Immune Function and Inflammatory Responses

Basic Concepts in Immune Function

• The primary function of the immune system is to prevent or eradicate infections
• Also involved in surveillance and destruction of cancer cells
• Immune response can cause cell injury and stimulate pathological inflammation
• The immune system recognizes and responds to tissue grafts

Comparison of Inflammatory and Immune Responses

• Inflammatory Response (Innate Immunity)

  • Rapid
  • Nonspecific
  • No Memory
  • Involves various cells, including neutrophils, monocytes/macrophages, eosinophils, endothelial cells, platelets, and plasma systems

• Immune Response (Adaptive Immunity)

  • Slower
  • Specific
  • Memory
  • Involves lymphocytes and antibodies
  • Can be induced by vaccination

Antigen

• A molecule recognized by lymphocytes and reacts with antibodies
• Foreign (non-human) antigen
  • Viruses
  • Bacteria
  • Pollens and other environmental allergens
  • Food or drugs
• Self-antigen
  • Human Leukocyte Antigen (HLA)
    • Cell surface proteins distinguishing self from non-self
    • Present on all cell membranes except red blood cells
    • Major Histocompatibility Complex (MHC): a genomic region consisting of four loci on chromosome 6 that directs synthesis of HLA antigen
  • RBC antigen (A, B, and Rh Antigen)

Overview of the Immune Response

• Two Phases: Generation of Clonal Diversity and Clonal Selection
• Generation of Clonal Diversity
  • The production of a population of lymphocytes that can recognize all foreign antigens
  • Bone marrow produces lymphoid stem cells that migrate to the primary (central) lymphoid organs
    • Thymus
    • Bone Marrow
  • Lymphocytes differentiate into immunocompetent (but still immature) T cells or B cells
  • The entire population of immunocompetent B and T cells has the ability to recognize all antigens, however each group of B or T cells (clones) has receptor specificity for one specific antigen
  • Lymphocytes are released from these organs into the circulation and migrate to secondary lymphoid tissues (e.g., spleen, lymph nodes, mucosal and cutaneous lymphoid tissues)
• Clonal Selection
  • The selection and proliferation of mature B and T cells in response to exposure to a specific antigen
  • Involves antigen processing and presentation by antigen-presenting cells (APCs) to immature lymphocytes
  • Immunocompetent B and T cells with receptor specificity are selected and stimulated to mature and proliferate (clonal expansion)
    • B cells differentiate into antibody-producing plasma cells
    • T cells differentiate into cytotoxic and other T cells
  • These antigen-selected cells mount a defensive response against the foreign antigen
  • Production of B and T memory cells

Induction of the Immune Response

• Formation of B and T cells, and antibodies in response to antigen
• Steps in Antigen Processing and Presentation
  • Macrophage and other antigen presenting cells (e.g., dendritic cells, B cells) phagocytosis of foreign organism or tissue
  • Expression of foreign antigen on surface receptors (MHC Class II) of macrophage
  • Macrophage produces interleukin-1 (IL-1)
  • Antigen presentation to Helper T (Th or CD4) cells: processed antigen on MHC Class II receptor binds to T cell receptor (TCR) on Th (CD4) cell
  • Th secretes interleukin-2 (IL-2) which stimulates Th to mature into functional Th1 and Th2 cells
  • IL-2 secreted by Th1 and Th2 cells also stimulates proliferation and differentiation of lymphocytes:
    • B lymphocytes (stimulated by Th2 cells)
      • B cells proliferate and differentiate into plasma cells
      • Plasma cells produce antibodies
    • T lymphocytes (stimulated by Th1 cells)
      • Cytotoxic T (Tc or CD8 T cells) cells proliferate and are responsible for cell-mediated destruction
      • Memory Cells (B and T memory cells are also formed)

B Lymphocyte Response

• Also called the humoral response
• Bursal bound (immunocompetent) B cells are activated by T helper cells
• Postbursal B cells (plasma cells) produce immunoglobulins (antibodies)
• Immunoglobulins are glycoproteins produced by plasma cells
  • Immunoglobulin: term used to denote all types
  • Antibody: Immunoglobins that have specificity for a particular antigen
• Structure of Immunoglobulins
  • Antigen-binding fragment (Fab)
    • Contains recognition sites (receptors) for antigenic determinants
    • Confers specificity
  • Crystalline fragment (Fc)
    • Provides biologic function by activation of the complement system and inflammatory cells
    • Informs inflammatory mediators that the antigen has invaded the body

