GOOD MORNING
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BASICS OF IMMUNITY
Dr. Ramesh. K.S.V. Dr. L. Kavya Sri
Associate Professor II MDS
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CONTENTS:
• Introduction
• History
• Definition
• Components of immune system
• Classification
• Innate immunity
- Mechanisms of innate immunity
- Cells responsible for innate immunity
- Determinants of innate immunity
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• Adaptive immunity
- Mechanisms of acquired immunity
- Cells responsible for acquired immunity
- Major Histocompatibility Complex
- Humoral response
- Cell mediated response
• Conclusion
• References
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INTRODUCTION:
• Immunity is referred to the resistance exhibited by the host towards injury
caused by microorganisms and their products .
• It is normally beneficial, but sometimes, it is injurious.
• The immune system is a versatile defense system that has evolved to protect us
from invading pathogenic microorganisms with the help of enormous variety of
cells and molecules capable of specifically recognizing and eliminating foreign
invaders.
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HISTORY:
• Edward Jenner (1798) discovered - inoculation with cowpox crusts protected
humans from smallpox.
• E. Metchin Koff (1880’s) developed the first theory of cell mediated immunity.
• Louis Pasteur (1881) coined the term “vaccine”.
• Paul Ehrlich (1908) proposed the humoral theory of antibody formation.
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DEFINITION:
• The term immunity refers to the body’s specific protective response to an
invading foreign agent or organism.
• IMMUNITY:
A reaction to foreign substances, including microbes, as well as to
macromolecules such as proteins and polysaccharides, regardless of the
physiologic and pathologic consequences of this reaction.
- Roitt’s essential Immunology 10thed
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• IMMUNE SYSTEM:
It is a network designed for homeostasis of large molecules (oligomers) and
cells based on specific recognition process.
- Describes the cells, tissues and molecules involved in host defense
- Carranza 13th edition
• IMMUNOLOGY:
The study of the immune system, immunity, and immune responses.
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FUNCTIONS OF IMMUNE SYSTEM:
• Prevents pathogens from entering.
• Eliminates pathogens from body.
• Provide memory against future infections from same pathogen.
• Distinguishes self from non-self.
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COMPONENTS OF IMMUNE SYSTEM:
• CELLS
• TISSUES
• MOLECULES
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CELLS OF IMMUNE SYSTEM:
BLOOD
Neutrophil Eosinophil Basophil Monocyte
TISSUES
Macrophage Dendritic cell Mast cell
BLOOD AND
TISSUES
Lymphocyte
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TISSUES OF IMMUNE SYSTEM:
Lymphoid organs
Generative
Peripheral
(Central/
(SECONDARY)
PRIMARY)
Thymus Spleen
Bone marrow Lymph nodes
Lymphoid tissues
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LYMPHOID TISSUES:
• Skin associated lymphoid tissue (SALT)
• Mucosal associated lymphoid tissue
- Gut associated lymphoid tissue
- Bronchial associated lymphoid tissue
- M cell associated lymphoid tissue
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• Peyers patches – M cells
• Microfold (M) cells - specialized transporter of antigens
• Can bring in lymphocytes and monocytes
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MOLECULES OF IMMUNE SYSTEM:
• Antibodies
• Complement
• Cytokines
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ANTIBODIES:
Natural Antibodies
• Subsets of B cells that produce antibodies with only a
limited number of specificities without overt exposure to
foreign antigens, and these are called Natural antibodies.
• Most of them are mainly Ig M
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COMPLEMENT SYSTEM:
• Classical Pathway
• Alternate Pathway
• Lectin Pathway
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CYTOKINES:
• Low molecular weight polypeptides or proteins secreted by immune cells.
• Mediate and regulate immune response
• Example: – Chemokines, Interferons , Interleukins etc..,
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CLASSIFICATION OF IMMUNITY:
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INNATE IMMUNITY ADAPTIVE IMMUNITY
• Resistance to infection which individual • The resistance that an individual acquires
possesses by virtue of genetic and during life
constitutional make up
• Early defense response against microbes • Later defense response
• Immune response Non specific • Immune response is highly specific
• Innate response do not alter on repeated • Adaptive response improves with each
exposure successive encounter with same pathogen
• Memory effect absent • Memory effect present
• Not affected by immunization or prior • Is improved by immunization
contact
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NATURAL (INNATE) IMMUNITY:
The basis of natural defense mechanisms is the ability to distinguish between self and
non-self.
