Immunology: Innate and Adaptive Immunity
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Questions and Answers

What is the primary role of the innate immune system during pathogen infection?

  • To create memory cells for future infections
  • To eliminate all pathogens immediately
  • To provide long-term protection against pathogens
  • To stimulate adaptive immunity while controlling pathogen replication (correct)

    • What occurs during the resolution phase of an immune response?

  • Depletion of immune cells to prevent over-reactivity
  • Activation of memory cells for immediate response
  • Increased production of pro-inflammatory cytokines
  • Activation of anti-inflammatory pathways to return to homeostasis (correct)

    • Which mechanism contributes to pathogen killing by the immune system?

  • Only cytokines that directly kill pathogens
  • Only chemokines that communicate with other immune cells
  • Direct cytotoxicity and indirect communication through signaling molecules (correct)
  • Adaptive immunity solely relying on memory cells

    • What characteristic is true about memory cells in the adaptive immune system?

    <p>They allow for a faster and more powerful response upon reinfection</p> Signup and view all the answers

    What is a critical requirement for a successful immune response?

    <p>The ability to resolve inflammation and return to homeostasis</p> Signup and view all the answers

    What initiates the classical pathway of complement activation?

    <p>C1q detecting antibodies bound to microbes</p> Signup and view all the answers

    Which complement proteins are activated first in the classical pathway?

    <p>C4 and C2</p> Signup and view all the answers

    What is the role of C3b in the alternative pathway?

    <p>It facilitates binding to the pathogen surface</p> Signup and view all the answers

    How does the alternative pathway distinguish between self and foreign microbes?

    <p>By the presence or absence of regulatory proteins</p> Signup and view all the answers

    What amplifies the activation process in the alternative pathway?

    <p>Interaction of Bb with C3b</p> Signup and view all the answers

    What is the role of perforin in the process of cytotoxicity?

    <p>Creates pores in the target cell membrane.</p> Signup and view all the answers

    Which ligands do NK cells express to initiate apoptosis via death receptor interactions?

    <p>Fas ligand (FasL) and TRAIL.</p> Signup and view all the answers

    What mechanism do NK cells use to mediate antibody-dependent cellular cytotoxicity (ADCC)?

    <p>Recognition of IgG antibodies via CD16.</p> Signup and view all the answers

    Which cytokine secreted by NK cells primarily activates macrophages to enhance their pathogen-killing ability?

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

    How do NK cells enhance the recognition of target cells by cytotoxic T cells?

    <p>By upregulating MHC class I expression on target cells.</p> Signup and view all the answers

    Which type of ILC is primarily responsive to allergens and helminths?

    <p>ILC2</p> Signup and view all the answers

    What type of signals do ILC3 respond more to?

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

    Which molecule, produced by commensal microbes, influences ILC3 activation?

    <p>Short-chain fatty acids</p> Signup and view all the answers

    What type of peptide can directly activate ILC2 during allergic reactions?

    <p>Vasoactive intestinal peptide</p> Signup and view all the answers

    What triggers ILC3-to-ILC1 plasticity?

    <p>IL-12</p> Signup and view all the answers

    What is the primary function of NK cells?

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

    What characterizes bright CD56 NK cells?

    <p>High killing potential</p> Signup and view all the answers

    Which NK cell subtype is associated with a pro-inflammatory function?

    <p>Dim CD56</p> Signup and view all the answers

    How do NK cells recognize and eliminate target cells?

    <p>By detecting stressed cell signals</p> Signup and view all the answers

    What is a feature of NK cells concerning their response speed?

    <p>They have a rapid response to stressed cells.</p> Signup and view all the answers

    What is the primary role of positive selection in T cell development?

    <p>To ensure T cells can recognize self-MHC molecules</p> Signup and view all the answers

    What happens to T cells that have a too low affinity for self-MHC molecules during selection?

    <p>They undergo apoptosis due to neglect.</p> Signup and view all the answers

    What does junctional diversity contribute to in T cell receptor (TCR) formation?

    <p>It produces a wide range of TCR variants.</p> Signup and view all the answers

    How does the α chain of T cell receptors differ from the β chain?

