BLD 434 Final Exam

primary vs secondary immunity

- 1st time infected: several days for B-cells to proliferate (get sick before killing all pathogens) - after first infection: some B-cells and T-cells remain as memory cells - at next exposure: reaction to antigen is faster (secondary immune response; may not even "get sick")

Professional Antigen-Presenting Cells and Phagocytes

APCs: Dendritic cells, macrophages, B cells. Phagocytes: Neutrophils, macrophages.

active vs passive immunity

Active: Developed through natural infection or vaccination, long-lasting, Gradual development of immune response, Exposure to antigens (either from natural infection or through vaccines) stimulates the immune system to produce an active response, B cells generate antibodies, and T cells provide cellular immunity, has memory Passive: Immunity is transferred from one individual to another, Temporary, Immediate response, Transfer of pre-formed antibodies or immune cells to the recipient. Does not involve the recipient's immune system in producing a response

T-cell dependent response

Antigen Presentation: APCs capture, process, and present antigens derived from pathogens on their surface using MHC class II molecules T Cell Activation: Naïve CD4+ helper T cells recognize the antigen-MHC class II complex presented by APCs through their TCRs; co-stimulatory signals, such as the interaction between CD28 on the T cell and B7 on the APC. Clonal Expansion: leads to generation of effector T cells with the same antigen specificity Cytokine Release: Activated helper T cells secrete cytokines, such as IL-2, IL-4, IL-10, IL-17 B Cell Activation: B cells that have captured and processed the same antigen present it on their surface using MHC class II molecules Differentiation of B Cells: leads to the differentiation of B cells into plasma cells and memory B cells. Plasma Cell Activity: Antibodies circulate in the bloodstream and other body fluids, targeting and neutralizing the pathogen and memory is formed

T-cell independent response

Antigen Recognition: The immune system recognizes antigens directly without the need for antigen processing and presentation by APCs B Cell Activation: B cells can be activated directly by binding to T cell-independent antigens without T cell help. Proliferation and Differentiation: Activated B cells undergo proliferation and differentiation into plasma cells Isotype Switching: T cell-independent responses are often associated with IgM antibody production. Isotype switching is limited NO MEMORY CELLS Limited Affinity Maturation: limited affinity maturation of antibodies Effective Against Certain Pathogens: T cell-independent responses are particularly effective against encapsulated bacteria

B-1 vs B-2 cells

B-1: found in body cavities, Primarily generated during fetal development, Produces natural poly reactive antibodies, mainly IgM, Involved in the early immune response to infections, ability to self-renew ; carb and protein antigens, low somatic hypermutation B-2: found in secondary lymphoid organs, Generated throughout life from hematopoietic stem cells, Produces antibodies upon encountering specific antigens, Can produce IgM, IgG, IgA, and IgE; Primarily involved in adaptive immune responses, Critical for the generation of memory B cells, Lacks ability to self-renew; high somatic hypermutation

Identify the common CD markers used to identify human T cells (including subsets), B cells, and NK cells by flow cytometry

CD3, CD4 (helper), CD8 (cytotoxic) for T cells CD19, CD20, CD21 for B cells CD56, CD16 for NK cells. MHC class I is expressed by most nucleated cells, B cells, and Tcyto cells MHC class II is expressed by APCs, activated Thelper cells, and B cells

cell mediated vs. humoral immunity

Cell-mediated immunity: does not involve antibodies, but rather involves the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. ... CD4 cells or helper T cells provide protection against different pathogens Humoral immunity: mediated by macromolecules found in extracellular fluids such as secreted antibodies, complement proteins, and certain antimicrobial peptides. Humoral immunity is so named because it involves substances found in the humors, or body fluids. CD8

Linked recognition

Cells and Receptors/Ligands Involved: B Cells: Receptor: B Cell Receptor Ligand: Antigen. T Cells: Receptor: T Cell Receptor Co-receptor: CD4 or CD8. Ligand: Peptide-MHC complex. Mechanism: - B cells capture and present antigens using their BCRs. - T cells recognize specific peptide antigens presented by B cells in the context of MHC class II molecules. - The CD4+ T cell interacts with the peptide-MHC class II complex on the B cell surface. Outcome of Linked Recognition: B Cell Activation: The interaction provides critical signals for the B cell to become activated and undergo proliferation. T Cell Help: The T cell, through the CD4 co-receptor, delivers signals to the B cell, including cytokines and other co-stimulatory signals. Antibody Production: B cells differentiate into plasma cells, producing antibodies with high specificity for the recognized antigen. Memory Formation: The activation and interaction between B and T cells contribute to the formation of immunological memory, enabling a more rapid and effective response upon re-exposure to the same antigen

