Immunology Lecture 11: Importance of MHC
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Questions and Answers

What is clonal selection?

Clonal selection is when cells expressing mutations with higher affinity are selected and proliferated, while cells with lower affinity mutations are eliminated.

Explain somatic hypermutation. What is the key enzyme?

Somatic hypermutation is when the BCR locus undergoes extreme mutations in the CDRs. The key enzyme is activation-induced deaminase (AID).

What is class or isotype switching?

Isotype switching is the process that changes the heavy chain constant regions of antibodies, leading to different antibody isotypes.

What are plasma cells and memory B cells?

<p>Plasma cells are terminally differentiated B cells committed to producing antibodies, while memory B cells are long-lived cells that express surface Ig and can rapidly respond during secondary exposure.</p> Signup and view all the answers

What is antibody feedback?

<p>Antibody feedback is a regulatory mechanism where increased IgG secretion leads to decreased antibody responses.</p> Signup and view all the answers

Which of the following is true about T cell-dependent antibody responses?

<p>Antibody has a high level of isotype switching and affinity maturation.</p> Signup and view all the answers

What is the role of J chain in antibody structure?

<p>The J chain holds the monomers together in antibodies such as IgM and IgA.</p> Signup and view all the answers

Match the antibody isotype to its function.

<p>IgG = Most abundant serum antibody with numerous effector functions IgM = First antibody produced during primary response IgA = Most abundant in mucosal tissues IgE = Mediates allergic reactions and fights parasitic infections</p> Signup and view all the answers

What are regional immune systems? Give examples.

<p>Regional immune systems serve specialized functions in specific anatomical locations, such as the mucosal and cutaneous immune systems.</p> Signup and view all the answers

What are mucins and defensins?

<p>Mucins are glycoproteins that compose mucus, providing a barrier to microbes. Defensins are small antimicrobial peptides that disrupt pathogen membranes.</p> Signup and view all the answers

What is the importance of IgA in mucosal immunity?

<p>IgA is the most abundant antibody isotype in mucosal tissues and neutralizes microbes and toxins.</p> Signup and view all the answers

How are maternal antibodies transferred to the fetus?

<p>Maternal IgG is transported across the placenta via FcRn, while secretory IgA is transferred through breast milk after birth.</p> Signup and view all the answers

What characterizes the adaptive immune response in the GI tract?

<p>GALT is crucial for initiating adaptive immunity.</p> Signup and view all the answers

What does a low red blood cell (RBC) count indicate?

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

Which proteins are examples of positive acute phase proteins (APP)?

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

What is the clinical significance of C-reactive protein (CRP)?

<p>Indicates acute inflammation</p> Signup and view all the answers

List the 5 major fractions of serum electrophoresis.

<p>Albumin, Alpha globulins, Beta globulins, Gamma globulins, CRP</p> Signup and view all the answers

What is the difference between direct and indirect tests?

<p>Direct tests look for antigens, while indirect tests look for antibodies.</p> Signup and view all the answers

What type of antibodies are produced from a single clone?

<p>Monoclonal antibodies</p> Signup and view all the answers

How does agglutination work?

<p>Agglutination detects antibodies in serum or antigens on particles.</p> Signup and view all the answers

What do ELISAs detect?

<p>ELISAs detect antibodies and antigens.</p> Signup and view all the answers

The lateral flow immunoassay, also known as ________, is used for pregnancy testing.

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

What does PCR amplify?

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

What method uses antibodies attached to magnetic beads to isolate cell populations?

<p>Magnetic-activated cell sorting (MACS)</p> Signup and view all the answers

What does the DCF-DA assay measure?

<p>Oxidative burst of neutrophils</p> Signup and view all the answers

Match the following leukocyte function tests to their targets:

<p>DCF-DA assay = Neutrophils Phagocytosis assay = Neutrophils, monocytes, macrophages Cytokine profiles = Monocytes, macrophages, lymphocytes Mitogen assay = Lymphocytes Cytotoxic assay = Lymphocytes</p> Signup and view all the answers

What triggers activation in T cells?

<p>Coreceptors and proteins part of the TCR complex</p> Signup and view all the answers

List the proteins involved in the TCR complex.

