Immunology: Adaptive Immunity PDF

Last edited: 8/8/2021 1. ADAPTIVE IMMUNITY Immunology: Adaptive Immunity Medical Editor: Dr. Sofia Suhada M. Uzir OUTLINE (B) ACTIVATED B-LYMPHOCYTE...

Last edited: 8/8/2021 1. ADAPTIVE IMMUNITY Immunology: Adaptive Immunity Medical Editor: Dr. Sofia Suhada M. Uzir OUTLINE (B) ACTIVATED B-LYMPHOCYTE Have B-cell receptors (usually IgD antibodies) including I) HUMORAL IMMUNITY the MHC II molecules with the foreign antigen on its II) B-LYMPHOCYTES membrane → important to make more specific types of III) T- LYMPHOCYTES antibodies specific to the antigens IV) CELL MEDIATED IMMUNITY V) NATURAL KILLER CELLS It still cannot undergo proliferation VI) REVIEW QUESTIONS (C) PROLIFERATION OF THE B-LYMPHOCYTES VII) REFERENCES Occurs when there is a stimulus: the macrophages (APC) → interacts with T-helper cell I) HUMORAL IMMUNITY (1) Interactions of APC and T-cell The antigens are exogenous o Antigens outside the cell trigger the B-cell Before interacting with the antigens, the T helper cell is a proliferations naïve T-helper cell → have receptors which can respond to the molecule but still not activated and unspecific (A) CELLULAR EVENTS Before entering the lymph nodes, there are cellular Remember: events happening in order to bring the antigens inside the On the membrane of the macrophages, there are: lymph node o MHC I molecules with some type of self-antigen  All nucleated cells must have this molecule (1) Macrophages o MHC II molecules which expresses the antigen o In macrophages the antigens that were pulled away from bacterial microbe may be expressed on MHC II Signals sent to the nucleus of naïve T-cells for activation molecules on cell surface → these macrophages are include: referred to as Antigen Presenting cells (APCs) → these APCs then interact with T-helper cells (i) Primary signal o Antigen Presenting cells (APCs) MHC II molecules on cell membrane of macrophages  Macrophages o Which interact with CD4 molecule on T helper cells  Dendritic Cells  B-cells Antigen which is expressed on the MHC II molecule o Interact with T-cell receptor specific to that antigen (2) Neutrophils on T-helper cells o In neutrophils these antigens are exocytosed into o Like the B-cell, due to recombination, every T-cell interstitial fluid and then carried to nearby lymph have different types of receptors specific to the type nodes of antigens o This is the free antigen o This interaction sends primary signals to the nucleus II) B-LYMPHOCYTES (ii) Secondary signal Co-stimulation B7 molecules Lymph nodes contain germinal centers which contains o Which interact with CD28 on naïve T helper cells → large amount of B-cells/ B-lymphocytes send secondary signal/co-stimulation to the B-lymphocytes contains specific types of receptor on their nucleus membrane which is called the B-cell receptors o Designed to be IgD antibody (iii) The third signal o The B-cell receptors are formed through recombination. This means like the DNA inside the B- The macrophages secrete IL-1 molecule cell, the MHC II molecules on cell membrane undergo o Binds to specific receptor on the naïve T-helper cells shuffling producing different types of binding domains → this sends the third signal to the nucleus o Hence, each receptor can bind different types of Activation of the T-cell leads to the production and antigen secretion of IL-2 → IL-2 can bind on the T-cell  Example: Square antigen binds with the square (autocrine) → activation of the cell sends signal to the receptor and the circular antigen binds with the nucleus again to produce IL-4 and IL-5 circular receptor (A) NAÏVE B-LYMPHOCYTE Note: Before the binding, the B-lymphocyte is technically naïve Autocrine: Binding to the same cell that secretes it since it hasn’t gone any immunogenicity response → activation happens when the free antigen circulating (2) B-cell proliferation – cytokines released inside the lymph node, by random chance binds onto the The B-cell and T-helper cell interaction as listed above B-cell receptor which was perfectly designed to fit that triggers T-helper cells to release cytokines: antigen → activates the B-cell through signaling IL-4 and IL-5 → converts naïve T cell into TH2 cells mechanisms → the B-lymphocytes, now more mature, undergo receptor mediated endocytosis of antigen- (i) IL-4 antibody complex into B cell → chromosome number 6 of activates B-cells to start proliferating (clonal expansion) the B cell produce MHC II molecules which fit perfectly to →activated B-cells will ↑ →immunocompetent the antigen → fused on to the cell membrane ADAPTIVE IMMUNITY IMMUNOLOGY: Note #1. 