[MICRO] Immunology 2.pdf

MICROBIOLOGY AND PARASITOLOGY 08/28/2024. MOD 4: IMMUNOLOGY 2 Ludivina Tesoro-Sol...

MICROBIOLOGY AND PARASITOLOGY 08/28/2024. MOD 4: IMMUNOLOGY 2 Ludivina Tesoro-Solis, MD, FPSP Trans Group/s: 8B PART 2A Their name arises from their ability to generate antibodies I. ADAPTIVE IMMUNITY Immunogens: antigens that can elicit antibody production Our body’s third line of defense Importance: Body’s ability to recognize and mount a defense ○ Elicit immune response against distinct invaders and their products (e.g., ○ Determine important individual characteristics (e.g. protozoa, fungi, bacteria, viruses, or toxins) blood types) Also referred as acquired or specific immunity ○ Determine if an organ transplant will be rejected or Activated once the innate immunity is breached, and accepted by a recipient based on specific responses to a specific microbe KEY PLAYERS & COMPONENTS OF ADAPTIVE IMMUNITY 1 Antibodies 2 Antigens 3 Lymphocytes 4 Cytokines 5 Complement System Antigen with antibodies binding on their epitopes (antigenic MAIN CELLS determinant site). 1 Lymphocytes (T cells and B cells) MICROBIAL ANTIGEN NON-MICROBIAL ANTIGEN 2 Antibodies COMPOUNDS COMPOUNDS A. SALIENT FEATURES OF ADAPTIVE IMMUNITY Capsules Pollens 1. SPECIFICITY Ensures that distinct antigens elicit specific Cell walls Egg white responses Example: Antibodies against chicken pox will function Fimbriae Blood cell surface against that virus, and not measles or other viruses Bacterial toxins Serum proteins 2. DIVERSITY Surface of other Surface molecules Enables the immune system to respond not only to a microbes (transplanted tissues & organs) small group but to a large variety of antigens Viral coats 3. MEMORY Produces memory cells to specific pathogens 1. ANTIGEN GROUPING It makes use of memory cells One important way to group antigens is according to ○ In repeated exposure to an antigen, the body’s their relationship to the body immune responses are enhanced 4. CLONAL EXPANSION 1.1 Exogenous Antigens The ability of lymphocytes to reproduce or clone itself Antigens found outside the host cells once induced by a pathogen Examples: toxins and other secretions, component of Effect of this is greater felt in the second encounter of microbial cell wall, membranes, flagella, pili, capsules, the pathogen and fimbriae, viral coats, and surface of other microbes 5. NON-REACTIVE TO SELF 1.2 Endogenous Antigens Adaptive immunity does not act against normal body Protozoa, fungi, bacteria, and viruses that reproduce cells inside the body cells to produce endogenous antigens It allows prevention of self-injury during responses to Immune system cannot assess the health of the body foreign antigens cells. ○ It only responds to endogenous antigens if it is B. ANTIGENS already incorporated into the body’s cells’ Molecules (proteins or polysaccharides) that can cytoplasmic membranes (leading to its external stimulate an immune response by binding display). specifically to an antibody Microbio and Para - Mod # Topic Title 1 of 12 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Macrophage (blue), virus (yellow), and endogenous antigen (black) being displayed externally as pointed by the red arrow. 1.3 Autoantigens Antigenic molecules derived from normal cellular processes (aka self-antigens) 2. ANTIGEN-SPECIFIC RESPONSES One important way to group antigens is according to their relationship to the body Types of antibodies. 