<p>TCR, CD3, and zeta chain</p> Signup and view all the answers

What is the main function of adhesion molecules?

<p>Stabilize APC-T cell interaction and facilitate T cell trafficking</p> Signup and view all the answers

What is the immune synapse?

<p>The point of interaction between the T cell and APC or target cell</p> Signup and view all the answers

What do NK-B, NFAT, AP-1, Ras/Rac, and PI3-Akt have in common?

<p>They are involved in T cell signaling and response.</p> Signup and view all the answers

What is the mechanism of action of cyclosporine?

<p>It binds to Calcineurin, preventing it from activating NFAT.</p> Signup and view all the answers

What changes occur in the IL-2 receptor during an immune response?

<p>Naive T cells express low affinity IL-2R, and activation increases expression of IL-2Ra for a high affinity receptor.</p> Signup and view all the answers

What are the main types of conventional T cells and their functions?

<p>Helper T cells (CD4), Cytotoxic T cells (CD8), Regulatory T cells, NKT cells.</p> Signup and view all the answers

What are the main functions of Th1, Th2, and Th17 cells?

<p>Th1 activates macrophages, Th2 promotes destruction of helminths, Th17 recruits neutrophils.</p> Signup and view all the answers

What is the immunological synapse?

<p>A stable cell junction between a CTL and APC target cell.</p> Signup and view all the answers

How do NK and NKT cells differ?

<p>NK cells recognize infected cells via death receptors, while NKT cells respond to lipid antigens.</p> Signup and view all the answers

What pathways are used by CTLs for killing target cells?

<p>Perforin/Granzyme pathway, Fas/FasL pathway, TNF receptor family pathway.</p> Signup and view all the answers

How are host cells protected from CTL activity?

<p>Serpins protect CTLs from granzymes and cathepsin B degrades perforin.</p> Signup and view all the answers

What is the role of macrophages in CMI?

<p>Kill intracellular pathogens using ROS and NO, amplify CMI responses.</p> Signup and view all the answers

What is the contraction phase in immune responses?

<p>The decrease in lymphocytes after an infection is cleared.</p> Signup and view all the answers

What distinguishes memory cells from effector cells?

<p>Memory cells can rapidly respond upon re-exposure and live longer.</p> Signup and view all the answers

What is a hapten?

<p>Small molecules that illicit an immune response only when attached to a carrier protein.</p> Signup and view all the answers

Define somatic hypermutation.

<p>Numerous random mutations at V regions of heavy and light chains.</p> Signup and view all the answers

What is the structure of antibodies?

<p>Antibodies have a Y shape with two functional regions: Fab and Fc.</p> Signup and view all the answers

What types of signals are necessary for B cell activation?

<p>BCR signaling and helper T cell signals.</p> Signup and view all the answers

What are the phenotypic changes that result from BCR signaling?

<p>Increased expression of CCR7, B7 costimulators, T-cell cytokine receptors, and anti-apoptotic proteins.</p> Signup and view all the answers

Why do we need MHC?

<p>To distinguish self from non-self and present antigens to T cells.</p> Signup and view all the answers

What do the 3 sub-loci of MHC genes encode?

<p>Class I, Class II, and Class III MHC genes.</p> Signup and view all the answers

Define haplotype.

<p>A group of alleles that are inherited together from one parent.</p> Signup and view all the answers

What are anchor residues?

<p>Residues that hold the peptide into the binding groove of the MHC pocket.</p> Signup and view all the answers

MHC restriction occurs during T cell development in the thymus.

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

What characteristics are involved in MHC peptide binding?

<p>Broad specificity, serial monogamy, and stable peptide-MHC interaction.</p> Signup and view all the answers

Which cytokine increases MHC expression?

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

What are TAP and tapasin associated with?

<p>TAP transports peptides to the ER; Tapasin links TAP and Class I MHC.</p> Signup and view all the answers

What is the role of MHC molecules in the recognition of infected host cells by NK cells?

<p>MHC Class I signals to NK cells that the cell is self.</p> Signup and view all the answers

Define cross-presentation.

<p>The process by which exogenous antigens are presented on MHC Class I molecules.</p> Signup and view all the answers

What cells are APCs and how do they interact with B cells?

<p>B cells are APCs that present antigens to CD4 T cells for activation.</p> Signup and view all the answers

What are ITAMs and ITIMs?

