Presentation on theme: "Immune system - Specifics of children's immunity Oral immunity and immunopathological processes in the mouth."— Presentation transcript:
Immune system - Specifics of children's immunity Oral immunity and immunopathological processes in the mouth
Immunity Microorganisms are in the air we breathe and in/on the food we eat; Thus our epithelial surfaces are continuously exposed to microorganisms; Disease occurs when microorganisms invade epithelial surfaces; However, we have a long infection-free periods and that infections are the exception rather than the rule; This resistance (immunity) of epithelial surfaces to invasion, is a characteristic which is present from birth, and is therefore called innate (natural) immunity.
Immunity A complex of physiological processes whose function is to store the constancy of the internal environment of the body; Protects the body from all foreign endogenous and exogenous factors.
Innate Immunity This prevents entry of microorganisms into tissues or, once they have gained entry, eliminates them prior to the occurrence of disease.
Characteristics Present from birth; Non-specific - acts on many organisms and does not show specificity; Does not become more efficient on subsequent exposure to same organisms.
Prevention of entry of organisms Mechanical barriers at body surfaces, skin, mucous membranes - disruption leads to infection; Antibacterial substances in secretions, lysozyme, lactoferrin, low pH of stomach contents.
The immune system is composed of two main categories: Nonspecific immunity - provides general protection; ▫First line of defense; ▫Second line of defense; Specific immunity - the body recognizes specific pathogens; ▫Third line of defense.
Nonspecific immunity First line of defense: ▫mechanical barriers; Skin; Mucosa; ▫Chemical barriers: Saliva: Enzymes; Secretory immunity.
Second line of defense Nonspecific inflammation; Phagocytosis: ▫Neutrophils; ▫Macrophages; ▫Histiocytes; Natural "killer" cells: ▫Kill tumor cells; ▫Kill infected cells.
Tissue factors Skin; Mucosa; In the mouth - continuous oral mucosa.
Cellular factors Act after overcoming tissue barrier; Vascular cell phenomenon – inflammation; Sensitized cells; From the stem cells of the bone marrow; Hematopoietic - neoplastic cells; Cells of specific immunity.
Protection`s cells Macrophages; Microphages; ▫PMNs; ▫Three cell populations; ▫Mature cells: Neutrophils; Eosinophils; Basophils; Mast cells; Platelets; Killer cells. The light micrograph shows the multilobed nucleus, because of which these cells are also called polymorphonuclear leukocytes, and the faint cytoplasmic granules.
Macrophages Mononuclear phagocytes; Derived from monocytes; They are: ▫Histiocytes; ▫Fixed macrophages (in the lymph nodes and spleen); ▫Osteoclasts; ▫Kupffer cells; ▫Microglial cells; ▫Langerhans cells.
Characteristics of the macrophages They have receptors for: ▫Immunoglobulins; ▫Complement; ▫Antigens; ▫Lymphokines; Cause "oxidative burst“: ▫Released superoxide anion; ▫It turns into H 2 O 2; ▫Kill pathogenic factor; ▫Digest it intracellularly.
The next steps are: They transfer antigens to lymphocytes; lymphocytes are sensitized; Induce a specific immune response; Separate bioactive substances; Regulate the immune response.
Serotonin Synthesized in nerve endings; Shortens the smooth muscle fibers; Dilates blood vessels; Increased permeability.
Plasma proteins Complement system; ▫It consists of 20 serum proteins; ▫They react with the cascade of reactions; ▫The enzyme catalyzes the reaction of a following: They are involved in specific and nonspecific protection.
Kinin system Plasma proteins of the beginning of the reaction; Bradykinin: ▫Increases vascular permeability; ▫Causes contraction of smooth muscle fibers; ▫Follows vascular dilatation; ▫Causes a pain.
Coagulation system Activated by various substances in the tissue destruction; Stops the movement of microorganisms; Makes them available for phagocytosis; Stops bleeding; Decreased neutrophil chemotaxis; Reduces permeability.
Other mediators - interferons They are low molecular weight proteins: ▫Leukocytes - α-interferon; ▫Fibroblasts - β-interferon; ▫Lymphocytes - immune interferon; Their action is to block: ▫Replication of the viral RNA; ▫The reproduction of the tumor cells; ▫Regulate the immune system.