BCR structure

Composed of two identical heavy chains and two identical light chains linked by disulfide bonds. Has variable (V), diversity (D), joining (J), and constant (C) regions in both heavy and light chains. The variable region of the BCR is responsible for antigen recognition and binding Class Switching: B cells can undergo class switching, changing the constant region of the heavy chain to produce different antibody isotypes

TCR structure

Composed of two protein chains: an alpha chain and a beta chain. Each chain has variable (V), diversity (D), joining (J), and constant (C) regions. The variable region of the TCR is responsible for antigen recognition. Class Restriction: CD4+ T cells recognize antigens presented by MHC class II molecules, while CD8+ T cells recognize antigens presented by MHC class I molecules. No Class Switching: Unlike B cells, T cells do not undergo class switching to change the constant region of the TCR

negative selection

Goal: Eliminate self-reactive T cells to prevent autoimmune responses. Where: Also occurs in the thymus during T cell development. How: T cells with TCRs strongly reacting to self-antigens presented by self-MHC molecules undergo apoptosis (programmed cell death). Cells: CD4+ and CD8+ T cells

positive selection

Goal: Ensure the maturation of T cells with functional T cell receptors that can recognize self-MHC molecules. Where: Primarily occurs in the thymus during T cell development. How: T cells with TCRs that can weakly bind to self-MHC molecules receive survival signals, promoting their maturation and exit from the thymus. Cells: CD4+ and CD8+ T cells

Significance of Specific Detection of Antibody Isotypes in Serology Testing

IgM Antibodies: Early Immune Response: IgM is the first antibody class produced in response to an infection.High levels of IgM indicate recent or acute infection. Primary Response: Used for staging and diagnosing primary infections.Often declines as the immune response transitions to IgG production. Diagnostic Value: Elevated IgM levels may suggest an ongoing infection.Used in the diagnosis of diseases like viral infections (e.g., hepatitis, dengue) and certain bacterial infections. IgG Antibodies: Memory and Long-Term Immunity: IgG is the predominant antibody class in the secondary immune response; indicates the establishment of immunological memory. Past Infection or Vaccination: Persistent and often increases over time; Useful for assessing past exposure or vaccination status. Diagnostic Value: valuable for confirming a history of infection or immunity; Essential for seroprevalence studies and monitoring vaccination efficacy IgE Antibodies: Allergic Responses: IgE is associated with allergic reactions and hypersensitivity; Elevated levels indicate an allergic response. Parasitic Infections: defense against certain parasitic infections. Diagnostic Value: Useful in diagnosing allergic conditions; Can be elevated in conditions like asthma, allergic rhinitis, and atopic dermatitis

classical complement pathway

Initiation: Antibodies, usually IgM or IgG, bind to antigens on the pathogen surface, initiating the classical pathway; C1 complex binds to the antibody-antigen complexes Formation of C3 Convertase: Activated C1s cleaves C4 into C4a and C4b. C4b binds to the pathogen surface and recruits C2. C1s then cleaves C2 into C2a and C2b. The resulting C4b2a complex forms the C3 convertase (C4b2a). Formation of C5 Convertase: C3 convertase (C4b2a) cleaves C3 into C3a and C3b. C3b binds to the pathogen surface and recruits more C3 convertase components (C4b2a). The resulting C4b2a3b complex forms the C5 convertase (C4b2a3b). Formation of Membrane Attack Complex (MAC): C5 convertase (C4b2a3b) cleaves C5 into C5a and C5b. C5b initiates the assembly of the MAC by binding to C6, C7, C8, and multiple C9 molecules. The assembled MAC forms a pore in the pathogen's membrane, leading to lysis

Lectin complement pathway

Initiation: Mannose-binding lectin (MBL) or ficolins bind to microbial surfaces containing specific carbohydrates. MBL-associated serine proteases (MASPs) are activated. Formation of C3 Convertase: MASP-2 cleaves C4 and C2, leading to the formation of C4b2a, similar to the classical pathway. Formation of C5 Convertase: C3 convertase (C4b2a) cleaves C3, leading to the formation of C4b2a3b, similar to the classical pathway. Formation of Membrane Attack Complex (MAC): C5 convertase (C4b2a3b) cleaves C5, initiating the assembly of the MAC, similar to the classical pathway.