<p>ITAMs are activation motifs; ITIMs are inhibitory motifs on receptors.</p> Signup and view all the answers

Which of the following are involved in enhancing antigen presentation in macrophages?

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

What are the mechanisms contributing to the diversity of Ig molecules?

<p>Combinatorial and junctional diversity.</p> Signup and view all the answers

Explain V(D)J recombination.

<p>It's a process where segments of DNA are rearranged to create diverse receptors for B and T cells.</p> Signup and view all the answers

What is receptor editing?

<p>A process where self-reactive receptors are replaced to prevent autoimmunity.</p> Signup and view all the answers

Which of the following are mechanisms of innate immunity to extracellular bacteria?

<p>Complement activation</p> Signup and view all the answers

What is the major protective immune response against extracellular bacteria?

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

What cytokine promotes plasma cell differentiation?

<p>IL-4</p> Signup and view all the answers

The spleen is essential to antibody response to polysaccharide antigens.

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

Which cell types are primarily involved in innate immunity to intracellular bacteria?

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

What is the role of Th17 cells in immune response?

<p>Recruit neutrophils and promote inflammation</p> Signup and view all the answers

How do encapsulated bacteria evade host immune responses?

<p>Antiphagocytic properties and resistance to complement</p> Signup and view all the answers

List some examples of pathogenic encapsulated bacteria.

<p>S.pneumoniae, Neisseria spp., H influenzae, N.meningitidis, C.neoformans</p> Signup and view all the answers

Antibody responses are the most effective way to respond to toxins.

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

Which cytokines are produced by CD4 cells to assist in B cell functions?

<p>IL-4</p> Signup and view all the answers

How are maternal antibodies transmitted to a fetus?

<p>Transplacental via FcRn receptor</p> Signup and view all the answers

What is the function of adjuvants in vaccines?

<p>Enhance the immune response to an antigen</p> Signup and view all the answers

Match the following types of immunity with their descriptions:

<p>Active immunity = Host makes immune response; stronger and long-lasting Passive immunity = Host receives preformed antibodies Natural immunity = Exposure leads to innate or adaptive immune response Artificial immunity = Induced through vaccines or immune therapies</p> Signup and view all the answers

Live-attenuated vaccines cannot replicate.

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

What are inactivated whole agent vaccines?

<p>Vaccines that cannot replicate</p> Signup and view all the answers

What is herd immunity?

<p>Indirect protection of unimmunized individuals when a large percentage of the population is immune</p> Signup and view all the answers

What are the three main cell types in a CBC?

<p>Red blood cells, white blood cells, platelets</p> Signup and view all the answers

Study Notes

Importance of MHC

  • MHC (Major Histocompatibility Complex) distinguishes self from non-self for immune response.
  • Also known as Human Leukocyte Antigen (HLA).
  • Elicits strong immune responses and determines acceptance or rejection in organ transplants.

Types of Histocompatibility Complexes

  • Major Histocompatibility Complex (MHC)

    • Antigens presented to T cells; critical for immune reactions.

  • Minor Histocompatibility Complex

    • Less immunogenic but involved in self/non-self recognition, important for graft vs host disease.

MHC Genes and Functions

  • MHC genes are located on chromosome 6 (more than 200 genes).

  • Class I MHC Genes

    • Present endogenous peptides to CD8 T cells.
    • Includes classical: HLA-A, HLA-B, HLA-C and nonclassical: HLA-G in fetal cells.

  • Class II MHC Genes

    • Present exogenous peptides to CD4 T cells.
    • Includes classical: HLA-DP, HLA-DQ, HLA-DR and non-classical: HLA-DM and DO.

  • Class III MHC Genes

    • Encode complement and inflammation proteins, like TNF-a.

Key Terms in MHC Genetics

  • Haplotype: Group of alleles inherited together from one parent.
  • Codominance: Maternal and paternal alleles are expressed equally.
  • Polygenic: MHC proteins are a result of multiple genes, not a single trait.
  • Polymorphic: High genetic diversity in MHC genes, providing survival advantages.