Arachidonic acid lipid mediator; Formed quickly; Acts locally; It produces: ▫Prostaglandins; ▫Leukotrienes; ▫Hypoxines.
Nonspecific defense mechanisms Inflammation
Inflammatory reaction Major defense mechanism; Is a sequence of vascular and cellular reactions; They provide counteraction of the pathogens; The basic phenomenon of the inflammation is phagocytosis.
Types of inflammation Nonspecific inflammatory response: ▫Before the formation of antibody; Specific inflammatory reaction: ▫At the second meeting with the pathogen antigens; ▫Or at a later stage of the initial meeting; Sensitization occurs of the immunocompetent cells; It include specific immune responses.
The process of the inflammation Starting with local hypoxia; Starting release of the vasoactive substances; Separated the histamine, serotonin, prostaglandins, kinins; They cause vasodilation; This leads to congestive hyperemia; Follows hypoxia; The next result is acidosis; Began massive migration of the microphages and macrophages; Performed phagocytosis.
Phagocytosis is mediated by macrophages and polymorphonuclear leucocytes Phagocytosis involves the ingestion and digestion of the following: ▫Microorganisms; ▫Insoluble particles; ▫Damaged or dead host cells; ▫Cell debris; ▫Activated clotting factors.
1.Phagocytosis - ingestion and killing of microorganisms by specialised cells (phagocytes) Phagocytes - polymorphonuclear leukocytes (neutrophils); Mononuclear phagocytes (monocytes, macrophages); 2. Opsonisation - the process of coating micro- organisms with some of the proteins found in plasma, to make them more easily phagocytosable.
INFLAMMATORY RESPONSE - INFLAMMATION Complement and phagocytes exist mainly in blood so a mechanism is required to recruit these elements to the site of tissue invasion.
Inflammation involves: a) opening up of junctions between endothelial cells in post-capillary venule to allow plasma proteins to escape; b) adhesion of leukocytes to endothelial cells of post- capillary venule, followed by emigration of phagocytes into tissues. Inflammation is localised to area of infection or tissue injury by release of substances from micro- organisms or chemicals (chemical mediators) released from cells in tissues, e.g. histamine from MAST CELLS. Once organisms destroyed inflammation settles down (RESOLVES).
There are several stages of phagocytosis: 1. Chemotaxis; 2. Adherence; 3. Pseudopodium formation; 4. Phagosome formation; 5. Phago-lysosome formation.
1. Chemotaxis This is the movement of cells up a gradient of chemotactic factors; It may be directly induced by a substance, produced as a result of complement activation; It can also be indirectly induced as a consequence of release of preformed mediators within mast cells by the action of eosinophil chemotactic factor, or neutrophil chemotactic factor; Leukotrienes, produced by the metabolism of mast cell arachidonic acid, are also chemotactic.
2. Adherence This works reasonably well for whole bacteria or viruses, but less so for proteins or encapsulated bacteria; In order to deal more effectively with encapsulated bacteria, antibodies directed against the capsule enable the phagocytic cells to ingest the organisms, using their Fc receptors.
Adhesion Performed by serum opsonins; Some objects have receptors for antibodies and complement; Their presence facilitates adhesion.
3. Pseudopodium formation This is the protrusion of membranes to flow round the "prey".
4. Phagosome formation Fusion of the pseudopodium with a membrane enclosing the "prey" leads to the formation of a structure termed a phagosome.
5. Phago-lysosome formation The phagosome moves deeper into the cell, and fuses with a lysosome, forming a phago-lysosome; These contain hydrogen peroxide, active oxygen species (free radicals), peroxidase, lysozyme and hydrolytic enzymes; This is known as the oxidative burst, and leads to digestion of the phagolysosomal contents, after which they are eliminated by exocytosis; Some peptides however, undergo a very important separate process at this stage; Instead of being eliminated, they attach to a host molecule and end up being expressed on the surface of the cell within a groove on the molecule (antigen presentation).
