNATE IMMUNITY} which ingest and destroy the microbes.
  • 16. WHAT ARE THE TYPES OF ADAPTIVE IMMUNITY …. ADAPTIVE IMMUNITY Humoral Immunity Cell- Mediated Immunity
  • 17. WHAT IS HUMORAL IMMUNITY …  Humoral immunity is mediated by proteins called ANTIBODIES , which are produced by B LYMPHOCYTES .
  • 18. HOW DO ANTIBODIES WORK …  Antibodies are secreted into the circulation and mucosal fluids, and they neutralize and eliminate microbes and microbial toxins that are present outside the host cells ,like in the blood and in the lumens of gastrointestinal and respiratory tracts  They stop the microbes that are present at mucosal surfaces and in the blood from gaining access to and colonizing in the host cells and connective tissues.  In other words, antibodies prevent infection from ever getting established .  But, antibodies cannot gain access to microbes that live and divide inside infected cells .
  • 19. WHAT IS CELL-MEDIATED IMMUNITY …  Defense against intracellular microbes is by CELL MEDIATED IMMUNITY and it is mediated by cells called the T LYMPHOCYTES .  T lymphocytes activate phagocytes to destroy microbes that have been ingested by the phagocytes into intracellular vesicles.  Other T lymphocytes kill any type of host cells that are harboring infectious microbes in the cytoplasm .
  • 20. The CELL MEDIATED and HUMORAL immune responses will be explained again later in the presentation ….
  • 21. WHAT IS THE DIFFERENCE BETWEEN THE CELL MEDIATED AND HUMORAL IMMUNITY … HUMORAL IMMUNITY CELL MEDIATED IMMUNITY Antibodies produced by B lymphocytes , recognize extracellular microbial antigens . T lymphocytes recognize antigens produced by intracellular microbes. Antibodies are able to recognize many different types of molecules such as proteins, carbohydrates , lipids . T cells recognize only protein antigens.
  • 22. WHAT ARE THE PROPERTIES OF ADAPTIVE IMMUNITY … FEATURE FUNCTIONAL SIGNIFICANCE Specificity Ensures distinct antigens elicit specific responses Diversity Enables immune system to respond to a large variety of antigens Memory Leads to enhanced responses to repeated exposures to the same antigens Clonal expansion Increases numbers of antigen specific lymphocytes to keep pace with microbes Specialization Generates responses that are optimal for defense against different types of microbes Contraction and Homeostasis Allows immune system to respond to newly encountered antigens Nonreactivity to self Prevents injury to the host during responses to foreign antigens
  • 24. WHAT ARE THE CELLS OF THE IMMUNE SYSTEM …  Lymphocytes  Specialized cells that capture and display microbial antigens , called ANTIGEN PRESENTING CELLS  EFFECTOR CELLS , that eliminate the microbes.
  • 25. WHAT ARE LYMPHOCYTES …  Lymphocytes are the only cells that produce specific receptors for antigens.  Thus , they are the key mediators of adaptive immunity .  The types , as mentioned before ,  B lymphocytes  T lymphocytes  Natural Killer cells  All lymphocytes arise from stem cells in the bone marrow
  • 26. WHAT ARE B LYMPHOCYTES …  B lymphocytes are the only cells capable of producing antibodies .  Thus , they are the cells which mediate humoral immunity .  All lymphocytes arise from stem cells in the bone marrow , and B lymphocytes mature in the bone marrow .
  • 27. HOW DO B LYMPHOCYTES WORK …  They express membrane forms of antibodies which serve as receptors .  These receptors recognize antigens and initiate process of activation of cells.  Soluble antigens and antigens on the surface of microbes and other cells bind to these B lymphocyte antigen receptors and elicit humoral immune response .
  • 28. HOW B LYMPHOCYTES WORK…
  • 29. WHAT ARE T LYMPHOCYTES …  T lymphocytes are the cells of cell-mediated immunity .  All lymphocytes arise from stem cells in the bone marrow , but T lymphocytes mature in the Thymus .  The important T lymphocytes are ,  CD 4+ T cells  CD 8+ T cells
  • 30. HOW DO T LYMPHOCYTES WORK …  Antigen receptors of most T lymphocytes only recognize peptide fragments of protein antigens that are bound to specialized peptide display molecules  These display molecules are called MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) molecules .  MHC molecules are present on the surface of specialized cells called ANTIGEN PRESENTING CELLS (APC’S).
