Host defense mechanism

• Host Defense Mechanism


  The collection of cells, tissues and molecules that mediate resistance to infections

  
• First Line of Defense

  • Physical
  • Chemical and cellular
  • Biological
• Physical defenses


  • Skin
  • Nasal hair
  • Eyelashes and Eyelids
  • Mucous membrane
  • Urination
• Chemical and cellular defenses

  • Mucociliary clearance
  • Lysozyme
  • Low pH (skin, gastric acid, vagina)
  • Sweat (lysozyme)
  • Mucus (lysozyme, lactoferrin, lactoperoxidases)
  • Lactoferrin (binds iron)
  • Lactoperoxidase (produces superoxide radicals)
  • Tears
  • Saliva
  • Digestive enzymes, acidic pH of stomach, alkaline pH of intestine, bile
• Biological defenses


  • Microbiome - non-pathogenic microbes found within strategic locations of the body (nasopharynx, mouth and throat, skin, GIT, vagina)
  • Microbial antagonism - normal flora inhibit the growth of pathogenic microorganisms

  
• Second Line of Defense

  • Transferrin
  • Fever
  • Complement
  • Acute Phase Proteins
  • Cytokines
  • Inflammation
  • Phagocytosis

  
• Fever


  • Body temperature > 37.5C
  • Stimulus: Pyrogens/ Pyrogenic substances
  • Augments host defenses: Stimulating WBC to deploy to side of infection, Decreasing the free plasma iron, Inducing production of IL-1 (promoting maturation, proliferation and activation of lymphocytes), Slowing the growth rate of pathogens

  
• Interferons


  • "INTERFERE" with viral replication
  • Antiviral proteins produced by virally infected cells
  • Types: Alpha (B cells, Monocytes and Macrophages), Beta (fibroblast and other virus infected cells), Gamma (T cells and NK cells)
  • Non-specific but specie specific
  • Immunotherapy/Biologic response modifiers (BRM)
  • Activate NK cells: kill virus infected cells
  • Cause non-specific flu like symptoms

  
• Complement System


  • 30 different proteins (C1-C9)
  • Functions: Opsonization, Initiation and amplification of inflammation, Attraction and activation of phagocytes, Lysis of bacteria

  
• Acute Phase Proteins


  CRP, Serum amyloid A protein, Protease inhibitors, Coagulation proteins

  
• Cytokines


  Chemical messengers/mediators that are released from cells between immune system and other systems

  
• Inflammation


  • Primary purpose: Immunity, Hematopoiesis
  • Cardinal signs: Redness, Swelling, Heat, Pain

  
• Cells of Innate Immunity

  • Neutrophils
  • Eosinophils
  • Basophils
  • Monocytes

  
• Cells of Adaptive Immunity

  • Lymphocytes

  
• Neutrophils


  • Aka PMN, segmented neutrophils
  • 50-75% of the total peripheral WBC in adults
  • Function: First responder to infection, Phagocytosis
• Steps in Phagocytosis


  1. Chemotaxis

  2. Attachment

  3. Ingestion

  4. Digestion
• Eosinophils


  • 1% and 3% of the circulating WBCs
  • Participate in allergic reaction or in response to certain parasitic infection
  • Function: Kill parasites, Neutralize basophil and mast cell product

  
• Basophils


  • <1% of all circulating WBCs
  • Function: Induce and maintain allergic reactions, Stimulate production of IgE
• Monocytes


  • 4% and 10% of total circulating WBCs
  • Professional phagocyte
• Lymphocytes


  • T cells (61-80%)
  • B cells (20%)
  • NK cells (10-15%)

  
• B Cells


  • Mature and differentiate in the BM
  • Only cells capable of producing antibodies
  • Mediate humoral immunity
  • Membrane bound antibodies: IgM and IgD

  
• T Cells


  • Thymocytes (T-cell precursor) -> Thymus
  • Differentiate in the thymus
  • Responsible for CMI
  • Subtypes: CD4+ T cells (helper T cells), CD8+ T lymphocyte (cytotoxic T lymphocytes), Regulatory T lymphocytes
• Natural Killer (NK) Cells

  • Mature in BM
  • Have the ability to kill target cells w/o prior exposure to them
  • First line of defense against virally infected cells & tumor cells
  • Located in liver, spleen & peripheral blood
  • Recognize and lyse antibody coated cells - Antibody-dependent cell cytotoxicity (ADCC)

  
• Organs of the Immune System

  • Primary/Central: Bone marrow, Thymus
  • Secondary/Peripheral: Spleen, Lymph nodes, Mucosal-associated lymphoid tissues (MALT)

  
• Spleen


  • Largest secondary lymphoid organ
  • Filters foreign substance from the blood
  • 2 main types of splenic tissue: Red pulp (destroy old RBC), White pulp (lymphoid tissue, critical line versus blood borne infections)
• Lymph Node


  • Encapsulated nodular aggregated of lymphoid tissue located along lymphatic channels
  • Central collecting points for lymph fluid from adjacent tissues
  • Major antigen-trapping sites of the body
  • Filters foreign substances from the tissue fluids and lymph
  • Central organ for lymphocyte traffic and circulation

  
• Other Secondary Organs


  • Mucosal Associated Lymphoid Tissues: Gastrointestinal tract, Respiratory tract, Urogenital tract, Tonsils, appendix, Payer's Patches
  • Cutaneous Associated Lymphoid Tissue: Mostly T cells located in the epidermis (intraepidermal lymphocytes), (+) monocytes, macrophages and dendritic cells
• Mechanism by which Pathogens Escape Destruction by Phagocytes

  • Capsule
  • Leukocydin
  • Waxes in the cell wall of Mycobacterium tuberculosis
  • Ability to survive within phagocytes
  • Intraleukocytic bacteria

  
• Disorders and Conditions That Adversely Affect Phagocytic and Inflammatory Processes

  • Leukopenia
  • Decrease neutrophil chemotaxis
  • Defect in production of actin
  • Drugs
  • Chediak-Higashi Syndrome (Impaired intracellular killing of phagocyte)
  • Chronic granulomatous disease
  • Malnutrition, Increase Iron, Stress, Age, Cancer and chemotherapy, Drugs