The speed of phagocytosis can be increased markedly by bringing into action two attachment devices present on the surface of phagocytic cells: Fc receptor: which binds the Fc portion of antibody molecules, chiefly IgG. The IgG will have attached the organism via its Fab site. Complement receptor: the third component of complement (C3) also binds to organisms and then attaches to the complement receptor. This coating of the organisms by molecules that speed up phagocytosis, is termed 'opsonization', and the Fc portion of antibody, and C3 are termed 'opsonins'.
Absorption Invagination of the cell wall; Coverage of the site; Formation of phagosomes; Fusion with the lysosome; Phagolysosome formation; Follows hexose-monophosphate cycle; Release of superoxide anion; Superoxide explosion; Acidosis.
Digestion - enzymatic digestion Phagocytosis graduated with digestion; At incomplete phagocytosis part of the pathogenic properties of the particles are retaining; Microphages digest them completely; Macrophages digest them partially.
Specific immunity - the third line of defense Specific immune responses after primary inflammation - acquired immunity
Acquired Immunity (adaptive Immunity/specific Immunity) This type of immunity occurs in response to infection called ADAPTIVE as the immune system must adapt itself to previously unseen molecules; Following recovery from certain infections with a particular microorganism, individuals will never again develop infection with the same organism, but can become infected with other microorganisms; This form of protection is called IMMUNITY and an individual is said to be IMMUNISED against that organism; The induction of immunity by infection or with a vaccine is called ACTIVE IMMUNITY.
PASSIVE IMMUNITY Historically it has been shown that a non- immune individual can be made immune by transferring serum or lymphocytes from an immune individual - PASSIVE IMMUNITY ; In passive immunity are involved: ▫Serum constituents (antibodies); ▫Lymphocytes.
Immune system responds to microorganisms but not to its own cells and that the system knows that the body has been infected previously with a particular organism This implies: ▫IMMUNOLOGICAL RECOGNITION; ▫SELF/NON-SELF DISCRIMINATION; ▫IMMUNOLOGICAL SPECIFICITY; ▫IMMUNOLOGICAL MEMORY.
Immunity is mediated by the IMMUNE SYSTEM, which responds to infection by mounting an IMMUNE RESPONSE An immune response must: ▫RECOGNISE a microorganism as foreign (non- self) as distinct from self (AFFERENT LIMB); ▫RESPOND to a micro-organism by production of specific antibodies and specific lymphocytes; ▫MEDIATE the elimination of micro-organisms (EFFERENT LIMB).
IMMUNOGEN and ANTIGEN An agent which evokes an immune response is called an IMMUNOGEN. The term ANTIGEN is applied to a substance which reacts with antibody.
Cellular Basis Of Immune Response Key cells are lymphocytes - have capacity to recognise microorganisms; There are two types which develop in bone marrow from a common precursor: ▫T-cells - mature in thymus; ▫B-cells - mature in bone marrow; These two types of lymphocyte are used in 3 ways to fight infection.
Strategy One: elimination of extracellular microorganisms In response to infection B-cells mature into PLASMA cells which secrete soluble recognition molecules (ANTIBODIES); B-cells recognise microbes because they express membrane bound antibody which acts as an antigen receptor; At time of first infection there is no antibody in blood and level does not begin to increase until between 7-10 days afterwards; The level of antibody rises slowly to a low peak and then gradually declines towards baseline - PRIMARY RESPONSE.
SECONDARY RESPONSE On subsequent exposure to same micro- organisms the level of antibody begins to increase within 24 hours and reaches a high level which is sustained.
Epitope or Antigenic determinant Antibody recognises structures on surface of bacteria - proteins, carbohydrates, lipids; When we have an infection we produce antibodies which recognise many different types of structure on bacterial surface; Thus serum from an immune individual contains many different types of antibodies each of which recognise different structures on surface of membrane; Each of these structures is called an epitope or antigenic determinant.
Effector mechanisms Antibody is soluble and diffuses through tissues to target extracellular microorganisms; Binding of antibody to microorganisms activate two effector mechanisms to eliminate micro- organisms; ▫Activation of complement system - bacterial lysis or opsonisation; ▫Phagocytosis by neutrophils and macrophages with intracellular killing.Phagocytosis
Strategy Two: Elimination of micro- organisms which normally survive for long periods in macrophages Even when antibody and complement opsonise certain bacteria and phagocytosis occurs, they are not killed but survive and multiply in macrophages (e.g. Mycobacterium tuberculosis); Elimination occurs by use of a subpopulation of cells called Helper T-cells; These cells recognise macrophages containing intracellular bacteria by means of T-cells antigen receptor, which is not an antibody; They help macrophages to kill bacteria by synthesising soluble molecules (cytokines) which stimulate bacterial killing mechanisms of macrophages.
