NATIONAL DENTAL COLLEGE AND HOSPITAL

DERA BASSI

DEPARTMENT OF PEDODONTICS AND PREVENTIVE DENTISTRY

SEMINAR ON IMMUNITY

SUBMITTED BY: PARVEEN BATHLA MDS 2st PROF.

CONTENTS

IMMUNITY DEFINITION AND CLASSIFICATION INNATE IMMUNITY ADAPTIVE IMMUNITY Active immunity Passive immunity ANTIGEN ANTIBODY/IMMUNOGLOBLIN ARCHITECTURE OF IMMUNE SYSTEM CELLS OF IMMUNE SYSTEM CYTOKINES MAJOR HISTOCOMPATIBILITY COMPLEX IMMUNE RESPONSE

Immunity
Resistance of host to pathogens and their toxic products. The immune system produces antibodies or cells that can deactivate pathogens.

Immunity classified as 1) Innate immunity 2) Acquired immunity Innate immunity a) non specific b) specific species racial individual

Innate immunity may be specific against a particular organism or non specific. Species immunity : Total or relative immunity shown by all members by all members of a species. Racial immunity : Within a species, there may be marked racial differences in resistance to infection. Individual immunity : Different individuals in a race differ in their resistance to microbial infections. Factors influencing innate immunity : 1) Age : very young and very old are more suspectible to infectious diseases than persons in other old age group. 2) Hormonal influences : endocrine disorders diabetes mellitus , hypothyroidism and adrenal dysfunction more suspectible. 3) Nutritional factors: both antibody mediated and cell mediated immunity lowered in malnutrition.

Mechanism of innate immunity :

Mechanical barriers and surface secretions Skin physical barrier to microbes. Keratin resistant to most bacterial enzymes & toxins. Mucosa physical barrier & produces a variety of protective chemicals. Gastric mucosa

acidic & produces proteolytic enzymes.

Saliva contain Antimicrobial enzymes that kill bacteria.

Lysozyme Salivary lactoperoxidase Lactoferrin

Immunoglobulin A Antibacterial compounds -thiocyanate, hydrogen peroxide, and secretory immunoglobulin A

Mucous traps bacteria & moves them away from epithelial surface.

Humoral defence mechanism Lysozyme Basic polypeptide Complement Interferon

Complement system 1890 Jules Bordet, Paul Ehrlich Heat-labile Augments the opsonization and killing of bacteria by antibodies (the major effector of the humoral branch of the immune system). Evolved as part of the innate immune system. The complement system comprises a group of serum proteins,many of which exist in inactive forms. Complement activation occurs by the classical, alternative, or lectin pathways, each of which is initiated differently. The three pathways converge in a common sequence of events that leads to generation of a molecular complexthat causes cell lysis. The classical pathway is initiated by antibody binding to acell target; reactions of IgM and certain IgG subclassesactivate this pathway. Activation of the alternative and lectin pathways is antibody independent. These pathways are initiated by reaction of complement proteins with surface molecules of microorganisms. In addition to its key role in cell lysis, the complement system mediates opsonization of bacteria, activation of inflammation,and clearance of immune complexes. Interactions of complement proteins and protein fragments with receptors on cells of the immune system control bothinnate and acquired immune responses. Complement activation pathways Classical pathway: requires antibodies. Antibodies bind to target (antigen). Complement protein C1 binds to the antibody-antigen complex (complement fixation). Alternative pathway: complement factors interact with microorganism glycocalyx. Both pathways lead to a cascade of protein activation, leading to activation of C3. C3 is the start of the; Final Common Pathway . C3 cleaves to form C3a & C3b. C3a (& C5a) enhance inflammation by increasing histamine release, increasing vascular permeability & stimulating chemotaxis. C3b coats bacterial membrane supplying adhesion points (opsonization)

C3b initiates the cascade forming the membrane attack complex (MAC). The MAC forms a hole in the cell membrane & enhances Ca2+ influx cell lysis . Complement also helps rid the body of antigen-antibody complexes. Complement proteins are the culprits that cause blood vessels to become dilated and leaky, causing redness and swelling during an inflammatory response. Complement proteins circulate in the blood in an inactive form. The so-called "complement cascade" is set off when the first complement molecule, C1, encounters antibody bound to antigen in an antigen-antibody complex. Each of the complement proteins performs its specialized job, acting, in turn, on the molecule next in line. The end product is a cylinder that punctures the cell membrane and, by allowing fluids and molecules to flow in and out, dooms the target cell.