    <p>The α chain has no D segment, making it simpler.</p> Signup and view all the answers

    What is the key function of IL-7 in the context of T cell development?

    <p>To block the locus of CD4 in CD8+ T cells.</p> Signup and view all the answers

    Which process is necessary for gene rearrangement in T cell receptors?

    <p>Epigenetic regulation influenced by environmental cues.</p> Signup and view all the answers

    What role do cTECs play in T cell maturation?

    <p>They express self-antigens for positive selection.</p> Signup and view all the answers

    Which statement accurately reflects the fate of T cells that bind too strongly to self-MHC?

    <p>They undergo apoptosis due to auto-reactivity.</p> Signup and view all the answers

    What is the primary mechanism through which the innate immune system responds to microbial invasion?

    <p>Through immediate, non-specific defenses and inflammation</p> Signup and view all the answers

    Which cells are considered the first responders at the site of an infection within the innate immune system?

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

    Which of the following substances contributes to breaking down the cell walls of pathogens in the innate immune response?

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

    How do cytokines primarily function in the immune system?

    <p>As mediators of communication between immune cells</p> Signup and view all the answers

    What is the role of the epithelial barrier in the skin regarding the innate immune system?

    <p>Provides a physical barrier that hinders pathogen entry</p> Signup and view all the answers

    What are defensins primarily known for in the context of the immune response?

    <p>Forming pores in microbial membranes</p> Signup and view all the answers

    What type of immune cells are dendritic cells best known for?

    <p>Presenting antigens to other immune cells</p> Signup and view all the answers

    What is the source of hematopoietic stem cells (HSCs) in adults?

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

    Which component of the innate immune system is responsible for initiating the inflammatory response?

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

    What is the specific function of eosinophils in the immune response?

    <p>Targeting parasites with toxic proteins</p> Signup and view all the answers

    What function do macrophages serve in the context of the innate immune system?

    <p>Engage in phagocytosis and inflammation</p> Signup and view all the answers

    Which type of cytokine primarily influences the migration of immune cells to infection sites?

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

    What generally happens during the neonatal period in terms of immune system development?

    <p>The innate immune system matures while adaptive system begins development</p> Signup and view all the answers

    What process is responsible for the clearance of apoptotic cells during tissue remodelling?

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

    Which cytokines are cleaved and activated as a result of inflammasome activation?

    <p>IL-1β and IL-18</p> Signup and view all the answers

    What is the primary function of matrix metalloproteinases (MMPs) in the context of wound healing?

    <p>Degradation and remodelling of extracellular matrix</p> Signup and view all the answers

    What type of immune cells promote inflammation by secreting pro-inflammatory cytokines?

    <p>M1 macrophages</p> Signup and view all the answers

    Which component is NOT involved in the activation of the inflammasome?

    <p>Caspase-3</p> Signup and view all the answers

    What is one of the main roles of the complement system during an immune response?

    <p>Directly killing microbes</p> Signup and view all the answers

    What is the result of activation of the complement system?

    <p>Amplification of proteolytic cascades</p> Signup and view all the answers

    Which cell type is primarily responsible for sensing microbes during the early phase of inflammation?

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

    What is a key feature of immature dendritic cells in terms of their function?

    <p>They are highly efficient at capturing antigens.</p> Signup and view all the answers

    Which cytokine is primarily produced by cDC1s?

    <p>IL-12</p> Signup and view all the answers

    Which type of dendritic cells are primarily responsible for inducing Th1 responses?

    <p>cDC1s</p> Signup and view all the answers

    From which precursor do conventional dendritic cells develop?

    <p>Myeloid precursors</p> Signup and view all the answers

    What is a primary function of plasmacytoid dendritic cells (pDCs)?

    <p>Production of type I interferons</p> Signup and view all the answers

    What is the role of TLRs expressed by dendritic cells?

    <p>They detect and respond to pathogens.</p> Signup and view all the answers

    Which statement correctly describes follicular dendritic cells?

    <p>They are involved in B cell activation.</p> Signup and view all the answers

    What type of immune response do immature dendritic cells primarily promote?

    <p>Innate responses</p> Signup and view all the answers

    What common surface marker is found on cDC2s?

