The immune system and the oral cavity 2nd part Adaptive or acquired immunity Done by Dr. Zubaida Najat

Adaptive Immune System – Introduction Adaptive: responds to specific foreign substances Innate & adaptive mechanisms work together

Types of Acquired Immunity Figure 21.11

Types of Acquired Immunity 1- Passive acquired immunity includes a- Naturally passive acquired immunity antibodies are pass through placenta of fetus b- Artificially passive acquired immunity:The injection of alredy prepared antibodies such as gamma globulin

2- Active immunity a- Natural active acquired immunity Following clinical or subclinical infections b-Artificial active acquired immunity:- [[[[[Following vaccination with live or killed infectious agents or their products

Adaptive Immune System: Cells Lymphocytes T-cells B-cells Antigen Presenting Cells (APCs)

Acquired immunity is triggered in vertebrates when a pathogen evades the innate immune system and (1) generates a threshold level of antigen and (2) generates "stranger" or "danger" signals activating dendritic cells The major functions of the acquired immune system include: Recognition of specific "non-self" antigens in the presence of "self", during the process of antigen presentation. Generation of responses that are tailored to maximally eliminate specific pathogens or pathogen-infected cells systemic action . Development of immunological memory, in which pathogens are "remembered" through memory B cells and memory T cells.

Antibody Targets & Functions Immune complex formation = antigen-antibody binding. All the following events are initiated by antigen-antibody binding. Complement fixation: Neutralization: Agglutination: Precipitation: Inflammation & phagocytosis prompted by debris

Adaptive, Humoral Immunity Antigen – “any substance when introduced into the body stimulates the production of an antibody” Bacteria, fungus, parasite Viral particles Other foreign material Pathogen – an Antigen which causes disease

Adaptive, Humoral Immunity Complete antigens (proteins, nucleic acids, lipids, polysaccharides): Immunogenicity: the ability to stimulate specific lymphocytes & specific antibodies Reactivity: the ability to react with activated lymphocytes & antibodies Hapten (an incomplete antigen): a smaller molecule that is not immunogenic until attached to proteins

Adaptive, Humoral Immunity Antigenic determinants: sites on an antigenic molecule that are immunogenic Epitope Major Histocompatibility Complex (MHC): cell surface glycoproteins associated with self recognition

Humoral Immunity Active humoral immunity: Passive humoral immunity: B-cells encounter & respond to antigen to produce an antibody Passive humoral immunity: Introduced “non-native” antibody

Antibodies Antibody – “a Y-shaped protein, found on the surface of B-Cells or free in the blood, that neutralize antigen by binding specifically to it” Also known as an Immunoglobulin Constant (C) region defines antibody class determines chemical & cellular interactions determines how class functions to eliminate antigens

Humoral Mediated Immunity T-Cell Cytokines Plasma Cell B-Cell

Antibodies Immunoglobulins & gamma globulins Structure variable hypervariable constant Figure 21.13a

Antibody Classes Antibody Classes: IgM, IgG, IgA, IgD, IgE (Ig = immunoglobulin)

Antibody Classes IgM: occurs as a monomer & a pentamer Occurs on the B-cell surface (Monomer). The Ig of early primary plasma cell response, circulating antibody; a potent agglutinator. Complement binding (Pentamer).

Antibody Classes IgE: the Ig associated with allergies. Stem binds to mast cells & basophils. Receptor binding results in histamine release & inflammation. Found mostly in mucosa of respiratory & GI tract (Monomer).

Antibody Classes IgG: the most abundant circulating Ig. The dominant circulating Ig of the primary & the secondary response. Crosses the placenta. Complement binding (Monomer). IgA: the Ig of secretions. Helps prevent antigen penetration of membranes (Dimer). IgD: the Ig of B-cell activation. Found on B-cell surface (Monomer).

Adaptive Immune System: Cells Immunocompetence: as T- or B-cells mature they become immunocompetent, they display receptors on their cell membrane for a specific antigen. All of the receptors on one cell are identical; immunity depends upon genetic coding for appropriate receptors.

