Lecture V

• Innate immunity is the first line of defense and reacts immediately
• Mediated by cells and molecules that recognize products of microbes and dead cells
• Adaptive immunity is stimulated by exposure to microbes and foreign substances
• Develops more slowly than innate immunity but is more powerful in combating infections
• Key components of the innate immune system:

  • Physical barriers: epithelium (e.g., skin, mucous membranes)
  • Secreted effector proteins and complement
  • Cells: Antigen-presenting cells, Natural killer cells, Granulocytes
• Key components of the adaptive immune system:

  • B cells, T cells
  • Immunoglobulins
  • Genetics: Germline encoded, does not change over the course of a lifetime
• Response time of innate immunity: Fast - within minutes to hours
• Response time of adaptive immunity: Slower with a longer lag between antigen exposure and full effect
• Specificity of innate immunity: Nonspecific
• Specificity of adaptive immunity: Highly specific, constant expansion over time
• Memory response in adaptive immunity: Present and becomes more potent and faster after subsequent exposures to an antigen
• Effector proteins in immune systems:

  • Innate: Lysozyme, Defensins, Cytokines, Complement, CRP
  • Adaptive: Five types of immunoglobulin (IgA, IgM, IgG, IgD, and IgE)
• Recognition in immune systems:

  • Innate: Pattern recognition receptors (PRRs)
  • Adaptive: Activated B cells and memory T cells can recognize specific antigens on pathogens
• Innate immune system host defense mechanisms:

  • Immune cells: Granulocytes, Natural killer cells, Mast cells
  • Physical and biochemical barriers
  • Humoral defenses (e.g., complement)
• Biochemical barriers in immune systems:

  • Production of mucus and body secretions containing protective substances
  • Enzymes: Lysozyme, Lactoferrin, Acid hydrolases, RNases
  • Peptides: defensins
  • Acids: gastric acid and vaginal flora with acidic pH
• Pattern recognition receptors (PRRs) in immune systems:

  • Recognize pathogen-related molecules
  • Types: Toll-like receptors (TLRs), NOD-like receptors
• Natural killer cells (NK cells) function in immune systems:

  • Detection and destruction of tumor cells and cells infected with viruses
  • Mechanisms for pathogen elimination: Induction of apoptosis, Antibody-dependent cell-mediated cytotoxicity
• T lymphocytes in adaptive immunity:

  • Helper T lymphocytes stimulate B lymphocytes to make antibodies and activate other leukocytes
  • Cytotoxic (killer) T lymphocytes (CTLs) kill infected cells
  • Regulatory T lymphocytes limit immune responses and prevent reactions against self-antigens
• 1. cell receptors (TCR) in adaptive immunity:

  • Each T cell expresses a TCR variant that binds to one specific antigen
  • Antigen fragment must be presented by an MHC molecule of an antigen-presenting cell to be recognized by the TCR
• Surface markers of T lymphocytes determine the specific function of T cell subtypes
• T lymphocytes:

  • Surface markers determine the specific function of T cell subtypes
  • All T cells carry membrane-bound marker proteins: CD3, CD28, and the T-cell receptor
  • T cells are divided into CD8+ T cells (cytotoxic T cells) and CD4+ T cells (T helper cell subpopulations)
• B lymphocytes:

  • Originate and mature in the bone marrow
  • Naive B cell: a mature B cell that has not come in contact with antigens yet
  • Express numerous surface proteins: CD19, CD20, CD21, and CD40
  • B cells differentiate into plasma cells that produce and secrete antibodies
• 1. cell receptors (BCRs):

  • BCRs are highly specific to certain antigens
  • Naive BCR: a BCR that has not interacted with an antigen yet
  • BCR allows recognition of complete antigens and is anchored to the cell membrane via Ig α and Ig β chains
• Tissues of the Immune System:

  • Primary Lymphoid Organs: Thymus (T cell development) and Bone marrow (maturation of B cells)
  • Secondary Lymphoid Organs: Lymph nodes, spleen, cutaneous, and mucosal lymphoid systems
• Major Histocompatibility Complex Molecules:

  • MHC molecules display peptide fragments of protein antigens for recognition by antigen-specific T cells
  • MHC class I and class II proteins have specific structures and present different types of antigens
• T cell activation:

  • Antigen presentation: MHC II presents exogenous antigens to TCR/CD4, while MHC I presents endogenous antigens to TCR/CD8
  • Costimulatory signal mediated by B7 protein on dendritic cells interacting with CD28 on naive T cells
  • Superantigens can lead to T cell activation without a costimulatory signal
• T cell effects:

  • CD8+ T cells: direct cell lysis or induction of apoptosis
  • Th1 cells: cell-mediated response with cytokine production
  • Th2 cells: immune response to extracellular pathogens with cytokine release
• B cell activation:

  • Requires initial and costimulatory signals
  • T cell-dependent activation involves B cell recognition of antigens, endocytosis, antigen presentation to Th cells, and CD40 receptor costimulation
  • T cell-independent activation leads to the production of IgM antibodies
• Hypersensitivity:

  • Immunologically mediated tissue injury