Cellular Mechanism of Defence Phagocytes Microphages (PMNL) Macrophages Natural killer cells Eosinophil

Macrophages: derived from monocytes Free Macrophages: roam through tissues. Fixed Macrophages: Kupffer cells (liver) & microglia (brain) . Ingest cellular debris, foreign material, bacteria, fungi.

 Neutrophils: ingest pathogens Eosinophils: weakly phagocytic of pathogens. Attack parasites (degranulation). Mast Cells: phagocytic of various bacteria. Phagocytic mechanisms: Adherence: cell binds to invader Aided by opsonization (a chemical process that enhances binding via complement & antibodies).

Ingestion: formation of phagolysosomes . Respiratory Bursts: merge phagosome with lysosome & flood phagolysosome with free radicals (macrophage). Defensins: proteins that crystallize out of solution & pierce pathogen membranes (neutrophils)

Natural Killer Cells: Small population of large granular lymphocytes. Non specific for non-self. Not phagocytic: attack is by release of perforins that perforate the target cell plasma membrane. Shortly after perforation the target nucleus disintegrates. Release chemicals that enhance the inflammatory response. cardinal signs of inflammation Redness Heat Swelling Pain (functional impairment Rigor) Inflammatory response: signs are associated with vasodilation & increased vascular permeability.

 Dilation: redness, heat Permeability: edema, (increased pressure) pain Pain also associated with bacterial toxins & some mediators (kinins, PGs) Mechanisms causing vasodilation & vascular permeability Injured cells release inflammatory mediators Histamines Kinins Prostaglandins Complement Cytokines (also activated by receptors on macrophages in response to microbial glycocalyx).

Edema Dilutes harmful substances. Provides nutrients (& O2) for repair. Enhances entry of clotting protein. Epithelial breaches also stimulate b-defensin release from epithelial cells.

Adaptive: responds to specific foreign substances.

Innate & adaptive mechanisms work together.

Active immunity Natural - clinical infection subclinical infection Artificial - vaccination live and killed vaccine Artificial active immunity Bacterial vaccines Live - BCG Killed-TAB Bacterial products Tetanus toxoid Diptheria toxoid Viral vaccines Live-sabin,MMR Killed -salk Passive immunity Natural - placenta, breast milk Artificial - immune serum ,immune cells

Active immunity
Produced actively by hosts immune system. Induced by infection/contact with antigen. Long lasting. Immunity effective only after a lag period. Negative phase. Not applicable in immunodeficient.

Passive immunity
Received passively by host. Conferred by administration of antibodies. Transient. Effective immediately. No negative phase. Applicable.

Local immunity Immunity at a particular site, the site of invasion and multiplication of pathogen. Conferred by secretory IgA ab produced locally by plasma cells.

Herd immunity Overall level of immunity in a community.

ANTIGEN A substance, which is recognized by immune system and induces the immune response. It comes from environment (exoantigen), or from individuals own structures (autoantigen).

Hapten Incomplete Ag. Reactive, but not immunogenic. Provokes no response by itself . Bind to other proteins immunogenic.

Epitope

The portion of antigen, which is recognized by the immune system (lymphocytes, Ig). Some epitopes are on the antigens surface, others are internal. Epitopes may be linear (amino acid sequence important), conformational (space conformation important) Cross-reactive antigens share one or more identical or similar epitopes .

Factors affecting antigenicity Molecular size of antigens Molecules < 5 kDa are not able to induce immune response, the optimal molecular size for mmune response induction is approximately 40 kDa.

Chemical nature Proteins and polysaccharide most antigenic.

Degree of foreignness An antigen must be foreign or alien to the host. Autologous are found within the same individual (e.g. a skin graft from an individuals thigh to his chest); that is, they are not foreign. Syngeneic are found in genetically identical individuals (e.g. identical twins); that is, they are not foreign. Allogeneic (alloantigens) are found in genetically dissimilar members of the same species (e.g. a kidney transplant from mother to daughter); it is foreign. Xenogeneic (heterogeneic) are found in different species (e.g. a transplant of monkey kidneys to human); it is foreign.

