MIC 205 Specific Defence Ch 16 S21 PDF

MIC 205 - Microbiology Lecture 14: Heat-Seeking Missiles Ch. 16 Specific Defense: The Immune Response Lecturer: Patrick Daydif Office: UCENT 356 Phone: (602) 496-0599 Email: [email protected] Office Hours: Please refer to Canvas (or by appointment)...

MIC 205 - Microbiology Lecture 14: Heat-Seeking Missiles Ch. 16 Specific Defense: The Immune Response Lecturer: Patrick Daydif Office: UCENT 356 Phone: (602) 496-0599 Email: [email protected] Office Hours: Please refer to Canvas (or by appointment) The best way to get in touch with me and to answer your questions is Face to Face. 1 Defense Mechanisms (Overview) Innate defenses – Natural “inborn” resistance to most pathogens Nonspecific defenses – First line: skin, mucous membranes, microbial antagonism – Second line: phagocytosis, inflammation, fever, signaling molecules Specific defenses – Third line: lymphocytes, antibodies (specific immune response, Ch. 16) – Note: AB→ antibody AG→ antigens 2 2 Third Line of Defense Specific immunity – The body’s ability to recognize and defend itself against distinct invaders and their products – “Smart” system – memory functions allow for rapid response to subsequent encounters with familiar pathogens – Acquired over time as the body “teaches” its immune cells about differences between foreign and self Brief outline... – Antigens – Lymphatic system – B cells and antibodies – Humoral immune response – Cell-mediated immune response 3 3 1  Antigens Any molecule or molecular fragment that triggers a specific immune response is an antigen – Include components of bacterial cell walls, capsules, pili, and flagella, as well as proteins of viruses, fungi, and protozoa – Epitope – defined region or fragment of a molecule that has antigenic properties; note that a single large molecule (e.g., protein) may possess multiple epitopes – Food and dust also can contain antigenic particles May enter the body by various methods – Through breaks in the skin and mucous membranes – Direct injection, as with a bite or needle – Through organ transplants and skin grafts 4 4 Antigens epitope 5 5 Lymphatic System Lymphatic system – a network of organs, fluid-return vessels, and clean-up cells that screen the tissues of the body for foreign antigens – Lymphoid cells – Lymphatic vessels – Lymph nodes – Spleen, tonsils, etc. Lymph – liquid similar in composition to blood plasma that arises from fluid leaked from blood vessels into surrounding tissues 6 6 2  Lymphatic System Components Lymphoid cells: includes lymphocytes (T-cells & B-cells), the smallest of the white blood cells; develop from stem cells in red bone marrow lymphocyte erythrocyte Lymphatic vessels: one-way system that collects lymph from tissues to the lymph nodes and returns it to circulatory system Lymph nodes – House leukocytes that recognize and attack foreign antigens in lymph – Concentrated in neck, groin, armpit, and abdominal regions 7 7 Lymphatic System 8 8 Lymphatic System Components (cont’d) Spleen – Similar in structure and function to the lymph nodes – Filters bacteria, viruses, toxins, and other foreign matter from the blood Tonsils and mucosa-associated lymphoid tissues (MALT) – Physically trap foreign particles and microbes – Mucosal tissues include the appendix, lymphoid tissue of the respiratory tract, and Peyer’s patches in the wall of the small intestine 9 9 3  Lymphocytes (Overview) Arise and mature in red bone marrow (B-cells) or thymus (T-cells) Clonal Deletion Found primarily in the spleen and lymph nodes Small percentage of circulate in blood Activated (Clonal selection) by a single matching antigen will result in cell division. Memory cells for later response. 10 10 Lymphocyte Editing by Clonal Deletion Occur with both B & T cells Critical that immune responses not be directed against antigens derived from your “self” molecules (autoantigens) Body “edits” lymphocytes to eliminate ALL self-reactive cells – B cells – T cells will undergo same process, but in a different manner they must also recognized MHC class 1molecules 11 11 Characteristics of B-cells Stem cells (in bone marrow) give rise to B cells – B cells that respond to self Ag are normally inactivated (Clonal Deletion) (self vs. non-self) Assortment of B cells (heterogeneity) – During maturation - randomization of variable region receptors – – Each cell has two matching receptors) Ag binds specifically to the antibody of the B cell (specificity) Activated B cells differentiate – Plasma cells synthesize/secretes Antibody – Memory cells wait for restimulation