Immune Cell Origin and Innate Functions
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Immune Cell Origin and Innate Functions

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What type of immune cells are derived from hematopoietic stem cells in the human bone marrow?

  • B cells
  • Myeloid and lymphoid cells (correct)
  • T cells
  • Lymphocytes

    • Cytokines play a role in the formation of white blood cells.

    True

    Name the two major types of reactions of the innate immune system.

    Inflammation and antiviral defense

    White blood cell formation is also known as __________.

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

    Match each type of immune cell with its source:

    <p>Neutrophils = Myeloid stem cells Macrophages = Lymphoid stem cells B cells = Lymphoid stem cells Eosinophils = Myeloid stem cells</p> Signup and view all the answers

    Which of the following cells are classified as phagocytes within the innate immune system?

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

    Lymphoid stem cells produce both myeloid and lymphoid cells.

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

    What stimulates the production of mature leukocytes in the bone marrow?

    <p>Interleukins and colony-stimulating factors</p> Signup and view all the answers

    What is primarily disrupted during the process affecting endothelial cells?

    <p>VE-cadherin complex</p> Signup and view all the answers

    Neutrophils are recruited to tissues after 24 to 48 hours following an infection or injury.

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

    What is the role of kinases in the disruption of the VE-cadherin complex?

    <p>Kinases phosphorylate the cytoplasmic tail of VE-cadherin.</p> Signup and view all the answers

    Neutrophils primarily express _____ and _____ which bind to chemokines supporting their migration.

    <p>CXCR1, CXCR2</p> Signup and view all the answers

    Which chemokine receptor is mainly expressed by classical monocytes?

    <p>CCR2</p> Signup and view all the answers

    Monocytes have shorter life spans than neutrophils after entering tissues.

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

    What key role does CCL2 (MCP-1) play in monocyte recruitment?

    <p>CCL2 binds to CCR2 and facilitates the recruitment of monocytes to inflammatory sites.</p> Signup and view all the answers

    Match the following leukocyte types with their primary characteristics:

    <p>Neutrophils = Short life span and rapid response to chemokines Monocytes = Longer life span and potential for proliferation in tissues</p> Signup and view all the answers

    What initiates acute inflammatory responses?

    <p>Transgression of epithelial barriers by microbes</p> Signup and view all the answers

    Vasodilation decreases vascular permeability during inflammation.

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

    What are PAMPs and DAMPs responsible for in the inflammatory process?

    <p>Activating sentinel cells such as macrophages and dendritic cells.</p> Signup and view all the answers

    The primary cells that secrete inflammatory mediators during the initial response are __________.

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

    Which of the following is NOT a function of leukocytes during an acute inflammatory response?

    <p>Formation of scar tissue</p> Signup and view all the answers

    Match the inflammatory mediators with their effects:

    <p>Histamine = Increases capillary permeability Prostaglandins = Causes vasodilation Cytokines = Attracts leukocytes Interleukin-1 = Promotes fever</p> Signup and view all the answers

    Complement proteins are involved in killing microbes.

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

    What role do adhesion molecules and chemokines play in inflammation?

    <p>They promote the migration of leukocytes into tissues.</p> Signup and view all the answers

    What triggers ILC3s to respond to infections?

    <p>IL-1β and IL-23</p> Signup and view all the answers

    ILC3s play a role in promoting mucus production in the intestine.

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

    What cytokines do ILC3s produce in response to DC-derived IL-23 and IL-1β?

    <p>IL-17 and IL-22</p> Signup and view all the answers

    ILC3s can promote tissue repair in the thymus through the production of __________.

    <p>IL-22</p> Signup and view all the answers

    Match the following cytokines with their effects:

    <p>IL-17 = Neutrophil recruitment IL-22 = Mucus production IL-25 = Limits ILC3 responses LTα1β2 = Restoration of stromal cells</p> Signup and view all the answers

    How do ILC3s contribute to inflammation resolution?

    <p>By increasing ILC3 numbers and cytokine production</p> Signup and view all the answers

    Upon intestinal damage, ILC3s are activated by DC-derived __________.

    <p>IL-1β, IL-23, TL1A, and RA</p> Signup and view all the answers

    ILC3 responses in the intestine are always amplified regardless of commensal bacteria presence.

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

    What is the primary way that ILC3s promote skin inflammation?

    <p>Production of IL-22 and IL-17</p> Signup and view all the answers

    ILC3s have no role in chronic inflammation.

