BIOL 318 MTSS
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Questions and Answers

What is the primary role of a ligand in receptor-ligand interactions?

  • To generate a cellular signal (correct)
  • To promote receptor internalization
  • To alter the cell's composition
  • To inhibit cell division

    • How can a cell modulate its sensitivity to a ligand?

  • By altering its genetic material
  • By changing its metabolic pathways
  • By increasing or decreasing receptor expression (correct)
  • By producing more ligands

    • Which receptors are primarily involved in pathogen recognition?

  • Cytokine receptors
  • Pathogen Recognition Receptors (PRRs) (correct)
  • T cell receptors
  • MHC class I

    • What is the function of cytotoxic T cell receptors?

    <p>To recognize foreign antigens</p> Signup and view all the answers

    Which of the following statements about cytokine receptors is accurate?

    <p>Cytokine receptors mediate communications between cells.</p> Signup and view all the answers

    What is the primary role of granulocytes in the immune response?

    <p>To directly harm pathogens and promote inflammation</p> Signup and view all the answers

    Which cells are considered antigen-presenting cells (APCs)?

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

    What is hematopoiesis?

    <p>The process of immune cells arising from bone marrow</p> Signup and view all the answers

    What are the primary progenitor cells that hematopoietic stem cells differentiate into?

    <p>Myeloid and lymphoid progenitor cells</p> Signup and view all the answers

    Which of the following is NOT a function of macrophages?

    <p>Differentiating into dendritic cells</p> Signup and view all the answers

    What characteristic distinguishes dendritic cells from other antigen-presenting cells?

    <p>Their capacity to mature and migrate after antigen capture</p> Signup and view all the answers

    Which type of immune cells are primarily involved in the adaptive immune response?

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

    What do pathogen recognition receptors (PRRs) do in immune cells?

    <p>Allow immune cells to recognize and bind to pathogens</p> Signup and view all the answers

    Which of the following cells are classified as lymphoid cells?

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

    What is the primary mechanism by which macrophages present antigens?

    <p>Via phagocytosis of the antigen</p> Signup and view all the answers

    What is a characteristic of cytokines regarding their secretion?

    <p>They are self-limited and brief in secretion.</p> Signup and view all the answers

    In the context of cytokines, what does the term 'pleiotropic' refer to?

    <p>Cytokines having different effects on different cells.</p> Signup and view all the answers

    What type of cytokine is primarily responsible for attracting leukocytes?

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

    What describes the interaction of different cytokines leading to the same response?

    <p>Cytokine redundancy</p> Signup and view all the answers

    Which action involves cytokines being released to affect nearby cells?

    <p>Paracrine action</p> Signup and view all the answers

    What occurs during cytokine synergism?

    <p>The effects of combined cytokines exceed their individual impacts.</p> Signup and view all the answers

    Which type of cytokines are specifically produced by activated lymphocytes?

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

    What is the result of a cytokine binding to a target cell?

    <p>It can induce metabolic changes in the target cell.</p> Signup and view all the answers

    What does the acronym CD stand for in the context of immune system proteins?

    <p>Cluster of Differentiation</p> Signup and view all the answers

    Where do B cells develop in the immune system?

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

    Which of the following is NOT a secondary lymphoid organ?

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

    What are the sites where immune responses are initiated?

    <p>Secondary lymphoid organs</p> Signup and view all the answers

    In which organ do T cells achieve full maturity?

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

    What is the primary function of secondary lymphoid organs?

    <p>Activation and differentiation of lymphocytes</p> Signup and view all the answers

    What is the role of Gut-Associated Lymphoid Tissue (GALT)?

    <p>Barrier function and organized immune response</p> Signup and view all the answers

    Which statement best describes the relationship between immune cells and lymphoid organs?

    <p>Immune cells must interact with lymphoid organs to respond effectively.</p> Signup and view all the answers

    Which component is a protective substance produced by epithelial layers?

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

    The innate immune response relies solely on the action of adaptive immune cells.

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

    What are the two main signaling mechanisms involved in the immune response?

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

    The skin produces an anti-microbial peptide known as __________.