1 Activate T Enhances phagocytosis and lymphocytes reduces number of infectious ANTIBODY FRAGMENTS units to be dealt with Fab fragment Binds to antigen 2 Activate B Activate B lymphocytes to become: lymphocytes 1. Memory cells: secondary Fc fragment Activates complement and phagocytes immune response to that antigen 2. Plasma cells: antibodies to attack TYPES OF ANTIBODIES that antigen IgM First immunoglobulin produced in an immune response IgA Prevents the attachment of microbial pathogens to mucosal surfaces IgE Elevated in patients with allergies and helminthic infections IgD Monomer and is concentrated along with IgM on plasma membrane of human B-lymphocytes IgG Most abundant in serum and can cross the placental membrane D. LYMPHOCYTES Although lymphocytes appear identical under the microscope, there are actually two main types: Antigen-Specific Responses. ○ B cells ○ T cells C. ANTIBODIES Differentiation of B cells and T cells depend on where Another key player in adaptive immunity they are processed They are anti-antigens ○ In the bone marrow → B cells A class of proteins also called immunoglobulins found ○ In the thymus → T cells on blood serums, body fluids, and tissues From the primary lymphoid tissues (bone marrow and Produced in response to a particular epitope on the thymus), the mature lymphocytes migrate to the surface of pathogens secondary lymphoid tissues and organs to interact Highly specific, soluble, and helps other cells or with the latter’s antigens molecules inactivate or destroy the infectious agents of ○ Secondary lymphoid tissues and organs: their products Spleen SALT (skin-associated lymphoid tissues) MALT (mucosa-associated lymphoid tissues) GALT (gut-associated lymphoid tissues) Microbio and Para - Mod 4 🏠 Immunology 2 2 of 12 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  blood produced by B Especially in situations cells wherein Ag are When stimulated by embedded in plasma an antigen, B membranes or inside lymphocytes initiate host cells which are process that leads to inaccessible to Ab the production and Most effective in release of antibodies defending the body Most effective in against viral infection, defending body fungi, helminths, against extracellular cancers and foreign microbes, bacteria, tissues such as viruses, and transplanted tissues bacterial toxins and organs ○ Reject tumors and transplanted tissues Differentiation of Stem Cells into B cells and T cells, depending on where they were processed. Immunology 2 MAIN TYPES OF LYMPHOCYTES B CELLS T CELLS Summary of How Lymphocytes interact with microbial When B cells are CD4 T cells (T helper cells) invaders. B cells defend outside the cells, T cells attack exposed to Provide chemical signals infected cells. antigens, they that help stimulate other become activated immune cells like B cells to MAJOR ADAPTIVE IMMUNE RESPONSES differentiate into differentiate into antibody plasma cells producing cells HUMORAL Plasma cells Also produces cytokines CELL-MEDIATED (antibody-mediated) produce Ab that regulate activities of against Ag that both B and T cells, Cell involved B cells T cells activate the monocytes, and other original B cells immune cells How are Via antigens Via antigens on the Those that do not Further differentiate into: pathogens floating in the surface of get activated ○ Th1 identified? blood infected cells undergo ○ Th2 (extracellularly) apoptosis, then ○ Th17 phagocytosed ○ Tfh (follicular helper T II. HUMORAL IMMUNITY before any cells) Antibody-mediated; with B cells playing a major role significant ○ T reg (regulatory T leakage occur cells) A. B CELLS Display a single homologous clonal immunoglobulin CD8 T cells (Cytotoxic T cells) on their surface which serves as receptor (B cell Identify body cells infected receptors or BCR) that responds ONLY to a specific with intracellular organisms antigen or closely-related group of antigens and eliminate these cells harboring them Immature B cells Have IgM and IgD on their surface The complexity of the immune function is largely due to lymphocytes working closely together with 1. B CELL ANTIBODY PRODUCTION macrophages. B cells develop from stem cells in the bone marrow of adults MAJOR ADAPTIVE IMMUNE RESPONSES ○ Liver of fetuses After maturation B cells migrate to lymphoid organs ○ Lymph node of spleen HUMORAL CELL-MEDIATED 1.1 Clonal Selection Carried out by Carried out by certain T When a B cell encounters an antigen it recognizes, it antibodies cells is stimulated and divides into many clones called circulating in the Occurs at a cellular