Such natural mechanisms include
• Physical and chemical barriers
• Skin and mucous membrane
• Antimicrobial substance in body secretions
• The action of WBCs
• Inflammatory response.
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CLASSIFICATIONS OF INNATE IMMUNITY:
Innate immunity may be considered at the level of :
- Species
- Race
- Individual
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FEATURES OF INNATE IMMUNITY:
• Act quickly
• Immediate direct response 0-4 hrs
• Rapid induction 4-96 hrs
• No clonal expansion of Ag specificity
• Does not generate immunologic memory
• Dependent upon germ line encoded receptors recognizing structures
common to many pathogens(PAMP)
• High discrimination of host and pathogen
• Failure ==> adaptive immune response
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MECHANISMS OF INNATE IMMUNITY:
Mechanisms
Anatomic Physiologic Inflammatory Cellular Humoral
barriers barriers barriers sentinels mechanisms
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ANATOMIC BARRIERS:
Skin
• mechanical barrier prevents entry of microbes.
• Keratin, Sebaceous glands
Mucous membrane
• normal flora compete with microbes for attachment sites and nutrition.
• mucus entraps foreign microorganisms.
• cilia propels microorganisms out of body.
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EPITHELIAL ANTIMICROBIAL PEPTIDES:
Have capacity to rapidly inactivate infectious agents by disrupting the integrity
of the microbial membranes.
Defensins:
• α defensins (HNP 1-2-3)
• β defensins (hBD1, 2, 3, 4)
Cathelicidins - In humans, only one cathelicidin, LL-37 has been found
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PHYSIOLOGIC BARRIERS:
Temperature :
• Normal body temperature inhibits the growth of some organisms.
• Fever inhibits the growth of some organisms.
• Low pH - acidity of stomach contents kills most ingested microorganisms.
Chemical mediators :
• Lysozyme kills the bacterial cell wall.
• Complement lyses microorganisms or facilitates phagocytosis.
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INFLAMMATORY BARRIERS:
• Tissue damage and infection induce
leakage of vascular fluid, containing
serum proteins with antibacterial
activity, and influx of phagocytic cells
into the affected area.
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CELLULAR SENTINELS:
• Phagocytes
• Antigen presenting cells
• Natural Killer cells
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PHAGOCYTES:
• Macrocytes: Macrophages
• Microphages: Polymorphonuclear cells
• Mast cells, Eosinophils, Basophils
• Primary function – to identify, ingest and
destroy microbes
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MONOCYTE-MACROPHAGE SYSTEM:
• Polymorphonuclear leucocytes
- Neutrophils
• Mononuclear cells (macrophages)
- Monocytes in blood
- Histocytes in connective tissues
- Fixed reticuloendothelial cells in liver, spleen, lymph nodes, bone marrow.
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ANTIGEN PRESENTING CELLS:
• Dermal dendrocytes (histiocytes)
• Collagen associated dendritic cells of myeloid origin.
• Function - express MHC II molecules.
• Show receptor for C3a - participate in inflammation
• Produce MMPs
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PERIPHERAL DENDROCYTES :
• Also called Langerhans cells
• Suprabasillar portion of squamous epithelium
• Function - ingest antigen and present it to the lymph nodes
• Express high leves of MHC class II molecules, CD1, and cell adhesion molecules
ICAM1, LFA3 etc
• Macrophages
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NATURAL KILLER CELLS:
Large, granular lymphocytes - 10% of blood lymphocytes
FUNCTIONS:
• Recognize and kill viral infected cells and tumor cells
• Release of interferon and other cytokines like IL12 and
GM-CSF
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PATHOGEN ASSOCIATED MOLECULAR PATTERNS
(PAMP’S) :
• Epitopes expressed by pathogens
• Example:- bacterial lipopolysaccharide, flagella, lipotechoic acid, mannose rich
glycans.
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DAMAGE ASSOCIATED MOLECULAR PATTERNS
(DAMP’S) :
• Endogenous molecules that are produced by or
released from damaged and dying cells.
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PATTERN RECOGNITION RECEPTORS
(PRR’S) :
• Germline encoded host receptors that PRR’s
recognize molecular patterns on pathogens.