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

    Match the following effector mechanisms of the immune response with their descriptions:

    <p>Phagocytosis = Engulfing and digesting pathogens Opsonization = Marking pathogens for destruction by immune cells NETosis = Releasing neutrophil extracellular traps Antimicrobial substances = Substances that directly kill microbes</p> Signup and view all the answers

    What are antimicrobial peptides primarily secreted by?

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

    Pattern recognition receptors (PRRs) are exclusive to immune cells.

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

    What initiates the immune cascade upon recognition by PRRs?

    <p>PAMPs or DAMPs</p> Signup and view all the answers

    The process by which cells engulf and internalize microbes for clearance is called _________.

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

    Match the following types of pattern recognition receptors with their recognition capabilities:

    <p>TLRs = Recognize PAMPs on bacterial cell walls NLRs = Detect intracellular pathogens RLRs = Identify viral RNA PRRs = Bind to PAMPs and DAMPs</p> Signup and view all the answers

    Which of the following statements accurately describes antimicrobial peptides?

    <p>They are effective against a range of microorganisms.</p> Signup and view all the answers

    Macrophages are considered specialized phagocytic cells.

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

    Name one type of cell that PRRs can be found on.

    <p>Epithelial cells or immune cells</p> Signup and view all the answers

    What process is primarily responsible for the engulfment of pathogens by immune cells?

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

    Phagocytosis typically results in bacterial death occurring within 1 hour.

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

    What is the role of the phagolysosome in the immune response?

    <p>It fuses with the phagosome to kill and digest pathogens.</p> Signup and view all the answers

    During phagocytosis, the formation of an internal vacuole that contains engulfed particles is called a ______.

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

    Which of the following molecules plays a crucial role in the recognition of pathogens during innate immune responses?

    <p>TLRs (Toll-Like Receptors)</p> Signup and view all the answers

    Chemokines are responsible for increasing vascular permeability to recruit immune cells.

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

    What is the controlled death of neutrophils called?

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

    In the immune response, dendritic cells serve as a key bridge between innate and ______ immunity.

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

    What major role do enzymes like iNOS and COX2 play in the immune response?

    <p>Inflammatory response regulation</p> Signup and view all the answers

    What is a key characteristic of MHC molecules in terms of genetic inheritance?

    <p>They exhibit co-dominance, inheriting alleles from both parents.</p> Signup and view all the answers

    All individuals in a species have the same MHC molecules, leading to equal susceptibility to infections.

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

    What is the role of MHC in T-cell mediated responses?

    <p>MHC presents peptides to T-cells, which is essential for their activation.</p> Signup and view all the answers

    MHC polymorphism is determined in the ______ and does not involve any recombination mechanisms.

    <p>germ-line</p> Signup and view all the answers

    Why is increased MHC diversity beneficial for a population?

    <p>It ensures better defense mechanisms against a variety of pathogens.</p> Signup and view all the answers

    Match the following aspects of MHC with their descriptions:

    <p>Co-dominant inheritance = Both parental alleles expressed Peptide binding = One binding site for various peptides MHC polymorphism = Genetic diversity among individuals Heterozygous expression = Output from both alleles in an individual</p> Signup and view all the answers

    MHC molecules can bind multiple peptides at the same time.

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

    What can lead to decreased MHC diversity in a species?

    <p>Population bottlenecks and inbreeding.</p> Signup and view all the answers

    What do T cells require in order to recognize antigens?

    <p>A specific self-MHC haplotype</p> Signup and view all the answers

    Humans prefer mating with individuals of the same MHC haplotype.

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

    What is the primary function of MHC molecules?

    <p>To present antigens to T cells.</p> Signup and view all the answers

    Cytokines such as IFN-γ and TNF-α can __________ MHC expression during infection.

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

    Match the following MHC-related concepts with their descriptions:

    <p>Self-MHC restriction = T cells only recognize antigens presented by identical MHC molecules. MHC Class I = Presents antigens from intracellular sources. MHC Class II = Presents antigens from extracellular sources. Genetic regulatory components = Promoters that enhance MHC transcription during infection.</p> Signup and view all the answers

    Which statement correctly describes the preference of mating in mice?

    <p>Mice preferentially mate with those having dissimilar MHC alleles.</p> Signup and view all the answers

    Viruses can increase MHC Class I expression to avoid immune destruction.