by the same Ag later (memory) 12 12 4  Antibodies Also called immunoglobulins (Ig) Soluble proteins composed of polypeptides that are held together by covalent bonds Circulate in blood and lymph, where they find and bind their counterpart antigens Secreted by plasma cells – B cells that are actively fighting antigens Considered part of the humoral immune response since bodily fluids like lymph and blood once 13 were called humor 13 Structure of Antibodies Antigen binding sites Light chain 1 4 Four polypeptides Covalent bonds Covalent Heavy (large) chains and bonds Heavy light (small) chains chain Two antigen-binding sites per antibody molecule 2 3 Fc region Fc region 14 14 Classes of Antibodies A single type of antibody is not sufficient for the multiple types of invaders to the body The class involved in the immune response depends on the type of foreign antigen, the portal of entry, and the antibody function needed Five different classes: IgA, IgD, IgE, IgG, and IgM Pentameric Similar to monomeric IgM IgA, IgD, IgE, and IgG Dimeric secretory IgA 15 15 5  Antibody Function Form strong, noncovalent interactions with antigen – Binding occurs because antibody’s antigen-binding sites are complementary to antigenic determinants (epitopes) – Interactions involve hydrogen bonds and other attractions Several roles... – Activation of complement – Stimulation of inflammation – Agglutination – Neutralization – Opsonization (phagocyte activation) 16 16 Humoral Immune Response Antibody-mediated responses mounted against exogenous pathogens Components... – B cell activation – Clonal selection 17 17 Humoral Immune Response Antibody-mediated responses mounted against exogenous pathogens Components... – B cell activation – Clonal selection – Formation of plasma B cells – Formation of memory B cells and immuno- logical memory 18 18 6  Remember! Plasma cells – Make up the majority of cells produced during B cell proliferation – Secretes only antibody molecules complementary to the specific antigenic determinant – Are short-lived cells that die within a few days of activation, though their antibodies and progeny can persist. Memory B cells – Do not secrete antibodies – Cells display on their membranes antibodies that are complementary to the specific antigenic determinant that triggered their production – Long-lived cells that divide only a few times and then persist in the lymphoid tissue – Available to initiate antibody production if the same antigen 19is encountered again 19 Humoral Immune Response (B-cells need Help!) The truth about antigen binding to B cells – Only rarely do free Ag bind directly with B cells – Usually: Ag presented by another cell will produce a signal (cytokines) to activate Antigen Presenting cell (APC) – Display Ag on their surface to T-helper cell. T helper cell (Th1 or Th2 cell) – Will direct the response via chemical signals such as interleukins (IL). 20 20 21 21 7  Cell-Mediated Immunity T cells – T helper cells (CD4) Recognize MHC (safeguard signal) /Ag complex from APC Direct the specific immune response – T cytotoxic cells (CD8) trigger apoptosis activated by interleukin 2 produced by T helper cells attack any cells carrying incorrect Ag/MHC complex Defense against cancer, virus-infected cells, tissue and organ transplants 22 22 Type T Lymphocytes (T cells) Produced in the red bone marrow and mature in the thymus T-cell must recognize MHC – This allows the Immune system to remove foreign cells Blood incompatibly Organ transplant Circulate in the lymph and blood and migrate to the lymph nodes, spleen, and Peyer’s patches 23 23 Cell-Mediated Immune Response Part of the cell-mediated immune response because they act directly against various antigens Responds to intracellular pathogens and abnormal body cells (cancer) – The most common intracellular pathogens are viruses, but the response is also effective against intracellular bacteria Triggered when the host cell displays pathogen- derived antigens on its cell membrane Memory functions established by the formation of memory T cell populations (not memory B cells) 24 24 8  Regulation of Cell-Mediated Response Careful regulation of cell- mediated activities prevents T cells from responding to autoantigens T cells require the establishment of additional “safeguard” signals with an antigen-presenting cell – Interaction of the T cell and the antigen- presenting cell stimulates the T cell to respond to the antigen – The antigen-presenting cell is destroyed by a lethal combination of the killing molecules perforin 25 and granzyme 25 9