plasma cells, which actively secrete antibodies level Microbio and Para - Mod 4 🏠 Immunology 2 3 of 12 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Each B cell produces antibodies that will recognize only one antigenic determinant 1 BCR of the B cell binds to the antigen 2 B cell activation is initiated 3 B cells divide into other B cells or clones 1.1 Clonal Selection Antigen selects lymphocytes that will multiply in clones of cells These B cells in turn produce plasma cells and memory cells Produce antibodies and live only for a Plasma few days Cells Produce 2,000 antibody molecules per second — primary immune response When infection is over, the plasma cells die but memory cells continue to circulate The host encounters the antigen for the first time initiated by B cells Takes about 1-2 weeks to fully develop IgM: first immunoglobulin produced 2. SECONDARY IMMUNE RESPONSE B-cell Antibody Production. When a similar microbe attacks again, memory B cells produce antibodies more rapidly and generate 2. B CELL ACTIVATION more antibodies Production of antibodies starts when B cells are Elicited by reinfection with the same previous antigen exposed to a free or extracellular antigens for the first Initiated by memory B cells time Antibodies are produced more rapidly (in a few days) Binding to an antigen activates it and allows it to divide and generated more (in numbers) due to memory B producing more B cells, that produce plasma cells as cells well as production of memory cells B cells in the resting stage which have BCR or B cell receptors (i.e. IgM and Naive B cells IgD) found on their surface If the B cell receptor binds to an antigen, then activation is initiated. B. PRIMARY AND SECONDARY IMMUNE RESPONSES – IMMUNOLOGICAL MEMORY 1. PRIMARY IMMUNE RESPONSE Secondary Immune Response. PRIMARY AND SECONDARY IMMUNE RESPONSE PRIMARY SECONDARY Initial encounter with Ag Second encounter with Ag Less memory and plasma More memory cells and cells produced plasma cells produced Antigen surrounded by B cells. Microbio and Para - Mod 4 🏠 Immunology 2 4 of 12 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Full response is slower Full response is faster ○ Liberation and/or phagocytosis of other Host cell in secondary immune response is more parasite antigens to further prepared to defend itself by producing B cells, more activate immunity plasma cells, and more antibodies Secondary immune response is more intense and The activation of the complement Antigen-Antibody binding is more stable Complement system, particularly the classic System pathway, may eventually lead to the lysis of the pathogen. Disruption of cells by complement/ reactive protein attracts phagocytic Inflammation and other defensive immune system cells. Primary vs. Secondary Antibody Responses showing the concentration of IgG and IgM. IgM: always the first to respond in an infection followed by IgG IgG concentration and total antibody are much greater in the secondary immune response PART 2B C. PROTECTIVE FUNCTIONS OF ANTIBODY Antibodies can cause antigens to Summary of Protective Functions of Antibody. clump together which makes it easier to eliminate the pathogen. D. COMPLEMENT SYSTEM Agglutination Enhances phagocytosis and reduces the number of INNATE IMMUNITY ADAPTIVE IMMUNITY infectious units to be dealt with. Alternative Pathway Classical Pathway Enhanced Coating antigen with antibody to make Phagocytosis the pathogen more prone to Mannan-binding Lectin (Opsonization) phagocytosis Pathway Antibodies can either: Neutralize toxins by blocking their active sites Neutralization They can coat microorganisms, preventing them from attaching to the cell host —blocks adhesion of bacteria and viruses to mucosa Antibodies attached to target cells cause destruction by non-specific immune system cells This process can eliminate large parasites. Antibody- ○ Starts by coating parasites Dependent Classical and alternative pathways. with antibodies Cell Mediated ○ Fc region receptors on the