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

    Name the mechanism by which T cells kill infected cells that match their MHC haplotype.

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

    Which class of MHC presents antigen peptides to CD8+ T cells?

    <p>MHC Class I</p> Signup and view all the answers

    MHC Class II molecules are found on all nucleated cells.

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

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

    <p>Bridge between innate and adaptive immune response</p> Signup and view all the answers

    MHC molecules present both intracellular and __________ antigens.

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

    Match the following MHC classes with their properties:

    <p>MHC Class I = Presents intracellular antigens MHC Class II = Presents extracellular antigens MHC Class III = Comprises complement and inflammatory proteins MHC molecules = Involved in antigen presentation to T cells</p> Signup and view all the answers

    What does MHC polymorphism allow for in the immune system?

    <p>Greater diversity in antigen presentation</p> Signup and view all the answers

    MHC alleles are co-dominantly expressed.

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

    What type of antigens do MHC Class I molecules present?

    <p>Intracellular antigens</p> Signup and view all the answers

    The T cell receptor (TCR) binds to the MHC-________ complex.

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

    Match the following immune response types with their MHC class:

    <p>Cytotoxic T cells = MHC Class I Helper T cells = MHC Class II Both cell types = MHC class restriction All nucleated cells = MHC Class I expression</p> Signup and view all the answers

    Which of the following best defines haplotype?

    <p>A group of genes inherited from one parent</p> Signup and view all the answers

    MHC Class II molecules are important for presenting self-peptides to T cells.

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

    Name one factor that can influence the type of immune response triggered by a pathogen.

    <p>Location of the pathogen</p> Signup and view all the answers

    Polarizing cytokines guide the development of __________ T cell responses.

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

    Why is MHC variation significant for tissue transplantation?

    <p>It creates a barrier for tissue transplantation.</p> Signup and view all the answers

    What is the purpose of gene segment recombination in B cells?

    <p>To generate a diverse repertoire of antibody combining sites</p> Signup and view all the answers

    All B cells in the immune system have the same antibody specificity due to gene segment recombination.

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

    What regions are involved in the immunoglobulin gene structure?

    <p>Variable (V), diversity (D), joining (J), and constant (C) regions.</p> Signup and view all the answers

    During B cell development, allelic exclusion ensures that only one heavy chain gene is expressed to form a functional ______.

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

    Match the B cell processes with their descriptions:

    <p>Recombination of gene segments = Generates antibody diversity Allelic exclusion = Ensures single heavy chain expression mRNA splicing = Produces different antibody isotypes B cell receptor editing = Alters specificity of existing receptors</p> Signup and view all the answers

    Which proteins are essential for V(D)J recombination in B cells?

    <p>RAG1 and RAG2</p> Signup and view all the answers

    D segments are utilized in both heavy and light chains of antibodies.

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

    What process generates antibody diversity in naive B cells?

    <p>V(D)J recombination</p> Signup and view all the answers

    RAG proteins cleave the DNA during the __________ process in B cells.

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

    Match the following antibodies' characteristics:

    <p>Heavy Chain = D variable segment inclusion Light Chain = Does not use D segments Combinatorial diversity = Combination of H and L chains Nucleotide addition = Random nucleotide insertion</p> Signup and view all the answers

    Which mechanism contributes to B cell receptor editing?

    <p>Recombination of heavy chain segments</p> Signup and view all the answers

    Exonuclease trimming can lead to the loss of nucleotides and alterations of reading frames.

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

    How many different H chain sequences can a mouse produce assuming 130 VH segments, 13 D segments, and 4 J segments?

    <p>7,000</p> Signup and view all the answers

    What does allelic exclusion ensure in B cells?

    <p>Each B cell synthesizes only one heavy and one light chain</p> Signup and view all the answers

    B cell receptor editing occurs primarily in heavy chains.

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

    What is the purpose of mRNA splicing in B cells?

    <p>To produce either membrane-bound or secreted antibodies.</p> Signup and view all the answers

    Heavy chain recombination is expressed first during B cell __________.

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

    Match the following processes to their descriptions related to B cell development:

    <p>Allelic exclusion = Only one allele is expressed in a B cell Receptor editing = Modification of autoreactive receptors mRNA splicing = Determines antibody form produced Heavy chain recombination = First step in B cell receptor formation</p> Signup and view all the answers

    Which process involves turning on recombination machinery again in B cells?