Strategy Three - Elimination of microorganisms which infect cells without an endogenous antimicrobial defence system Viruses are obligate intracellular pathogens, can infect any type of cells, and most cells do not possess antimicrobial mechanisms; During intracellular replication virus proteins appear on the surface of the infected cell; A second subset of T-cells - cytotoxic T-cells - recognises these viruses (foreign) antigens and secretes cytotoxic molecules which kill the infected cells.
Acquired immunity is characterized by: Specificity: ▫Immune responses are specific to each agent acting as an antigen; Memory: ▫At repeated meeting with antigen the body recognizes it; ▫It acts to store their information.
Specific immune responses Humoral immune responses: Cellular immune responses.
Antigens All substances carrying foreign genetic information and which are inducing a specific immune response.
Types of antigens According to the effect: ▫Strong; ▫Weak; ▫Haptens – They do not form antibodies, but is connected to them; According to its specificity: ▫Heteroantigens - of a different kind; ▫ Antigens of the same type but of another individual; ▫Autoantigens - These antigens should, under normal conditions, not be the target of the immune system, but, due to mainly genetic and environmental factors, the normal immunological tolerance for such an antigen has been lost in autoimmune disease.
Characteristics of the antigens Extrinsic - other than those of the host; Antigenicity - develop antibodies; Immunogenicity - create immunity; Specificity - sets of sites in a protein chain called antigenic determinants; High molecular weight proteins; Soluble and absorbable colloidal
Antigen-Antibody Interaction The specific association of antigens and antibodies is dependent on hydrogen bonds, hydrophobic interactions, electrostatic forces, and van der Waals forces
Adjuvants Substances that enhance the immunogenicity; They are in a dental plaque.
Antibodies Proteins to different immunoglobulins; Are formed at the entry of the antigen; They are constructed from a sensitized plasma cells; Types: ▫IgM; ▫IgA; ▫IgG; ▫IgD; ▫IgE; ▫IgA-S
Antibodies according to the type of reaction Precipitins; Agglutinins; Antitoxins; Lysines; Autoantibodies; Blocking monovalent antibodies.
immunoglobulins Proteins with a common structure and activity of antibodies.
Construction of the immunoglobulin molecule 1 – light chains; 2 – heavy chains; 3 – constant region; 4 – changing area - Binding antigen. 2 1 1 3 4
Immunoglobulin G - dimmer Represents 75-80% of all Immunoglobulins; Synthesized in utero; Cross the placental barrier; Activates complement; Causes: ▫Agglutination; ▫Precipitation; ▫Neutralization; ▫Opsonization.
Immunoglobulin A - monomer 10-15% of the total immunoglobulin; Do not synthesized in utero; Do not cross the placenta; Activates complement by alternative pathway; There are anti-adhesive and opsonized effect; Increases in chronic inflammation.
Immunoglobulin A - S (secretory) Dimer possessing a fragment of secretory component and connecting chain; In the mouth is secreted from the salivary glands; Participated in the first line of defense of the enamel and lining mucosa; The main factor of local immunity.
immunoglobulin M Represents 6-9% of the total immunoglobulins; Represents a pentamer with ten active centers; When sensitization it occurs a first; Its synthesis begins in early childhood or first meeting with antigens.
immunoglobulin D Receptor immunoglobulins of the mature beta- lymphocytes.
immunoglobulin E Antibodies of the allergic reactions; In the blood they are in low concentrations; Adsorbed to the surface of: ▫mast cells ▫basophil leukocytes ▫Platelets Cause hypersensitivity
Action of the antibodies Adsorption to microbial surface; Prevent its adhesion; Opsonized bacterial cells; Receptor binding between phagocytic cell and the particular antibody fragment; Agglutinate microorganisms; Precipitate molecular antigens; Defense and neutralize cell; Make them available to complement; Neutralize viruses; Cause hypersensitivity; Protective or pathological inflammation.