  • 31. WHAT IS THE FUNCTION OF CD4+T CELLS …  CD 4+ T cells are also called as Helper T cells  They help B lymphocytes to produce antibodies .  They also help phagocytes to destroy ingested microbes .  A special subset of helper cells , functions to prevent or limit immune responses .  These are called as regulatory T lymphocytes .
  • 32. HOW HELPER T CELLS WORK …
  • 33. WHAT ARE THE FUNCTION OF CD8+T CELLS …  CD8+ T Cells are also called as Cytotoxic or Cytolytic T lymphocytes .  This is because they kill cells harboring intracellular microbes .
  • 35. WHAT ARE NATURAL KILLER CELLS …  Natural killer cells are the third class of lymphocytes .  These kill infected host cells  But they do not express the clonal distribution antigen receptors like B cells and T cells .  They are a component of the innate immunity and are capable of rapidly attacking infected cells.
  • 36. HOW NATURAL KILLER CELLS WORK …
  • 37. HOW DO LYMPHOCYTES DEVELOP …  All lymphocytes develop from stem cells in the bone marrow .  The sites where mature lymphocytes are produced are called the generative lymphoid organs like the bone marrow or the thymus .  Mature lymphocytes leave the generative lymphoid organs and enter the circulation and the peripheral lymphoid organs .  In the peripheral lymphoid organs , they may encounter antigen for which they express specific receptors.  Normal adult has 1012 lymphocytes in the circulation and lymphoid tissues .
  • 38. RELATED TO DEVELOPMENT AGAIN, WHAT ARE THE TISSUES OF THE IMMUNE SYSTEM …  The tissues may be divided into ,  Primary/ Central / Generative lymphoid organs , in which T and B lymphocytes mature and become competent to respond to antigens .  Peripheral/ Secondary lymphoid organs , in which adaptive immune responses to microbes are initiated  Peripheral Lymph nodes consist of the lymph nodes , the spleen , the mucosal and cutaneous immune systems .  Within peripheral lymph nodes , B cells are concentrated in the FOLLICLES, T cells are concentrated in the PARACORTEX adjacent to the follicles .  Follicles contain a central region called a GERMINAL CENTRE , which play role in the production of antibodies .
  • 40. WHAT ARE ANTIGEN-PRESENTING CELLS …  The common portals for entry of microbes are ,  Skin  Gastrointestinal tract  Respiratory tract  These portals contain specialized antigen-presenting cells (APC’s) located in the epithelium that capture antigens.  It is then transported to the peripheral lymphoid tissues and display them to the lymphocytes .
  • 41.  For example, the dendritic cells.  The Dendritic cells capture the protein antigens , of microbes that enter through the epithelia and transport antigens to regional lymph nodes.  The antigen-bearing dendritic cells display portions of the antigens for recognition by T lymphocytes. WHAT ARE ANTIGEN-PRESENTING CELLS – DENDRITIC CELLS …
  • 42.  If a microbe has invaded through the epithelium, it may be phagocytosed by macrophages that live in tissues and in various organs.  Macrophages are also capable of presenting protein antigens to T cells. WHAT ARE ANTIGEN-PRESENTING CELLS – MACROPHAGES …
  • 43. WHAT ARE PROFESSIONAL APC’S …  Specialized cells which display antigens to T cells and provide additional activating signals are called as Professional APC’s .  The protypical professional APC’s are dendritic cells .  Macrophages may also serve the same function.
  • 44. WHAT CELLS DISPLAY ANTIGENS TO B LYMPHOCYTES ….  B lymphocytes may recognise antigens of microbes released or on surface of microbes .  Macrophages lining lymphatic channels may capture antigens and display them to B cells .  A type of Dendritic cell called Follicular Dendritc Cell (FDC) residing in the germinal centers of lymphoid follicles in the peripheral lymphoid organs .  These may display antigens that stimulate the differentiation of B cells in the follicles .
  • 45. WHAT ARE EFFECTOR CELLS ….  The cells that eliminate microbes are called effector cells  These consist of lymphocytes and other leukocytes.  When naïve lymphocytes recognize microbial antigens, the antigen specific lymphocytes proliferate and differentiate into EFFECTOR CELLS AND MEMORY CELLS .
  • 46.  Naïve Lymphocytes express receptors for antigens but DO NOT eliminate antigens .  These cells reside in and circulate between peripheral lymphoid organs and survive for several weeks or months, waiting to find and respond to antigen .  If they are not activated by antigens, naïve lymphocytes die by the process of apoptosis and are replaced by new cells that arise in generative lymphoid organs.  This cycle of cell loss and replacement, maintains a stable number of lymphocytes , and is called as homeostasis .  Homeostasis will be explained in detail later in the presentation… WHAT HAPPENS TO NAÏVE LYMPHOCYTES...