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

    What cytokine is produced by macrophages that is crucial for ILC3 activation in asthma?

    <p>IL-1β</p> Signup and view all the answers

    ILC3s can promote _____ growth in the intestine dependent upon DC-derived IL-23.

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

    Match the cytokine/element with its function:

    <p>IL-22 = Promotes skin inflammation IFN-γ = Influences immune tolerance GM-CSF = Promotes myeloid cell homeostasis LTα1β2 = Modulates IgA production</p> Signup and view all the answers

    In patients with asthma, ILC3s are found increased in which type of fluid?

    <p>Bronchoalveolar lavage fluid</p> Signup and view all the answers

    ILC3s can directly activate tissue-resident ILC1s.

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

    What is the role of DC-derived IL-23 in relation to ILC3s?

    <p>Induces ILC3 responses</p> Signup and view all the answers

    What is the primary function of dendritic cells in the immune system?

    <p>Initiating inflammation and stimulating adaptive immune response</p> Signup and view all the answers

    NK cells can only kill infected cells through phagocytosis.

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

    What cytokine do NK cells produce to activate macrophages?

    <p>IFN-y</p> Signup and view all the answers

    Dendritic cells respond to microbes by producing numerous __________.

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

    Match the following components with their role in NK cell function:

    <p>Perforin = Creates pores in target cell membrane Granzyme = Activates apoptotic pathways in target cells IFN-y = Activates macrophages IL-15 = Promotes NK cell maturation</p> Signup and view all the answers

    Which of the following cells provides cytotoxic activity similar to CD8+ T cells?

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

    IL-10 produced by CD8 T-cells can activate NK cells.

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

    What happens to NK cells when the specific immune system becomes active?

    <p>They are inactivated by IL-10.</p> Signup and view all the answers

    Which receptor type is primarily associated with recognizing bacterial components?

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

    DAMPs are involved in recognizing live cells in the body.

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

    What do PAMPs stand for?

    <p>Pathogen-associated molecular patterns</p> Signup and view all the answers

    PRRs are known to activate the __________ immune system upon recognizing patterns.

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

    Match the following receptor types with their primary recognition targets:

    <p>TLR = Microbial components NLR = Inflammasome activation RLR = Viral RNA CDS = Microbial DNA</p> Signup and view all the answers

    Which of the following receptors is located on the membrane of immune cells?

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

    Receptors from the adaptive immune system only function as primary sensors for pathogens.

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

    Name a cell type that can express TLRs.

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

    Which of the following proteins is considered a short pentraxin?

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

    PTX3 is produced solely by liver cells and has no role in innate immunity.

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

    What are the main roles of collectins in the innate immune system?

    <p>Opsonization of microorganisms and facilitating ingestion by alveolar macrophages.</p> Signup and view all the answers

    The two main short pentraxins are C-reactive protein (CRP) and __________.

    <p>serum amyloid P (SAP)</p> Signup and view all the answers

    Match the following components with their functions:

    <p>C-reactive protein = Binds to bacteria and activates complement MBL = Mediates internalization of opsonized microbes SP-A = Maintains alveolar fluid surface tension PTX3 = Produced in response to inflammatory cytokines</p> Signup and view all the answers

    What ligands do C-reactive protein (CRP) and serum amyloid P (SAP) recognize?

    <p>Phosphorylcholine and phosphatidylethanolamine</p> Signup and view all the answers

    Collectins can directly inhibit bacterial growth.

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

    What kind of proteins are CRP and SAP categorized as, in response to cytokines like IL-1 and IL-6?

    <p>Acute phase proteins</p> Signup and view all the answers

    Which interleukin is primarily responsible for the differentiation of ILCs?

    <p>IL-7</p> Signup and view all the answers

    ILCs are primarily found in the blood rather than in tissues.

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

    What transcription factor is crucial for the differentiation of common ILC precursors?

    <p>Id2</p> Signup and view all the answers

    ILCs differentiate from common lymphoid progenitors (CLPs) primarily in the __________.

    <p>bone marrow</p> Signup and view all the answers

    Match the ILC types with their primary functions:

    <p>ILC1 = Response to intracellular pathogens ILC2 = Allergic responses and helminth defense ILC3 = Mucosal immunity and tissue repair</p> Signup and view all the answers

    Which statement is true regarding the role of ILCs?