    <p>BDCA-3</p> Signup and view all the answers

    Which type of dendritic cells is known for their contribution to antiviral immunity?

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

    Which ILC is primarily activated by bacterial signals?

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

    What type of signals do short-chain fatty acids (SCFAs) influence in ILCs?

    <p>Cytokine production and barrier function</p> Signup and view all the answers

    Which of the following peptides can activate ILC2 during allergic reactions?

    <p>Vasoactive intestinal peptide (VIP)</p> Signup and view all the answers

    In what condition can ILC3 exhibit plasticity to convert to ILC1?

    <p>Presence of IL-12</p> Signup and view all the answers

    What is the main function of NK cells during the immune response?

    <p>Direct killing of infected or malignant cells</p> Signup and view all the answers

    Which NK cell subtype is primarily responsible for producing cytokines?

    <p>Dim CD56</p> Signup and view all the answers

    How do NK cells initiate their rapid response to stressed cells?

    <p>By directly recognizing infection or damage signals</p> Signup and view all the answers

    What is the characteristic of bright CD56 NK cells?

    <p>Cytokine production and regulatory function</p> Signup and view all the answers

    Which of the following best describes the functional capacity of ILCs?

    <p>They can switch types depending on environmental cues.</p> Signup and view all the answers

    Which type of ILC primarily responds to allergens and helminths?

    <p>ILC2</p> Signup and view all the answers

    What is the role of RAG1/2 in T cell receptor gene rearrangement?

    <p>To create a loop that is cut off and lost</p> Signup and view all the answers

    Which statement accurately describes the process of positive selection in T cell development?

    <p>It ensures T cells can recognize self-MHC molecules.</p> Signup and view all the answers

    What happens to T cells that bind too strongly to self-MHC during positive selection?

    <p>They undergo apoptosis.</p> Signup and view all the answers

    How does the junctional diversity in T cell receptors arise?

    <p>By filling gaps with P nucleotides during rearrangement</p> Signup and view all the answers

    What role do cTECs play in the thymus?

    <p>They present self-antigens for T cell selection.</p> Signup and view all the answers

    Which function is associated with the action of IL-7 in T cell maturation?

    <p>Supports the expansion of CD8+ T cell precursors</p> Signup and view all the answers

    What defines the process of central tolerance during T cell development?

    <p>Selection against T cells that strongly react to self-antigens</p> Signup and view all the answers

    What occurs if T cell receptors have too low affinity during positive selection?

    <p>They undergo cell death from neglect.</p> Signup and view all the answers

    Study Notes

    Innate and Adaptive Immunity

    • The innate immune system responds rapidly to a broad range of pathogens, controlling replication while activating adaptive immunity.
    • Adaptive immunity is slower but generates a robust, specific response to eliminate pathogens.
    • Innate immunity is transient, while adaptive immunity persists through memory cells.
    • Successful immune response requires:
      • Pathogen recognition via receptors
      • Activation of immune cells in response to infection
      • Effector mechanisms for pathogen elimination, including cytokines, chemokines, and signaling molecules.
      • Resolution of inflammation and return to homeostasis through self-downregulation.

    Complement System

    • Classical Pathway:
      • Activated by antibodies (IgM or IgG) bound to microbial surfaces.
      • C1q binds to the Fc portion of the antibody, activating C1r and C1s.
      • This initiates a proteolytic cascade, leading to the activation of C4/C2 and C3, ultimately generating C3a and C3b.
    • Alternative Pathway:
      • Initiated by spontaneous hydrolysis of C3, which is recognized by bacterial LPS.
      • Amplified by a loop involving C3b binding to the pathogen and the activation of Bf to Bb.
      • Distinguishes self from non-self based on the presence or absence of regulatory proteins.
    • Tissue-Specific Cues:
      • Lung: ILC2 respond to allergens and helminths.
      • Gut: ILC3 respond to bacterial signals.
    • Metabolic and Microbiota Signals:
      • SCFAs produced by commensal microbes modulate ILC activation, influencing cytokine production and barrier function.
      • Neuro-Immune Interactions:
      • Neuronal signals (VIP and neuromedin U) directly activate ILCs, influencing allergic responses and tissue repair.
    • Plasticity:
      • ILCs can switch from one type to another under certain conditions, like ILC3 to ILC1 in response to IL-12.
      • This allows for functional flexibility in response to environmental changes.

