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Dr. Kritika Jangid
MDS- Periodontics
 IMMUNITY: Resistance to infectious disease
 IMMUNE SYSTEM: Collection of cells,
tissues and molecules that mediate resistance
to infections
 IMMUNE RESPONSE: Coordinated reactions
of these cells and molecules to infectious
microbes
 IMMUNOLOGY: Study of immune system
and its response to invading pathogens
Role of the Immune System
• Defence against infections
• Recognises and responds to
tissue grafts and newly
introduced proteins
• Defence against tumors
Implications
• Deficient immunity results
in increased susceptibility
to infections. Vaccination
boosts immune defences
and protects against
infections
• Immune responses are
barriers to transplantation
and gene therapy
• Potential for
immunotherapy for cancer
 Also calledNaturalor Nativeimmunity.
 Components present before the onset of infection.
 Disease resistantmechanismsthatare not specificto a
particularpathogen
 Pathogensmust first breach barriers thatprotect host
 Provides the first line defence right after exposure.
 Most micro-organisms are readily cleared within a
few days by innate immune system before
adaptive immune system is activated
 Componentsofinnateimmunityrecognizestructuresthatare sharedby
variousclassesofmicrobesandare notpresentonthehostcells
 Foreg: Phagocytesexpressreceptorsfor
1. Bacterial LPS(endotoxin)-On cellwallofmany bacterialspecies
2. Terminalmannoseresidues-Typicalofbacterialgylcoproteins
3. DsRNA-Foundinviruses
4. UnmethylatedCpGoligonucleotide-CommoninmicrobialDNA
PATHOGEN ASSOCIATED MOLECULAR
PATTERNS:
The microbial molecules that are targets of
innate immunity .
Indicates that they are shared by microbes of
the same type
PATTERN RECOGNITION RECEPTORS:
The receptors of innate immunity that recognize
the shared structures.
 Recognizes structures of microbes that are often essential
for the survival and infectivity of these microbes.
 Recognize molecules that are released from stressed or
necrotic cells. (Damage associated molecular patterns)
 Does not react against the host
 Encoded in the germline; not produced by somatic
recombination of genes
 Two principal types of defences are:
1. Inflammation
2. Antiviral defence
EPITHLIAL
BARRIERS
PHAGOCYTES
DENDRITIC
CELLS
NK CELLS
OTHER
LYMPHOCYTES
COMPLEMENT
CYTOKINES
PLASMA
PROTEINS
 2 types: Neutrophils and monocytes recruited to the
site of infection where they recognize and ingest
microbes for intracellular killing.
 NEUTROPHILS (PMNs): MACROPHAGES
 PMNs
 Most abundant leukocytes (4000-10,000/µL)
 Infection: 20,000µL of blood
 1st cell type to respond to most infections (particularly
bacterial and fungal)
 Stimulated by cytokines (Colony stimulating factors)
which act on the bone marrow stem cells to produce
neutrophil precursors
 Ingest microbes in the circulation and rapidly enter
extravascular tissues at the site of infection where they
ingest microbes and die after a few hours.
 500-1000/µL of blood
 Monocytes that enter extravascular tissues survive in
these sites for long periods
Phagocytosis
and
intracellular
killing of
microbes
 Initiate T- cell responses
 Important bridge between
innate and adaptive immunity
 Respond to microbes by
producing cytokines that
recruit leukocytes and initiate
adaptive immune responses
 γδ T cells: Present in epithelia
 NK-T cells: Present in epithelia and lymphoid organs.
(Recognize microbial lipids bound to a class 1 MHC-
related molecule called CD1)
 B-1 cells: Most of the antibodies are specific for
carbohydrates that are present in the cell walls of many
bacteria.
 Marginal zone B cells: Responses that are characteristic of
adaptive immunity (eg. Antibody production) and have
features of innate immunity (eg. Rapid responses and
limited diversity of antigen recognition)
 Collection of circulating and membrane associated
proteins.
