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IMM BLOCK 2: LECTURE 1: NK CELLS AND BRIDGE TO ADAPTIVE/OVERVIEW OF ADAPTIVE
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IMM BLOCK 2: LECTURE 1: NK CELLS AND BRIDGE TO ADAPTIVE/OVERVIEW OF ADAPTIVE

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Questions and Answers

Which cells primarily produce type I interferons?

  • Macrophages
  • CD4 T Cells
  • Dendritic Cells
  • A variety of cells (correct)

    • What is the role of interferons in response to viral infections?

  • Inhibit macrophage function
  • Promote bacterial growth
  • Induce cells to undergo proliferation
  • Activate antiviral defenses (correct)

    • Which of the following statements about NK and NKT cells is correct?

  • NKT cells are primarily responsible for producing type I interferons.
  • Both NK and NKT cells originate exclusively from the thymus.
  • NK cells and NKT cells have distinct functions in the immune response. (correct)
  • NK cells are structurally similar to NKT cells.

    • Where are primary immune organs located in vertebrates?

    <p>In specific anatomical locations like the thymus and bone marrow</p> Signup and view all the answers

    How do NK cells interact with macrophages and dendritic cells?

    <p>To enhance the immune response</p> Signup and view all the answers

    What type of immune response does IFN-γ primarily influence?

    <p>Adaptive immune response</p> Signup and view all the answers

    Which of the following is a unique feature of the adaptive immune system?

    <p>Ability to recognize specific antigens</p> Signup and view all the answers

    Which signaling pathway is induced by type I interferons during viral infections?

    <p>RNA-dependent protein kinase pathway</p> Signup and view all the answers

    What is primarily activated by IFN in the immune response?

    <p>Macrophages</p> Signup and view all the answers

    Which type of immunity is Type 1 immunity primarily associated with?

    <p>Protection against intracellular microbes</p> Signup and view all the answers

    What is the primary function of dendritic cells in the lymph node?

    <p>To orchestrate division and differentiation of pathogen-specific lymphocytes</p> Signup and view all the answers

    What is the main role of NK cells in the immune system?

    <p>Attacking virally infected and tumor cells</p> Signup and view all the answers

    What happens to the plasma cells after they are formed in the lymph node?

    <p>Some move to the bone marrow to secrete antibodies in quantity</p> Signup and view all the answers

    What do Killer activation receptors (KARs) on NK cells recognize?

    <p>Stress-related molecules like MICA and MICB</p> Signup and view all the answers

    In which part of the spleen is red pulp found, and what is its function?

    <p>Inner region; removal of old and damaged red blood cells</p> Signup and view all the answers

    How do Killer inhibition receptors (KIRs) function on NK cells?

    <p>They monitor levels of MHC class I molecules</p> Signup and view all the answers

    What occurs when NK cells and macrophages interact at an infection site?

    <p>NK cells induce macrophage differentiation</p> Signup and view all the answers

    What is the role of helper T cells in the lymph node?

    <p>To stimulate the division of pathogen-specific B cells</p> Signup and view all the answers

    What is the significance of the marginal zone in the spleen?

    <p>It separates red pulp from white pulp and contains specialized macrophages and B cells</p> Signup and view all the answers

    What unique property do Natural Killer T (NKT) cells possess?

    <p>They respond to lipids and glycolipids presented by CD1d</p> Signup and view all the answers

    What is a primary consequence of activated cytotoxic NK cells killing dendritic cells?

    <p>Prevention of adaptive immunity activation</p> Signup and view all the answers

    Which of the following accurately describes the tissue layers of the spleen?

    <p>Most of the spleen consists of red pulp where white blood cells are housed</p> Signup and view all the answers

    How do NK cells retain memory of pathogen encounters?

    <p>By proliferating over time with each exposure</p> Signup and view all the answers

    How do antibodies travel to the infected tissue after being secreted by plasma cells?

    <p>By efferent lymph and blood circulation</p> Signup and view all the answers

    Where do dendritic cells move after they become residents in lymph nodes?

    <p>To T-cell areas to interact with small lymphocytes</p> Signup and view all the answers

    What is the effect of type I interferon on NK cells?

