Immunology and Inflammation Quiz

Immunity and the Immune System

• Immunity is the state of protection from infectious diseases and has two components: innate immunity and adaptive immunity
• Innate immunity provides the first line of defense against infection and is not specific to a particular pathogen
• Innate immunity includes:
  • Phagocytic cells (macrophages and neutrophils)
  • Barriers (skin and mucous membranes)
  • Antimicrobial compounds synthesized by the host

Physical Barriers

• Skin:
  • Consists of two layers: epidermis (outer) and dermis (inner)
  • Epidermis contains tightly packed epithelial cells and a waterproofing protein called keratin
  • Dermis contains blood vessels, hair follicles, sebaceous glands, and sweat glands
• Mucous membranes:
  • Line the conjunctivae, alimentary, respiratory, and urogenital tracts
  • Consist of an outer epithelial layer and an underlying layer of connective tissue

Physiologic Barriers

• Temperature:
  • Some species are not susceptible to certain diseases due to their high body temperature
• pH:
  • Gastric acidity is an innate physiologic barrier to infection
  • Newborns are susceptible to some diseases due to their less acidic stomach contents

Soluble Factors

• Lysozyme:
  • A hydrolytic enzyme found in mucous secretions and tears that cleaves the peptidoglycan layer of bacterial cell walls
• Interferon:
  • A group of proteins produced by virus-infected cells that induce a generalized antiviral state
• Complement:
  • A group of serum proteins that circulate in an inactive state and can be activated to damage the membranes of pathogenic organisms

Pattern Recognition

• Many molecules involved in innate immunity have the ability to recognize specific patterns of molecules
• Examples:
  • Toll-like receptors (TLRs) that recognize lipopolysaccharide (LPS) found on Gram-negative bacteria
  • Collectins that recognize and kill certain bacteria by disrupting their lipid membranes

Phagocytosis

• A type of endocytosis in which a cell's plasma membrane expands around particulate material to form large vesicles called phagosomes
• Conducted by specialized cells such as blood monocytes, neutrophils, and tissue macrophages

Inflammatory Response

• A complex sequence of events triggered by tissue damage or invading pathogenic microorganisms
• Characterized by:
  • Vasodilation and increased permeability of capillaries
  • Influx of fluid and cells from the engorged capillaries into the tissue
  • Phagocytosis by specialized cells
  • Release of chemical mediators such as histamine and kinins

Adaptive Immunity

• Capable of recognizing and selectively eliminating specific foreign microorganisms and molecules
• Characterized by:
  • Antigenic specificity
  • Diversity
  • Immunologic memory
  • Self/non-self recognition

Lymphocytes

• Produced in the bone marrow by the process of hematopoiesis
• Mediate the defining immunologic attributes of specificity, diversity, memory, and self/non-self recognition
• Two major populations:
  • B lymphocytes (B cells)
  • T lymphocytes (T cells)

B Cells

• Mature within the bone marrow and express a unique antigen-binding receptor on its membrane
• Produce antibodies in a secreted form that can recognize and bind to specific antigens

T Cells

• Mature within the thymus gland
• Express a unique antigen-binding molecule, called the T-cell receptor, on its membrane
• Recognize antigen that is bound to cell-membrane proteins called major histocompatibility complex (MHC) molecules### T Cells and Immune Response
• T cells can be distinguished into T helper (TH) cells and T cytotoxic (TC) cells based on the presence of CD4 and CD8 membrane glycoproteins.
• TH cells recognize antigen-MHC class II molecule complexes and secrete cytokines, which activate B cells, TC cells, macrophages, and other cells.
• Activated TH cells produce cytokines, which result in different immune responses.
• TC cells recognize antigen-MHC class I molecule complexes and become cytotoxic T lymphocytes (CTLs), which exhibit cell-killing activity.

Humoral and Cell-Mediated Immunity

• Humoral immunity refers to the protection conferred by serum antibodies from an immune individual.
• Cell-mediated immunity can be transferred only by administration of T cells from an immune individual.
• B cells interact with antigen, leading to antibody secretion, which neutralizes or facilitates the elimination of antigen.
• Antibody functions as the effector of the humoral response, and its binding to antigen can lead to various mechanisms of elimination.