  • 47. HOW ARE EFFECTOR CELLS FORMED…  Differentiation of Naïve lymphocytes into effector cells and memory cells is initiated by antigen recognition, ensuring that immune response develops is specific for the antigen .  Effector cells are the differentiated progeny of naïve cells that have the ability to produce molecules that function to eliminate antigens.
  • 48. WHAT ARE MEMORY CELLS …  Memory cells are generated from the progeny of antigen-stimulated lymphocytes.  Frequency of memory cells increases with age, probably due to exposure to environmental microbes.  Memory cells are functionally inactive.  They do not perform effector functions unless stimulated by antigens .  When memory cells encounter the same antigen that induced their development , cells rapidly respond to give rise to secondary immune responses.
  • 49. WHAT ARE EFFECTOR CELLS FOR B AND T LYMPHOCYTES ….  Effector cells in B lymphocyte lineage are antibody secreting cells called PLASMA CELLS.  Helper T cells produce proteins called CYTOKINES that activate B cells and macrophages.  Cytotoxic T Lymphocytes have the machinery to kill infected host cells.
  • 50. SO TO SUMMARIZE , THE CELLS OF THE IMMUNE SYSTEM …
  • 51. SO, WHAT ACTUALLY DOES HAPPEN, WHEN A MICROBE ATTACKS THE BODY ???  This can be explained, by seeing an overview of the immune responses , 1. Overview of the Innate immune response 2. Overview of the Adaptive immune response 3. Overview of the cell-mediated immune response 4. Overview of the humoral immune response 5. Overview of the homeostasis process
  • 52. OVERVIEW OF INNATE IMMUNE RESPONSE …  Principal barriers between the host and the environment are epithelia of the skin , gastrointestinal tract and respiratory tract .  When microbes enter through these routes , they attempt to colonize the host .  Epithelia serve as physical and functional barriers to infections which prevent the entry of microbes and interfere with their growth , by producing natural antimicrobial agents .
  • 53. OVERVIEW OF INNATE IMMUNE RESPONSE …(CONTD.)  When microbes cross the epithelia, they encounter defense mechanisms of the innate immunity .  Phagocytes , including neutrophils and macrophages, ingest microbes into vesicles and destroy them by producing microbicidal substances in these vesicles.  Macrophages and dendritic cells also secrete soluble proteins called CYTOKINES which stimulate inflammation and lymphocyte responses.
  • 54. OVERVIEW OF INNATE IMMUNE RESPONSE …(CONTD.)  Natural killer cells kill virus infected cells and produce macrophage activating cytokine interferon –γ(IFN–γ)  Many plasma proteins, including proteins of the COMPLEMENT system are activated by microbes, and their products , either kill microbes, or coat (opsonize) them for phagocytosis by macrophages and neutrophils .  Innate immunity stimulate adaptive immunity , by providing signals that are essential for initiating responses of antigen- specific T and B lymphocytes.
  • 55. OVERVIEW OF ADAPTIVE IMMUNE RESPONSE …  Adaptive immune response uses three main strategies to combat microbes,  Secreted antibodies bind to extracellular microbes, block their ability to infect host cells , and promote their ingestion and subsequent destruction by phagocytes.  Phagocytes ingest microbes and kill them , helper T cells enhance the microbicidal abilities of the phagocytes  Cytotoxic T lymphocytes destroy cells infected by microbes that are inaccessible to antibodies.
  • 56.  Microbes that enter through the epithelia, and their protein antigens , are captured by dendritic cells that are resident in these epithelia , and cell-bound antigens are transported to draining lymph nodes .  Protein antigens are processed in the dendritic cells to generate peptides that are displayed on the surface of the APC’s bound to MHC molecules.  Naïve T cells recognize the peptide MHC complexes and this is how T cell responses are mediated. OVERVIEW OF ADAPTIVE IMMUNE RESPONSE … (CONTD.)
  • 57.  Protein antigens also are recognized by B lymphocytes in the lymphoid follicles of the peripheral lymphoid organs.  Polysaccharides and other nonprotein antigens are captured in the lymphoid organs and are recognized by B lymphocytes , but not T cells.  As part of Innate immune response , Dendritic cells which present antigen to Naïve T cells , are activated to express molecules called COSTIMULATORS , and to secrete CYTOKINES, both are needed , alongwith the antigen , to stimulate proliferation and differentiation of T lymphocytes . OVERVIEW OF ADAPTIVE IMMUNE RESPONSE … (CONTD.)