Sequestered antigens The antigens, which are normally hidden from the immune system and thus the immune system cannot identify them (e.g. lens, testes). However, if these allergens are released (injury), the immune system could response to them.

ANTIBODY (Ab)

Described by Von Behring 1890. Gerald M. Edelman and Rodney Porter 1972 researchers structure and chemical nature of antibodies.

Glycoprotein molecules produced by plasma cells and can combine with the corresponding Ag specifically . Ig refers to all globulins that possess the activity of Ab or show a similar structure to Ab. Therefore, All Abs are Igs, but not all Igs possess the functions of Abs. An Antibody / immunoglobulin , is a large Y shaped protein produced in response to antigenic stimulation. Each tip of the "Y" of an antibody contains a paratope (a structure analogous to a lock) that is specific for one particular epitope (similarly analogous to a key) on an antigen.

Function of immunoglobulin : Specifically recognize and bind to a unique structural entity on microbial toxins (antigens). Perform a common biological function (effector function) after combining with the antigen e.g., binding to Fc receptors on immune cells.

BASIC STRUCTURE OF IMMUNOGLOBULINS

All Igs have the same basic structural units of 2 light chains and 2 heavy chains. All Igs have the same basic structural units of 2 light chains and 2 heavy chains. The heavy and light chains are joined together by interchain disulphide bonds and noncovalent interactions. L chain - and . The hinge region is the area of the Ig where the arms of the Abs form a Y,it is a flexible region. Light and heavy chains are composed of both a variable and constant region designated VL and CL (light chains) and VH and CH1 ,CH2 and CH3 (heavy chains).

Complementarity determining regions (CDRs). The variable regions of an Ig are also further divided into hypervariable or complementarity determining regions (CDRs). Hot spots . L chains have three CDRs and the H chains have four, although only three of the four have been associated with antibody activity.

IMMUNOGLOBIULINS TYPES AND CLASSES. Based on differences in the amino acid sequences in the constant region of the heavy chains there are five classes of Igs.

IgG- gamma heavy chain IgM-miu heavy chain IgA- alpha heavy chain IgD- delta heavy chain IgE- epsilon heavy chain.

IgG Most abundant 75 % IgM IgA Serum IgA is monomeric, but IgA found in secretions is a dimer having a J chain. Secretory IgA also contains a protein called secretory piece or T- piece, this is made in epithelial cells and added to the IgA as it passes into secretions helping the IgA to move across mucosa without degradation in secretions. the second most abundant Ig in serum. the major class of Ig in secretions- tears, saliva, colostrums, mucus,and is important in mucosal immunity. normally do not fix complement. It normally exists as a pen tamer in serum but can also occur as a monomer. It has an extra domain on the mui chain (CH4) and another protein covalently bound via S-S . called J-chain. This chain helps it to polymerize to the pentamer form. clumping microorganisms for eventual elimination from the body. first Ig to be made by fetus in most species . the 3rd most abundant Ig in serum. good complement fixing Ig . IgG1 - 59% IgG2 - 30% IgG3 - 8% IgG4 - 3% major Ig in serum as well as extravascular spaces. Only Ig that crosses the placenta. fixes complement . enhances phagocytosis.

IgD

found in low levels in serum.

 IgE

found primarily on B cells surface and serves as a receptor for Ag. does not fix complement.

the least common serum Ig, but it binds very tightly to Fc receptors on basophils and mast cells even before interacting with Ags. involved in allergic reactions because it binds to basophils and mast cells.

Architecture of immune system lymphoreticular system

Primary lymphoid organs: Secondary lymphoid organs:
lymph nodes Spleen Mucosa associated lymphoid tissues

Thymus Bone marrow

Bone marrow Site for haemopoiesis and initial differentiation of stem cells.

Thymus Bilobed, located in thoracic cavity and extending into the neck. Cortex and medulla. Major site of lymphocyte proliferation.

DiGeorge syndrome Genetic disorder caused by the deletion of a small section of chromosome 22. Results in a midline congenital defect including thymic aplasia, or congenital deficiency of a thymus. Lymph node Small bean shaped organs. Act as Filters.