MHC Polypeptide Binding Characteristics

  • Anchor Residues: Grip peptides in the MHC binding groove relevant for interactions.
  • MHC Restriction: T cells are limited in responding to an antigen presented by MHC, occurs during T cell development.
  • Peptide Binding: MHC can bind various peptides, but presents only one at a time due to binding groove limitations.

Cell Types Expressing MHC

  • MHC Class I: Found on all nucleated cells (non-professional APCs can express MHC I).
  • MHC Class II: Expressed by professional APCs like dendritic cells, macrophages, and B cells.

Structural Differences of MHC Classes

  • Class I MHC: Comprises a single transmembrane domain, a 45 kDa alpha chain, and a 12 kDa beta-2 microglobulin.
  • Class II MHC: Contains two transmembrane domains with a heterodimeric structure (33 kDa alpha and 30 kDa beta chains).

Cytokine Influence

  • IFN-y: Increases MHC expression during immune responses.

Immune Cell Recognition

  • MHC I binds with CD8 T cells and MHC II with CD4 T cells, forming the "Rule of 8."

Antigen Processing Pathways

  • Class I MHC (Endogenous Pathway):

    • Proteins are degraded by the ubiquitin-proteosome pathway.
    • Peptides transported to the ER for MHC binding by TAP (Transporter Associated with Antigen Processing).

  • Class II MHC (Exogenous Pathway):

    • Antigen internalization occurs in endosomes/lysosomes.
    • Peptides bind to MHC II in vesicles, mediated by the invariant chain and replaced by HLA-DM.

Molecule Functions in Antigen Processing

  • TAP: Transports peptides into the ER for Class I.
  • Tapasin: Connects TAP and Class I MHC for efficient peptide loading.
  • Invariant Chain: Stabilizes Class II MHC inside the cell.
  • CLIP: Blocks MHC II binding site until replaced with a peptide by HLA-DM.

MHC Role in NK Cells

  • MHC Class I recognition helps NK cells distinguish between infected or abnormal cells, influencing cell killing activity.

Cross-Presentation Significance

  • Enables APCs to present exogenous antigens on MHC I, crucial for CD8+ T cell activation without APC infection.

NKT Cell Antigen Recognition

  • NKT cells recognize lipid and glycolipid antigens via CD1, an MHC-like molecule.

Role of B Cells in Immune Activation

  • B cells function as APCs and require activation by CD4 T cells for effective antigen presentation.

Superantigen Activation

  • Superantigens can activate a significant number of T cells (up to 20%), causing severe inflammatory responses and potential shock.

BCR and TCR Structure

  • BCR: Membrane-bound antibodies with two Fab (antigen-binding) and one Fc (effector function) regions.
  • TCR: Composed of two chains (αβ or γδ), specific for peptide-MHC complexes, not free antigens.

Selection Processes in T Cell Development

  • Positive Selection: Thymocytes that bind MHC are selected; others undergo death by neglect.
  • Negative Selection: Self-reactive T cells are deleted to prevent autoimmunity.

Mechanisms of Immunoglobulin Diversity

  • Combinatorial Diversity: Formation of different antibody combinations limited by V,D,J segments.
  • Junctional Diversity: Generating diversity through imprecise joining and nucleotide additions.

V(D)J Recombination

  • Rearrangement of gene segments to create diverse antigen receptors during B and T cell development.

Immune Activation Signals

  • Activation requires three signals:
    • TCR-MHC binding.
    • Costimulatory signals (e.g., CD80/CD86 with CD28).
    • Cytokine signals for functional response.

Importance of Adhesion Molecules

  • Stabilize interactions between T cells and APCs for effective activation; include LFA-1 and VLA-4 integrins.

Immune Synapse Function

  • Region of interaction between T cells and APCs enhances signal strength and ensures proper immune response.

Transcription Factors in T Cell Signaling

  • NF-kB, NFAT, AP-1 activate transcription for T cell functions, while Ras/Rac and PI3-Akt are critical for intracellular signaling.

Cyclosporine and Rapamycin Mechanism

  • Cyclosporine reduces IL-2 production by inhibiting calcineurin, blocking NFAT activation.### Immune Response Mechanisms
  • Calcineurin dephosphorylates cytoplasmic NFAT, leading to T cell activation.
  • Rapamycin inhibits mTOR kinase, reducing cell growth and serving as an immunosuppressant for organ transplants.