    <p>Receptor editing</p> Signup and view all the answers

    Mature B cells express only one type of antibody.

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

    What occurs during class switching in B cells?

    <p>Recombination of CH genes to express different antibody classes.</p> Signup and view all the answers

    A functional variable region DNA sequence is present for each chain in a __________ cell.

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

    What is expressed by a B cell immediately after successful heavy chain recombination?

    <p>A pre-B cell receptor</p> Signup and view all the answers

    Which statement accurately describes the relationship between antigens and immunogens?

    <p>All immunogens are antigens, but not all antigens are immunogens.</p> Signup and view all the answers

    What is a key characteristic that distinguishes acute inflammation from chronic inflammation?

    <p>Chronic inflammation is characterized by prolonged tissue destruction.</p> Signup and view all the answers

    Which term is used synonymously with inflammation in a medical context?

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

    What are the cardinal signs of inflammation?

    <p>Pain, redness, heat, swelling, and loss of function</p> Signup and view all the answers

    What term refers to the protection that the immune system provides from pathogens?

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

    Which type of immunity involves antibodies produced by B cells?

    <p>Humoral Immunity</p> Signup and view all the answers

    Which pathogen is NOT considered one of the major categories recognized by the immune system?

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

    What mechanism does the immune system use to avoid destroying host tissue?

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

    Which cells are primarily responsible for mediating cell-mediated immunity?

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

    What is the function of pattern recognition receptors (PRRs) in immune cells?

    <p>To recognize generic molecules associated with many pathogens</p> Signup and view all the answers

    What is a characteristic of adaptive immunity?

    <p>Memory formation after exposure to antigens</p> Signup and view all the answers

    Which term describes the dysfunctions of immunity including allergies and autoimmune diseases?

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

    Which component of immunity is typically involved in eradicating intracellular pathogens?

    <p>Cell-mediated immunity</p> Signup and view all the answers

    How do passive immunity and active immunity differ?

    <p>Passive immunity is immediate while active takes time to develop.</p> Signup and view all the answers

    Study Notes

    Immune Response Overview

    • Understand triggers of the immune response and key cellular components involved.
    • Main cells include Granulocytes, Myeloid Cells, Lymphoid Cells, T cell receptors, B cell receptors, Clusters of differentiation, Pathogen Recognition Receptors (PRRs), Cytokines, and Variable molecules.
    • Immune response mechanisms are categorized into innate and adaptive responses.

    Immune Cell Development

    • Immune cells originate through hematopoiesis in the bone marrow.
    • Hematopoietic Stem Cells (HSCs) differentiate into Red blood cells (Erythrocytes) and White blood cells (Leukocytes).
    • Two major progenitor types: Myeloid progenitor cells and Lymphoid progenitor cells.

    Myeloid Cells: Granulocytes

    • Granulocytes perform direct harm to pathogens and exhibit antiviral and antiparasitic activities.
    • Involved in inflammation and allergic responses.
    • Granule proteins dictate their specific functions.

    Myeloid Cells: Other Functions

    • Other myeloid cells differentiate into macrophages, migrating to tissues.
    • Macrophages repair, remodel, phagocytose, and destroy pathogens while presenting antigens.
    • Antigen-presenting cells (APCs) can activate naïve T cells.

    Antigen Presenting Cells (APCs)

    • APCs ingest antigens through phagocytosis.
    • Dendritic cells, key specialized APCs, capture antigens, mature, and migrate to present them to T cells.
    • Most potent APCs for activating naïve T cells are dendritic cells.

    Lymphoid Cells

    • Major lymphoid cells include T cells, B cells, and Innate Lymphoid Cells (ILCs).

    Identification of Immune Cells

    • Cluster of Differentiation (CD) refers to cell membrane proteins that identify immune system cells.

    Lymphoid Organs

    • Primary lymphoid organs: Sites for immune cell development (e.g., bone marrow for B cells, thymus for T cells).
    • Secondary lymphoid organs: Locations for antigen encounter, activation, clonal expansion, and differentiation of lymphocytes (e.g., spleen).
    • Tertiary lymphoid organs: Sites where infections occur.