  • 58.  The innate immunity response to some microbes and polysaccharide antigens, also results in activation of complement, generating cleavage products of complement proteins ,that enhance the proliferation and differentiation of B lymphocytes .  Antigen and molecules produced during innate immune responses function cooperatively to activate antigen-specific lymphocytes.  This ensures that adaptive immune response is induced by microbes and not by harmless substances . OVERVIEW OF ADAPTIVE IMMUNE RESPONSE … (CONTD.)
  • 59. HOW IS CELL MEDIATED OR ADAPTIVE IMMUNE RESPONSE INITIATED ….  As previously mentioned …  Antibodies produced by B lymphocytes recognize EXTRACELLULAR microbial antigens , BUT , T lymphocytes recognize antigens produced by INTRACELLULAR microbes.  Antibodies are able to recognize MANY different types of molecules such as proteins, carbohydrates , lipids , BUT , T cells recognize ONLY protein antigens .
  • 60. OVERVIEW OF CELL MEDIATED IMMUNE RESPONSE …  When naïve T cells are activated by antigen and costimulators in lymphoid organs, they secrete cytokine growth factors , and respond to other cytokines secreted by APC’s .  The combination of Antigen , Cytokines , and Costimulators, stimulates the proliferation of T cells and their differentiation into effector Tcells.  Naïve CD 4+ T cells become Helper T cells, while CD 8+ T cells become CTL’s .  These are generated in the lymphoid organs , and then migrate back into the blood, and then into any site where the antigen (microbe) is present .
  • 61.  Effector T cells are reactivated by antigens at sites of infection and perform the functions that are responsible for elimination of the microbes.  Helper T cells produce cytokines and express cell surface molecules that bind to receptors on B cells and macrophages and promote antibody production , or macrophage killing of ingested microbes.  Helper T cells also function to activate neutrophils, which then phagocytose and destroy microbes. OVERVIEW OF CELL MEDIATED IMMUNE RESPONSE …(CONTD.)
  • 62.  CTL’s directly kill cells harboring microbes in the cytoplasm .  These microbes may be viruses that infect many cell types .  It may also be bacteria , which are ingested by macrophages, but are not phagocytosed.  Thus, CTL’s eliminate the reservoirs of infection itself . OVERVIEW OF CELL MEDIATED IMMUNE RESPONSE …(CONTD.)
  • 63. OVERVIEW OF HUMORAL IMMUNE RESPONSE …  On activation , B lymphocytes proliferate and differentiate into plasma cells that secrete different classes of antibodies with distinct functions.  Many polysaccharide and lipid antigens have multiple antigenic determinats, that are able to engage to many antigen receptor molecules , on each B cell and initiate the process of B cell activation.  But , globular protein antigens are not able to bind to many antigen receptors, and B cells requires help from the Helper T cells .
  • 64.  The B cells ingest protein antigens , and degrade them , and display peptides bound to MHC molecules for recognition by Helper T cells .  The Helper T cells express cytokines and cell surface proteins, which together activate the B cells .  Each B cell secretes antibodies , which first recognizes the antigen .  Polysaccharides and lipids stimulate secretion of a class of antibody called IMMUNOGLOBULIN M or IgM . OVERVIEW OF HUMORAL IMMUNE RESPONSE … (CONTD.)
  • 65.  Protein antigens stimulate helper T cells, which induce the production of antibodies of different classes ( IgG, IgA , and IgE ).  This production of different antibodies , is called as HEAVY CHAIN CLASS ISOTYPE SWITCHING .  It provides plasticity in the antibody response, which enables antibodies to function more efficiently . OVERVIEW OF HUMORAL IMMUNE RESPONSE … (CONTD.)
  • 66.  Helper T cells also stimulate production of antibodies with higher and higher affinity for the antigen .  This is called as AFFINITY MATURATION , and it improves the quatlity of the humoral immune response OVERVIEW OF HUMORAL IMMUNE RESPONSE … (CONTD.)
  • 67.  Antibodies bind to microbes and prevent them from infecting cells , thus neutralizing the microbes.  Antibodies coat or opsonize microbes , and make them a target for phagocytosis , as phagocytes like neutrophils and macrophages express receptors for the antibodies.  Antibodies also activate a system of serum proteases called Complement, and complement products promote phagocytosis and destruction of microbes. OVERVIEW OF HUMORAL IMMUNE RESPONSE … (CONTD.)