1 of 4  o This B-cell have specific B-cell receptor to the specific b. IL-4 → converts naïve T cell into TH2 cells (anti- foreign antigen and MHC II molecules with the foreign inflammatory pathway) antigen, expresses on its membrane → can c. IL-12 → ↑converts naïve T cells into TH1 cells (pro recognize any types of antigens due to the specific B- inflammatory pathway) cell receptor d. TGF-beta, IL-1/IL-6/IL-23→↑converts naïve T cells into TH17 cells (ii) IL-5 e. TGF-beta → converts naïve T cells into T ↑ differentiation of proliferated B cells into memory B regulatory cells cells and plasma cells T regulatory cells → promotes self-tolerance Prevents autoantibodies → reducing autoimmune (iii) IL-5/IL-6 reactions via TGF-beta and IL-10 release ↑ plasma cells to produce antibodies against specific (1) TH2 Cells antigens on pathogens o Neutralization Stimulated by IL-4  The antibodies bind to all the surface antigens on Genes to be activated the pathogen → block the antigen from attaching o IL-2 to healthy host cell which can cause damage o IL-4 o Precipitation reaction o IL-5  Antibody bind to the freely circulating antigen → Fight extracellular pathogens causes precipitation → enhance opsonization  Free antigen-antibody complexes may deposit into (i) Stimulate B cell pathway via IL-4/ IL-5 tissues causing type 3 hypersensitivity o B cells → Plasma cell → ↑antibody production (IgE) o Lysis  Antibodies binds to the same pathogen → this (ii) Stimulates pathogen killing by activating produces different types of proteins which eosinophils produces membrane attack complex → this causes lysis of the cell (2) TH1 Cell o Agglutination Stimulated from IL-12  When there’s a mismatch/incompatible blood → Genes to be activated antibodies bind to the antigen on the RBCs o Gamma interferon (IFN-gamma) o Opsonization o Tumor necrotic factor  When the pathogen is marked for destruction by the antibody → the pathogen will be destroyed by Fight intracellular pathogens the macrophages either through the antibody- dependent cellular phagocytosis or complement- (i) Stimulates macrophages via IFN-gamma dependent cytotoxicity o ↑ phagocytosis of pathogens o ↑ MHC-II expression III) T- LYMPHOCYTES (ii) Stimulates B cell pathway via IL-2 and IFN- Antigen presenting cells like macrophages, B-cells and dendritic cells present antigens on their MHC II molecules gamma and then present the antigen to T-helper cells o Triggers IgG antibody production from plasma cells (iii) Stimulates infected cellular killing via NK cells, cytotoxic T cells (3) TH17 Cells Regulates inflammation and fights extracellular pathogens Regulates Inflammation response (pro and anti- inflammatory) through use of neutrophils via IL-1/ IL-21 release Figure 1. T-cell [Biology Dictionary] (A) NAÏVE T-HELPER CELLS Contains CD3 molecules o Signaling molecule inside the cell It can be activated into → TH1 cell or TH2 cell Naïve T helper cells expresses: o CD4 molecules that binds to the MHC II molecule on the antigen presenting cells o T-cell receptor that binds to the antigen expressed on the MHC II molecule of antigen presenting cells o CD28 molecules that bind to B7 molecules on antigen presenting cells The antigen presenting cell and T-helper cell interaction as listed above activates T-helper cells to release the following cytokines: a. IL-2 → ↑T cell proliferation 2 of 4 IMMUNOLOGY: Note #1. ADAPTIVE IMMUNITY  IV) CELL MEDIATED IMMUNITY V) NATURAL KILLER CELLS Triggered by endogenous antigen It is not a part of the adaptive immunity, only the o The antigen is inside the cell causing damage to the mechanism of action is very similar to cytotoxic T- cell cells Mediated through the cytotoxic T-cells NK cells are large agranular lymphocytes The activated natural killer cells release Perforins and Granzymes which trigger apoptosis of viral infected cells They can kill by 3 ways: (1) Absent MHC I molecule expressed on the surface All nucleated cells must have MHC I molecule expressed on the surface If a viral pathogen infects tissue cells → virus induces abnormal MHC I complex or inhibit MHC I formation This foreign MHC I or Absent MHC I due to viral infection → activates natural killer cells (2) Different type of MHC I expressed on the surface (MICA) MICA doesn’t contain beta 2 molecule Structure of MHC I molecule contains the o Alpha 1, alpha 2, alpha 3 and beta 2 molecule This foreign MHC I like molecule activates natural killer Figure 2. Humoral vs cellular [Socratic] cells (3) Through IgG mechanism (A) CYTOTOXIC T-CELLS Via antibody dependent cell mediated cytotoxicity Kills virus infected cells and neoplastic (cancerous) cells If IgG antibodies made by plasma cells bind viral antigens When cells are infected by virus or are cancerous this expressed on MHC-I complex this allows natural killer o The virus can get integrated into the DNA → creates cells to bind to Fc portion of IgG antibody via their CD-16 viral proteins → endogenous proteins → can get protein this activates the natural killer cells→ the integrated into the self-peptide → leads to expression activated natural killer cells then release Perforins and of viral antigen or cancer antigens on MHC-I complex Granzymes which trigger apoptosis of viral infected cell o MHC-1 complex of infected or cancerous cells interact with CD8 molecule on cytotoxic T cell The cancerous or viral antigen on infected or cancerous cells interact with T cell receptor on cytotoxic T-cell o Once cytotoxic T-cells are activated they release perforins and granzymes (i) Perforins o This creates pores in infected or cancerous cells (ii) Granzymes o Moves through the pores and activates pro-apoptotic gene → production of BAX proteins → which removes BCL-2 from mitochondrial membrane which allows cytochrome C to leak into cytoplasm → which activate proteolytic enzymes called caspases → which leads to cell destruction (apoptosis) Figure 3. Cytotoxic T-cell [VectorStock] ADAPTIVE IMMUNITY IMMUNOLOGY: Note #1. 3 of 4  VI) REVIEW QUESTIONS VII) REFERENCES The specific targeted responses constitute the third Humoral vs Cellular response. Socratic Q&A 2017 [digital image] https://socratic.org/questions/what-are-examples-of- line of defense in response to an infectious agent is humoral-immunity called Biology dictionary. Helper T-cell [digital image] a. Third line of defense https://biologydictionary.net/helper-t-cell/ b. Adaptive immunity Cytotoxic T-cell. Vector Stock [digital image] https://www.vectorstock.com/royalty-free-vector/cytotoxic-t-cell- c. Acquire immunity vector-23523146 d. All of the above Le T, Bhushan V, Sochat M, Chavda Y, Zureick A. First Aid for the USMLE Step 1 2018. New York, NY: McGraw-Hill Medical; 2017 Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ: The characteristics of adaptive immunity include Pearson; 2020. a. Specificity Boron WF, Boulpaep EL. Medical Physiology.; 2017. b. Immunologic memory Urry LA, Cain ML, Wasserman SA, Minorsky PV, Orr RB, Campbell NA. Campbell Biology. New York, NY: Pearson; 2020. c. Discrimination of self from non-self-molecules Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, d. All of the above Loscalzo J. Harrison's Principles of Internal Medicine. New York etc.: McGraw-Hill Education; 2018. lberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Which of the cells are involved in adaptive Molecular Biology of the Cell. New York, NY: Garland Science; immunity? 2002 a. B cells and T cells Murphy K, Weaver C. Janeway's Immunobiology. Garland Science; 2016 b. B cells only Doan T, Melvold R, Viselli S, Waltenbaugh C. Immunology. c. T cells only Lippincott Williams & Wilkins; 2012 d. Macrophages and NK cells Levinson W. Review of Medical Microbiology and Immunology. Lange; 2012 T cell mediates a. Humoral immunity b. Non-specific defense c. Cell mediated immunity d. None of the above The ratio between T cells and B cells is a. 3:1 b. 1:3 c. 1:1 d. 1:2 B cells and T cells are originated from a. The spleen b. Thymus c. Bone marrow d. Lymph node Injection of anti-venom against snake bite is an example of a. Active immunity b. Passive immunity c. Non-specific immunity d. Phagocytic immunity Which of the following statement are true regarding adaptive immunity? a. Prior exposure to antigen is essential b. Prior exposure to antigen is not essential c. It is a non-specific defense mechanism d. Macrophages are the major cells involved Active immunity involves a. Contact with foreign antigens b. Immunologic memory c. Slow primary response d. All of the above Active immunity is produced by a. Clonal section b. Clonal expansion c. Both A and B d. All of the above CHECK YOUR ANSWERS 4 of 4 IMMUNOLOGY: Note #1. ADAPTIVE IMMUNITY