Antibody Classes

• Have antigenic, structural, and functional differences
  • IgM - general antibody, highest titers present during primary immune responses
  • IgG - general antibody, highest titers present during secondary immune responses
  • IgA - preformed antibody found in sweat, saliva, tears, and breast milk
  • IgE - antibody produced during allergic responses (type I hypersensitivity reactions)

Function of Antibodies

• Begins with antigen binding to form antigen-antibody complexes
  • Neutralize bacteria and viruses
  • Promotes phagocytosis of bacteria and viruses (opsonization)
  • Activate the complement cascade

Primary and Secondary Immune Responses

• Confer active acquired immunity
• Primary: antigenic challenge with production of measurable immunoglobins (antibodies), primarily IgM, after a latent period of about 5 days.
• Secondary: a second antigen challenge with more rapid and larger production of immunoglobins, primarily IgG.

T Lymphocyte Response

• Also called the cellular response
• Cytotoxic T cells (Tc): Attack antigen directly and kill cells bearing foreign antigen
• Memory T cells (Tm): Induce secondary immune response

Other Types of T Lymphocytes

• Lymphokine-producing T cell (Td): Likely a Th1 cell that is responsible for delayed hypersensitivity reactions
• Regulatory T cell (Treg): Develop in the thymus or peripheral tissues and suppress B cell and T cell activation

Natural Killer Cells

• Arise from the lymphoid stem cell lineage
• Account for ~ 10% of the lymphocyte population
• Recognize virally infected or stressed cells and once activated release interferon-gamma which helps macrophages kill the infected cell
• Can also engage in direct cell killing of virally infected and cancer cells

Vaccination

• A process of stimulating a protective immune response against microbes through exposure to nonpathogenic forms or components of the microbes

Types of Traditional Vaccines

• Most traditional vaccines mainly stimulate the B lymphocyte (i.e., antibody) response
• Inactivated
  • Virulent microbes are killed to abolish their infectivity and pathogenicity, yet still retain their immunogenicity
  • Large, multiple doses are often required
  • Booster vaccinations are required
• Live attenuated
  • Microbes are treated to reduce their infectivity and pathogenicity, yet still retain their immunogenicity
  • May not be safe for immunocompromised individuals
  • Boosters are required less often
• Toxoid
  • Vaccine is made from inactivated bacterial toxin
• Subunit vaccines
  • The vaccine is comprised of microbial proteins and/or polysaccharides that stimulate the immune system
• Conjugated vaccines
  • Microbial polysaccharides are chemically coupled with proteins so that they can stimulate Th cells
• Synthetic vaccines
  • Antigens are formed from recombinant proteins and other molecules in a laboratory environment

Types of Vaccines and Forms of Protection

• Type of Vaccine

  • Inactivated or killed virus
  • Inactivated or killed bacteria
  • Live attenuated virus
  • Live attenuated bacteria
  • Toxoid
  • Subunit (antigen) vaccines
  • Conjugate vaccines
  • Synthetic vaccines
  • Viral vectors
  • DNA vaccines

• Examples

  • Injected polio, hepatitis A
  • Cholera, bubonic plague, pertussis
  • Measles, mumps, rubella, varicella, flu, oral polio, rabies
  • BCG vaccine for TB
  • Tetanus toxoid, diphtheria toxoid, rattlesnake venom
  • HPV
  • H.influenza type B
  • Hepatitis B, H1N1
  • Clinical trials of HIV antigen in canary pox vector
  • Clinical trials ongoing for several infections

• Form of protection

  • Antibody response
  • Antibody response and T cell response
  • Antibody response and T cell response
  • Antibody response
  • Antibody response
  • Antibody response
  • Th response
  • Antibody response
  • Antibody response and T cell response
  • Antibody response and T cell response

This quiz covers the essential concepts of immune function, including the differentiation between innate and adaptive immunity. It explores how the immune system responds to infections and the role of antigens in immune responses. Test your understanding of these critical biological processes!