Cytotoxicity 1. THE CLASSICAL PATHWAY surface of eosinophils, (ADCC) macrophages, and NK cells bind to the antibody ○ These cells release cytokinins, perforins, and other lytic enzymes to damage parasite tissues Microbio and Para - Mod 4 🏠 Immunology 2 5 of 12 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Steps Involved in the Classical Pathway. Complement Pathways and Regulatory Proteins. The major difference between the Alternative, Lectin, and Classical Pathways is how they are initiated. In order to avoid constant complement activation and minimize tissue destruction, a regulatory network exists to terminate the complementary activity. CLASSICAL PATHWAY Several serum proteins regulate the complement system at different stages: 1 Binding of the antibodies to the antigen (proteins, polysaccharides) on the pathogen’s surface (bacteria) REGULATION OF COMPLEMENT PATHWAY 2 Formation of antigen-antibody complex REGULATORY FUNCTION PROTEIN 3 Antigen-antibody complex binds and activates C1 Blocks activation of C1 of ALL 3 4 Activated C1 activates C2 and C4 by splitting them pathways into C2a, C2b, C4a, and C4b, respectively. C1-INH Binds and inactivate the serine C1 esterase protease activity of C1r and C1s 5 C2a and C4b combine and activate C3 by splitting it inhibitor ○ C1r and C1s dissociates from into C3a and C3b C1q 6 C3 fragments initiate inflammation or chemotaxis C4BP through C5a Controls activation at the C4 level of C4 Binding Classical, Alternative, and Lectin pathway the Classical and Lectin Pathway Protein converge on this step Cleaves C3b and C4b 7 Consequently, C5a and C3a also promote Factor I Reduced amount of C5 convertase vasodilation and vascular permeability via anaphylatoxins Factor H Enhances the effect of Factor I on C3b This process increases blood flow to the infected area enabling essential phagocytes to travel to the infected site Factor I and Regulate C3 and C5 convertase Factor H 8 C3b promotes opsonization (an enhanced phagocytosis), while development of Membrane Attack Complexes (MAC) promotes cytolysis Includes: Membrane- CR1 (Complement Receptor 1) bound IMPORTANT: Membrane Attack Complex (MAC) MCP (Membrane Cofactor Protein) inhibitors consists of C5b + C6 + C7 + C8 + C9 = C5b6789 Act as cofactors for Factor I MAC inserts itself into the membrane of the organism DAF (Decay Accelerate dissociation of C3 → digests hosts in the cell membrane of the bacteria accelerating convertase or envelope of viruses → destruction of cell factor) membrane and rupture of microbes Protects C3b Factor P Stabilizes C3 convertase of the (Properdin) Alternative Pathway Microbio and Para - Mod 4 🏠 Immunology 2 6 of 12 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  ○ Responsible for T-cell antigen recognition Regulatory ○ Also play a vital role in Prevents assembly of C9 molecules to proteins Recognition of self; and form MAC present (CD59) Rejection of foreign tissues Polygenic: contain many genes Downgrade complement Polymorphic: have many alleles on a gene activation CD46, CD55, Prevents generation of C5b to 9 CD59, CLASSES OF MHC PROTEINS (or MAC) Clusterin CD58 Note: Clusterin is a membrane-bound inhibitor Class I Encoded by HLA-A, B, C genes Code for markers that allow recognition of self molecules and regulation of 3. COMPLEMENT AND DISEASES immune reaction Deficiencies of the complement molecules may pose Expressed on all nucleated cells problems and predispose the patients to be susceptible EXCEPT cells in retina and brain to infections Present peptide antigens to CD8 T-cells Class II Encoded by HLA-D region (namely, DEFICIENCY DEFECTS HLA-DP, DQ, DR genes) C1, C2, or C4 Collagen vascular disorders Expressed on antigen-presenting cells: macrophages, dendritic cells, & B-cells C3, C2 Increased susceptibility to infections Present peptide antigens to CD4 T-cells C5 to C9 Increased susceptibility to Neisseria Class III Locus encodes complement proteins and meningitidis & N. gonorrhoea several cytokines. III. CELL-MEDIATED