Humans have approximately 500-600 lymph nodes distributed throughout the body, with clusters found in the underarms, groin, neck, chest, and abdomen. Outer cortex and inner medulla. Cortex consist of lymphoid follicles and medulla consists of cords of lymphocyte. T cell concentrate in paracortex, b cell in and around germinal centre and plasma cell in medulla. Immune cells and foreign particles enter the lymph nodes via incoming lymphatic vessels or the lymph nodes' tiny blood vessels. All lymphocytes exit lymph nodes through outgoing lymphatic vessels. Once in the bloodstream, they are transported to tissues throughout the body. They patrol everywhere for foreign antigens, then gradually drift back into the lymphatic system to begin the cycle all over again. Lymphoid follicles and medullary cords contain B Lymphocyte while paracortex contains T lymphocytes.

Spleen The spleen, in healthy adult humans, is approximately 11 centimetres (4.3 in) in length. It usually weighs between 150 grams Large, encapsulated, lymphoid organ. White pulp of cortex and red pulp of medulla. it acts primarily as a blood filter. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock and also recycles iron. As a part of the mononuclear phagocyte system it metabolizes hemoglobin removed from senescent erythrocytes. The spleen synthesizes antibodies in its white pulp and removes antibody-coated bacteria and antibody-coated blood cells by way of blood and lymph node circulation. The spleen is a center of activity of the reticuloendothelial system and can be considered analogous to a large lymph node, as its absence causes a predisposition to infections.

Cells of immune system

TYPE
NEUTROPHIL EOSINOPHIL

DIAGRAM

APPROX %
62 2.3

DIAMETER(um)
10-12 10-12

BASOPHIL LYMPHOCYTE

.4 32

12-15 7-8 12-15

 Monocyte Macrophage
NK cells

5.3%

12-20 60-80

Plasma cells Dendritic

B cells can be distinguished from other lymphocytes, such as T cells and natural killer cells(NK cells), by the presence of a protein on the B cell's outer surface known as a B cell receptor (BCR). This specialized receptor protein allows a B cell to bind to a specific antigen. The principal functions of B cells are to make antibodies against antigens to perform the role of antigen-presenting cells (APCs), and to develop into memory B cells after activation by antigen interaction.

B lymphocyte

Humoral immunity.
B cell receptor (BCR) present on cell surface.

T lymphocytes
Cell-mediated immunity.
T-cell receptor (TCR) present on the cell surface. no antigen presenting properties

B cells work chiefly by secreting soluble substances known as antibodies. They mill around a lymph node, waiting for a macrophage to bring an antigen or for an invader such as a bacteria to arrive. When an antigen-specific antibody on a B cell matches up with an antigen, a remarkable transformation occurs.

The antigen binds to the antibody receptor, the B cell engulfs it, and, after a special helper T cell joins the action, the B cell becomes a large plasma cell factory that produces identical copies of specific antibody molecules at an astonishing pace--up to 10 million copies an hour.

Activation of B Cells to Make Antibody The B cell uses its antibody-receptor to bind a matching antigen, which it then engulfs and processes. This triggers the B cell to become a large plasma cell producing millions of copies of the same specific antibody. These antibodies then circulate in the bloodstream in search of more matching antigens. B cell antibodies cannot themselves kill an invading organism, but they can use their antibodies to mark invaders for destruction by other immune cells and by complement.

Functions of B cells : make antibodies against antigens. perform the role of antigen-presenting cells (APCs).

develop into memory B cells after activation by antigen interaction T cells or T lymphocytes are a type of lymphocytes that play a central role in cell-mediated immunity.

T cells subsets
Regulator cells Helper T cells
CD4+ T cells Help in ag specific activation of B cell and effector T cells.

Effectors cells Delayed type hypersensitivity T cells

Delayed hypersensitivity and cell mediated immune response.

Cytotoxic T cells

Suppressor T cells
Suppress expression of immune response by other lymphocytes.

CD8+ T cells
destroy virally infected cells ,tumor cells, and are also implicated in transplant rejection.