    Cytokines and Immune Communication

    • Cytokines are proteins that mediate immune system functions, with different types such as monokines, lymphokines, interleukins, and chemokines.
    • Cytokine functions include endocrine, paracrine, and autocrine actions.
    • Pleiotropic nature allows them to have various effects based on context.

    Cytokine Characteristics

    • Cytokines induce transcriptional changes in target cells, acting in a self-limited manner.
    • They display redundancy, synergism, and antagonism in action, affecting immune responses.

    Cytokine Signaling Cascade

    • Cytokines trigger further cytokine production creating complex signaling networks, influencing target cell responses dynamically.

    Upcoming Class Activities

    • Prepare for a pre-class quiz on Chapter 4 (Adaptive Immunity).
    • Lecture on Innate Immunity and engage in an in-class quiz using iClicker.
    • Discussion on Assignment 1 scheduled for the following class.

    Learning Objectives

    • Identify physical, chemical, and biological components of the innate immune response.
    • Explain immune response mechanisms:
      • Recognition (PRRs)
      • Signaling (Cytokines & Chemokines)
      • Effector response (Antimicrobial substances, Opsonization, NETosis, Phagocytosis)

    Components of Innate Immune Response

    • Innate immunity acts as the body's first defense against pathogens.
    • Epithelial layers secrete protective substances, including antimicrobial peptides (AMP).
    • Psoriasin, an antimicrobial peptide produced by the skin, targets and kills Gram-negative bacteria.
    • AMPs are short, positively charged peptides synthesized by neutrophils and some epithelial cells and disrupt microbial membranes.

    Pattern Recognition Receptors (PRRs)

    • PRRs detect and bind to invaders, activating immune responses.
    • Commonly found on epithelial and immune cells.
    • Ligands for PRRs include:
      • Pathogen-Associated Molecular Patterns (PAMPs) from microbes.
      • Damage-Associated Molecular Patterns (DAMPs) from damaged self-structures.
    • PAMP recognition leads to immune cascade activation.

    Innate Immune Effector Mechanisms

    • Phagocytosis: Engulfment and internalization of pathogens by specialized cells like macrophages and neutrophils.

      • Requires pathogen recognition via PRRs (e.g., TLR4 detecting E. coli LPS).
      • Phagocytosis involves adherence, ingestion (pseudopodia formation), and digestion (via phagolysosome fusion).
      • Destruction through enzyme degradation and oxidative species occurs within the phagolysosome.

    • NETosis: A form of programmed cell death in neutrophils that traps and degrades pathogens.

      • Controlled by chemokines affecting neutrophil recruitment to infection sites.

    • Cytokines and Chemokines: Essential for communication among immune cells, orchestrating the immune response.

    Additional Effector Mechanisms

    • Dendritic cells serve as a crucial link between innate and adaptive immune responses, facilitating communication.
    • Natural Killer (NK) cells play a role in directly lysing infected cells via granule secretion.
    • Opsonization improves pathogen recognition and clearance, to be discussed in further detail in Lecture 6.

    Summary of Innate Immunity

    • Functions as the first line of defense against infections.
    • Relies on recognizing general pathogen molecules rather than specific ones.
    • Involves various responses, including:
      • Phagocytosis
      • Inflammatory response activation
      • Direct cytotoxic activity from NK cells
      • Initiation of adaptive immune responses.

    Learning Objectives

    • Importance of Major Histocompatibility Complex (MHC) for immune response.
    • Antigen recognition and presentation mechanisms in relation to MHC.
    • MHC polymorphism and its implications for immune restriction.
    • Comparison of MHC expression in innate vs. adaptive immune responses.

    Major Histocompatibility Complex (MHC)

    • MHC proteins carry antigenic materials, indicating tissue compatibility.
    • MHC Class I is present on all nucleated cells, while MHC Class II is restricted to antigen-presenting cells (APCs).
    • T cells require antigens to be presented via MHC for activation.

    Antigen Presentation

    • MHC proteins bind to fragments of antigens, allowing T cell receptors (TCRs) to recognize them.
    • Dendritic cells play a crucial role in connecting innate and adaptive immunity.
    • MHC Class I presents intracellular antigens, whereas Class II presents extracellular antigens.