Alternative complement pathway

Initiation: Spontaneous hydrolysis of C3 into C3(H2O) on microbial surfaces. Properdin stabilizes the C3(H2O)B complex. Formation of C3 Convertase: C3(H2O)B complex recruits factor B, and factor D cleaves factor B into Ba and Bb. The resulting C3(H2O)Bb complex forms the C3 convertase (C3(H2O)Bb). Amplification Loop and Formation of C5 Convertase: C3 convertase (C3(H2O)Bb) cleaves C3 into C3a and C3b. C3b binds to the pathogen surface and recruits more factor B, leading to the formation of additional C3 convertase (C3bBb). C3bBb3b forms the C5 convertase. Formation of Membrane Attack Complex (MAC): C5 convertase (C3bBb3b) cleaves C5, initiating the assembly of the MAC

innate vs adaptive immunity

Innate immunity: Present from birth, Non-specific response to pathogens, Rapid response, Physical barriers (skin, mucous membranes), chemical barriers (enzymes, acids), phagocytes (macrophages, neutrophils), NK cells, and proteins (complement, interferons), response is the same regardless of the pathogen, No immunological memory, Activated by the presence of pathogens through PRRs recognizing PAMPs Adaptive immunity: Develops over time, Highly specific response, Slower response, T cells, B cells, antibodies, Highly adaptable, Possesses immunological memory Activated by the recognition of specific antigens presented by APCs to T cells

secondary lymphoid tissue

Lymph Nodes: Function: Filtering lymph, allowing interaction between immune cells and antigens; Site for activation and proliferation of B and T cells. Characteristics: Bean-shaped structures distributed throughout the body; Cortex and medulla regions with B cell follicles and T cell zones. Spleen: Function: Filters blood, removing old or damaged blood cells; Immune surveillance and response to blood-borne pathogens. Characteristics: Largest secondary lymphoid organ; White pulp contains lymphoid tissue, red pulp involved in blood filtration. MALT: Function: Defense against pathogens at mucosal surfaces Characteristics: Distributed in mucosal linings of various organs (e.g., GALT, BALT). Cellular Interaction: Provide an environment for the interaction of B and T cells with antigens presented by APCs Organization: Structurally organized with specific regions for B cell follicles, T cell zones, and germinal centers. Immune Activation: activate adaptive immune responses by bringing together antigen-presenting cells, B cells, and T cells. Proliferation and Differentiation: Facilitate the proliferation and differentiation of lymphocytes upon encountering antigens, leading to the generation of effector cells and memory cells. Effector Responses: Serve as sites for the generation of effector responses, (antibody production by plasma cells and cytotoxic activity of T cells)

somatic hypermutation

Mutation that occurs in the variable regions of immunoglobulin genes when B cells are first activated and in memory cells; introduces point mutations in the variable regions of BCR genes to increase antibody affinity.

cytokine requirements for T cell activation

Naïve T Cell: Cytokine Requirement: IL-2. Transcription Factor: NFAT (Nuclear Factor of Activated T cells) and AP-1 (Activator Protein 1). Th1: Cytokine Requirement: IL-12. Transcription Factor: T-beta Promote cell-mediated immunity, activate macrophages, and stimulate cytotoxic T cells. Associated with autoimmune diseases. Th2: Cytokine Requirement: IL-4. Transcription Factor: GATA-3 Promote humoral immunity, stimulate B cells to produce antibodies, and mediate allergic responses. Th17: Cytokine Requirement: TGF-β, IL-6. Transcription Factor: RORγt (Retinoic Acid Receptor-Related Orphan Receptor gamma t) Involved in defense against extracellular pathogens, implicated in autoimmune diseases. Treg: Cytokine Requirement: TGF-β, IL-2. Transcription Factor: Foxp3 (Forkhead Box P3) Suppress immune responses, maintain immune tolerance, prevent autoimmune reactions. TFH: Cytokine Requirement: IL-21. Transcription Factor: Bcl-6 (B-Cell Lymphoma 6) Facilitate B cell maturation in germinal centers, essential for the generation of high-affinity antibodies

somatic recombination

Occurs in B cells, involves rearrangement of V(D)J segments to generate diverse B cell receptors; DNA segments shuffled and form new combinations of base sequences to produce antibody genes

Two signal hypothesis

Signal 1 (Recognition of Antigen): Cell Involved: Naive T cell. Receptors/Ligands: TCR on the T cell recognizes and binds to a specific peptide presented by MHC molecules on the surface of APCs Signal 2 (Co-Stimulation): Cell Involved: Naive T cell. Receptors/Ligands: CD28 receptor on the T cell interacts with B7 molecules (CD80 or CD86) on the surface of the APC. This interaction provides a co-stimulatory signal that is essential for T cell activation. Consequences of Not Satisfying the Two Signal Hypothesis: Signal 1 Only: T cell may become unresponsive or anergic, leading to immune tolerance. The T cell may not fully activate, preventing an inappropriate immune response to self-antigens. Signal 2 Only: Without Signal 1, there is a risk of activating T cells in the absence of a specific antigen, leading to autoimmune responses. T cell activation might not result in a robust and effective immune response. No Signals: Naive T cells may not differentiate into effector T cells, hindering the adaptive immune response. Lack of co-stimulation may contribute to peripheral tolerance and prevention of excessive immune activation