    <p>ILCs play a role in both promoting and limiting chronic inflammation.</p> Signup and view all the answers

    IL-7 signaling can induce the generation of ILC progenitors.

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

    Which regions in the body are ILCs predominantly located?

    <p>Mucosal tissues such as the lung and intestines</p> Signup and view all the answers

    What is the mechanism called when NK cells kill infected cells coated with antibodies?

    <p>Antibody-dependent cell-mediated cytotoxicity</p> Signup and view all the answers

    Inhibitory receptors on NK cells recognize class II MHC molecules.

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

    What signals do CD16 on NK cells generate when binding to antibodies?

    <p>Activating signals</p> Signup and view all the answers

    The absence of class I MHC molecules on a cell indicates __________.

    <p>infection or damage</p> Signup and view all the answers

    Match the following terms related to NK cells and their functions:

    <p>CD16 = Binds to the Fc region of antibodies KIRs = Bind class I MHC molecules NKG2D ligands = Increased expression on stressed cells HLA-E = Class I MHC molecule recognized by CD94/NKG2A</p> Signup and view all the answers

    What happens to T cells when class I MHC expression is downregulated during viral infections?

    <p>T cells cannot effectively kill infected cells</p> Signup and view all the answers

    Normal healthy cells lack class I MHC molecules.

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

    What initiates the activation of NK cells during an infection?

    <p>Loss of class I MHC expression</p> Signup and view all the answers

    Study Notes

    Immune Cell Origin

    • Immune cells originate from hematopoietic stem cells (HSCs) in the bone marrow.
    • HSCs differentiate into myeloid and lymphoid lineages.
    • Myeloid cells include phagocytes and dendritic cells (DCs), representing the innate immune system.
    • Lymphoid cells include lymphocytes, responsible for adaptive immunity.
    • Leukopoiesis, the formation of white blood cells, is stimulated by interleukins and colony-stimulating factors (CSFs).

    Innate Immune System Functions

    • Two major functions: inflammation and antiviral defense.
    • Inflammation involves vascular permeability, recruitment of leukocytes (mainly neutrophils and monocytes), and phagocytosis of microbes.
    • Neutrophils are the first responders, entering tissues within 48 hours after injury or infection.
    • Monocytes arrive later and have longer lifespans.
    • Different chemokine receptors on neutrophils and monocytes mediate distinct recruitment patterns.
    • Neutrophils express CXCR1 and CXCR2, binding CXCL1 and CXCL8 (IL-8), attracting neutrophils to tissue.
    • Monocytes express CCR2, which binds CCL2 (MCP-1), promoting monocyte recruitment.
    • The process of Leukocyte migration requires transient disruption of VE-cadherin complex in endothelial cells.
    • Kinases activated by leukocyte integrins binding to ICAM-1 or VCAM-1 phosphorylate VE-cadherin, leading to the disruption.
    • Neutrophils die by apoptosis after entering tissues while monocytes can survive longer and proliferate.
    • The innate immune system response is triggered by pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) recognized by sentinel cells like macrophages, DCs, and mast cells.

    Innate Lymphoid Cells (ILC3s)

    • ILC3s are a type of innate lymphoid cell with roles in immunity and tissue repair.
    • Activated by IL-1β and IL-23, produced by DCs.
    • Produce IL-17 and IL-22, which promote innate immunity to fungi and bacteria.
    • Involved in the resolution of inflammation in lymphoid tissues and the intestine.
    • Promote restoration of stromal cells through production of LTα1β2 and IL-22.
    • Can limit chronic inflammation by regulating innate and adaptive immune responses in the intestine.
    • Contribute to the development of psoriasis, asthma, and cancer in the skin, lung, and intestine.
    • ILC3s can both promote and limit chronic inflammation, depending on the context.

    Sequence of Events in Acute Inflammatory Responses

    • Sentinel cells (mast cells, tissue-resident macrophages, DCs) detect PAMPs and DAMPs and trigger inflammation.
    • Mast cells release histamine and prostaglandins, leading to vasodilation and increased vascular permeability.
    • Increased blood flow and plasma proteins (complement, antibodies, antimicrobial proteins) enter the tissues.
    • Cytokines like IL-1 and TNF induce expression of endothelial adhesion molecules and chemokines, promoting leukocyte migration into tissues.
    • Leukocytes phagocytose and kill microbes, clear damaged cells, and promote further inflammation and repair.