    Antigen Processing Pathways

    • Virus in cytosol activates the MHC Class I pathway leading to cytotoxic T lymphocyte (CTL) response.
    • Extracellular pathogens activate the MHC Class II pathway and produce T helper responses for antibody production.

    MHC Diversity and Polymorphism

    • MHC genes exhibit high polymorphism, with over 100 allelic variants identified in humans.
    • This genetic diversity allows a higher chance of effective antigen presentation across populations.
    • Each individual has unique MHC proteins, except for identical twins, affecting tissue transplantation compatibility.

    MHC Expression and Inheritance

    • MHC genes are co-dominantly expressed, meaning offspring inherit and express both maternal and paternal alleles.
    • Mice models, including syngeneic and congenic strains, facilitate understanding of MHC self-restriction and transplantation compatibility.
    • Haplotype combinations inform an organism's capability to present a diverse array of antigen peptides.

    Functional Characteristics of MHC

    • Each MHC molecule contains a single peptide-binding site but can bind a variety of peptides sequentially.
    • MHC polymorphism arises from germ-line inheritance; no recombination generates diversity.
    • The specific binding of peptides to MHC is essential for initiating T-cell mediated immune responses.

    MHC and Disease Susceptibility

    • MHC polymorphism ensures that not all individuals within a species are equally susceptible to pathogens, enhancing species survival.
    • Outbreeding populations maintain genetic diversity which can be critical for resistance to diseases.

    MHC and Mate Selection

    • Mice and humans show preferences for mates with diverse MHC haplotypes.
    • Odor associated with MHC molecules influences mating choices, as individuals are drawn to partners with dissimilar MHC traits.

    Regulation of MHC Expression

    • MHC expression can fluctuate based on genetic regulatory components and environmental factors.
    • Viruses may downregulate MHC Class I expression to evade immune detection.
    • Cytokines like IFN-γ can enhance MHC expression during infections, while others can suppress it.

    Self-MHC Restriction in T Cell Recognition

    • T cells recognize antigens strictly in the context of their own MHC type, requiring matching haplotypes to activate.
    • Research by Zinkernagel and Doherty demonstrated that T cells can only lyse target cells exhibiting the same MHC-I haplotype as presented.

    Antibody Formation and Diversity

    • Gene segments are joined by RAG1/2 recombinase crucial for antibody production.
    • RAG stands for recombination activating gene; both RAG1 and RAG2 are essential for receptor gene recombination.
    • Severe combined immunodeficiency (SCID) arises from impaired receptor gene recombination, often treated through bone marrow transplantation.

    Immunoglobulin Gene Structure

    • Immunoglobulin genes consist of variable (V), diversity (D), joining (J), and constant (C) region segments.
    • D segments are exclusive to antibody heavy chains.
    • Recombination is guided by recombination signal sequences (RSSs) which flank each gene segment.

    V(D)J Recombination

    • RAG proteins bind to RSSs and cleave DNA, leading to complex processing of hairpin loops.
    • Results include a recombined coding joint and a signal joint that is degraded later.

    Mechanisms of Antibody Diversity

    • Recombination of multiple gene segments creates diverse antibodies, akin to shuffling cards.
    • Combinatorial diversity arises from pairing heavy (H) chains with light (L) chains.
    • Specific mechanisms include nucleotide addition by terminal deoxynucleotidyl-transferase (TdT) and exonuclease trimming, altering nucleotides at junctions.

    Antibody Chain Variability

    • A mouse can generate approximately 7,000 different heavy chain sequences based on available gene segments (130 VH, 13 D, 4 J).
    • With 346 light chain sequences, the resultant diversity yields around 2 million unique immunoglobulin molecules.

    Research Contributions

    • Hozumi and Tonegawa (1976) established that variable and constant regions are encoded on different restriction fragments and can co-locate in antibody-producing cells.

    B Cell Receptor Recombination

    • Each B cell synthesizes only one heavy and one light chain due to allelic exclusion, ensuring B cell specificity.
    • V rearrangement occurs during B cell maturation in the bone marrow, expressing one functional variable region for each chain.

    Recombination and Apoptosis

    • Nonproductive rearrangements can trigger programmed cell death (apoptosis) during B cell development.