Specific Detection of Antigen vs. Antibody in Serology Testing

Specific Detection of Antigen: Identifies the presence of a pathogen or foreign substance directly; Useful for early diagnosis of infections; Commonly employed in rapid diagnostic tests (e.g., lateral flow assays). Specific Detection of Antibody: Indicates a host's immune response to a previous infection or vaccination; Useful for assessing immune status, determining past exposure, and monitoring the course of an infection; Differentiates between recent and past infections based on the presence and type of antibodies

IgA

Structure: Monomeric or dimeric structure. Fc Region: Contains an alpha heavy chain in its Fc region. FcR: Binds to Fcα receptors Functions: Predominantly found in mucosal secretions, Prevents the attachment of pathogens to mucosal epithelial cells, transfers passive immunity to newborns through breast milk

IgD

Structure: Monomeric structure. Fc Region: Contains a delta heavy chain in its Fc region. FcR: Less well-defined Fc receptor interactions compared to other isotypes Functions: Functions as a membrane-bound BCR on the surface of naive B cells, Involved in the activation of B cells, working with IgM

IgE

Structure: Monomeric structure. Fc Region: Contains an epsilon heavy chain in its Fc region. FcR: Binds to Fcε receptors (FcεR), primarily on mast cells and basophils. Functions: Involved in allergic reactions and defense against parasites, triggers the release of histamine and other mediators from mast cells and basophils during allergic responses, enhances eosinophil activity against parasites

IgG

Structure:Monomeric structure. Fc Region:Has four subclasses: IgG1, IgG2, IgG3, IgG4, each with distinct functions FcR:Binds to Fcγ receptors which are classified into different subtypes (e.g., FcγRI, FcγRII, FcγRIII). Functions: Can be passed via placenta; Opsonization: Enhances phagocytosis by macrophages and neutrophils. Neutralization: Blocks the activity of toxins and viruses. Complement activation: Activates the classical complement pathway.

IgM

Structure:Pentameric structure in its secreted form. Fc Region:Possesses a mu (μ) heavy chain in its Fc region. FcR:Binds to Fcμ receptors (FcμR). Functions:Primary antibody produced during the early stages of an immune response, agglutination of pathogens, membrane-bound BCR on B cells, activates the classical complement pathway

alpha beta T cells

TCR Structure: TCR composed of an alpha chain and a beta chain. Function: Predominantly involved in recognizing peptides derived from antigens presented by MHC molecules Location: Predominantly found in lymphoid organs Subsets: Differentiated into various subsets based on the co-receptors they express, such as CD4 and CD8. CD4+ T cells which interact with MHC class II molecules. CD8+ T cells interact with MHC class I molecules. Roles: CD4+ T cells play a role in coordinating immune responses, helping B cells produce antibodies, and activating other immune cells. CD8+ T cells are primarily responsible for recognizing and eliminating cells infected with intracellular pathogens. Antigen Recognition: Recognize peptide antigens presented by MHC molecules on the surface of APCs or infected cells. Activation: Activated by interactions with antigens and co-stimulatory signals provided by antigen-presenting cells

gamma delta T cells

TCR Structure: TCR of gamma and delta chains Function: roles in innate and adaptive immune responses, and immune surveillance of epithelial tissues Antigen Recognition: non-peptidic molecules and stress-induced self-antigens; Can recognize antigens independently of MHC molecules. Location: Found in mucosal and epithelial tissues Abundant in the skin, intestines, and other barrier tissues. Roles in Immunity: Involved in the early response to infections, particularly those at epithelial surfaces Adaptive Immunity: Some gamma-delta T cells have memory-like properties and can respond rapidly upon re-exposure to specific antigens Tissue Surveillance: associated with the surveillance of stressed or infected cells in epithelial tissues Activation: Activation can occur independently of conventional antigen presentation by APCs Functions Beyond Infection: Involved in tissue repair and maintenance. May contribute to immune regulation and tolerance. Heterogeneity: Gamma-delta T cells are a heterogeneous population with distinct subsets that may have specialized functions

signature cytokines

Tc: Perforin and granzymes, killing infected cells Th1: IFN-γ, IL-2, macrophage activation Th2: IL-4, IL-5, IL-13, eosinophil activation, switching to IgE, allergic responses Th17: IL-17, IL-21, IL-6 neutrophil recruitment Treg: TGF-β, IL-10, immune suppression TFH: IL-21, B cell help

primary lymphoid tissue

Thymus (T Cells): Function: Maturation of T cells. Characteristics: Site of T cell development; Thymic epithelial cells play a crucial role in positive and negative selection of T cells Bone Marrow (B Cells): Function: Maturation of B cells. Characteristics: Hematopoietic tissue where B cells develop and mature; Site of BCR rearrangement and expression

Isotype switching

cells change which isotype of antibody they produce when stimulated by specific cytokines; occurs in B cells, involves changing the constant region of the antibody to alter its effector function without changing antigen specificity