IMMUNITY Provides defense against intracellular microbes ○ Can control intracellular infections that antibodies cannot reach Mediated by T-lymphocytes that recognize antigens produced by intracellular microbes COMPONENTS OF CELL-MEDIATED IMMUNE SYSTEM Helper T Cells Activate macrophages (CD4 cell) Assist in B-cell process Help activate cytotoxic T cells Cytotoxic T Destroy infected host cells and other cells foreign cells (CD8 cell) 2 Classes of MHC: Class 1 (left) & Class 2 (right). Each is composed of 2 polypeptides that form an 1. IMMUNE RESPONSE antigen-binding groove. During an immune response, a recognition system In order for an antigen to be recognized as foreign by capable of distinguishing self from non-self is the T-cells, the antigen must be presented by the MHC essential for effective immunity of an antigen-presenting cell (APC). INNATE Cells make use of toll-like receptors IMMUNITY (TLRs) to identify parts of a microbe ADAPTIVE Makes use of the following in the IMMUNITY identification, processing, & presentation of antigens: Antibody-antigen complex: antigens bind directly to antibodies MHC (Major Histocompatibility Complex) proteins: T cell receptors only recognize peptide antigens if presented by the MHC molecule on the APCs (antigen presenting cells, e.g., macrophages) A. MAJOR HISTOCOMPATIBILITY COMPLEX Also known as “Human Leukocyte Antigen System” Major receptors on lymphocytes and macrophages Process of MHC. Set of genes located at chromosome 6 that: ○ Code for human cell receptors; and is Microbio and Para - Mod 4 🏠 Immunology 2 7 of 12 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  PROCESS OF MHC 2. ENDOGENOUS ANTIGENS 1 An antigen is attached to the MHC on its groove. 2 Presented to the T-cell for recognition 3 Elimination B. ANTIGEN PROCESSING FOR MHC PRESENTATION 1. EXOGENOUS ANTIGENS 1 Antigens arising outside the body cells are phagocytized by an APC. 2 They then load epitopes into the complementary antigen binding groups of MHC II molecules 3 The MHC II protein-epitope complex are then displayed on the outside of the APC cytoplasmic membrane to be recognized by T-cells. Key points in Processing Endogenous Antigens. 1 Molecules of each polypeptide produced within nucleated cells are catabolized into smaller pieces, including polypeptides that are either: Produced by intracellular bacteria; or Coded by viruses 2 These small peptides bind onto complementary antigen-binding groups of the MHC Class I molecules in the membrane of the endoplasmic reticulum. 3 This membrane loaded with MHC Class I proteins is then packaged into a vesicle by a golgi body and inserted into the cytoplasmic membrane. 4 Result: The cell displaced the MHC Class Iprotein-epitope complex on the cell surface. For antigens to be recognized as foreign by T cells, Ag must be presented by the MHC of an APC. The presented Ag attaches to MHC (groove) and then presented to T cells for recognition and eventually elimination. Key points in Processing Exogenous Antigens. Microbio and Para - Mod 4 🏠 Immunology 2 8 of 12 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  IV. B CELL ACTIVATION 1. B-CELL RECEPTORS “BCRs” B-cells have receptors which are immunoglobulins They serve as receptors for a specific antigen or a closely related group of antigens All immature B-cells carry IgM on their surface and most also express IgD An antigen interacts with B-cells that show the best fit A. MECHANISM OF B-CELL ACTIVATION Interaction of B cells (blue) and T cells (magenta) in the Lymph Node (white). 4 This interaction can occur since the B and T lymphocytes that have encountered antigen migrate towards the boundaries between the T and B cell areas in the secondary lymphoid tissues. 5 The CD40 ligand (CD40L) of T cells binds to CD40 on B cells. Antigen (yellow) and BCR (igM) bound together as they are internalized by the B cells. 6 T cells produce IL4, IL5, IL6 which induce B cell proliferation. 