They can be distinguished from other lymphocytes, such as cells and natural killer cells (NK cells), by the presence of a T-cell receptor (TCR) on the cell surface. They do not have antigen-presenting properties (but rather, requiring B cells or NK cells for its antigen-presenting property). They are called T cells because they mature in the thymus. There are several subsets of T cells, each with a distinct function. T cells contribute to your immune defenses in two major ways. Some help regulate the complex workings of the overall immune response, while others are cytotoxic and directly contact infected cells and destroy them. Chief among the regulatory T cells are helper T cells. They are needed to activate many immune cells, including B cells and other T cells.

Function of T lymphocyte regulate the complex workings of the overall immune response . directly contact infected cells and destroy them. activate many immune cells, including B cells responsible for the rejection of tissue and organ grafts. Cytotoxic T cells (sometimes called killer T cells) help rid your body of cells that have been infected by viruses as well as cells that have been transformed by cancer but have not yet adapted to evade the immune detection system. They are also responsible for the rejection of tissue and organ graft.

Activation of T Cells: Helper Helper T cells only recognize antigen in the grasp of Class II MHC markers. An antigen-presenting cell--such as a macrophage or a dendritic cell--breaks down the antigen it devours, then it places small pieces (peptides) on its surface along with a Class II MHC marker. By exhibiting its catch in this way, antigen-presenting cells enable specific receptors on helper T cells to bind the antigen and confirm (via CD4 protein) that an invasion has occurred. After binding, a resting helper T cell quickly becomes an activated helper T.

Activation of T Cells: Cytotoxic Killer T cells only recognize antigen in the grasp of Class I MHC markers. Here a resting cytotoxic T cell recognizes virus fragments, which are displayed by a macrophage in combination with a Class I MHC marker. A receptor on a circulating, resting cytotoxic T cell (and CD8 protein) recognizes the antigen-protein complex and binds to it. The binding process and an activated helper T cell activate the cytotoxic T cell. Because the surfaces of other infected cells bear the same virus fragments in combination with Class I MHC markers, the activated cytotoxic T cells can quickly recognize, attack, and destroy the diseased cell

Cytokines Cytokines are diverse and potent chemical messengers secreted by the cells of immune system. They are the chief communication signals of T cells. Cytokines include interleukins, growth factors, and interferons. Lymphocytes, including both T cells and B cells, secrete cytokines called lymphokines, while the cytokines of monocytes and macrophages are dubbed monokines. Many of these cytokines are also known as interleukins because they serve as a messenger between white cells, or leukocytes. Interferons are naturally occurring cytokines that may boost the immune system's ability to recognize cancer as a foreign invader. Binding to specific receptors on target cells, cytokines recruit many other cells and substances to the field of action. Cytokines encourage cell growth, promote cell activation, direct cellular traffic, and destroy target cells--including cancer cells. When cytokines attract specific cell types to an area, they are called chemokines. These are released at the site of injury or infection and call other immune cells to the region to help repair damage and defend against infection.

Major histocompatibility complex MHC -cell surface glycoproteins associated with self recognition. In humans, MHC is also called human leukocyte antigen (HLA). HLA-A, HLA-B, HLA-C, HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLADRA, and HLA-DRB1.

The importance of MHC proteins is that they allow T cells to distinguish self from nonself.

Immune response

Primary response First exposure to antigen Natural or artificial IgM

Secondary response Subsequent exposure Much more vigorous than primary IgG

CONCLUSION Our Creator has indeed provided us with a wonderful defense mechanism, preventing us from disease. The immune system is one of nature's most fascinating inventions. With ease, it protects us against billions of bacteria, viruses, and other parasites. Immunity is a fascinating subject that still conceals many secrets. When the immune system is fully understood, it will most likely hold the key to ridding humankind of many of its most feared diseases.

REFERENCES

Textbook of microbiology 5th ed. By Anantnarayan Textbook of microbiology by Arora Roitts essential immunology 10TH ed. Brender, md, erin; allison burke, ma, illustrator, richard m. (2005-11-23). "spleen patient page"(pdf). Journal of the american medical association 294 (20): 2660. Heyman b (1996). "complement and fc-receptors in regulation of the antibody response".immunt 54 (23): 195199 Borghesi l, milcarek c (2006). "from B cell to plasma cell: regulation of v(d)j recombination and antibody secretion". Immunol res 36 (13): 2732