    Natural Killer (NK) Cells

    • Type of ILC that plays a crucial role in the immune system's defense against viral infections and tumors.
    • Do not require prior sensitization or antigen-specific receptors.
    • Respond rapidly to "stressed" cells by directly killing them and secreting cytokines.
    • Exhibit various killing mechanisms, including granzyme-mediated apoptosis.
    • Two subtypes based on CD56 expression:
      • Bright CD56: Cytotoxic NK cells.
      • Dim CD56: Cytokine-producing helper NK cells, with a more regulatory function.
    • Can become memory cells.
    • In the blood, they are predominantly mature dim CD56 cells with pro-inflammatory and cytotoxic functions.

    NK Cell Functions

    • Cytotoxicity:
      • Direct Killing (Fast): Induces apoptosis via release of cytotoxic granules like perforin (pore formation) and granzymes (trigger apoptosis by activating caspases).
      • Death Receptor Ligand Interactions (Slow): NK cells express FasL and TRAIL which bind to death receptors on target cells, leading to caspase activation and apoptosis.
    • Antibody-Dependent Cellular Cytotoxicity (ADCC):
      • NK cells mediate ADCC through CD16 recognition of IgG bound to target cells.
      • Triggers release of cytotoxic granules and killing of the target cell.
    • Cytokine Production:
      • NK cells secrete IFN-γ, TNF-α, and GM-CSF to modulate immune responses.
      • Activated macrophages, enhance antigen presentation, and stimulate adaptive immunity.

    T Cell Receptor Diversity

    • TCR Diversity:
    • Achieved through gene rearrangement and junctional diversity.
    • VDJ recombination of TCR β chain segments:
      • Variable (V) region- for antigen recognition.
      • Diversity (D) region: for diversity.
      • Joining (J) region: for joining variable and diversity regions.
      • Constant (C) region: for signaling.
    • α chain has no D segment, is simpler and lacks diversity.
    • Epigenetic Regulation:
      • Environmental cues open up DNA for gene rearrangement, driven by RAG1/2.
    • Junctional Diversity:
      • P nucleotides are added during recombination, further increasing diversity.

    T Cell Selection

    • Central Tolerance:
      • Positive Selection: In thymic cortex, ensures T cells recognize self-MHC molecules.
        • Successfully binding to self-MHC class I leads to CD8+ T cells.
        • Successfully binding to self-MHC class II leads to CD4+ T cells.
      • Negative Selection: In thymic medulla, eliminates autoreactive T cells that bind too strongly to self-antigens.
      • Tregs: Low-affinity binding during positive selection can give rise to regulatory T cells (Tregs).
    • Peripheral Tolerance:
      • Keeps T cells in check after they leave the thymus, as they are exposed to a broader range of self-antigens.

    Innate Immune System

    • Present at birth, inherited, first line of defense, antigen-nonspecific
    • Defends against microbes immediately or within hours of exposure.
    • Works through inflammation:
      • recruits phagocytes and other leukocytes to destroy microbes
      • initiates pathogen cleanup
      • begins repairing barriers and cleansing damaged tissues
      • strengthens barriers

    Innate Immune System Components

    • Physical (epithelial cells), chemical (compounds in sweat, tears, saliva - low pH) and physiological (normal commensal bacterial microflora) barriers
    • Phagocytic cells (neutrophils, macrophages), dendritic cells (DCs), mast cells, natural killer (NK) cells, and other innate lymphoid cells
    • Blood proteins, including components of the complement system and other mediators of inflammation
    • Creates signals for the adaptive immune system