Cytokines - common name of a group of proteins Small protein molecules; Mediators and regulators of: ▫Immunity; ▫Inflammation; ▫Hematopoiesis; ▫They are produced in at immune stimulus.
Types of cytokines Lymphokines - by lymphocytes; Monokines - from the monocytes; Chemokines – with chemotaxis activity; Interleukins - from one leukocyte and acting on other; Interferons.
Cytokines, due to the action Antiinflammatory - activate macrophages and cellular immune response; ▫IL 1 ▫IL 6 ▫TNF Antiinflammatory - suppress cellular immune responses and stimulate antibody-dependent immunity ▫IL 4 ▫IL 5 ▫IL 10 ▫IL 13
Specific immunity cells - lymphocytes Immunocompetent cells; Start development in: ▫Bone marrow; ▫Thymus; ▫lymph nodes; ▫Spleen.
There are two classes lymphocytes B-lymphocytes ▫Produce antibodies; ▫They attack the antigens; ▫Perform antibody-dependent immunity; T-lymphocytes ▫Directly attack pathogens; ▫Mediate cell dependent immunity.
B lymphocytes and humoral immunity First stage of development ▫Precursors of the B-lymphocytes the first months after birth; Second stage ▫After antigenic stimulation; ▫Development of sensitized B-lymphocytes in the spleen and lymph nodes; ▫They form clonal cell lines; ▫Produce antibodies; ▫Connect with antigens; ▫Antigen-antibody reaction.
Humoral immune responses - with the participation of antibodies Formed antigen-antibody complexes are more vulnerable to phagocytosis; Nutralization; Precipitation; Agglutination + complement; Improving imunoadhezion; Cytolysis; Release of mediators; Stimulation of immune responses.
T-cell and cell-dependent immunity T-lymphocytes mediate cell immune responses
Development of T-lymphocytes First stage: ▫Development of precursor T- cells (thymocytes); ▫Derived from the bone marrow; ▫Differentiate in the thymus; Second stage: ▫By the blood; ▫To T-dependent areas; ▫In lymph nodes and spleen; ▫Antigen by macrophages; ▫Activated surface receptors; ▫Repeated divisions of T- lymphocytes; ▫A branch of the T- lymphocytes to antibody; ▫Connect with them; ▫Release lymphokines.
Types T-lymphocytes Tk - killer cells: ▫Released lymphotoxins; ▫Kill the target cell; Th - helper cells: ▫Regulate the function of B-lymphocytes; Ts - suppressor cells: ▫Inhibit the differentiation of plasma cells to B- lymphocytes; Tm - memory cells were performed immunological memory.
Cellular immune responses Direct cytolysis; Release of mediators; TM creates immunological memory; This Immunity is against: ▫Bacteria; ▫Fungi; ▫Protozoa; ▫The invasion tissues; ▫Malignant cells.
Immune tolerance Tolerance to the resident microflora; In the mouth - "adaptive immunity" or "immune tolerance“; Regulatory system and integrated processes for maintaining immune homeostasis.
Development of the immune system in childhood
Intrauterine development Passive immunity from mother + Developing own immunoreactivity = Protection of the fetus from congenital infections
Newborn Rejected zero immunity; Presence of the phagocytic activity of: ▫Complement; ▫Interferon; ▫Other factors of nonspecific immunity; Congenital and acquired infections occur: ▫Undifferentiated clinic; ▫Tendency to generalization.
Maternal antibodies From the second month of the infant began to decline; Within six months disappear; When breast-fed infants are retained longer.
Oral immunity of the newborn Oral mucosa adapts as a barrier; Supported by the emergence of immunoregulatory network; Depend on microbial colonization; Of food allergens; Breastfeeding is the best way to shape the immune phenotype.
Breastmilk Contains immune cells; Cytokines; Growth factors; Immunoglobulin A; Provides early postnatal development of the secretory imunity.
Secretory IgA till 8 months is obtained from the mother - secretion begins thereafter Modeling; Inhibits: Surface colonization of microorganisms; Prevents penetration of harmful factors; Neonatal period is critical for infections and allergies.
