Immunology

From "PATH3610 04 C07 Immunology Presentation (1).pdf":

• Front: What is immunity?

  • Back: Host pathogen disease interaction.

• Front: List important innate mechanisms of immunity.

  • Back: Barriers, phagocytes, pattern recognition molecules.

• Front: Describe the two arms of the adaptive immune response including the interaction with antigen.

  • Back: Mediated by B-cells and T-cells following exposure to antigen that exhibits specificity, diversity, memory, and self non-self discrimination.

• Front: Outline autoimmune and immune mediated disease.

  • Back: (This learning objective is listed, but the content explaining it is in source).

• Front: Explain the development of immunodeficiency disease and common outcomes.

  • Back: (This learning objective is listed, but the content explaining it is in source).

• Front: What are the characteristics of innate immunity?

  • Back: Minutes to hours response time, limited and fixed specificity, response to repeat infection is the same, major components are barriers, phagocytes, pattern recognition molecules.

• Front: What are the characteristics of adaptive immunity?

  • Back: Days to weeks response time, highly diverse specificity that improves during the course of response.

• Front: List anatomical barriers and mechanisms of innate immunity.

  • Back: Antimicrobial peptides, enzymes, acidic pH, normal flora, mechanical barriers, directional flow of fluid, cilia, coughing, sneezing.

• Front: Give examples of antimicrobial proteins and peptides.

  • Back: Lysozyme (in saliva, tears, respiratory tract fluids, cleaves bacterial peptidoglycan), Surfactant proteins SP-A and SP-D (in respiratory tract secretions, block bacterial surfaces, promote phagocytosis), α and β-defensins and cathelicidins (secreted by epithelial cells, neutrophil granules, interact with lipid bilayers of microbes).

• Front: What is phagocytosis?

  • Back: Engulfment and internalization of materials such as microbes for their clearance and destruction.

• Front: How are microbes recognized during phagocytosis?

  • Back: By receptors on phagocytes that may recognize pathogen-associated molecular patterns (PAMPs) using Pathogen Recognition Receptors (PRRs) or soluble opsonin proteins bound to microbes.

• Front: List the cells that develop from myeloid progenitors.

  • Back: Red blood cells, Granulocytes (Neutrophils, Basophils/mast cells, Eosinophils), Monocytes (Macrophages, Dendritic Cells), Megakarocytes.

• Front: List the cells that develop from lymphoid progenitors.

  • Back: B lymphocytes, T lymphocytes (CD4+ T helper cells [Th1, Th2, Th17, Treg], CD8+ T cytotoxic cells), NKT cells, Natural killer (NK) cells.

• Front: What is the function of neutrophils?

  • Back: Direct harm to pathogens by phagocytosis.

• Front: What are the key features of neutrophils?

  • Back: 50-75% of circulating leukocytes, circulate in blood → migrate into tissue → die, recruited to infection sites by chemokines, phagocytose microbes and secrete antimicrobial peptides in tissue, dominant cell type during acute infection (main component of pus).

• Front: What are the functions of basophils and mast cells?

  • Back: Inflammation, allergy, non-phagocytic response against parasites.

• Front: What is a major granule component of basophils and mast cells?

  • Back: Histamine.

• Front: Where do mast cells reside?

  • Back: Skin and epithelium of gut and genitourinary tract.

• Front: What is the activated function of eosinophils?

  • Back: Killing of IgE-antibody coated parasites, antiviral and anti-parasitic activity.

• Front: What is the role of monocytes?

  • Back: Migrate into tissues and can differentiate into macrophages or dendritic cells.

• Front: What are the activated functions of macrophages?

  • Back: Phagocytosis, activation of T-cells (act as Antigen Presenting Cells - APCs).

• Front: What are the activated functions of dendritic cells?

  • Back: Antigen uptake in peripheral sites and antigen presentation (most effective activator of T-cells). Bridge between innate and adaptive immunity, critical to initiating an adaptive immune response.

• Front: How do dendritic cells initiate an adaptive response?

  • Back: DCs in blood monitor for pathogens, engulf and process encountered antigens, migrate to lymph nodes, and present processed antigen to T-cells.

• Front: What are the activated functions of Natural Killer (NK) cells?

  • Back: Release granules that kill some virus-infected cells and tumour cells (attack abnormal/altered self-cells).

• Front: Do NK cells possess antigen-specific receptors?

  • Back: No.

• Front: What is the complement system?

  • Back: A group of serum proteins circulating in inactive form that, once activated, can lead to target cell membrane lysis, chemotaxis, and opsonization to enhance phagocytosis.