    Receptor Editing

    • Autoreactive receptors in immature B cells can undergo receptor editing, enabling change to avoid self-reactivity.

    Expression of Antibodies

    • Mature B cells can express both IgM and IgD antibodies through mRNA splicing, which regulates the type of heavy chain produced.

    T Cell Receptors (TCR)

    • TCRs, while not immunoglobulins, share structural similarities with immunoglobulins, including variable (V) and constant (C) domains.
    • Two main TCR types are αβ and γδ, both with unique antigen-binding characteristics.
    • Each T cell expresses a TCR with a single specificity and requires CD3 for surface expression and signaling.

    TCR Gene Rearrangement

    • TCR genes undergo rearrangement akin to immunoglobulin genes, although their locations vary between species such as mice and humans.

    Clonal Selection and Antigen Exposure

    • Prior to encountering specific antigens, receptor gene rearrangements are predetermined, equipping B and T cells with antigen receptors.
    • The clonal selection hypothesis suggests that antigens select specific clones of B and T cells possessing the appropriate receptors.

    Class Switching

    • Class switching to express different antibody types (IgG, IgA, IgE) necessitates prior antigen exposure and stimulation from T cells.
    • Cytokine signals activate new rounds of recombination, reconfiguring VDJ segments adjacent to new constant heavy chain (CH) regions.

    Lecture Overview

    • Instructor: Andrea Verdugo Meza, PhD Candidate in BIMB.
    • Lecture date: September 4, 2024.
    • Introduction to coursework, expectations, and learning tools like Canvas and Achieve.
    • Discussion about students' interests in immunology.

    Key Terminology in Immunology

    • Antigen: Any foreign substance that specifically binds to antibodies or T-cell receptors; synonymous with immunogen.
    • Immunogen: Substance that elicits an immune response; all immunogens are antigens, but not all antigens are immunogens.
    • Antibody: Y-shaped proteins from the adaptive immune response that identify and neutralize foreign invaders.
    • Inflammation: White blood cells infiltrate the site of injury, characterized by pain, heat, redness, swelling, and loss of function.
    • Acute vs. Chronic Inflammation: Acute is the initial response to harm, while chronic is a prolonged response without healing.

    Historical Perspective of Immunology

    • Immunity: Protective mechanism to eliminate foreign pathogens; derived from Latin "immunis," meaning exempt.
    • Historical observations date back over 2000 years, notably from Thucydides concerning immunity during the Athenian plague.

    Overview of the Immune System

    • Purpose: Protect against pathogens (viruses, bacteria, fungi, parasites) and eliminate altered self-cells (cancer).
    • Immune responses adapt based on the intruding organism type.
    • Example: Survivors of smallpox demonstrated immunity without disease presence.

    Components of Immunity

    • Humoral Immunity: Mediated by B cells and antibodies; involves body fluids and can provide passive immunity.
    • Cell-mediated Immunity: Involves T lymphocytes and innate immune cells to fight pathogens and infected cells, activating immune responses through cytokine release.

    Categories of Pathogens

    • Major categories include viruses, bacteria, fungi, and parasites.
    • Immune responses vary by pathogen type and their location (intracellular vs. extracellular).

    Important Concepts in Immune Response

    • Recognition Molecules:
      • Germ-line encoded molecules (PRRs) bind to PAMPs, generic molecules on various pathogens.
      • Randomly generated receptors from B and T cells bind to specific antigens.

    Clonal Selection and Tolerance

    • Diversity Generation: B- and T-cell receptor arrangements allow for diverse immune recognition.
    • Tolerance: Ensures the immune system avoids attacking host tissues; prevents anti-self recognition from entering the bloodstream.

    Adaptive and Innate Immunity

    • Vertebrate immune systems use two interconnected systems for pathogen response.
    • Memory is a critical feature of adaptive immunity, enabling long-lasting defense.

    Immune System Dysfunctions

    • Overly Active/Misdirected Responses: Can lead to allergies, asthma, and autoimmune diseases (e.g., multiple sclerosis, Crohn’s disease).
    • Immunodeficiency: Can be primary (genetic loss of function) or secondary (acquired loss), leading to opportunistic infections like oral thrush.

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