 Complement activation involves the sequential
activation of proteolytic enzymes sometimes called an
enzymatic cascade.
 3 pathways:
 Alternative pathway
 Classical pathway
 Lectin pathway
 Secreted in small amounts in response to an external
stimulus and bind to high affinity receptors on target
cells
 MBL: Plasma Mannose binding lectin:
 Recognizes microbial carbohydrates and can coat
microbes for phagocytosis or activate the complement
cascade by lectin pathway.
 Belongs to collectin family of proteins which shares
homology to collagen and contain a carbohydrate
binding (lectin) domain.
 CRP: Binds to phosphoryl-choline on microbes and
coats the microbes for phagocytosis.
 Triggered only if microbes or their
antigens pass through epithelial
barriers and are delivered to the
lymphoid organs where they can be
recognized by lymphocytes.
 Specialized to combat different types of infections:
 Antibodies: Eliminate microbes in extracellular fluids
 Activated T lymphocytes: Eliminate microbes living
inside cells
 Protection from an infectious disease
agent that is mediated by B- and T-
LYMPHOCYTES following exposure to
specific antigen, and characterized
by IMMUNOLOGIC MEMORY.
 Active immunity: Immunity induced in an
individual by infection or vaccination
 Passive immunity: Immunity conferred in
an individual by transfer of antibodies or
lymphocytes from an actively immunized
individuals
 Antigen receptors of B lymphocytes (Membrane
bound antibodies) can recognize a wide variety of
macromolecules (proteins, polysaccharides, lipids and
nucleic acids) as well as small chemicals in soluble or
cell surface associated form.
 Most T lymphocytes can see only peptide fragments of
protein antigens, and can do so only when these
peptides are presented by specialized peptide display
molecules on host cells
 Majority of T lymphocytes recognize peptide
antigens that are bound to and displayed by major
histocompatibility complex (MHC) molecules of
antigen presenting cells (APCs)
 Capture of
protein
antigens by
antigen
presenting
cells (APCs)
 Antigen Presentation to T
cells
 MHC (major histocompatibility
complex) 1
 all nucleated cells
 MHC-encoded alpha (hvy)
chain and beta 2 (lt)
microglobulin
 Polymorphic alpha 1 and alpha
2 domains for closed binding
cleft
 Conserved alpha 3 domains =
binding site for CD8
 Beta 2 interacts noncovalently
with alpha 3
 MHC-II = dimer of alpha
and beta subunits
 APCs
 Both chains MHC
encoded
 Alpha 1 and beta 1
domains variable and form
open binding cleft
 Most of variability on
beta chain
 Alpha 2 and beta 2 folded
into Ig domains
 B2 Ig domain binds to
CD4
 FEATURES OF
PEPTIDE
BINDING TO
MHC
MOLECULES
 T cells can be distinguished by their different antigen
receptors
 The definitive T cell linage marker is the T cell antigen
receptor (TCR).
 2 different types of TCR are:
 A heterodimer of two disulfide- linked polypeptides (α
and β)
 A structurally similar heterodimer consisting of γ and δ
polypeptides
90-95% of blood T cells are αβ T cells
 There are 3 major subpopulations of αβ T cells
 Helper T cells (TH) that expresses the CD4 marker
(CD4+ T cells) and mainly ‘helps’ or ‘induces’ immune
responses
 TH1 cells secrete IL2 and IFN γ
 TH2 cells produce IL4. IL5, IL6 and IL10
 Regulatory T cells (Treg) that expresses the CD4+ T cells
and regulate immune responses.