    <p>It induces NK cell proliferation and differentiation</p> Signup and view all the answers

    What is the primary function of pattern recognition receptors (PRRs) in the innate immune system?

    <p>To differentiate between self and nonself molecules.</p> Signup and view all the answers

    In which organs do immune cells primarily develop?

    <p>Bone marrow and thymus.</p> Signup and view all the answers

    What role do CD4+ helper T cells play in the immune response?

    <p>Assist in activating B-cells.</p> Signup and view all the answers

    What occurs in the germinal centers of lymph nodes?

    <p>B-cells mature and increase antigen affinity.</p> Signup and view all the answers

    How do lymphocytes that are not activated by specific antigens proceed after leaving the lymph node?

    <p>They re-enter the bloodstream through the efferent lymph.</p> Signup and view all the answers

    What is the primary site of antigen processing for lymph-borne pathogens?

    <p>Lymph nodes.</p> Signup and view all the answers

    Which type of T-cells directly attack and destroy infected cells?

    <p>CD8+ cytotoxic T cells.</p> Signup and view all the answers

    What is class switching in the context of B-cell maturation?

    <p>The process of changing the type of antibody produced.</p> Signup and view all the answers

    What is the fate of lymphocytes activated by a specific antigen within the lymph node?

    <p>They stay in the lymph node to proliferate.</p> Signup and view all the answers

    What distinguishes the adaptive immune system from the innate immune system?

    <p>The presence of somatically generated receptors.</p> Signup and view all the answers

    What is primarily found in the periarteriolar lymphoid sheath (PALS) surrounding the central arteriole?

    <p>T cells</p> Signup and view all the answers

    Which component of the lymphoid follicles contains macrophages and differentiating B cells?

    <p>Marginal zone</p> Signup and view all the answers

    What unique feature do liver-resident natural killer (NK) cells possess?

    <p>They cannot leave the liver.</p> Signup and view all the answers

    What aspect differentiates NKT cells in sooty mangabeys from those in other species?

    <p>Sooty mangabeys lack CD4+ NKT cells.</p> Signup and view all the answers

    In the lymphoid structure, what does the perifollicular zone primarily contain?

    <p>Erythrocytes, macrophages, T cells, and B cells</p> Signup and view all the answers

    What potential role might liver-resident NK cells play according to current research?

    <p>They function as an early warning system for liver-infecting viruses.</p> Signup and view all the answers

    What are the regions comprised in lymphoid follicles?

    <p>Germinal center, B-cell corona, and marginal zone</p> Signup and view all the answers

    Which cells are predominantly found near the central arteriole in the PALS?

    <p>T cells</p> Signup and view all the answers

    Study Notes

    Instructor Information

    • Office Hours: Tuesday, 4-5 pm (virtual) and Thursday, 4-5 pm (316J)
    • DITKI due: Wednesday by 12:59 pm
      • Adaptive Immunity- Cellular (with quiz)
      • Re-view Thymus, Spleen, and Lymph Nodes (no quiz)

    Objectives

    • Identify the locations of adaptive immune system receptors within the context of cells.
    • Correlate the ligands and receptors of two types of immune cells, focusing on their signaling outcomes (KIR & KAR).
    • Compare and contrast NK and NKT cells.
    • Describe the interplay between NK cells, macrophages, and dendritic cells in initiating an immune response.
    • Outline the movement of lymphocytes throughout the body, highlighting key anatomical features.
    • Differentiate the adaptive immune system from the innate immune system, emphasizing specific characteristics of the adaptive system.
    • Recognize and describe the microenvironments where adaptive immune cells mature, and the adaptive immune response develops.
    • Identify primary and secondary immune organs in vertebrates, clarifying their functions in relation to the adaptive immune system.

    Immune Response Refreshers

    • Interferons are a family of cytokines specifically designed to induce cellular resistance against viral infections.
    • Interferons are rapidly produced during viral PAMP interactions with PRRs.
    • The primary interferons are IFN-α and IFN-β (type 1 interferons).
      • They induce cells to activate antiviral defenses such as the RNA-dependent protein kinase pathway and apoptotic (programmed cell death) pathway.
    • IFN-γ (type II interferon) is structurally and functionally distinct from type 1 interferons but is produced by activated lymphocytes such as CD4 T cells, CD8 T cells, NK cells, and ILCs.
      • Primarily activates macrophages in both innate and adaptive immunity.

