MICROPARA

• Host Defense Mechanism


  The collection of cells, tissues and molecules that mediate resistance to infections
• Non-specific defences (Innate Immunity)


  • First line of defense
  • Second line of defense
  • Third line of defense
• First line of defense

  • Skin
  • Mucous membranes
  • Secretions of skin and mucous membranes
  • Phagocytic leukocytes
  • Antimicrobial proteins
  • Inflammatory response
  • Fever

  
• Cellular and Chemical Factors

  • Skin: dryness, acidic pH (<5.0), temperature (<37C) and perspiration
  • Sweat: (+) lysozyme
  • Mucus: lysozyme, lactoferrin and lactoperoxidases
  • Mucocillary clearance: mucous layer, airway surface liquid layer and the cilia
  • Tears
  • Saliva
  • GIT: Digestive enzymes, acidic pH of the stomach, alkaline pH of intestine, bile
• Biological Microbes


  • Non-pathogenic microbes found within strategic locations of the body
  • Microbial antagonism: normal flora inhibit the growth of pathogenic microorganism
• 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
• Interferons


  • "INTERFERE" with viral replication
  • Antiviral proteins produced by virally infected cells
  • Types: Alpha, Beta, Gamma
  • 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 immune system and other system
• Inflammation


  • Primary purpose: To localize infection, To prevent spread of pathogens, To destroy and detoxify pathogens, To aid in repair and healing
  • Cardinal signs: Pain, Heat, Redness, Swelling, Loss of Function
• 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
  • Maturation of Mononuclear Phagocyte
• Lymphocytes


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

  1. Mature and differentiate in the BM

  2. Only cells capable of producing antibodies

  3. Mediate humoral immunity

  4. Membrane bound antibodies: IgM and IgD

  
• Maturation of T Cells

  1. Thymocytes (T-cell precursor) -> Thymus

  2. Differentiate in the thymus

  3. Responsible for CMI

  4. Subtypes: CD4+ T cells, CD8+ T lymphocyte, regulatory T lymphocytes, Natural killer (NK) cells
• Natural Killer 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
  • 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
  • Two main types of splenic tissue: Red pulp, White pulp
  • 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
  • Impaired intracellular killing of phagocyte
  • Malnutrition, Increase Iron, Stress, Age, Cancer and chemotherapy, Drugs
• Antigen


  Foreign body or a molecule, which has the ability to bind to the antibody but does not necessarily initiate an immune response

  
• Immunogen


  Foreign molecule or a type of an antigen which can elicit an immune response by triggering the host immune system
• Parts of Antigen


  • Carrier portion: The bigger part that is responsible for the MW of antigen
  • Epitope/Antigenic Determinant: Determines specificity of antigen, therefore, an antigen w/out epitope is said to be nonspecific

  
• Properties of Antigens


  • Immunogenicity: Ability to induce specific immune response resulting to formation of antibodies or immune lymphocytes
  • Antigenicity/Specificity: The ability to react specifically with the antibody or cell that caused it to be produced

  
• Features of Molecules that Determine Immunogenicity

  • Foreigness: Non-self
  • Molecular size: Molecular mass less than 5,000 to 10,000 Da are poor immunogens
  • Chemical-Structural Complexity: Protein > polysaccharide > lipid > nucleic acid
  • Susceptibility to Antigen processing and Presentation: Ability to be processed and presented with an MHC molecule on the surface of APCs

  
• Haptens


  Molecule that is not immunogenic by itself but can react w/ specific antibody

  
• 5 Major Classes of Immunoglobin

  • IgG
  • IgA
  • IgM
  • IgE
  • IgD
• Antibody Responses to Different Antigen

  1. T-cell dependent

  2. T-cell independent

  
• Antibody Synthesis


  1. cell dependent
• Vaccine


  • Antigen suspension derived from a pathogen
  • Form of immunoprophylaxis
  • Can also be given as immunotherapy
• Variolation


  • Pioneered by Chinese in 1500s
  • Earliest attempt to induce immunity
  • Inhalation of powder made from smallpox scabs
  • Goal: to induce a mild but protective infection