  • 68. SO , TO SUMMARIZE , THE DIFFERENT PHASES IN ADAPTIVE IMMUNE RESPONSE…
  • 69. IN SUMMARY , THE HUMORAL AND CELL MEDIATED IMMUNE RESPONSE ….
  • 70. OVERVIEW OF HOMEOSTASIS …  After the microbe is eliminated, a majority of effector lymphocytes die by apoptosis.  It returns the immune system to its basal resting state.  This return to a stable state is called as homeostasis.  It happens as microbes provide essential stimuli for lymphocyte survival and activation and effector cells are short lived.  When the stimuli are eliminated, the activated lymphocytes are also eliminated.
  • 71.  Initial activation of lymphocytes generates long lived memory cells, which may survive years after infection .  Memory cells,as already explained , are expanded pool of antigen-specific lymphocytes .  They respond faster and more effectively against the antigen than do naïve cells.  This property of generation of memory cells is important for vaccines to work . OVERVIEW OF HOMEOSTASIS …(CONTD.)
  • 72. SO FINALLY , WHY IS IMMUNITY IMPORTANT TO PERIODONTICS ???  Although periodontal disease is caused by bacterial infection, the resulting tissue damage is due to the immune response .  The first response triggered by bacterial infection is the innate immune response.  Bacteria are taken up by macrophages, causing the macrophage to release cytokines.  The cytokines cause the inflammation associated with periodontal disease.  Cytokines cause the blood vessels to dilate and become permeable, leading to increased local blood flow, thus causing inflammation.
  • 73.  The inflammation attracts neutrophils and more macrophages.  Studies have shown that polymorphonuclear neutrophils (PMN) are the most abundant immune cells found in areas of periodontal disease.  Interleukin-8 (IL-8) is a chemoattractant for neutrophils, therefore increased levels of IL-8 are found in gingival cells.  The increase PMN and IL-8 are likely contributors to the inflammatory response WHY IS IMMUNITY IMPORTANT TO PERIODONTICS …(CONTD.)
  • 74.  The adaptive immune response is initiated by dendritic cells which act as antigen presenting cells (APC) to stimulate naive T cells.  Porphyromonas gingivalis, one of the many bacteria involved in periodontal disease, is able to sensitize and activate dendritic cells .  Once dendritic cells are activated and presenting bacterial peptide, they travel to the nearest lymph node in order to activate T cells.  A major source of bone loss has been attributed to the presence of CD4+ T cells and the cytokines they secrete . WHY IS IMMUNITY IMPORTANT TO PERIODONTICS …(CONTD.)
  • 75.  T cells activate B cells to secrete antibodies.  The epithelial cells of patients with periodontitis contain high levels of IgA and IgG, while IgM is found in deeper tissues .  The antibodies are able to aid in the fight of infection through neutralization, opsonization, and/or complement activation .  The latter two scenarios utilize the abundance of neutrophils and macrophages in order to phagocytize the bacteria. WHY IS IMMUNITY IMPORTANT TO PERIODONTICS …(CONTD.)
  • 76.  The bacteria that cause periodontal disease have adapted in a couple of different ways to increase their effectiveness.  The first adaptation is displayed by Porphyromonas gingivalis; they cause apoptosis of lymphocytes, thereby increasing the spread of infection and leading to greater pathogenesis .  The second adaptation by periodontal causing bacteria is the production of superantigens .  Superantigens are able to activate a large subset of T cells by binding to MHC class II molecules on the T cell receptor . WHY IS IMMUNITY IMPORTANT TO PERIODONTICS …(CONTD.)
  • 77.  Research has been conducted that associates periodontal disease with cardiovascular disease, premature births, and other problems.  A possibility is that the cytokines and other inflammatory mediators, produced during periodontal disease could reach levels where they begin affecting the cardiovascular system and/or placental tissues.  The mouth may serve as a "bacterial reservoir" for the lungs, possibly resulting in bacterial pneumonia .  But , Research is currently being done to further substantiate the above mentioned associations. WHY IS IMMUNITY IMPORTANT TO PERIODONTICS …(CONTD.)
  • 78.  BasicImmunology ,Functions anddisordersoftheImmuneSystem,AbdulK. AbbasandAndrewH.Lichtman  CellularandMolecularImmunology ,AbdulK. AbbasandAndrewLichtman  TheWorldWideWeb
  • 79. Thank You for your patience and time … Have a good day ….