Intro to the Immune System III and IV.pdf

Intro to the Immune System III and IV 31/10/23, 3:39 PM Intro to the Immune System III and IV Acquired (adaptive) immunity • Induced by the presence of ‘foreign’ material • Able to discriminate between self and non-self • Includes cytokines, antibodies, B and T cells B cells • Mature in the bone...

Intro to the Immune System III and IV 31/10/23, 3:39 PM Intro to the Immune System III and IV Acquired (adaptive) immunity • Induced by the presence of ‘foreign’ material • Able to discriminate between self and non-self • Includes cytokines, antibodies, B and T cells B cells • Mature in the bone marrow • Important in humoral immune response • B and T cells normally circulate around their primary lymphoid tissue (site of development bone marrow/thymus) in their inactive form • Antigen presentation activates the B cells and T cells in secondary lymphoid tissue (e.g. lymph nodes, spleen, MALT) B cell activation and the generation of high affinity antibodies 1. Membrane-bound antibodies on the B cells bind to target antigen IgM (or IgD) within the B cell zone of lymph nodes 2. B cells require 2 signals to become fully active and begin proliferation - the antigen and ‘helper signals’ e.g. from TH cells, PRR and PAMPs or from multiple antigens 3. Once activated, they clonally proliferate and become either a plasma cell (antibodies) or a memory B cell - germinal centre response 4. High affinity antibodies are generated - IgM (produced by plasma cells) → IgG (produced by B cells responding to certain antigens), assisted by TH cells Transport of lymphocytes • Lymph and lymphocytes leave lymph node → medullary sinus → efferent lymphatic vessels → blood circulation via lymphatic ducts at the subclavian vain Antibodies • Made up of 2 light chains and 2 heavy chains • Each has a unique variable region (antigen binding site) which is specific against one antigen • Membrane bound antibody: located on surface of B cell • Secreted antibody: secreted by plasma cells, present in serum and tissue fluids IgM - first antibody to be made in in an infection • • Monomer when bound to B cell membrane but pentamer when released into plasma Functions: B cell activation, agglutination (immune complex formation - enhances phagocytosis), complement system activation through classical pathway IgG - the most abundant antibody in the plasma https://galvanized-borogovia-4fa.notion.site/Intro-to-the-Immune-System-III-and-IV-5ad442db684c4d5f803ac5755796fe12 Page 1 of 3 Intro to the Immune System III and IV 31/10/23, 3:39 PM • • • Monomer Dominant type during secondary response Functions: foetal immunity (placental transfer), complement activation, NK cell activation, neutralisation IgA - the second most abundant antibody • • Monomer in serum, helps with neutralization of pathogens (membrane bound form) Dimer in secretory fluids (e.g. colostrum) ◦ Neonatal defense - protects GI tract of neonates IgD - the second least abundant antibody • • Monomer B cell activation IgE - least abundant antibody normally • • Monomer Produced in allergic response T cells • Mature in the thymus • CD4+ Helper T cells: activate B cells & stimulate production of memory B cells • CD8+ Killer T cells: kill infected cells via perforin/granzymes/granulysin • Regulatory T cells: lymphocyte suppression • Memory T cells: involved in the adaptive immune response MHC molecules • T cells can only recognise peptide antigens that are presented to their TCR by MHC molecules • • Class I MHC: expressed on all nucleated cells, present peptide antigens to CD8+ killer T cells Class II MHC: expressed only on antigen presenting cells (e.g. dendrites, macrophages), present peptide antigens to CD4+ helper T cells T cell activation 1. Dendritic cells recognise and phagocytose antigenic debris 2. In the presence of pro-inflammatory mediators (e.g. TNF⍺), the dendritic cells mature and increase expression of stimulatory molecules on their surface 3. Dendritic cells phagocytose the pathogenic antigens, break the antigens down into short peptides and load them onto MHC II molecules 4. MHC II molecules transported to cell surface a. At the same time, the maturing dendritic cells migrate into the lymph nodes via the afferent lymphatic vessels 5. Co-stimulatory molecules enable T cell to respond to antigen and fully differentiate T cell differentiation CD4+ T cells → T helper cells • Antigen-activated CD4+ T cells secrete IL-2 and express IL-2 receptors (T cell growth factor) https://galvanized-borogovia-4fa.notion.site/Intro-to-the-Immune-System-III-and-IV-5ad442db684c4d5f803ac5755796fe12 Page 2 of 3 Intro to the Immune System III and IV 31/10/23, 3:39 PM • CD4+ T cells → T helper (THO) cells → Effector TH cells e.g ◦ TH1 cells: secrete pro-inflammatory cytokines (IL2, IFN𝛾) which stimulates production of ROS (macrophage-mediated) ◦ TH2 cells: secrete mainly IL4, IL5 and IL6 which promote B cell proliferation and induces antibody production ◦ TFH cells: stimulated by presented antigen peptides + MHC II molecules on B cell, then stimulate the B cells to proliferate and differentiate (plasma + memory) by secreting IL4 and IL21 CD8+ T cells → CTLs (TC cells) • IL-2 (provided by TH cells) promotes differentiation and proliferation of antigen activated (via MHC I) CD8+ cells into cytotoxic T lymphocytes (CTLs) • CTLs migrate out of secondary nodes and enter site of infection (via transendothelial migration) and then kill virally infected host cells by recognizing pathogenic antigens attached to MHC class I ◦ Also involved in killing cancer cells Pathogens and their immune system components Immunesystemcomponent Bug Phagocytes Bacteria TLymphocytes Viruses AntibodyandBLymphocytes Fungi Eosinophils Protozoa Mastcells Worms Complement https://galvanized-borogovia-4fa.notion.site/Intro-to-the-Immune-System-III-and-IV-5ad442db684c4d5f803ac5755796fe12 Page 3 of 3