IL-2 Receptor Structure and Function

  • IL-2 receptor consists of IL-2Ra (CD25), IL-2RB, and γC chain.
  • IL-2Ra lacks signaling function; IL-2RB and γC are responsible for signaling.
  • Naive T cells express low-affinity IL-2R without IL-2Ra.
  • Activated T cells express high-affinity IL-2R with IL-2Ra, promoting proliferation and clonal expansion.
  • T-regs express high affinity IL-2Ra, enhancing their proliferation in the presence of IL-2.

Types and Functions of T Cells

  • Helper T Cells (CD4): Produce cytokines to assist other cells and bind to MHC Class II.
  • Cytotoxic T Cells (CD8): Kill altered self-cells and produce IFN-γ to activate macrophages and NK cells, binding to MHC Class I.
  • Regulatory T Cells (Tregs): Suppress immune responses and express CD25 to outcompete T cells for IL-2.
  • NKT Cells: Produce cytokines and direct cytotoxic activity against pathogens with lipid antigens.

Cell-Mediated Immunity

  • Major effector cells: T cells, responsible for immune response promotion and pathogen killing.
  • T cells exert direct actions through contact or indirectly via cytokine signaling.

Th Subsets Properties

  • Each Th subset has unique polarizing cytokines, master gene regulators, and effector cytokines.

Functions of Th Subsets

  • CD4 Th1: Activate macrophages via IFN-γ.
  • CD4 Th2: Target helminths and regulate macrophage activation.
  • CD4 Th17: Recruit neutrophils and monocytes to address extracellular bacteria and fungi.
  • T Regulatory Cells: Prevent autoimmunity and regulate immune responses.
  • CD4 Tfh Cells: Provide cytokine signals to B cells during antigen presentation.

Effector Cytokines of Th Subsets

  • Th1: IFN-γ, TNF for macrophage activation and inflammation.
  • Th2: IL-4, IL-5, IL-13 for allergic and anti-helminth responses.
  • Th17: IL-17A, IL-17F, IL-22 for promoting inflammation.
  • Treg: IL-10, TGF-β for suppression of immune responses.
  • Tfh: IL-4 and IL-21 for B cell activation in germinal centers.

Immunological Synapse

  • Stable junction between cytotoxic T lymphocytes (CTL) and APCs, essential for T cell activation.
  • Formation relies on accessory molecules like LFA-1 and CD8 binding to ICAM-1 and MHC I, respectively.

Functions of NK and NKT Cells

  • NK cells detect and kill infected/damaged cells by recognizing upregulated death receptors.
  • NKT cells, which have both T and NK characteristics, respond to lipid antigens presented by CD1.

Cytotoxicity Mechanisms of CTLs

  • Perforin/Granzyme Pathway: CTLs release perforin to create pores; granzymes activate apoptosis.
  • Fas/FasL Pathway: CTLs express FasL to bind Fas on target cells, triggering apoptosis.
  • TNF Receptor Pathway: TNF-α binding on target cells initiates a death signal, leading to apoptosis.

Protection of Host Cells from CTLs

  • CTLs contain serpins to inhibit granzymes and cathepsin B to degrade perforin.

Role of Macrophages in Cell-Mediated Immunity (CMI)

  • Macrophages kill pathogens using reactive oxygen species (ROS) and nitric oxide (NO).
  • They amplify CMI responses through IL-12 and IFN-γ signaling.

Humoral Mediators in CMI

  • Complement Dependent Cytotoxicity: C1 binds Fc portion of antibodies, leading to cytolysis.
  • Antibody Opsonization: Fab binds the target, while FcR on effector cells trigger phagocytosis.
  • Antibody-Dependent Cellular Cytotoxicity (ADCC): Fab binds target; FcR on effector cells promote cytolysis.

Contraction Phase of Immune Response

  • Decrease in lymphocytes after infection clearance, returning the immune response to homeostasis.

Differences Between Memory and Effector Cells

  • Memory cells respond rapidly to re-exposure, survive longer, and exhibit different markers than effector cells.

Targets for Drug Therapy in T Cell Activation

  • Cyclosporine inhibits calcineurin, impairing T cell receptor (TCR) signaling.
  • IL-2 receptor antagonists inhibit T cell growth.
  • JAK inhibitors block cytokine signaling.