 Cytotoxic T cells (TC) that express the CD8+ T cells- also
called as cytotoxic T lymphocytes (CTLs)
 Initiation of T cell responses requires multiple
receptors on the T cells recognizing ligands on the
APCs:
 The TCR recognizes MHC associated peptide antigens,
CD4 and CD8 c0-receptors recognize the MHC
molecules strengthen the binding of T cells to APCs, and
receptors for co-stimulators recognize second signals
provided by the APCs
 The molecules other than antigen receptors that are
involved in T cell responses to antigens sometimes are
called Accessory molecules of T lymphocytes
 Humoral immunity is mediated by antibodies and is
the arm of adaptive immune response that functions
to neutralize and eliminate extracellular microbes and
microbial toxins
 More important in defending against microbes with
capsules rich in polysaccharides and lipids and against
polysaccharide and lipid toxins
 PLASMA B CELLS
 MEMORY B CELLS
 B1 CELLS
 B2 CELLS
 B cell activation
Antibody Forming Cells
Plasma Cells
 glycoprotein molecules that are produced by plasma
cells
 Major Ig in serum
 Crosses the placenta
 Macrophages, monocytes, PMNs and some
lymphocytes have Fc receptors for the Fc region of IgG.
 Opsonin
 Third most common serum Ig
 Good complement fixing Ig
 Good agglutinating Ig
 IgM exists as a monomer and lacks J chain
 2nd most common serum Ig.
 Major class of Ig in secretions - local (mucosal)
immunity.
 Does not fix complement, unless aggregated.
 IgA can binding to some cells - PMN's and some
lymphocytes.
 IgD is found in low levels in serum
 IgD is primarily found on B cell surfaces
 IgD on the surface of B cells has extra amino acids at
C-terminal end for anchoring to the membrane. It also
associates with the Ig-alpha and Ig-beta chains.
 IgD does not bind complement
 IgE is the least common serum
 Involved in allergic reactions - various
pharmacological mediators that result in allergic
symptoms.
 IgE also plays a role in parasitic helminth diseases.
Eosinophils have Fc receptors for IgE and binding of
eosinophils to IgE-coated helminths results in killing
of the parasite.
 IgE does not fix complement.
 Basic Immunology 3e By: Abbas and Lichtman
 Immunology 8e By: Roitt et. al.
 Carranza’s Clinical Periodontology 10e, 11e
Basics of Immunity

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Basics of Immunity

  • 1.
  • 2. Dr. Kritika Jangid MDS- Periodontics
  • 3.  IMMUNITY: Resistance to infectious disease  IMMUNE SYSTEM: Collection of cells, tissues and molecules that mediate resistance to infections  IMMUNE RESPONSE: Coordinated reactions of these cells and molecules to infectious microbes  IMMUNOLOGY: Study of immune system and its response to invading pathogens
  • 4. Role of the Immune System • Defence against infections • Recognises and responds to tissue grafts and newly introduced proteins • Defence against tumors Implications • Deficient immunity results in increased susceptibility to infections. Vaccination boosts immune defences and protects against infections • Immune responses are barriers to transplantation and gene therapy • Potential for immunotherapy for cancer
  • 5.
  • 6.
  • 7.
  • 8.
  • 9.  Also calledNaturalor Nativeimmunity.  Components present before the onset of infection.  Disease resistantmechanismsthatare not specificto a particularpathogen  Pathogensmust first breach barriers thatprotect host
  • 10.  Provides the first line defence right after exposure.  Most micro-organisms are readily cleared within a few days by innate immune system before adaptive immune system is activated
  • 11.  Componentsofinnateimmunityrecognizestructuresthatare sharedby variousclassesofmicrobesandare notpresentonthehostcells  Foreg: Phagocytesexpressreceptorsfor 1. Bacterial LPS(endotoxin)-On cellwallofmany bacterialspecies 2. Terminalmannoseresidues-Typicalofbacterialgylcoproteins 3. DsRNA-Foundinviruses 4. UnmethylatedCpGoligonucleotide-CommoninmicrobialDNA
  • 12. PATHOGEN ASSOCIATED MOLECULAR PATTERNS: The microbial molecules that are targets of innate immunity . Indicates that they are shared by microbes of the same type PATTERN RECOGNITION RECEPTORS: The receptors of innate immunity that recognize the shared structures.