    Innate Immune Cell Types and Functions

    • Neutrophils: Granulocytes, two types: band and segmented neutrophils
      • Function: engulf microorganisms, enclosed in a phagosome -> granules release enzymes from the inside
      • First cells to arrive at the site of infection, amoeboid motion + chemotaxis
    • Eosinophils: Granulocytes, motile, phagocytic
      • Function: Defense against parasites, release toxic proteins, degrade pathogen walls
      • Activated by cytokines or allergens coated with IgE
    • Basophils: Agranulocyte, leukocyte, granules with histamine and hydrolytic enzymes
      • Function: Influences adaptive immune responses + exerts tissue repair function
    • Monocytes: Agranulocyte, leukocyte
      • Function: Influences adaptive immune responses + exerts tissue repair function
    • Macrophages: Agranulocyte, phagocytosis, immune surveillance + inflammation, pathogen recognition and presentation
    • Dendritic Cells: Agranulocyte, reside in superficial tissues, connect innate and adaptive immunity
      • Function: Collect antigen and release cytokines that notify leukocytes, acts as antigen presenting cells

    Substances Released by Innate Immune Cells

    • Bactericidal substances: Epithelial cells (skin, intestine, lungs, urogenital, salivary glands, tear glands etc) and immune cells (monocytes, neutrophils).
      • Lysozyme: Enzyme that degrades peptidoglycan in tears, saliva, blood, and immune cells
      • Peroxidases: Enzymes that break down hydrogen peroxide to produce oxidizing compounds in saliva and immune cells
      • Lactoferrin: High affinity for iron (needed for microorganisms to proliferate, so it limits proliferation and ability to enter the body) found in saliva, phagocytes, blood, and tissue fluids
      • Defensins: Antimicrobial peptides that form pores
    • Cytokines: Mediators of communication between immune cells, used for communication between immune cells and other cell types
      • Bind to surface receptors and induce changes in cells: growth, differentiation, movement, and cell death
      • Interleukins: Various functions, important in innate and adaptive immune systems
      • Chemokines: Promote migration of cells to appropriate sites
      • Interferons: Control of viral infections, promote tumour cell recognition

    Cytokines - Local and Systemic Effects

    • Promote inflammation (local):
      • Increases permeability of endothelial cells + more adhesion molecules (IL-1, TNF)
      • Leukocytes release more cytokines under the influence of other cytokines
    • Affect the hypothalamic center in the brain = fever:
      • Decrease viral and bacterial replication and increase immune response
    • Acute-phase proteins:
      • Biomarker of inflammation, cytokines force the liver to make more complement proteins
    • Increase leukocyte production

    Chemotaxis

    • Where the cells should go - stimulated by bacterial products, chemokines:
      • Mcp-1: Made by epithelial cells, attracts monocytes
      • IL-8: Used by neutrophils to get to the site of infection
      • C3a and C5a: Complement activation creates a gradient

    Physiological Barriers of the Innate Immune System

    • Breaking the barrier grants entrance to tissues, blood, and lymph, potentially spreading pathogens
    • Mucosal Barriers: First line of defense (urogenital tract, respiratory tract, eye, digestive tract, and mucous barriers)
      • Mucous barriers:
        • Glycoproteins produced by goblet cells
        • Sticky - traps microbes
        • Propels pathogens to areas where they can be eliminated
    • Epithelial Barrier of the Skin:
      • Most difficult to penetrate (supported by keratin + many layers of cells)
      • Shedding of the outer layer takes microbes with it
      • Antimicrobial protein production (sebocytes and eccrine glands)
    • Epithelial Barrier of the intestine:
      • Only one cell layer
      • Tight junctions (JAMs and Zos)
      • Goblet cells
      • Colon - thick, very loose layer of mucosal cells

    Immune Cell Development

    • Innate immunity: Active since birth, provides immediate, non-specific defense mechanisms
    • Adaptive immunity: Develops later, derived from hematopoietic stem cells (HSCs) in the bone marrow

    Fetal and Neonatal Immune Development

    • Fetal development:
      • Yolk sac and fetal liver (other pathway of resident immune cell development - immature DCs, mast cells, and macrophages)
    • Neonatal period:
      • Innate immune system relatively mature
      • Adaptive immune system begins to develop (highest thymic activity + vaccine responses)

    Hematopoietic Stem Cells (HSCs)

    • Multipotent cells, origin of all immune cells (both myeloid and lymphoid)
    • Common myeloid progenitors (CMPs)
    • Common lymphoid progenitors (CLPs)

