Chapter 17

• Immunology


  The study of the mechanisms the body uses to defend itself
• Why immunology is important

  • Pathogens enter our bodies everyday
  • Microbiome – Immunity Connection
  • Autoimmune disorders and microbiome dysbiosis
  • Immune system disorders: genetic & acquired
  • Opportunistic infections
  • Cytokine storm: Life-threatening systemic inflammatory syndrome caused by elevated levels cytokines
  • Understand vaccination & antibody therapy
  • Vaccines train the immune system
  • Antibodies bind toxins, pathogens and odd-looking human cells
• Why immunology is important

  • Detect and investigate bacteria and viruses
  • Abs are used to detect microbes
  • Experiments employ immune cells and Abs to investigate mechanisms of pathogenicity
  • Home test kits contain antibodies
  • Educate patients and discredit pseudo-science
• Exercise will protect you from Sars-CoV-2 (it doesn't)
• Ginger, turmeric, beet extract, and wheat grass boost immunity (they don't)
• Abs


  Antibodies or immunoglobins
• The immune system is often described as having

  • multiple parts, or Lines of Defense
• Lines of Defense


  • 1st Line of Defense: Innate - Non-specific, Present at birth, Includes external barriers
  • 2nd Line of Defense: Adaptive – Specific, Develops as the body is exposed to antigens throughout life
• Immune system includes


  • Innate = nonspecific defense
  • Adaptive = antigen-specific immune response
  • Humoral = serum antibodies
  • Cellular = Antigen presenting cells, B cells and T cells
• Innate immunity


  • Always present & ready to go upon infection
  • Not antigen specific and reacts similarly to a variety of organisms
  • Consists of both cellular and non-cellular components, physical barriers, antimicrobial substances, and normal microbiota
  • Lacks immunological memory
• First-Line Defenses


  • Physical Barriers: Skin, mucous membranes, Endothelia, Blood brain barrier, Mechanical defenses, Microbiome
  • Antimicrobial Substances: Salt, Lysozyme, Lactoferrin and transferrin, Antimicrobial peptides (AMPs)
• Figure 17.5 shows ciliated and nonciliated epithelial cells from the human trachea. The mucociliary escalator pushes mucus away from the lungs, along with any debris or microorganisms that may be trapped in the sticky mucus, and the mucus moves up to the esophagus where it can be removed by swallowing.
• Skin


  • Difficult for microbes to penetrate
  • Dermis: tightly woven fibrous connective tissue
  • Epidermis: many layers of epithelial cells, Outermost are dead, filled with keratin, Repels water, maintains dry environment, Continually flake off along with any attached microbes
• Cells of the Immune System

  • Red blood cells (erythrocytes) carry oxygen
  • Platelets (from megakaryocytes) involved in clotting
  • White blood cells (leukocytes) important in host defenses
• Leukocytes (white blood cells)

  • Granulocytes
  • Mononuclear Phagocytes
  • Lymphocytes (T and B cells)
• Granulocytes


  • Contain cytoplasmic granules; named based on staining properties
• Granulocytes


  • Neutrophils
  • Basophils
  • Mast cells
  • Eosinophils
• Neutrophils


  Phagocytic - engulf and destroy bacteria; granules contain enzymes, antimicrobials; also called PMNs, increase in number during infection
• Basophils


  Involved in allergic reactions and inflammation; granules contain inflammatory histamine and anti-coagulant heparin
• Mast cells


  Similar to basophils, but confined to tissues
• Eosinophils


  Fight parasitic worms; involved in allergic reactions; granules contain antimicrobials and histaminase
• Mononuclear Phagocytes


  • Comprise mononuclear phagocyte system (MPS)
  • Includes monocytes (circulate in blood), mature into dendritic cells and macrophages as they leave bloodstream
  • Macrophages - found in nearly all tissues, Move throughout the body and scavenge bacteria, fungi, spores, dust, and dead body cells, Fixed macrophages stay within a define area or organ
• Dendritic Cells