  • 13.  Recognizes structures of microbes that are often essential for the survival and infectivity of these microbes.  Recognize molecules that are released from stressed or necrotic cells. (Damage associated molecular patterns)  Does not react against the host  Encoded in the germline; not produced by somatic recombination of genes  Two principal types of defences are: 1. Inflammation 2. Antiviral defence
  • 14.
  • 15.
  • 17.
  • 18.  2 types: Neutrophils and monocytes recruited to the site of infection where they recognize and ingest microbes for intracellular killing.  NEUTROPHILS (PMNs): MACROPHAGES
  • 19.  PMNs  Most abundant leukocytes (4000-10,000/µL)  Infection: 20,000µL of blood  1st cell type to respond to most infections (particularly bacterial and fungal)  Stimulated by cytokines (Colony stimulating factors) which act on the bone marrow stem cells to produce neutrophil precursors  Ingest microbes in the circulation and rapidly enter extravascular tissues at the site of infection where they ingest microbes and die after a few hours.
  • 20.  500-1000/µL of blood  Monocytes that enter extravascular tissues survive in these sites for long periods
  • 21.
  • 23.  Initiate T- cell responses  Important bridge between innate and adaptive immunity  Respond to microbes by producing cytokines that recruit leukocytes and initiate adaptive immune responses
  • 24.
  • 25.
  • 26.  γδ T cells: Present in epithelia  NK-T cells: Present in epithelia and lymphoid organs. (Recognize microbial lipids bound to a class 1 MHC- related molecule called CD1)  B-1 cells: Most of the antibodies are specific for carbohydrates that are present in the cell walls of many bacteria.  Marginal zone B cells: Responses that are characteristic of adaptive immunity (eg. Antibody production) and have features of innate immunity (eg. Rapid responses and limited diversity of antigen recognition)
  • 27.  Collection of circulating and membrane associated proteins.  Complement activation involves the sequential activation of proteolytic enzymes sometimes called an enzymatic cascade.  3 pathways:  Alternative pathway  Classical pathway  Lectin pathway
  • 28.
  • 29.  Secreted in small amounts in response to an external stimulus and bind to high affinity receptors on target cells
  • 30.
  • 31.  MBL: Plasma Mannose binding lectin:  Recognizes microbial carbohydrates and can coat microbes for phagocytosis or activate the complement cascade by lectin pathway.  Belongs to collectin family of proteins which shares homology to collagen and contain a carbohydrate binding (lectin) domain.  CRP: Binds to phosphoryl-choline on microbes and coats the microbes for phagocytosis.
  • 32.
  • 33.
  • 34.  Triggered only if microbes or their antigens pass through epithelial barriers and are delivered to the lymphoid organs where they can be recognized by lymphocytes.
  • 35.  Specialized to combat different types of infections:  Antibodies: Eliminate microbes in extracellular fluids  Activated T lymphocytes: Eliminate microbes living inside cells
  • 36.
  • 37.  Protection from an infectious disease agent that is mediated by B- and T- LYMPHOCYTES following exposure to specific antigen, and characterized by IMMUNOLOGIC MEMORY.
  • 38.  Active immunity: Immunity induced in an individual by infection or vaccination  Passive immunity: Immunity conferred in an individual by transfer of antibodies or lymphocytes from an actively immunized individuals
  • 39.
  • 40.
  • 41.  Antigen receptors of B lymphocytes (Membrane bound antibodies) can recognize a wide variety of macromolecules (proteins, polysaccharides, lipids and nucleic acids) as well as small chemicals in soluble or cell surface associated form.  Most T lymphocytes can see only peptide fragments of protein antigens, and can do so only when these peptides are presented by specialized peptide display molecules on host cells
  • 42.