    Macrophages

    • Release of immune cells from bone marrow:
      • Immature cells in the bone marrow are retained by adhesive interactions with stromal cells and extracellular matrix.
    • Wound healing and tissue remodeling:
      • Clear apoptotic cells and debris - efferocytosis (clearance of dead cells)
      • Secrete growth factors (VEGF for angiogenesis), produce matrix metalloproteinases (MMPs) to degrade and remodel extracellular matrix (ECM)
    • Role in inflammation and resolution:
      • Pro-inflammatory: M1 promote inflammation by secreting cytokines and mediators
      • Sentinel cells: Sense the presence of microbes and respond accordingly
      • Anti-inflammatory: M2 secrete cytokines, promote tissue repair, and help clear remaining debris (inflammatory -> reparative)
    • Efferocytosis: Clearance by macrophages of apoptotic cells, including apoptotic neutrophils.
    • Inflammasome activation:
      • Cholesterol crystals, ATP levels, urea, efflux of potassium, cytosolic flagellin, urea -> can lead to activation of inflammasome
      • 3 Parts: NLRP3 + adaptor protein + caspase-1
      • PRRs recognize PAMPs or DAMPs -> Activation and assembly of inflammasome (from NLRP3) -> activation of caspase-1 -> maturation of pro-inflammatory cytokines IL-1β (cleaves Pro-IL-1β into its active form) and IL-18⁠ ⇒ strong pro-inflammatory response⁠

    Complement System

    • Consists of several plasma proteins that work together to opsonize microbes, promote recruitment of phagocytes to the site of infection, and potentially directly kill microbes
    • Activation: proteolytic cascades in which an inactive protein (zymogen) gets altered to become an active protease that cleaves and thereby induces the proteolytic activity of the next complement protein in the cascade
    • Enzymatic cascades: amplification of the number of proteolytic products generated at each step
    • They perform the effector functions of the complement system

    Innate Lymphoid Cells (ILCs)

    • Tissue-specific cues:
      • Lung: ILC2 are primed to respond to allergens and helminths
      • Gut: ILC3 are more responsive to bacterial signals
    • Metabolic and microbiota signals:
      • Short-chain fatty acids (SCFAs) produced by commensal microbes modulate ILC activation (ILC3) by influencing cytokine production and barrier function
    • Neuro-immune interactions:
      • Neuronal signals (VIP - vasoactive intestinal peptide; neuromedin U) can directly activate ILCs (ILC2) influencing response during allergic reactions and tissue repair processes
    • Plasticity: ILCs can switch from one type to another under certain conditions
      • ILC3-to-ILC1 plasticity: in response to IL-12, which has been associated with intestinal inflammation
      • Allows for functional flexibility in response to environmental changes/disease

    Natural Killer (NK) Cells

    • Type of ILCs, critical role in the immune system's defense against virally infected cells and tumors
    • Do not require prior sensitization or antigen-specific receptors to recognize and eliminate target cells
    • Rapid response to “stressed” cells that exhibit changes (infection, malignant transformation, damage)
    • Kill these cells directly and secrete cytokines to modulate the broader immune response
    • Have different types of killing -> granzymes is the fastest way of killing
    • CD56 level is different in 2 subtypes of NK cells:
      • Bright CD56: Killing, NK cells
      • Dim CD56: Cytokine producing, helper NK cells
      • Found in low levels in the blood, produce more cytokines, become more anti-inflammatory, with more of a regulatory function.
    • Can become memory cells
      • In the blood, most mature state with Cd56 dim expression (killers)
      • Pro-inflammatory function/cytotoxic function

    Dendritic Cells (DCs)

    • Follicular DCs: Come back in the last case
      • Morphology not derived from bone marrow precursors, not involved in protein antigen presentation to T cells
      • Involved in B cell activation in the germinal centers of secondary lymphoid organs
      • TLRs, NLRs, important for T cell activation, MHC-I always (in healthy conditions - self-antigen is expressed)