Definitions and Concepts in Immune Response

  • Epitope: The specific part of an antigen recognized by antibodies or T cell receptors.
  • Affinity vs. Avidity: Affinity is the strength of antibody-antigen binding; avidity considers multiple binding sites.
  • Hapten vs. Immunogen: Haptens elicit no immune response alone, while immunogens do provoke an immune response.

Antibody Structure

  • Antibodies consist of heavy and light chains, with Fab regions for binding and Fc regions for effector functions.
  • Hypervariable regions within variable regions form antigen binding sites.

Types of Epitopes

  • Linear Epitopes: Recognized by antibodies as continuous sequences.
  • Conformational Epitopes: Recognized by T cells, formed from distant residues that fold together.

B Cell Activation Signals

  • In T-dependent responses, helper T cells provide necessary second signals via CD40-CD40L interaction.
  • T-independent responses are activated directly by the antigen itself.

Somatic Hypermutation and Affinity Maturation

  • Occurs in germinal centers, where B cells mutate V regions and are selected based on binding affinity.
  • Results in more effective secondary immune responses compared to primary responses.

Class Switching

  • Isotype determined by heavy chain regions and is influenced by T helper cell signals and cytokine context.

Functions of B Cells

  • Plasma Cells: Produce high amounts of antibodies and can be short-lived or long-lived in the bone marrow.
  • Memory B Cells: Express surface immunoglobulin and are poised for rapid response upon re-exposure.

Antibody Feedback Mechanism

  • Excess IgG can inhibit further antibody production through Fc receptor binding leading to reduced BCR signaling.

Differences in Antibody Responses

  • T-dependent responses require helper T cells, while T-independent responses do not.

These notes highlight essential facts about immune mechanisms, T cell and B cell functions, cytokines, and the structure and roles of antibodies, facilitating a better understanding of the immune response.### T Dependent vs T Independent Antigens

  • T dependent antigens are protein-based, allowing for complex immune responses.
  • High levels of isotype switching and affinity maturation occur, resulting in long-lived plasma cells.
  • Memory B cells enable a robust secondary immune response.
  • T independent antigens are polymeric (e.g., polysaccharides, glycolipids) and mainly produce IgM, with minimal isotype switching and affinity maturation.
  • Secondary responses to T independent antigens are uncommon and only observed with certain polysaccharide antigens.
  • T dependent responses are superior due to refined antibody responses and sustained plasma cells.

Structures and Functions of Antibodies

  • IgM is a pentamer; IgA occurs as a dimer at mucosal surfaces.
  • J chains connect monomers in IgM and IgA, crucial for mucosal transport.
  • Cysteines in Fc regions facilitate disulfide linkages between monomers, stabilizing antibody structures.

Functions of Specific Antibody Isotypes

  • IgG: Most abundant in serum, monomeric, versatile, enables opsonization, classical pathway activation, and neutralization of microbes and toxins.
  • IgM: First antibody produced during primary response; crucial for bloodstream infections and triggers classical complement pathway.
  • IgA: Predominantly a dimer in secretions; protects mucosal surfaces by neutralizing toxins and preventing pathogen adhesion.
  • IgE: Binds to receptors on mast cells and basophils; involved in allergic reactions and defense against parasites.
  • IgD: Present on mature B cells; has a less understood role in the immune response.

Regional Immune Systems

  • Regional immune systems, like mucosal and cutaneous, have specialized functions in their respective anatomical locations.
  • Protect against pathogens and help avoid unwanted immune responses.

Functions of Specialized Immune Cells

  • Cytokine-secreting epithelial cells: Release cytokines to recruit immune cells.
  • Goblet cells: Produce mucins that form the mucosal barrier.
  • M cells: Facilitate antigen delivery from gut lumen to GALT for immune interaction.
  • Paneth cells: Secrete antimicrobial peptides, including defensins.

Mucins and Defensins

  • Mucins form a viscous barrier that protects epithelium and displays antimicrobial agents.
  • Defensins disrupt pathogen membranes, providing innate immune protection.