  • 43.  Majority of T lymphocytes recognize peptide antigens that are bound to and displayed by major histocompatibility complex (MHC) molecules of antigen presenting cells (APCs)
  • 44.  Capture of protein antigens by antigen presenting cells (APCs)
  • 45.  Antigen Presentation to T cells  MHC (major histocompatibility complex) 1  all nucleated cells  MHC-encoded alpha (hvy) chain and beta 2 (lt) microglobulin  Polymorphic alpha 1 and alpha 2 domains for closed binding cleft  Conserved alpha 3 domains = binding site for CD8  Beta 2 interacts noncovalently with alpha 3
  • 46.  MHC-II = dimer of alpha and beta subunits  APCs  Both chains MHC encoded  Alpha 1 and beta 1 domains variable and form open binding cleft  Most of variability on beta chain  Alpha 2 and beta 2 folded into Ig domains  B2 Ig domain binds to CD4
  • 48.
  • 49.  T cells can be distinguished by their different antigen receptors  The definitive T cell linage marker is the T cell antigen receptor (TCR).  2 different types of TCR are:  A heterodimer of two disulfide- linked polypeptides (α and β)  A structurally similar heterodimer consisting of γ and δ polypeptides 90-95% of blood T cells are αβ T cells
  • 50.  There are 3 major subpopulations of αβ T cells  Helper T cells (TH) that expresses the CD4 marker (CD4+ T cells) and mainly ‘helps’ or ‘induces’ immune responses  TH1 cells secrete IL2 and IFN γ  TH2 cells produce IL4. IL5, IL6 and IL10  Regulatory T cells (Treg) that expresses the CD4+ T cells and regulate immune responses.  Cytotoxic T cells (TC) that express the CD8+ T cells- also called as cytotoxic T lymphocytes (CTLs)
  • 51.  Initiation of T cell responses requires multiple receptors on the T cells recognizing ligands on the APCs:  The TCR recognizes MHC associated peptide antigens, CD4 and CD8 c0-receptors recognize the MHC molecules strengthen the binding of T cells to APCs, and receptors for co-stimulators recognize second signals provided by the APCs  The molecules other than antigen receptors that are involved in T cell responses to antigens sometimes are called Accessory molecules of T lymphocytes
  • 52.
  • 53.  Humoral immunity is mediated by antibodies and is the arm of adaptive immune response that functions to neutralize and eliminate extracellular microbes and microbial toxins  More important in defending against microbes with capsules rich in polysaccharides and lipids and against polysaccharide and lipid toxins
  • 54.
  • 55.
  • 56.  PLASMA B CELLS  MEMORY B CELLS  B1 CELLS  B2 CELLS
  • 57.  B cell activation Antibody Forming Cells Plasma Cells
  • 58.  glycoprotein molecules that are produced by plasma cells
  • 59.
  • 60.  Major Ig in serum  Crosses the placenta  Macrophages, monocytes, PMNs and some lymphocytes have Fc receptors for the Fc region of IgG.  Opsonin
  • 61.
  • 62.  Third most common serum Ig  Good complement fixing Ig  Good agglutinating Ig  IgM exists as a monomer and lacks J chain
  • 63.
  • 64.  2nd most common serum Ig.  Major class of Ig in secretions - local (mucosal) immunity.  Does not fix complement, unless aggregated.  IgA can binding to some cells - PMN's and some lymphocytes.
  • 65.
  • 66.  IgD is found in low levels in serum  IgD is primarily found on B cell surfaces  IgD on the surface of B cells has extra amino acids at C-terminal end for anchoring to the membrane. It also associates with the Ig-alpha and Ig-beta chains.  IgD does not bind complement
  • 67.
  • 68.  IgE is the least common serum  Involved in allergic reactions - various pharmacological mediators that result in allergic symptoms.  IgE also plays a role in parasitic helminth diseases. Eosinophils have Fc receptors for IgE and binding of eosinophils to IgE-coated helminths results in killing of the parasite.  IgE does not fix complement.
  • 69.
  • 70.
  • 71.
  • 72.  Basic Immunology 3e By: Abbas and Lichtman  Immunology 8e By: Roitt et. al.  Carranza’s Clinical Periodontology 10e, 11e