    Dendritic Cell Types and Functions

    • cDC2s: CD11c, BCDA-1 (CD1c)
      • Transcription factors: IRF4
      • Cytokines produced: Various
      • Function (innate): Source of inflammatory cytokines
      • Function (adaptive): Capture and presentation of antigens mostly to CD4+ T cells
    • cDC1s: CD11c, BDCA-3 (CD141), CLEC9A, XCR1+
      • Transcription factors: IRF8, BATF3
      • Cytokines produced: IL-12
      • Function (innate): Early innate response, priming of antiviral T cells
      • Function (adaptive): Capture and cross-presentation of antigens to CD8+ T cells; induction of Th1 responses
    • pDCs: BDCA-2 (CD303), BDCA-4 (CD304), CD123
      • Transcription factors: E2-2
      • Cytokines produced: Type I IFN
      • Function (innate): Early innate response
      • Function (adaptive): Antiviral immunity
    • Langerhans cells: CD11b, Langerin (CD207), EPCAM, BDCA1, CD1a
      • Transcription factors: PU.1
      • Cytokines produced: Various
      • Function (innate): Source of inflammatory cytokines
      • Function (adaptive): Capture and presentation of antigens mostly to CD4+ T cells
    • moDCs: CD11b, CCR2, CD14
      • Transcription factors: Various
      • Cytokines produced: Various
      • Function (innate): Source of inflammatory cytokines
      • Function (adaptive): Unknown

    Dendritic Cell Development

    • From hematopoietic stem cells in the bone marrow:
      • From both CMPs and CLPs
      • Conventional DCs: From myeloid precursors, specialized in antigen presentation and T cell activation
      • Plasmacytoid DCs: From lymphoid precursors, key precursors of type I interferons in response to viral infections
    • Immature DCs:
      • Located in peripheral tissues (skin, mucosal surfaces) where they are highly specialized for antigen capture
      • Express PRRs to detect pathogens
      • High phagocytotic activity - capturing pathogens, apoptotic cells, or foreign particles
      • Low expression of costimulatory molecules (CD80, CD86) necessary for T cell activation

    Dendritic Cell Antigen Uptake

    • Immature DCs are highly efficient at capturing antigens, including pathogens, dead cells, and soluble molecules.

    T Cell Receptor (TCR)

    • Signal transduction: TCR complex: composed of α and β chains, each having a variable (V), a constant (C), and a transmembrane domain.
      • TCR binds to antigen-MHC complexes presented on antigen-presenting cells
      • Has a signal transduction domain called an immunoreceptor tyrosine-based activation motif (ITAM) - in the ζ chain
      • No D segment in the α chain - simpler than the β !zeta chain - important for intracellular signaling, works as an extension cord.

    TCR Gene Rearrangement

    • Epigenetic regulation of gene transcription: Environmental cue that opens up the DNA in order to get gene rearrangement
    • RAG1/2: Enzyme responsible for TCR rearrangement
      • Creates a loop that gets cut off and lost, it will never come back
      • The two ending are being connected into a coherent line
    • Junctional diversity: Filling in the gaps with P nucleotides (matching to where the gap was), which also means there is an endless amount of TCR variants

    T Cell Selection

    • Central tolerance:
      • Positive selection:
        • Location: Thymic cortex
        • Purpose: Ensure T cells can recognize self-MHC molecules
      • T cells bind to self-MHC class I: CD8+
        • IL-7 is important for CD8 - blocks the locus of one of CD4
      • T cells bind to self-MHC class II: CD4+ (presentation by endosomes and merging, NOT cross presentation)
        • CD4 - they have inhibition of IL-7, which I think downregulates CD8
      • Positive selection: Downregulation of either CD4 or CD8 (just stop making one) - single positive cells
      • cTECs: Cortex thymic epithelial proteins - in MHC we have self-antigens, can't be empty (than they are degraded if they are)
    • Regulation:
      • By chance depending on which one they encounter first, or they might have a preference (genetic encoded) - 2 hypothesis
    • Low-high affinity model:
      • If too low - die from neglect
      • If too high - die from auto-reactivity
      • If a bit lower than perfect → Tregs cells

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    Explore the foundational concepts of innate and adaptive immunity in this quiz. Understand the rapid response of the innate immune system and the slower, but more specific actions of the adaptive immune system. Test your knowledge on the complement system and its pathways as integral components of immune responses.

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