• Recognize a common set of antigen mottifs.
Membrane
• Expressed mainly by cells of the innate bound Cytoplasmic
immune system such as dendritic cells,
macrophages, monocytes, neutrophils, as
well as by epithelial cells. TLR’s NLR’s
CLR’s RLR’s
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TOLL LIKE RECEPTORS :
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TAK1
MKK/p38
Stabilize cytokine
NUCLEUS
mRNA– amplify
cytokine
synthesis
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TLR’s IN THE PERIODONTIUM :
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B- CELL MEDIATED DEFENSE MECHANISMS :
• Lysozyme
• Natural antibodies
• Neutral Proteases - Cathepsin G
• Antimicrobial peptides - Defensins, Cathelicidins, Pentraxins, Ficolins
• Complement System
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DETERMINANTS OF INNATE IMMUNITY :
• Species and strains
• Individual differences
• Age
• Hormonal influences
• Nutritional factors
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INNATE IMMUNITY AND PERIODONTITIS :
BACTERIAL HOST
CHALLENGE RESPONSE
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ADAPTIVE IMMUNITY :
• Also known as Acquired/specific immunity.
• The resistance that an individual acquires during life is called acquired immunity.
• React to specific antigenic challenges.
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PROPERTIES OF ADAPTIVE IMMUNITY :
• Antigenic specificity
• Diversity
• Immunologic memory
• Self/non self recognition
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MECHANISM OF ACQUIRED IMMUNE RESPONSE :
• Recognition of the antigen by specific lymphocytes
• Activation of these specific lymphocytes
• Proliferation and differentiation into effector cells
• The effector cells eliminate the antigen and return of homeostasis & development of
memory cells
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TYPES OF ADAPTIVE IMMUNITY :
Cell
mediate Against Humoral
d Against extra
intracellular
cellular
pathogens &
pathogens
Tumour cells
Mediated by Mediated by
T cells B cells
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COMPONENTS OF ADAPTIVE IMMUNITY
• B Lymphocytes
• T Lymphocytes
• Antigen Presenting Cells (APCs)
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LYMPHOCYTES :
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B LYMPHOCYTES :
• Only cells capable of producing antibodies.
• Produced in bone marrow.
• Recognize extracellular antigens and
differentiate into antibody - secreting cells,
thus functioning as a mediator of humoral
immunity.
• Types of Immunoglobulins - IgG, IgA, IgM, IgE,
IgD
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TYPES OF IMMUNOGLOBULIN :
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T LYMPHOCYTES :
• Non antibody-producing lymphocytes.
• Produced in the bone marrow but sensitized in the
thymus and constitute the basis of cell-mediated
immunity.
• T cells have a restricted specificity for antigens; they
recognize only peptide antigens attached to host
proteins that are encoded by genes in the MHC and
that are expressed on the surface of other cells.
• T cells include 2 functionally distinct populations,
helper T-cells and cytolytic or cytotoxic T- cells
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T HELPER CELL CYTOTOXIC T CELL
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ANTIGEN PRESENTING CELLS :
• The initiation and development
of adaptive immune responses
requires that antigens be
captured and displayed to
specific lymphocytes.
- Dendritic cells
- Langerhan cells
- Macrophages
- B cell
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RECOGNITION OF ANTIGENS :
• Antigenic determinants or Epitopes.
• Epitopes are the immunologically active regions on a complex antigen, the
regions that actually bind to B cell or T cell receptors.
• Cell membrane molecules responsible for antigen recognition are :
- membrane bound antibodies on B cells
- T cell receptors
- class I MHC molecules
- class II MHC molecules
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ANTIGEN PROCESSING AND ANTIGEN
PRESENTATION :
• In order for an antigen to be recognized by a T cell,
proteins must be degraded into small peptides that
form complexes with class I or class II MHC
molecules.
• The process of conversion of proteins into MHC
associated peptide fragments is called Antigen
processing.
• The MHC peptide complex travels to the cell surface
and displays antigen to T cells. This process is known
as Antigen presentation.
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MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) :
• MHC molecules are membrane proteins on APCs that display peptide antigens for
recognition by T lymphocytes.
• Large genetic complex with multiple loci.
