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Adaptive Immunity Stuart James

La Trobe University CRICOS Provider Code Number 00115M

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Adaptive (Specific) Immunity • The ability of the body to defend itself against invading agents such as bacteria, toxins, viruses and foreign tissues

• When it operates effectively, the adaptive immune system protects us from a wide variety of infectious agents

• How does this differ from Innate Immunity? • Specificity for a particular foreign molecule (antigens) – It recognizes and targets particular pathogens that initiate an immune response • Memory for previously encountered antigens whereby a second encounter provokes a more rapid response

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Adaptive (Specific) Immunity • Two types of Adaptive Immunity • Antibody Mediated (or Humoral) Immunity is provided by antibodies present in the bodies “humours” or fluids • Lymphocytes produce and release antibodies into circulation

• Cell mediated Immunity is when lymphocytes themselves, rather than antibodies, fight an invading pathogen • lymphocytes act against ‘cellular targets’ either directly by killing the infected cells, or indirectly, by releasing chemicals that enhance the inflammatory response

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Antigens • Substances that are recognised as foreign and ‘trigger’ immune responses are called antigens meaning ‘antibody generators’ • They are foreign or ‘non-self’ • Antigens have two important characteristics: • Immunogenicity – the ability to provoke an immune response by stimulating the production of specific antibodies • Reactivity – the ability of the antigen to react specifically with antibodies or cells it provoked

• Typically, certain parts of a large antigen molecule act as triggers for an immune response • These are called epitopes or antigenic determinants • Antibodies or lymphocyte receptors bind to these antigenic determinants Slide 4 | Version 2

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Major Histocompatibility Complex (MHC) • Group of glycoproteins on the plasma membrane • ‘Self antigens’ allow immune cells to recognise own cells

• Two classes of MHC antigens • MHCI (Class 1) – found surface of each of your body cells (apart from RBCs) • MHCII (Class 2) – found on the surface of dendritic cells, macrophages and B cells (antigen presenting cells)

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Antigen Presentation Infected cells will breakdown antigenic proteins, and combine the fragments with MHC-I proteins

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Presented on the cell surface as a marker for immune cells

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MHC-I:antigen complex

Macrophages, dendritic cells and B cells can take in antigens from the extracellular space

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Combine fragments with MHC-II for presentation to the immune system

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MHC-II:antigen complex

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Antigen Presenting Cells (APCs)

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Cells of Adaptive Immunity: Lymphocytes B cells mature in bone marrow

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Each contains unique set membrane-bound antibodies which act as antigen receptors for that cell

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Bind to antigens present in ECF

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Secrete large quantities of any unique antibody into extracellular fluid if activated during antibodymediated immunity

T Cells mature in thymus

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Membrane bound antibodies (B cell receptors) act as antigen receptor

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Cytotoxic T cells - Recognise and kill infected cells in cell-mediated immunity

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Helper T cells – release costimulators to facilitate both types of adaptive immunity

T Cell Receptors can only bind to an antigen if combined with MHC

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T cell receptor

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Clonal Selection  Initially, invading antigens outnumber receptors for that antigen on B and T cells  Once lymphocytes have bound to an antigen it will undergo clonal selection which involves – Proliferation: rapidly create clones that have the capacity to recognise that specific antigen – Differentiation: forming highly specialised cells

 Ultimately, the response will produce – Effector cells which will participate in the immediate immune response – Memory cells which hold the “memory” of that antigen and reside in lymphatic tissue • Allows a rapid and powerful response if antigen is present again in future (secondary immune response) • Basis for vaccines Slide 8 | Version 2

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Helper T Cell Activation  T lymphocytes - cells that have special T cell receptors (TCR) that can recognise antigens but only when in an MHC:antigen complex – Like with B cells each T cell has a unique set of TCRs

 Helper T cells contain the CD4 protein and will bind to antigens presented on MHC II containing APCs

 Once activated T cells undergo clonal selection

 Active cells produce cytokines that boost immune responses – Memory cells hold a memory of that antigen in case of future exposure Slide 9 | Version 2

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Antibody-mediated Immunity  Antigens in ECF will bind to a membrane-bound B cell antibody – Primed to make copies of that specific antibody

 Presentation of antigen fragments on their MHC-II – Allows for recognition and co-stimulation by helper T-cells which release cytokines – Rapid proliferation and differentiation of B cells in to plasma cells and memory B cells – Plasma cells mass produce specific AB for that antigen • Distribute themselves throughout ECF and mark every antigen they find • Signals phagocytes to destroy them – Memory cells keep a file of the antigen and Slide 10 | Version 2

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Cell-mediated Immunity  Cytotoxic T cells contain CD8 membrane protein – Also contains a unique set of TCRs

 Recognise and bind with MHC-I:antigen complexes – Present on cells that have been invaded by a foreign substance, microbe, or are cancerous

 Co-stimulation by helper T cells leads to clonal selection – Active cells destroy the cells marked for death – Memory cells keep a file on the antigen presented in case of future exposure Slide 11 | Version 2

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Cytotoxic T cells vs Natural Killer Cells • Both can attack infected cells so how are they different? • Natural killer cells do not undergo clonal selection • Cannot hold a memory of specific antigen • T cells can produce potent secondary immune response at a systemic level

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