    Innate Immune System & Adaptive Immune System

    • Dendritic cells act as a bridge between the innate and adaptive immune systems by activating T cells.
    • Dendritic cells respond to microbes by producing cytokines, which initiate inflammation and stimulate the adaptive immune response.

    Natural Killer Cells (NK cells)

    • NK cells have cytotoxic activity similar to CD8+ T cells.
    • NK cells circulate in the blood and are present in lymphoid tissues.
    • NK cells recognize and kill infected and stressed cells.
    • NK cells produce IFN-y, which activates macrophages.
    • NK cells are active until CD8+ cytotoxic T cells are produced, which then take over cell killing.
    • NK cells are inactivated by IL-10 produced by CD8+ T cells.
    • NK cells use perforin and granzymes to kill cells, similar to CD8+ T cells.
    • NK cells activate macrophages through IFN-y.
    • Macrophages produce IL-12.

    Pattern Recognition Receptors (PRRs)

    • PRRs are receptors that recognize and respond to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).
    • PRRs are located on cells of the innate immune system (neutrophils, monocytes, dendritic cells) and adaptive immune system (second signal role).
    • Cellular Associated PRRs:
      • Toll-like receptors (TLRs): important in defense against microbial components (bacteria and viruses).
      • Nucleotide-binding oligomerization domain-like receptors (NLRs): play an important role in inflammasome activation.
      • Retinoic acid-inducible gene I-like receptors (RLRs): important for viral RNA.
      • Cyclic GMP-AMP synthase (cGAS): detects microbial DNA.
      • C-type lectin receptors (CLRs): recognize sugars on the surface of microorganisms.
    • Soluble PRRs
      • Complement: a system of proteins that helps to destroy pathogens.
      • Pentraxins: plasma proteins that recognize microbial structures and participate in innate immunity.
        • Short pentraxins: C-reactive protein (CRP) and serum amyloid P (SAP).
        • Long pentraxin: PTX3.
      • Collectins: soluble effector molecules in the innate immune system with collagen-like tails and C-type lectin heads.
        • Mannose-binding lectin (MBL): similar structure to C1q, mediates internalization of microbes.
        • Pulmonary surfactant proteins A (SP-A) and D (SP-D): lipophilic properties in the lungs, maintain alveolar function, bind to microorganisms, act as opsonins, inhibit bacterial growth, and activate macrophages.

    Innate Lymphoid Cells (ILCs)

    • ILCs produce cytokines similar to those secreted by CD4+ helper T cells.
    • ILCs play a key role in mediating acute inflammation in response to infection.
    • ILC responses are altered in several disease states.
    • ILC Types:
      • ILC1
      • ILC2
      • ILC3
    • ILC Origins:
      • ILCs develop in the fetal liver and bone marrow from common lymphoid progenitors (CLPs).
      • All ILCs develop from CLPs.
      • A common ILC precursor differentiates into the three subsets of ILCs.
      • Differentiation of ILCs requires transcription factors Id2, NFLI3, and Tox.
    • ILC Locations:
      • ILCs are rare in the blood and are mostly present in tissues, especially mucosal tissues.

    NK Cell Inhibitory Receptors

    • NK cells express inhibitory receptors that recognize class I MHC molecules.
    • This prevents them from attacking normal healthy cells.
    • Inhibitory receptor types:
      • KIRs (killer immunoglobulin-like receptors)
      • CD94/NKG2A heterodimer

    NK Cell Activation

    • NK cells kill infected cells through antibody-dependent cell-mediated cytotoxicity (ADCC).
      • IgG1 and IgG3 antibodies bind to microbial antigens on infected cells.
      • CD16 on NK cells binds to the Fc region of these antibodies.
    • NK cells also use activating receptors, such as NKG2D, which recognize stress-induced ligands on infected and tumor cells.
    • Loss of cell surface expression of class I MHC signals infection or damage.
    • NK cells are activated when the inhibitory signals are absent.
    • Viruses often downregulate MHC class I expression, making them less visible to T cells.

    Summary

    • The innate immune system is the first line of defense against infection.
    • NK cells are important cytotoxic cells of the innate immune system.
    • PRRs recognize PAMPs and DAMPs to activate the immune response.
    • ILCs are a type of innate immune cell with cytokine-producing capabilities.
    • NK cells use inhibitory receptors to distinguish between normal and infected cells.
    • NK cells are activated through ADCC and activating receptors.

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