Host Response to Infection

• Properties of Antigens


  • Foreignness and genetic composition
  • Chemical composition and complexity
  • Molecular size and stability
  • Mode of entry of the antigen

  
• Primary lymphoid organs


  Primary site of maturation of T cells and B cells
• Primary lymphoid organs


  • Thymus
  • Bone Marrow
• Secondary lymphoid organs


  • Spleen
  • Nodes
  • Tonsils
  • Adenoids
  • Bronchus
• Lines of Defense


  • Integumentary System, Mucus Membranes
  • Nonspecific immune cells (phagocytes, natural killer cells, granulocytes)
  • Lymphocytes
• Cells of the Immune System

  • Granulocytes (50-80%)
  • Lymphocytes (20-45%)
  • Monocytes & Macrophages (3-8%)

  
• Neutrophils


  Acute inflammation, bacterial infection
• Lymphocytes and Macrophage


  Chronic inflammation
• Mononuclear-phagocyte system


  Also antigen presenting cells
• Eosinophils


  Type I hypersensitivity reaction/allergy, secretes major basic protein that is toxic to parasites
• Basophil


  Granules contain histamine which cause inflammation
• Natural killer cells


  Has the same mechanism of killing target antigens with T cells, do not possess T-Cell Receptor (TCR)

  
• 1. cell


  One of the most important cells of immune system, most concentrated in spleen and lymph nodes, involved in body's humoral immunity
• 1. cells


  Located in spleen and lymph nodes, involved in cell-mediated immunity
• Innate Immunity


  Consists of first and second line of defense, does not improve after exposure to antigens, natural killer cells are activated upon pathogen-associated molecular patterns (PAMP) recognition

  
• Adaptive Immunity


  Pathogens able to pass the second line of defense is acted upon, specific, activated upon exposure to a particular antigen, production of antibodies, response is delayed, longer immunity

  
• Immune Response


  First exposure activates helper T cells (Th1 cells), Th1 cells activates B cells to produce antibodies, serum can be detected in serum about 7-10 days, secondary immune response occurs after re-exposure, Th2 cells are activated, further production of antibodies initiated

  
• Humoral Immunity


  • Innate humoral immunity involves cytokines and the complement system, adaptive humoral immunity involves actions of antibodies
• Antibodies


  Globulin proteins (immunoglobulins) that reacts specifically with the antigen that stimulate their production
• Functions of Antibodies


  • Neutralization of toxins and viruses
  • Opsonize microbes so that they are easily phagocytosed
  • Activate complement system
  • Prevent attachment of microbes to mucosal surfaces
• Antibody structure


  1. shaped, consists of polypeptide chains linked by disulfide bonds, two identical heavy chains and two identical light chains, heavy chain is 50-70 kD with 440-550 amino acid residues, light chain is 23kD with 220 amino acid residues

  
• Classes of Immunoglobulins


  • IgG
  • IgA
  • IgE
• IgG


  Monomer, predominant antibody in the secondary immune response, approximately 73% in the serum, together with IgM activates the complement system, functions as an opsonin, four subclasses: IgG1, IgG2, IgG3, IgG4

  
• IgA


  Called secretory immunoglobulin, found in secretions such as colostrum, saliva, and tears, as well as gastrointestinal, respiratory, and genitourinary tract, exists as monomer and dimer (Jchain)
• IgE


  Mediates immediate or anaphylactic hypersensitivity reaction, provides defense against parasites such as helminths, binds to surface of mast cells and basophils where it serves antigen receptor for allergens

  
• Cell Mediated Immunity


  Cytotoxic T cells (CD8+) destroy antigens primarily though perforin-granzyme mechanism, perforin induce formation of pores on walls of antigens, granzyme enters the pores which will cause destruction of antigens and activates capsase triggering apoptosis

  
• Complement System


  • Consists of a group of proteins (C1-C9) which are protease, secreted as zymogens which are activated by other complement proteins
• Effects of Complement System Activation

  • Cell Lysis
  • Inflammatory mediator Generation
  • Opsonization leading to enhanced phagocytosis

  
• Complement System Activation (Type I)

  1. Initiation

  2. Formation of C3 convertase

  3. Formation of C5 convertase

  4. Formation of membrane attack complex

  
• Complement Pathways


  • Alternative or Properdin Pathway
  • Classical Pathway
  • Mannose Binding Lectin or MBL Pathway
• Alternative/ Properdin Pathway


  Activated by bacterial products such as endotoxin or complexes of immunoglobulins, C3 will undergo spontaneous hydrolysis and binds to activated factor B forming C3bBb (C3 convertase), C3 convertase cleaves to C3 to form C3bBb3b (C5 convertase) which cleaves to form C5b6789 (MAC)

  
• Classical Pathway


  Activated by antigen-antibody complexes, C1 binds to antigen-antibody complex, this complex will lead to spontaneous activation and cleavage of complement proteins C2 and C4 to C2a and C2b, and C4a and C4b, C4b and C2b will combine to form C4b2b (C3 convertase) which will cleave C3 to form C4b2b3b (C5 convertase)

  
• Mannose Binding Lectin/MBL Pathway


  Pathway is activated by specific patterns of sugars found on bacterial cell wall, lectin are proteins that are capable of binding to sugars, upon binding of lectin to sugar, there is simultaneous activation of C2 and C4 by MASP-2 (MBL-Associated Serine Protease) to C2a and C2b and C4a and C4b which produces C4b2a (C3 convertase), C4b2a3b (C5 convertase)

  
• All three pathways produce C3b, called the central molecule of the complement system, C3b functions as opsonin
• Type I Hypersensitivity


  Commonly known as allergic reactions and is mediated by IgE, common allergens/triggers include pollens, animal fur, foods, and various drugs, the process begins when an allergen is presented by dendritic cells to naïve CD4+ T cells which differentiate into Th2 cells, the Th2 in return release IL-4 (interleukin) which will then stimulate production of IgE from B cells, the allergen binds to IgE and forms a complex which triggers the release of histamine from mast cells

  
• Type I Hypersensitivity Phases

  • Immediate Phase
  • Late Phase
• Immediate Phase


  Represents the vascular events of inflammation which include vasodilation and increased vascular permeability, the reaction occurs within minutes of re-exposure to allergen and will eventually subside
• Late Phase


  Characterized by the recruitment of inflammatory cells, such as eosinophils, neutrophils, and T cells, to the site of allergen exposure, these cells release additional inflammatory mediators and cytokines, leading to prolonged inflammation and tissue damage

  
• Type I Hypersensitivity Clinical Manifestations

  • Local anaphylaxis (food allergy, urticaria, eczema, allergic rhinitis, asthma)
  • Systemic anaphylaxis (circulatory relapse, severe bronchoconstriction, laryngeal edema)
• Type II Hypersensitivity


  Formerly known as cytotoxic or cytolytic hypersensitivity, three subtypes: (1) opsonization and phagocytosis; (2) Complement and Fc receptor-mediated inflammation; and (3) Antibody-mediated hypersensitivity