  Long, thin cytoplasmic extensions, Phagocytic, Present in tissues that are in contact with the body's external environment, Migrate to lymph nodes after activation, Perform diapedesis, Stimulated by PAMP's, Function as "scouts", Engulf material in tissues, bring it to cells of adaptive immune system for "inspection" (Antigen presenting cells), Messengers between the innate and adaptive immune systems, Usually develop from monocytes
• Lymphocytes


  • B cells
  • T cells
  • Innate lymphoid cells (ILCs)
  • Natural killer (NK) cells
• Figure 17.13 shows the formed elements of blood include erythrocytes (red blood cells), leukocytes (white blood cells), and platelets.
• Other First Line Defenses

  • Pathogen associated molecular patterns
  • The complement system
  • Cytokines
  • Phagocytosis
  • Inflammation
  • Physiological changes and the immune system
• Pathogen Associated Molecular Patterns (PAMP's)


  Structures or molecules common to many groups of pathogens (note: not exclusive to pathogens)
• Examples of PAMP's


  • Peptidoglycan, found in bacterial cell walls
  • Flagellin, a protein found in bacterial flagella
  • Lipopolysaccharide (LPS) from the outer membrane of gram-negative bacteria
  • Lipopeptides, molecules expressed by most bacteria
  • Nucleic acids such as viral DNA or RNA
• Toll-like receptors (TLRs)


  Host cell receptors that recognize unique bacterial components, Signal danger, Cell often stimulated to produce substances with "anti-microbial" properties
• Pattern Recognition Receptors (PRRs)

  • Located on cell surface, In endosomes and phagosomes, Free in cytoplasm
  • Detect microbial components present in the cell's surroundings, in phagosomes and endosomes, in the cytoplasm
  • Lead to cytokine secretion, Present on cells that are part of innate immunity
• Cytokines


  Low molecular weight, soluble proteins; chemical messengers, Produced in response to an antigen, Regulate the Innate and Adaptive immune systems, Stimulate hematopoiesis; formation of blood cells, Produced by almost all cells involved in Innate and Adaptive immunity
• Different Types of Cytokines

  • Chemokines: chemotactic factors
  • Colony-stimulating factors (CSFs): multiplication and differentiation of leukocytes
  • Interferons (IFNs): control of viral infections, regulation of immune responses
  • Interleukins (ILs): produced by leukocytes; important in innate and adaptive immunity
  • Tumor necrosis factor (TNF): inflammation, apoptosis
• Interferons


  Antiviral cytokines, Type I interferons (interferon-α and interferon-β) are produced and released by virally infected cells, stimulate nearby cells to stop transcription, shut down protein synthesis, promote apoptosis in cells infected with the virus, Type II interferons (interferon-γ) activate immune cells, Made by lymphocytes
• Cytokines


  Regulatory molecules involved in communication between cells
• Different Types of Cytokines

  • Chemokines: chemotactic factors
  • Colony-stimulating factors (CSFs): multiplication and differentiation of leukocytes
  • Interferons (IFNs): control of viral infections, regulation of immune responses
  • Interleukins (ILs): produced by leukocytes; important in innate and adaptive immunity
  • Tumor necrosis factor (TNF): inflammation, apoptosis
• Chemokines


  Cytokines produced during inflammation, that organize the leukocytes
• Interferons


  • All are antiviral cytokines
  • Type I interferons (interferon-α and interferon-β) are produced and released by virally infected cells
  • Type II interferons (interferon-γ) activate immune cells and are made by lymphocytes
• Interferon signaling


  1. Interferon-α and interferon-β signal uninfected neighboring cells to inhibit mRNA synthesis, destroy RNA, and reduce protein synthesis

  2. Interferon-α and interferon-β promote apoptosis in cells infected with the virus

  3. Interferon-γ alerts neighboring immune cells to an attack
• Complement system


  Proteins circulating in blood and tissue fluid (~30) that "complements" activities of adaptive immune system
• Complement activation pathways


  • Alternative pathway
  • Lectin pathway
  • Classical pathway