Microbiology Chapter 12 Adaptive Immunity PDF

Smallpox – the 1st vaccine and eradicated illness https://youtu.be/LxVdGSiOyAM Chapter 12 Adaptive Immunity  Defense Mechanisms of the Host Host Defenses – Innate, natural defenses: present at birth, provide nonspecific resistance to infecti...

Smallpox – the 1st vaccine and eradicated illness https://youtu.be/LxVdGSiOyAM Chapter 12 Adaptive Immunity  Defense Mechanisms of the Host Host Defenses – Innate, natural defenses: present at birth, provide nonspecific resistance to infection – Adaptive immunities: specific, must be acquired To protect the body against pathogens, the immune system relies on a multilevel network of physical barriers, immunologically active cells, and a variety of chemicals – First line of defense – any barrier that blocks invasion at the portal of entry – nonspecific – Second line of defense – protective cells and fluids; inflammation and phagocytosis – nonspecific – Third line of defense – acquired with exposure to foreign substance; produces protective antibodies and creates memory cells – specific 2  An Overview of Adaptive Immunity The adaptive branch of immunity is the third line of defense Two features that characterize specific immunity: – Specificity – antibodies produced, function only against the antigen that they were produced in response to Antigen – Molecules that stimulate a response by T and B cells; consist of protein, polysaccharide, and other compounds from microbial cells and viruses – Immunological Memory – lymphocytes are programmed to “recall” their first encounter with an antigen and respond rapidly to subsequent encounters Subdivided into two branches: the cellular response (also called T cell–mediated immunity) and the humoral response (also called B cell- or antibody–mediated 3 immunity)  Antigen Features An antigen is any substance that, if presented in the right context, may trigger an immune response Most antigens are microbial proteins or polysaccharides Any antigen that can successfully trigger an immune response is said to be immunogenic – Dependent antigen size, overall molecular complexity, and chemical composition Haptens, or incomplete antigens, are unable to stimulate an immune response unless they are linked to a more larger carrier molecule (i.e. protein) – A number of medications i.e. penicillin act as a hapten The parts of an antigen that B and T cells recognize and mount an immune response to are called epitopes, or antigenic 4 determinants  T Cell and B Cell Receptors B cells and T cells are covered in thousands of antigen recognition receptors – Each receptor on a particular lymphocyte recognizes the same epitope Antigen binding to receptor triggers lymphocyte activation, allowing for proliferation (clonal expansion) – Clones develop into effector cells (plasma cells) that make antibodies and memory cells 5 An Overview of T Cells There are two main classes of T cells that are distinguished based on the presence of cluster of differentiation (CD) proteins (specialized surface glycoproteins): 1. T cytotoxic cells (TC cells) directly destroy infected or cancerous cells and have CD8 surface molecules 2. T helper cells (TH cells) coordinate an adaptive immune response by stimulating other white blood cells and have CD4 surface molecules (‘call 4 help’) Once activated TH cells may differentiate into: T helper 1 cell - mainly activate T cytotoxic cells, macrophages, and natural killer cells to destroy pathogens T helper 2 cell - primarily stimulate B cells to make antibodies T regulatory cell - control functions of other white blood cells, to ensure that immune responses taper off once a threat subsides 6 T Cell Classes and Subclasses and Their Functions 7  Self Tolerance Screening T and B cells recognize a wide variety of antigens due to gene shuffling mechanisms that generate an incredibly diverse repertoire of antigen receptors during lymphocyte development To prevent autoimmunity, the body has screening mechanisms that select for immune cells with self- tolerance, meaning they will not attack normal self-cells T cells are screened in the thymus based on the ability to recognize major histocompatibility complex (MHC) proteins (“self-proteins” also known as human leukocyte antigens (HLAs)) B cell are screened in the bone marrow to ensure that any future antibodies they make won’t cross-react with self-antigens T and B cells that don’t exhibit self-tolerance are signaled to undergo apoptosis 8 (programmed cell death) Presentation of