• Front: List the three activation pathways of the complement system.

  • Back: Classical, Lectin, Alternative.

• Front: What types of cells are lymphocytes?

  • Back: Cells of the adaptive immune system (including CD4+ and CD8+ T cells).

From "PATH3610 04 C08 Immunology Presentation (1).pdf":

• Front: What is antibody-mediated (humoral) adaptive immunity?

  • Back: Combats pathogens via antibodies produced by B-cells which can be found in bodily fluids.

• Front: What is cell-mediated adaptive immunity?

  • Back: CD4+ and CD8+ T cells eliminate pathogens by a variety of mechanisms (including cytotoxic T cells and NK cells).

• Front: What is the hallmark of adaptive immunity?

  • Back: Memory.

• Front: Describe the primary immune response.

  • Back: First exposure to an antigen, during which antigen-specific memory lymphocytes are generated.

• Front: Describe the secondary immune response.

  • Back: Secondary exposure to the antigen stimulates memory lymphocytes, yielding a response of greater speed and magnitude with improvement of antigen specificity.

• Front: What are the primary lymphoid organs?

  • Back: Bone Marrow (for B cell development) and Thymus (for T cell development).

• Front: What happens in the bone marrow regarding B-cells?

  • Back: B-lymphocytes develop from hematopoietic stem cells. Mature antibody secreting B-cells (plasma cells) can return to become resident cells of the bone.

• Front: What happens in the thymus regarding T-cells?

  • Back: Immature T-cells develop. Immature T-cells travel to the thymus from the bone marrow via blood. The thymus helps to educate T-cells (recognize self from non-self).

• Front: What are the secondary lymphoid organs?

  • Back: Lymph nodes, Spleen, Mucosal-associated lymphoid tissue (MALT).

• Front: What are the functions of lymph nodes and the spleen in immunity?

  • Back: Highly specialized, connected to blood vessels and the lymphatic system, areas of antigen recognition by lymphocytes, and areas of lymphocyte activation. Lymph brings antigens from all parts of the body to lymph nodes. The spleen plays a major role in mounting immune response to blood-borne antigens.

• Front: What are the antigen recognition molecules for B cells?

  • Back: Soluble (antibody) or membrane-bound Ig (B-Cell Receptor).

• Front: What are the antigen recognition molecules for T cells?

  • Back: Membrane-bound T cell receptor (TCR).

• Front: What is required for T-cell receptors to recognize antigen?

  • Back: Antigen to be processed and presented in the context of self-antigen (MHC).

• Front: What is an epitope?

  • Back: A single antigenic determinant that each lymphocyte recognizes.

• Front: What is the Major histocompatibility complex (MHC)?

  • Back: Required for antigens to be recognized by the TCR and is also responsible for graft rejection.

• Front: What is antigen processing?

  • Back: Cellular pathways that lead to antigen degradation and association with MHC.

• Front: What is antigen presentation?

  • Back: Appearance of MHC-peptide complexes on the cell surface for recognition by T cells.

• Front: What are the two different forms of MHC?

  • Back: MHC-I (present on all nucleated cells) and MHC-II (present only on antigen-presenting cells).

• Front: What are antigen-presenting cells (APCs)?

  • Back: Cells that process antigen and present antigenic peptides on their cell surface via MHC-II (macrophages, dendritic cells, and B cells).

• Front: What happens when naive T cells are activated by APCs?

  • Back: They differentiate and become effector cells (CD8+ become killer T cells, CD4+ differentiate into several subsets).

• Front: What type of antigen does MHC-I present?

  • Back: Intracellular antigen peptides (self-proteins or cells infected with viruses).

• Front: To what type of T cell does MHC-I present antigen?

  • Back: CD8+ T cells.

• Front: What type of antigen does MHC-II present?

  • Back: Extracellular antigen peptides.

• Front: On what type of cells is MHC-II generally found?

  • Back: Antigen Presenting Cells (APCs).

• Front: To what type of T cell does MHC-II present antigen?

  • Back: CD4+ T cells.

• Front: What is the basic structure of an antibody?

  • Back: Consists of 4 polypeptide chains (2 identical heavy chains and 2 identical light chains), both heavy and light chains have constant and variable regions, the variable region recognizes the epitope on the antigen, one antibody has 2 identical epitope binding sites.

• Front: What are the effector functions of antibodies?

  • Back: Neutralization, Opsonization, Complement fixation, Antibody-dependent cell-mediated cytotoxicity (ADCC).