Functions of Innate Lymphoid Cells and Dendritic Cells

  • Innate lymphoid cells (ILCs) are key in mucosal defense, activating via alarmins. They produce cytokines like IL-17, IL-5, IL-13 to recruit immune cells and bolster epithelial barriers.
  • Dendritic cells capture antigens, linking innate and adaptive immunity; vital for processing and presenting antigens to T cells.

Initiation of Adaptive Immune Responses in the GI Tract

  • Adaptive immune responses are initiated primarily in GALT, including Peyer’s patches and mesenteric lymph nodes.

Importance and Transport of IgA

  • IgA is the most abundant antibody isotype in mucosal immunity, neutralizing toxins and pathogens.
  • Transport involves the J chain binding to poly-IgR on epithelial cells, followed by transcytosis into the gut lumen.

Maternal Antibody Transfer

  • Maternal IgG crosses the placenta via FcRn before birth; post-birth, secretory IgA is present in breast milk, providing neonatal immunity.

Functions of T Cells in Mucosal Immunity

  • Intraepithelial lymphocytes (IELs): Predominantly CD8 T cells, they recognize and kill infected mucosal cells.
  • Lamina propria T cells: Mainly CD4 T cells, promote inflammation and support IgA production.

Cytokine Functions in the GI Tract

  • Th17 cells: Influence mucosal defenses, recruiting neutrophils and enhancing barrier function through IL-17 and IL-22.
  • Tregs: Suppress immune responses, protecting against unnecessary reactions to commensal bacteria.
  • Th2 cells: Key in helminth defense, producing IL-4, IL-5, and IL-13, influencing eosinophil activation and mucus secretion.

Mucosal Pathogen Exploitation

  • Pathogens may traverse epithelial barriers via M cells, directly infect epithelial cells, or evade humoral immunity through antigenic variation.

Tolerance and Allergies

  • Tolerance is systemic unresponsiveness to non-harmful antigens, preventing inappropriate reactions.
  • Allergies arise when tolerance is disrupted, often linked to environmental factors influencing immune education.

Functions of Surfactant

  • Surfactant proteins help in pathogen binding and gas exchange, produced by type II pneumocytes.

Immune Dysfunction in Various Diseases

  • HIV/AIDS: Targets CD4+ T cells, compromising immunity and leading to opportunistic infections.
  • Allergies: Result from altered immune responses to environmental antigens, causing symptoms via Th2 activation.
  • Inflammatory Bowel Disease (IBD): Dysregulated responses to gut microbiota, varying between Crohn's disease and ulcerative colitis.
  • Celiac Disease: Chronic inflammation due to gluten sensitivity, leading to intestinal mucosal damage.
  • MALT Lymphoma: Associated with chronic immune activation due to microbial infections.

Comparing Regional Immune Systems

  • Respiratory mucosal immunity features limited commensal organisms, with specialized cells like alveolar macrophages that balance immune response.
  • Genitourinary immunity is similar in function to GI immunity but differs in epithelial structure and immunoglobulin presence, emphasizing the role of IgG over IgA.

General Roles of Innate and Adaptive Immunity

  • Innate immunity is rapid, non-specific, and relies on preformed components; principal cells include phagocytes and granulocytes.
  • Adaptive immunity is slower, specific, and memory-driven, involving T and B lymphocytes, producing antibodies for targeted responses.

Immune Responses to Pathogens

  • Bacterial infections: Involves complement activation, phagocytosis, and adaptive antibody responses.
  • Fungal infections: Phagocyte involvement and Th17 responses are critical.
  • Viral infections: Focus on type I IFN responses to inhibit replication and NK cell activity for infected cell clearance.
  • Parasitic infections: Innate phagocyte activity and adaptive Th2 responses drive clearance, especially through IgE-mediated mechanisms.

Pathogen Evasion Techniques

  • Encapsulated bacteria evade immune detection by resisting phagocytosis and complement activation, necessitating antibody responses.
  • Toxin-producing pathogens inflict damage through direct action or superantigen roles, and antibody-mediated responses are vital for counteraction.

Antigenic Variation, Drift, and Shift

  • Antigenic variation allows pathogens to alter surface proteins, evading host immunity.
  • Antigenic drift: Small mutations causing minor changes in antigens; Antigenic shift: Large changes often due to recombination of viral genes, affecting immune recognition.

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