Intracellular and Extracellular Antigens 9  Key MHC Features MHCs have an important role in differentiating self from foreign (allorecognition), and are thus the main proteins that must be matched for tissue transplantations If donor and recipient’s MHCs are not closely matched, then the developing B and T cells mount an immune response against their new host, which leads to a scenario called graft-versus-host disease 10  Lymphocyte Activation T cells require two signals for full activation – Requiring two activation signals prevents immune system misfires and provides a way for T cell populations to become specialized T cytotoxic cells will interact with antigens presented in the cleft of MHC I molecules, while T helper cells will bind to antigens present in the cleft of MHC II molecules If a given T cell successfully binds to one of the MHC–antigen complexes on the APC’s surface, then activation occurs 1. The primary activation signal involves the T cell’s TCR interacting with the MHC–antigen complex 2. The secondary activation signal involves co-stimulatory proteins on the surface of the APC binding to co-stimulatory proteins on 11 the T cell’s surface  Superantigens Superantigens are especially potent T helper cell activators Examples of superantigens include bacterial toxins such as staphylococcal enterotoxins, staphylococcal toxic shock toxin, and streptococcal exotoxins that generate the features of scarlet fever Superantigens are not processed and presented to T helper cells like normal antigens but are instead directly crosslinked to MHC II and the T helper cell TCR to cause a bulk, nonspecific activation – Up to 20% of the T helper cells in the lymphatic tissues may become activated if superantigens are in the bloodstream In response to bulk activation, T helper cells create cytokine storms (especially of interleukin 2, interferon gamma, and tumor necrosis factor alpha) that can lead to 12 shock and even death  T Cell Proliferation and Differentiation Once T cytotoxic and T helper cells bind to an epitope presented by an APC, the T cells undergo clonal expansion by repeated rounds of mitosis Chemical signals influence T cell differentiation into subclasses containing effector and memory cells, but no matter what class or subclass it belongs to, it will recognize the same epitope that activated the original parent cell 13  T Helper Cell Differentiation Proliferation and differentiation signals that lead to various cell subclasses are best understood for T helper cells The types of cytokines released by APCs in lymphatic tissues influence what T helper cell subclasses develop The types of cytokines released depend on numerous factors that include the antigen’s nature and the amount of antigen present The T helper cell subclasses generated as a result of the initial APC interaction are important in dictating the nature of the developing immune response – Cellular response is favored if TH1 cells develop (TH1 cells release cytokines that are potent T cytotoxic cell stimulators) – Humoral response is favored if TH2 cells develop (TH2 cells release B-cell activating cytokines) 14  Antigen Elimination and Memory Each T cell subclass includes effector cells and memory cells T cytotoxic subclasses of effector cells will “seek and destroy” cells that display the activating antigen in the grip of MHC I – When the TCR of a patrolling T cytotoxic cell binds to an MHC I–antigen complex, the T cytotoxic cell releases perforins that form pores in the target cell and granzymes, which enter through the pore to break down host cell proteins and induce apoptosis T helper subclasses of effector cells do not directly attack invaders but support the action of the cells that will actually do the work in the immune response Memory cells of these various subclasses remain in lymphatic tissues following a threat, ready to rapidly proliferate and differentiate 15 upon a subsequent exposure A Comparison of B Cells and T Cells 16  B Cell Activation Most antigens are T dependent, and require T helper cells to fully activate B cells – 1st activation signal is the binding of the antigen to the B cell receptor (BCR)/MHC II – T helper cells then interact with the MHC II–antigen complex on the B cell surface and co-stimulatory proteins on the B cell and T helper cell surface interact, allowing the T helper cells to release cytokines that provide the 2nd required activation signal Repetitive antigens (usually surface polysaccharides) may act as T-independent antigens – Multiple BCRs on the given B cell directly bind to the antigen (1st activation signal) and some other immune system cell (not TH cell) provides the 2nd activation signal 17  B Cell Proliferation and Differentiation Once fully activated, B cells undergo proliferation by repeated rounds of mitosis and eventually differentiate into effector cells called plasma cells (majority) and some become memory cells All of the resulting B cell clones recognize the exact same epitope of the antigen 18  Key Antibody Functions Plasma cells secrete proteins called antibodies, also known as immunoglobulins (Ig) Antibodies bind to the antigen that triggered the B cell’s activation and can activate complement cascades, neutralize antigens, and promote phagocytosis of targeted antigens 19  Antibody Structure An antibody’s single-unit, monomeric structure consists of two heavy chains and two light chains held together by covalent bonds The tips of the “Y”-shaped molecule are the antigen-binding sites A given plasma cell makes antibodies that all recognize the same epitope There are five antibody isotypes: IgG, IgA, IgM, IgE, and IgD (“GAME Day”) A given B cell can undergo isotype switching, which alters what class (subtype) of antibody is made Each isotype has unique structural and functional features that allow it to perform certain tasks The isotype made depends on numerous factors such as stimulatory cytokines and the time frame of antigen exposure 20 Antibody Isotypes 21 Key Players in Adaptive Immunity 22  The Anamnestic Response Unlike effector cells, memory cells are long-lived and reside in lymphoid tissues to provide for immunological memory Our memory cells allow for a rapid reactivation of the cellular and humoral adaptive response (the anamnestic response aka secondary immune response) if the same antigen is encountered again later In the primary antigen exposure, a lag period exists after which low levels of IgM are made first, followed by IgG The secondary antigen response is faster (no lag period) and stronger (high IgG titers and moderate IgM) than the primary antigen exposure – Antibodies made in a secondary response have enhanced binding affinity for antigens Tracking antibody titers (amount of antibody in blood) is useful for determining disease exposure and the degree of vaccine protection  Subcategories of Acquired Immunity There are four classifications for adaptive immunity that are based on the process through which the immunity is acquired (whether the immunity is acquired naturally or via human intervention) and the source of the antibodies (if antibodies are self-made or from other sources): – Naturally acquired active immunity (example: infection) – Artificially acquired active immunity (example: vaccination) – Naturally acquired passive immunity (example: maternal antibodies in utero or in colostrum) – Artificially acquired passive immunity (example: antiserum, a preparation of antibodies developed to neutralize specific toxins or venoms) Active immunity provides long-term immunological protection (compared to passive immunity) because the host actively makes memory cells and antibodies 24  Q & A: Question 1 All the following apply to T cells except A) Originate in the bone marrow B) Mature in the thymus C) Reside in the lymphoid tissue D) Coordinate the humoral response by making antibodies  Q & A: Question 1 Answer: D (Coordinate the humoral response by making antibodies)  Q & A: Question 2 Consider a genetic mutation which causes T helper cells to be unable to respond to stimulation by the cytokines which lead to TH2 differentiation. This mutation would cause a patient to be deficient in which activity? A) Action of cytotoxic T cells B) Action of macrophage C) Production of antibodies D) Production of memory cells  Q & A: Question 2 Answer: C (Production of antibodies)  Q & A: Question 3 Which number on the diagram is labeling the portion of the antibody that makes it specific for the antigen is binds to? A) 5 B) 3 C) 4 D) 2 Q & A: Question 3 Answer: C (4)  Q & A: Question 4 Antibodies do all the following except A) Activate the complement cascade B) Activate killing by T cytotoxic cells C) Neutralize antigens to prevent binding to host cells D) Increase phagocytosis by opsonization  Q & A: Question 4 Answer: B (Activate killing by T cytotoxic cells)  Q & A: Question 5 During a primary response to an antigen, which of the following is the first immunoglobulin to appear? A) IgG B) IgD C) IgE D) IgM Q & A: Question 5 Answer: D (IgM)