• Front: What are the cell-mediated effector functions involving Fas-FasL interaction?

  • Back: Activates the Caspase 8 pathway, leading to granzyme/perforin mediated cytolysis.

From "PATH3610 04 C09 Immunology Presentation.pdf":

• Front: What are the two broad categories of dysfunctions of immunity?

  • Back: Overly active or misdirected immune responses (e.g., allergies, autoimmune disease) and Immunodeficiency (primary/genetic or secondary/acquired).

• Front: What is autoimmunity a result of?

  • Back: A failure in tolerance toward self-antigen.

• Front: What is peripheral tolerance?

  • Back: Eliminates, regulates, or renders self-reactive lymphocytes that have reached circulation to be non-responsive.

• Front: List factors that can influence susceptibility to autoimmune disease.

  • Back: Environmental factors (diet, geographic area, etc.) and Genetic susceptibility (MHC genes linked, self-reactive T-helper cells).

• Front: What are primary (genetic) immunodeficiencies?

  • Back: Genetic loss of immune function (examples listed include Chediak-Higashi syndrome and Mendelian susceptibility to mycobacterial diseases). Complement deficiencies are relatively common.

• Front: What are secondary (acquired) immunodeficiencies?

  • Back: Acquired loss of immune function causing heightened susceptibility to common and opportunistic infections (causes include drug treatment, metabolic disease, malnutrition, HIV/AIDS).

• Front: How is HIV-1 spread?

  • Back: By intimate contact with infected body fluids.

• Front: How does HIV-1 infect CD4+ T cells?

  • Back: Dendritic cells in virus-exposed areas may take up and harbor the virus, passing it to CD4+ T cells.

• Front: Describe the acute phase of HIV-1 infection.

  • Back: Anti-HIV antibody production.

• Front: Describe the asymptomatic phase of HIV-1 infection.

  • Back: Slow decrease in CD4+ T cells and an increase in viral load.

• Front: What characterizes AIDS in HIV-1 infection?

  • Back: Depletion of CD4+ T cells and a high concentration of HIV in the blood.

From "PATH3610 Course Materials Required reading Course Notes (1).pdf" (Focusing on Immunology - Section 2.3):

• Front: What is the general term for foreign material within a host?

  • Back: Antigen.

• Front: Are all antigens immunogens?

  • Back: No, not all antigens elicit an immune response (immunogens).

• Front: What is a pathogen?

  • Back: Disease-causing organism composed of many different antigens, often virulence factors.

• Front: What is the primary role of the innate immune system in recognizing pathogens?

  • Back: Carried out by cells like professional antigen-presenting cells (APCs) which recognize "danger signals".

• Front: List the first line of defense mechanisms (innate immunity).

  • Back: Mechanical (skin, mucous membranes, cilia, sloughing, cough, sneeze, flush), Soluble/chemical (enzymes like lysozyme, peptides like defensins, cytokines like interferon α/β, complement, coagulation), Biological (commensal flora), Cellular (phagocytes like neutrophils and macrophages).

• Front: What are the key features of the specific (adaptive/acquired) immune response?

  • Back: Response directed specifically toward the foreign material (antigen) that induced it, results in neutralization and enhanced resistance to subsequent infection (memory).

• Front: What are antigens usually composed of?

  • Back: Usually peptides that are recognized by cells of the adaptive immune system as self or foreign.

• Front: What are lymphocytes?

  • Back: Small round cells found in blood, lymph nodes, spleen, thymus, and mucosal surfaces that mediate the antigen-specific immune response. They replicate in response to antigen exposure, producing clones of antigen-specific cells.

• Front: Where do immature lymphocytes originate?

  • Back: Bone marrow.

• Front: What are the two main classifications of lymphocytes based on maturation site?

  • Back: B cells (mature in bone marrow in most mammals) and T cells (mature in the Thymus).

• Front: What are the key features of B cells?

  • Back: Have specific surface markers (immunoglobulin, CD19, CD20, CD21, CD32), naive B cells activated by antigen exposure give rise to antibody-producing plasma cells (effector cells) and mediate "humoral immunity".

• Front: What are the key features of T cells?

  • Back: Mature in the Thymus, have specific surface markers (CD3, CD4, CD8 etc.), several functional subsets including CD4+ helper T cells (Th1, Th2, Th3, Th17, Treg) and CD8+ cytotoxic T cells.

• Front: What is the role of CD4+ helper T cells?