Between the ages of 3 and 6 months Immune reactions are more subdued; More difficult recovery from infections; Low productivity of lymphoid tissue; Homeostasis is easily broken by: ▫Malnutrition; ▫Antibiotics.
Between the ages of 6 and 12 months The child is creeping; He is started walking; In contact with the environment; First viral infections: ▫respiratory; ▫Retavirusi; ▫ bowel; ▫Herpes; ▫Measles; ▫Chickenpox; ▫Rubella; Disease is more severe.
Aged 1 to 3 years Close contact with adults; Child is exposed to a variety of infections; Cross-bacterial viral, mycoplasma, viral and infectious: ▫Immunological reactivity is better - organ development on immune Serum reactions are weak The antibody concentration is low In the re-encounter with antigen antibody titer increases.
After three years Viral infections occur more easily; Often subclinical and asymptomatic; In school and adolescence incidence is close to that in adults.
immunopathological reactions Protection and adaptation of body
Types of immunopathological reactions Allergic; Autoimmune; Immunodeficiencies.
Allergic reactions Upon re-entry of the antigen immune system responds in three ways: ▫A protective immune response; ▫With increased sensitivity - an allergic reaction; ▫No reaction – anergy.
Allergic reactions can be four types An antigen that causes an allergic response is called an allergens
First type - allergic immediate reactions Hypersensitivity by humoral type; Called anaphylactic or atopic; Rapid immune response involving IgE; It binds to mast cells; Exempt mediators.
The second type - the cytotoxic response Humoral-mediated; Immediate-type; Toxic effects on cells; Cytolysis involving IgM, IgD and complement; Target cells are erythrocytes, leukocytes and platelets.
Third type - the antigen-antibody reaction Immediate reactions; Toxic effect of antigen-antibody complex.
Fourth type - cell-mediated delayed reactions Similar to cellular immune reactions; Affects allergy; Bacteria; Viruses; Fungi.
Autoimmune reactions The immune system is tolerant to its own tissues and antigens; Breach of this tolerance; Autoimmune reactions; The body produces antibodies against its own cells and antigens.
Adaptive immunity in the mouth may be impaired Commensal microorganisms have similar antigens; They bind to the molecules of macroorganism; Macroorganism did not perceive them now as foreign; Or develop cross-immune response; The body perceives its own cells as foreign.
Common autoimmune diseases Manifestation in the oral mucosa; Dermato Bullous: ▫Pemphigus; ▫lupus erythematodes; ▫Epidermolysis bullosa.
Immunodeficiency states Deficits in the humoral immunity or in the cellular immunity; Susceptibility to infections.
Congenital immunodeficiency conditions Heritage, most often recessive; Rare syndromes; Appear in childhood; Patients do not survive long; Infections are fatal; Affect the oral mucosa, gingiva and periodontium.
Acquired immunodeficiency conditions Malnutrition; Viruses and bacteria; Radiotherapy; Prolonged cytostatics treatment ; Corticosteroids and antibiotics.
Oral immunity - defense mechanisms A combination of local and systemic immune responses and mechanisms; The basic function – protecting; Preventing the entry of foreign antigens; Tolerance to the resident microflora; Food.
Protective mechanisms of the oral mucosa - the first line of defense Barrier; Physiological exfoliation; The degree of keratinization - nonspecific mechanism; Protection, regardless of age; Masticatory act; Washout effect of saliva; Mucin and secretory immunoglobulin A.
Protective role of oral lymphoid tissue Oral immune response is carried out by: ▫Intraoral lymphoid formations: Palatal tonsils; Lingual; Pharyngeal; Submucosal lymphoid aggregations: soft palate; Floor of the mouth; Tongue; Cheeks; Lips; ▫Extraoral lymph nodes.
Protective role of saliva Mechanical action; Salivary enzymes; Leukocytes; Buffer systems: ▫Bicarbonate; ▫Phosphate; ▫Protein; Secretory immunity.
Protective role of gingival fluid Transudate of gingival capillary network Dependent is: ▫The composition of the blood serum; ▫Permeability of the gingival epithelium; Permanent presence of: ▫PMNL; ▫Phagocytic cells; ▫Monocytes.