1 BCR together with its bound antigen is internalized by the B cells and the antigens are degraded to V. T CELL ACTIVATION form peptides. How T-cells are activated. MHC Class II-peptide complex (red and yellow, respectively) as recognized by CD4 Helper T Cells (magenta). Occurs primarily in secondary lymphoid organs 1. MECHANISM OF T-CELL ACTIVATION 2 The degraded peptides then return to the surface bound to MHC Class II molecules. 1 T cell in the resting state bind to an antigen 3 The MHC Class II-peptide complex on the B cell is fragment on the MHC protein of an APC recognized by the CD4 helper T-cells. 2 This stimulates T cells to divide and secrete These T cells have already interacted with lymphokines antigen-presenting dendritic cells and have T helper cells are the first to be activated differentiated in response to the same pathogen. T helper cells stimulate themselves by producing IL-2 Thus, a combination of antigen recognition and IL-2 causes these cells to multiply. A. ACTIVATION OF HELPER T CELLS Microbio and Para - Mod 4 🏠 Immunology 2 9 of 12 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  Helper T-cells. B. ACTIVATION OF CYTOTOXIC T CELLS Activation of Helper T-cells and what occurs when a T cell 1. MECHANISM OF CYTOTOXIC T CELLS spots the Peptide on an MHC. This activates cytotoxic T-cells to attack infected cells, especially abnormal or virus infected cells 1 A macrophage processing an antigen. 2 The antigen is degraded. 3 The antigen or peptide fragment is inserted on the MHC of the macrophage to be presented to a T helper cell. 4 T helper cell recognizes the peptides on the MHC 5 T helper cell binds to the complex stimulating the antigen presenting cell to secrete IL-1. 6 The IL-1 stimulates the T helper cell to produce IL-2. Macrophage presenting a peptide in the form of toxins on MHC class I to cytotoxic T-cells (red arrow) 7 This activates the T helper cell to form its clones. 2. CYTOTOXIC T CELLS IN VIRUS INFECTED CELLS 8 Activation of the T helper cell and the production of IL-2 initiates cell division into: T helper 1 (TH1) cell; T helper 2 (TH2) cell; and Memory cells. 9 T Helper 1 cell recognizes peptide on the MHC of a infected macrophage. This activated infected macrophage destroys bacterial infection in the cell mediated immune response. 9 T Helper 2 cell activates the B cell by attaching to b it. This produces a humoral response against the foreign antigen. Cytotoxicity. Note: Helper T cells, T helper cells, and CD4+ T cells are used interchangeably but are one and the same. 1 In a virus infected cell, fragmented viral proteins bind to Class I MHC proteins. 2 Class I MHC proteins then transport the viral fragment to the cell surface so that cytotoxic T-cells may recognize them. 3 They remain attached to one another for about 10 mins while the cytotoxic cell secretes perforin. 4 After an hour, the weakened membranes of the infected cell rupture and lyse. Microbio and Para - Mod 4 🏠 Immunology 2 10 of 12 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  VI. SUMMARY Adaptive immunity is the third line of defense of the body. ○ Antigen, antibodies, and B & T lymphocytes play an important key role in its mechanism. Primary immune response compared to the secondary immune response gives a slower response and with a lesser amount of antibodies produced. The secondary immune response gives a more rapid intense response in the second activation because of the involvement of memory cells. Cells are recognized via the MHC and antigen-antibody complex. Microbes can be eliminated via the complement system using the classical pathway wherein pathogens are coated by antibodies which are eventually eliminated through cytolysis. Microbio and Para - Mod 4 🏠 Immunology 2 11 of 12 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.  ANNEX A: HELPER T CELLS (FROM HANDOUT 📖) Microbio and Para - Mod 4 🏠 Immunology 2 12 of 12 The use of trans, practice questions, and evals ratio must be used discreetly and social media/public exposure of the aforementioned shall be strictly prohibited.