Immunocompetent B or T cells Key: = Site of lymphocyte origin Red bone marrow = Site of development of immunocompetence as B or T cells; primary lymphoid organs = Site of antigen challenge & final differentiation to activated B & T cells Immature lymphocytes Circulation in blood 1 1 1 Lymphocytes destined to become T cells migrate to the thymus & develop immunocompetence there. B cells develop immunocompetence in red bone marrow. Thymus Bone marrow 2 After leaving the thymus or bone marrow as naive immunocompetent cells, lymphocytes “seed” the lymph nodes, spleen, & other lymphoid tissues where the antigen challenge occurs. Immunocompetent, but still naive, lymphocyte migrates via blood 2 2 Lymph nodes, spleen, & other lymphoid tissues 3 Mature (antigen-activated) immunocompetent lymphocytes circulate continuously in the bloodstream & lymph & throughout the lymphoid organs of the body. 3 3 Activated immunocompetent B & T cells recirculate in blood & lymph Figure 21.8

Adaptive Immune System: Cells Antigen Presenting Cells (APCs) APCs ingest foreign material, then present antigenic fragments on their cell surface where they are recognized by T-cells APCs: Macrophages & B lymphocytes Interactions between APCs & lymphocytes & lymphocyte-lymphocyte interactions are critical to immune response

Adaptive, Humoral response Humoral response (clonal selection)

Figure 21.14

Cellular Immunity Tcell CD4& CD8

Adaptive Immune System: Cells Lymphocytes: initially uncommitted T-cells: are sorted in the Thymus Positive selection: recognize MHC survive Negative selection: react against to self-antigens on MHC killed 2% of initial T-cell precursors T-cells manage the immune response

Cell Mediated Immune Response T-cell activation: involves recognition of PM surface antigens only Antigen is combined with MHC & displayed on PM T-cell receptors: bind to the MHC & are stimulated by the associated antigen The addition of a co-stimulator (cytokines, interleukins, etc) prompts the T-cell to form a clone

Helper T Cells (TH) Figure 21.17a

Professional APCs CD4+ Th1-Cells IL-2 Protein IFN-gamma Macrophage TNF-alpha

Cell Mediated: MHC MHC occurs as two classes MHC I on virtually all tissue cells MHC II only on PM some immune system cells

Cell Mediated: MHC display properties MHC I on virtually all tissue cells Display only proteins produced inside the cell Endogenous antigens = foreign proteins produced by the cell (viral / cancer) Stimulate the CD8* cell population form cytotoxic T-cells (Killer T, TC) *formerly T8 cells

Cell Mediated: MHC display properties Figure 21.16b MHC II found only on PM of B-cells, some T-cells & APCs Display proteins derived from a phagocytized target Exogenous antigen: foreign protein from outside the cell – presented to PM surface Stimulates the CD4* cell population form Helper T-cells (TH)

Cell Mediated: T-cell roles Helper T-cells (TH) stimulate B-cells & other T-cells to proliferate Figure 21.18

Cell Mediated: T-cell roles Activated TH cells interact with B-cells displaying antigen & produce cytokines that prompt the B-cell to mature & form antibody

Cell Mediated: T-cell roles TH cells also produce cytokines that promote TC cells TH cells recruit other WBCs & amplify innate defenses (inflammatory) Subpopulations of TH cells specialize in specific sets of activations

Cell Mediated: T-cell roles Cytotoxic T-cells (TC, Killer T): directly attack & kill cells with specific antigen Activated TC cells are co-stimulated by TH cells

Cell Mediated: T-cell roles TC mechanism (Cytotoxic T-cells, Killer T) TC binds to cell & releases perforin & granzymes In the presence of Ca2+ perforin forms pores in target cell PM Granzymes enter through pores & degrade cellular contents TC then detaches & moves on Macrophages clean up

Cell Mediated: T-cell roles Other T-cells *Regulatory T-cells (TReg): release inhibitory cytokines that suppress B-cell & T-cell activity Help to prevent autoimmune events *formerly Suppressor T (TS) Gamma Delta T-cells (Tgd): live in the intestine. Function in surveillance & are triggered much like NK cells

Cellular Mediated Immunity

Summary of the Primary Immune Response Figure 21.19