Antigen Recognition

• Lymphocytes recognize discrete sites on the antigen called antigenic determinants or epitopes.
• B cells can recognize an epitope alone, while T cells recognize an epitope only when associated with an MHC molecule.
• Each branch of the immune system is suited to recognize antigen in a different milieu.
• The humoral branch (B cells) recognizes epitopes on the surface of bacteria, viral particles, and soluble proteins, while the cell-mediated branch (T cells) recognizes protein epitopes associated with MHC molecules.

MHC Molecules

• MHC molecules function as antigen-recognition molecules, but lack fine specificity for antigen.
• Each MHC molecule can bind to a spectrum of antigenic peptides derived from the intracellular degradation of antigen molecules.
• Different allelic forms of MHC molecules confer different structures on the antigen-binding cleft, influencing the ability to present antigen to T lymphocytes.

Antigen Processing and Presentation

• Antigen processing and presentation involve the degradation of proteins into small antigenic peptides that form complexes with MHC molecules.
• Exogenous antigen is processed and presented with class II MHC molecules, while endogenous antigen is processed and presented with class I MHC molecules.

Immune Dysfunction

• Immune dysfunction can result in allergy, asthma, graft rejection, autoimmune disease, and immunodeficiency.
• Allergy and asthma are caused by inappropriate immune responses to common antigens.
• Autoimmune disease occurs when the immune system loses its sense of self and nonself, leading to an immune attack on the host.
• Immunodeficiency can be caused by genetic abnormality or damage to immune components, resulting in varying degrees of disease severity.### Immunogens and Immune Response
• Proteins are the most potent immunogens, followed by polysaccharides, while lipids and nucleic acids are not immunogenic unless complexed with proteins or polysaccharides.
• Proteins and polysaccharides are commonly used as immunogens in experimental studies of humoral immunity.
• For cell-mediated immunity, proteins, lipids, and glycolipids serve as immunogens, but they must be combined with MHC-like membrane molecules called CD1.

Properties of Immunogens

• Immunogenicity is not an intrinsic property of an antigen, but depends on several factors, including:
  • Foreignness: the degree of phylogenetic distance between the species from which the antigen is derived and the species being immunized.
  • Molecular size: larger molecules are more immunogenic than smaller ones.
  • Chemical composition and complexity: certain structures, such as branched chains, contribute to immunogenicity.
  • Ability to be processed and presented with MHC molecules: macromolecules that cannot be degraded and presented with MHC molecules are poor immunogens.

Antigen Presentation and Recognition

• T cells recognize peptides derived from protein antigens when presented as peptide-MHC complexes.
• Lipids can also be recognized by T cells, specifically glycolipids and phospholipids, which are presented as complexes with CD1 molecules.
• B cells recognize soluble antigens that bind to their membrane-bound antibody, and tend to recognize highly accessible sites on the exposed surface of the immunogen.

Genetic Control of Immune Response

• The genetic constitution of the recipient influences the type of immune response and the degree of response.
• Genes within the MHC play a central role in determining the degree of response to an immunogen.
• Other genes, such as those encoding B-cell and T-cell receptors, also affect the immunogenicity of a given macromolecule.

Factors Affecting Immune Response

• Dose and route of antigen administration: different doses and routes can induce different immune responses.
• Adjuvants: substances that enhance the immunogenicity of an antigen, such as alum and Freund's adjuvants.
• Genetic variability: differences in genes involved in immune response affect the immunogenicity of a given macromolecule.

Epitopes and Antibody-Antigen Interactions

• Epitopes are the immunologically active regions of an immunogen that bind to antigen-specific membrane receptors on lymphocytes or to secreted antibodies.
• Lymphocytes recognize discrete sites on the macromolecule called epitopes, which can involve elements of the primary, secondary, tertiary, and quaternary structure of the protein.
• Antibody binds to an epitope through weak noncovalent interactions, requiring complementary shapes and sizes.