    NK & NKT Cells

    • NK cells are circulating lymphocytes of the innate immune response, providing an early defense against viral infections.
    • NK cells kill certain virally infected cells and tumor cells without prior sensitization.
      • NK cells target virus-infected cells, antibody-coated cells, and cells lacking normal levels of class I MHC.
    • NK cells play a role in both innate AND adaptive immunity despite their CLP origin.
      • They are similar to Innate Lymphoid Cells (ILCs) and Lymphoid Tissue Inducer (LTi).
      • NK cells are lymphoid cells functioning within the innate immune system.
    • Natural Killer T cells (NKT cells) are a unique subset of T cells which develop in the thymus and express a rearranged TCR with a limited repertoire.
      • Unlike T cells, NKT cells respond to lipids, glycolipids, or hydrophobic peptides presented by CD1d (a specialized nonclassical MHC class I molecule), secreting large amounts of cytokines, particularly IL-4.

    NK Cell Activation Receptors & Inhibition Receptors

    • NK cells lack variable antigen-specific receptors like other lymphoid lineage cells.
    • Killer Activation Receptors (KARs) recognize stress-related molecules, such as MICA and MICB molecules expressed by unhealthy or infected host cells.
      • KAR binding to MICA or MICB induces NK cell attachment and destruction of the targeted host cell.
    • Killer Inhibition Receptors (KIRs) monitor MHC class I molecules, which are normally displayed on the surfaces of all nucleated cells.
      • KIRs assess the normality of host cells; cancers and viruses decrease MHC class I expression.
      • After KAR binding, KIRs evaluate MHC class I expression on the target cell.
        • If MHC class I is subnormal, the target cell is killed.

    Interactions Between Dendritic Cells & NK Cells

    • In virus-infected tissue, immature dendritic cells expressing viral antigens can activate NK cells and drive their differentiation into effector cells (leading to cell killing).
    • When activated cytotoxic NK cells are abundant and innate immunity is effectively controlling infection, NK cells kill dendritic cells, preventing their activation of adaptive immunity.
    • When NK cells are scarce and innate immunity struggles to control infection, NK cells induce dendritic cells to differentiate into a form that migrates to secondary lymphoid tissue and initiates the adaptive immune response.

    NK Cell Memory

    • The NK cell population retains a memory of its encounters with pathogens.

    The Immune System: Self vs. Nonself

    • The immune system distinguishes self (own molecules, cells, and organs) from nonself (foreign origin).
    • The innate immune system distinguishes self from nonself through germline-encoded pattern recognition receptors (PRRs) on its cell surfaces, which recognize structures on potentially invasive organisms.
    • The adaptive immune system utilizes somatically generated, epitope-specific T-cell and B-cell receptors (TCRs and BCRs).

    Primary and Secondary Lymphoid Organs

    • Primary lymphoid organs: Where immune cells develop.
      • Bone marrow
      • Thymus
    • Secondary lymphoid organs: Where immune responses are initiated.
      • Lymph nodes
      • Spleen
      • Barrier Tissues
    • Tertiary lymphoid organs: Organize and maintain immune responses.

    Secondary Lymphoid Tissue: Lymph Nodes

    • Lymph nodes filter and process antigens present in lymphatic fluid as it travels from afferent to efferent vessels.
    • Activation into effector cells occurs in the follicles of secondary lymphoid organs.
      • CD4+ helper T cells assist in B-cell activation.
      • CD8+ cytotoxic T cells destroy virally infected cells.
    • B lymphocytes mature further in germinal centers.
      • Antigen affinity increases.
      • Class switching can occur.
    • Both B and T lymphocytes develop into long-lived memory cells.

    Secondary Lymphoid Tissue: Spleen

    • The spleen is the first line of defense against blood-borne pathogens.
    • It consists of two distinct tissues:
      • Red pulp: Removes old and damaged red blood cells from circulation. Makes up most of the spleen.
      • White pulp: Contains white blood cells.
        • A specialized region of macrophages and B cells called the marginal zone borders white pulp and separates it from red pulp.

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