  • Back: "Help" to orchestrate the immune response through direct cell-cell interaction and cytokine production (effector/regulatory cells). Different subsets have specific roles (e.g., Th1 activate macrophages, Th2 help B cells produce antibody, Th17 enhance neutrophil responses). Treg cells regulate/suppress immune responses.

• Front: What is the role of CD8+ (Tc) cytotoxic T cells?

  • Back: Kill pathogen-infected and transformed cells (effector cells).

• Front: How is antigen transported to lymphoid tissues?

  • Back: Via blood or lymphatics to lymph nodes, spleen, and lymphoid tissue lining respiratory and alimentary tracts.

• Front: What are specialized antigen-presenting cells (APCs) that pick up antigen in lymphoid tissues?

  • Back: Macrophages, dendritic cells, and B cells.

• Front: What is the humoral immune response mediated by?

  • Back: Antibody (immunoglobulin) produced by plasma cells.

• Front: What is the basic structure of an antibody molecule?

  • Back: Y-shaped molecule with two heavy chains and two light chains linked by disulfide bonds, has two sites for combining specifically with the antigen that stimulated its production (bivalent).

• Front: Give examples of different isotypes of immunoglobulins (Ig).

  • Back: IgA, IgD, IgE, IgG, IgM.

• Front: Where is IgA primarily found and what is its function?

  • Back: In secretions and on mucous membranes, helps protect mucosal surfaces.

• Front: Where is IgE primarily found and what is its role?

  • Back: Principally in tissues, attached to the surface of mast cells (important effectors in allergy); cross-linking of IgE on mast cells by antigen causes release of inflammatory mediators.

• Front: What is the general function of antibodies?

  • Back: Combine specifically with antigens, blocking their normal function or growth and facilitating their clearance.

• Front: List protective mechanisms mediated by antibodies.

  • Back: Blocking of attachment to host cells, opsonisation (enhanced phagocytosis), agglutination (clumping), complement activation, immobilization of motile organisms, toxin or virus neutralization.

• Front: What is the complement system and how is it activated by the classical pathway?

  • Back: A series of enzymes and other proteins in serum that, when activated particularly by antigen-antibody interaction (Classical pathway), results in chemotaxis, opsonisation, and lysis of cells bearing antigen.

• Front: What is humoral immunity especially important in defense against?

  • Back: Extracellular pathogens.

• Front: How can the presence of antibody be detected?

  • Back: By in vitro serological tests (e.g., agglutination, ELISA). Antibody titer can be determined by serial dilutions.

• Front: What does a rise in antibody titer between acute and convalescent serum samples often indicate?

  • Back: Recent infection.

• Front: What is active immunity?

  • Back: Results from exposure to antigen and the subsequent proliferation of antigen-sensitive lymphocytes within the host (can be natural or induced by vaccination).

• Front: What is the anamnestic (secondary) immune response?

  • Back: More rapid onset and greater magnitude than the primary response due to the expanded population of antigen-specific lymphocytes from the first exposure.

• Front: What is vaccination?

  • Back: Intentional introduction of antigen into a host to stimulate immunological memory (anamnesis) for enhanced response upon exposure to the pathogen.

• Front: What is passive immunity?

  • Back: Results from the transfer of antibody (or sensitized lymphocytes) from an immunized animal to a naive individual; does not elicit memory. Can occur naturally (maternal transfer) or artificially (injection of antiserum).

• Front: What does cell-mediated immunity depend on?

  • Back: The presence of Tc cells specifically reactive to antigen on infected or transformed host cells.

• Front: How do Tc cells recognize infected cells?

  • Back: The TCR recognizes foreign antigens "presented" on the cell surface by MHC class I molecules.

• Front: What is the role of Th1 (CD4+) cells in cell-mediated immunity?

  • Back: Recognition of antigen-MHC complex on APCs leads to the release of cytokines (e.g., IL-2, IFN-γ) that stimulate other cells (CD8+ Tc and macrophages) to enhance killing of intracellular pathogens or infected cells.

• Front: What is a delayed-type hypersensitivity (DTH) reaction (Type IV)?

  • Back: Cell-mediated immune response characterized by induration and erythema after 24-48 hours, due to infiltration of mononuclear cells (lymphocytes, macrophages) attracted by cytokines from activated Th1 cells.

• Front: What are some in vitro tests to assess cell-mediated immunity?

  • Back: Culturing lymphocytes with antigen and measuring cytokine production (ELISA), Fluorescence activated cell sorting (FACS) to measure T cell proportions, Lymphocyte proliferation (blastogenesis).