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Dr. Kritika Jangid
MDS- Periodontics
BASICS OF IMMUNITY
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
TERMS ASSOCIATED
IMPORTANCE OF IMMUNE SYSTEM
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
OVERVIEW OF IMMUNE SYSTEM
INNATE IMMUNITY
Also called Natural or Native immunity.
Components present before the onset of infection.
Disease resistant mechanisms that are not specific to a particular pathogen
Pathogens must first breach barriers that protect host
INNATE IMMUNITY
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
INNATE IMMUNITY
Components of innate immunity recognize structures that are shared by various classes of microbes and are not present on the host cells
For eg: Phagocytes express receptors for1. Bacterial LPS (endotoxin)- On cell wall of
many bacterial species2. Terminal mannose residues- Typical of
bacterial gylcoproteins3. Ds RNA- Found in viruses4. Unmethylated CpG oligonucleotide- Common
in microbial DNA
RECOGNITION OF MICROBES
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 hostEncoded in the germline; not produced by
somatic recombination of genes
Two principal types of defences are:1. Inflammation2. Antiviral defence
...contd
CELLULAR RECEPTORS- LOCATION
Specificity and
functions of TLRs
EPITHLIAL BARRIERS
PHAGOCYTES
DENDRITIC
CELLS
NK CELLSOTHER
LYMPHOCYTES
COMPLEMENT
CYTOKINES
PLASMA PROTEI
NS
COMPONENTS OF
INNATE IMMUNITY
EPITHELIAL BARRIERS
2 types: Neutrophils and monocytes recruited to the site of infection where they recognize and ingest microbes for intracellular killing.
NEUTROPHILS (PMNs): MACROPHAGES
PHAGOCYTES
PMNsMost abundant leukocytes (4000-10,000/µL)Infection: 20,000µL of blood1st 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.
NEUTROPHILS
MONOCYTES500-1000/µL of bloodMonocytes that enter extravascular tissues
survive in these sites for long periods
Sequence of events in the migration of blood leukocytes to the site of infection
Phagocytosis and
intracellular killing
of microbes
Initiate T- cell responsesImportant bridge
between innate and adaptive immunity
Respond to microbes by producing cytokines that recruit leukocytes and initiate adaptive immune responses
DENDRITIC CELLS
NK cells
γδ T cells: Present in epitheliaNK-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)
OTHER CLASSES OF LYMPHOCYTES
Collection of circulating and membrane associated proteins.
Complement activation involves the sequential activation of proteolytic enzymes sometimes called an enzymatic cascade.
3 pathways:Alternative pathwayClassical pathwayLectin pathway
COMPLEMENT SYSTEM
COMPLEMENT
Pathways of complement activation
Secreted in small amounts in response to an external stimulus and bind to high affinity receptors on target cells
CYTOKINES OF INNATE IMMUNITY
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.
OTHER PLASMA PROTEINS OF INNATE IMMUNITY
ROLE OF INNATE
IMMUNITY IN
STIMULATING ADAPTIVE
IMMUNE RESPONSES
ADAPTIVE IMMUNITY
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
PROPERTIES
OF ADAPTIVE IMMUNE
RESPONSES
TYPES OF
ADAPTIVE IMMUNIT
Y
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
Antigen capture and Presentation to lymphocytes
CELL MEDIATED IMMUNE RESPONSES
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 cellsMHC-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 subunitsAPCs Both chains MHC
encodedAlpha 1 and beta 1
domains variable and form open binding cleftMost of variability on
beta chainAlpha 2 and beta 2
folded into Ig domainsB2 Ig domain binds
to CD4
FEATURES OF PEPTIDE BINDING TO MHC MOLECULES
Steps in activation of T lymphocytes
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
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 responsesTH1 cells secrete IL2 and IFN γTH2 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
Antigen recognition and Co-stimulation
HUMORAL IMMUNE RESPONSES
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
Phases of humoral immune response
Subset of B cells
PLASMA B CELLSMEMORY B CELLSB1 CELLSB2 CELLS
B Cell Subsets
B cell activation
Antibody Forming Cells
Plasma Cells
B cells differentiate into Antibody Secreting Plasma Cells
glycoprotein molecules that are produced by plasma cells
Immunoglobulins
Major Ig in serumCrosses the placenta
Macrophages, monocytes, PMNs and some lymphocytes have Fc receptors for the Fc region of IgG.
Opsonin
IgG
IgM
Third most common serum IgGood complement fixing IgGood agglutinating IgIgM exists as a monomer and lacks J chain
IgA
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
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
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.
Interactions of TH cells and B cells in lymphoid tissues
Anatomy of humoral immune responses
Antibody Feedback
Basic Immunology 3e By: Abbas and Lichtman
Immunology 8e By: Roitt et. al.Carranza’s Clinical Periodontology 10e, 11e
REFERENCES