• Two major classes of membrane bound glycoproteins :
- class I MHC molecules (Tc cells)
- class II MHC molecules (Th cells)
- class III MHC molecules
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EXOGENOUS ANTIGEN – MHC II – CD4 PATHWAY :
• Exogenous antigen is produced outside the host cell.
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ENDOGENOUS ANTIGEN – MHC I – CD8 PATHWAY :
• Endogenous antigen is produced within the cell itself ( eg - virus infected cell )
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FEATURES OF PATHWAYS OF ANTIGEN PROCESSING :
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ACTIVATION AND PROLIFERATION OF T HELPER
CELLS:
• The generation of both humoral and cell mediated immune responses depends on the
activation of TH cells.
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ABNORMAL IMMUNE REACTIONS:
• Antibody mediated
• Cell-mediated
• Mixed antibody
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ANTIBODY MEDIATED REACTIONS:
• These occur within minutes of exposure to an allergen (antigen).
• The most common manifestations of this type of allergic reaction include: food
allergies, childhood eczema, hay fever, extrinsic asthma.
• In these conditions the released chemicals act locally, causing different effects
that depend on the site.
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ACUTE SYSTEMIC ANAPHYLAXIS (ANAPHYLACTIC
SHOCK):
• It is caused by the entry of an allergen into the blood e.g. snake venom, injectable
penicillin.
• There are profound effects throughout the body, including generalized vasodilatation,
leading to severe hypotension and contraction of smooth muscle in the respiratory
tract, causing acute breathing difficulties.
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OTHER ANTIBODY MEDIATED REACTIONS:
• Reaction of antibodies with cells that have antigens on their cytoplasmic
membranes may cause the cells to rupture.
• Abnormal reactions to antibody/antibody complexes sometimes result in them
adhering to the endothelium of blood vessels causing inflammation and local
damage.
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CELL MEDIATED REACTIONS:
The antigen include:
• Intracellular microbes, e.g. those causing tuberculosis, measles, mumps.
• Some vaccines, e.g. against smallpox.
• Some metals and compounds that combine with protein in the skin and cause allergic
contact dermatitis.
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MIXED REACTIONS:
Autoimmune diseases:
• Tissue damage and signs of disease as the body fails to recognize its own tissues.
Destruction of the body’s own cells may be either humoral or cell-mediated.
- Thyroid- Hashimoto’s thyroiditis
- Stomach- Addisonian pernicious anemia
- Cortex of the adrenal gland- Addison’s disease.
- Pancreas-type I diabetes mellitus
• Organ transplantation and rejection
• GVHD
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CONCLUSION:
• Immunity is one of the most complex and effective system developed by the
human body.
• It has been continuously evolving itself along with the evolution of
microorganisms and it has been effective for most of the infections. Some
infections such as HIV poses challenge to the immune system and hence future
research towards these infections is warranted.
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• Newman MG, Takei HH, Klokkevold PR, Carranza FA. Carranza’s Clinical
Periodontology. 14th ed. Saunders, Elsevier Inc.
• Newman MG, Takei HH, Klokkevold PR, Carranza FA. Carranza’s Clinical
Periodontology. 13th ed. Saunders, Elsevier Inc.
• Clinical periodontology & implant dentistry. Jan Lindhe 5th ed.
• Abbas AK, Lichtman AH. Cellular & Molecular Immunology 6th ed.
• Delves P, Martin S Burton D, Roitt I. Roitt’s Essential Immunology 10th ed.
• Guyton AC, Hall JE. Textbook of Medical Physiology. Eleventh edition. Philadelphia;
Saunder (Elsevier) : 2006.
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• Ananthamarayan R, Paniker CKJ. Textbook of Microbiology. 6th ed. Hydrabad,
Orient Longman 2000.
• Hajishengallis G. Immunomicrobial pathogenesis of periodontitis: keystones,
pathobionts, and host response. Trends Immunol. 2014 Jan;35(1):3-11. doi:
10.1016/[Link].2013.09.001. Epub 2013 Oct 23. PMID: 24269668; PMCID:
PMC3947349.
• Krauss Jl, Potempa J, Lambris Jd, Hajishengallis G. Complementary Tolls in the
periodontium: how periodontal bacteria modify complement and Toll-like
receptor responses to prevail in the host. Periodontol 2000, 2010; 52: 141–162
• Mahanonda R, Pichyangkul S. Toll‐like receptors and their role in periodontal
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THANK YOU
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