Basic Immunology

• Antigen 


  Substance that is recognized by the immune system as foreign and stimulates an adaptive immune response.
• Immunoglobulin


  The general name for antibodies & B-cell antigen receptors.
• B-cell receptor


  (Also B-cell receptor complex) is the antigen receptor on B cells, made up of a transmembrane protein. Each B cell is programmed to make a single type of immunoglobulin. The cell-surface form of this immunoglobulin serves as the B-cell receptor for specific antigens.
• Effector cell


  Any of the terminally differentiated cells in the immune response that are responsible for killing pathogens or removing them from the body.

  Innate response: neutrophils, NK cells, & innate lymphocytes

  Adaptive response: antibody-producing plasma cells & differentiated T cells
• Granulocytes


  (AKA polymorphonuclear leukocytes) White blood cell with irregular shaped, multi-lobed nuclei, & cytoplasmic granules.

  There are 3 types: neutrophil, eosinophil, & basophil.
• Plasma cell


  Terminally differentiated form of B cell that synthesizes & secrets antibodies.
• Natural killer cell (NK cell)


  Kills virus-infected cells.
• Macrophage


  Phagocytosis & killing of microorganisms.
• Megakaryocyte


  Used in platelet formation & wound repair.
• Erythrocyte


  Red blood cell responsible for oxygen transport.
• T cell or "T lymphocyte"


  1 of 2 main cells responsible for adaptive immunity.

  Originate in the bone marrow, develop in thymus, & are responsible for cell-mediated immunity. Including effector T-cells, the regulatory T-cell, & subsets of helper T-cells.
• There are many different sources of foreign antigens, including: bacterial, viral, tumors, & allergens.
• Normal immunity varies over time and is influenced by age & overall health. We want the immune response to target NON-SELF substances.
• Biologics are natural products, relatively crude, have macromolecules as active constituents, are standardized by bioassay, immunogenic, & can have special hazards.
• Preparations of biologics often have significant lot-to-lot variations in potency or activity. Bioassays measure the concentration or potency of a substance by its effect on living cells or tissues.

  The assay allows for the assignment of units of activity to a particular preparation.
• Enzyme activity = moles of substrate converted per unit of time
• One unit of neutralization activity is defined as the amount of antibody serum required to inactivate one unit of Interferon Beta activity in a viral resistance assay.

  Neutralization activity measures the ability of the antibody to block the interferon's protection of a specific cell line from VSV virus infection.
• The 3 major characteristics of acquired (adaptive) immunity are:

  1. Specific response to foreign substance (antigen)
  2. Ability to discriminate between SELF & NON-SELF
  3. Memory
• Adaptive immunity has two arms: humoral and cell mediated
• Maternal antibodies & antibody serum (human/animal plasma donors) are 2 examples of passive immunity.
• Innate vs Adaptive; Time course of response

  Innate - Rapid response (hours)

  Adaptive - Slow response (days to weeks)
• Innate vs Adaptive; Immunologic memory

  Innate - No

  Adaptive - Yes, long-lasting & more efficient over time
• Innate vs Adaptive; Source

  Innate - Components are naturally present and are not specific to pathogens. Including: physical barriers (skin), phagocytic cells (macrophages, neutrophils), and NK cells.

  Adaptive - Specialized cells are activated in response to specific pathogens. B & T lymphocytes, as well as specific antibodies are produced.
• Innate vs Adaptive; Potential problems upon subsequent exposure

  Innate - Immediate & nonspecific

  Adaptive - More specific and effective, but can lead to autoimmune disorders or allergies if the immune system responds inappropriately.
• The afferent immune response involves the detection and recognition of pathogens, leading to the initiation of the immune response.
• The efferent immune response encompasses the effector cell production with their mechanisms that work to actively eliminate the identified pathogens. (T cell subsets & antibodies)
• Acute inflammation:

  • Erythema (redness)
  • Edema
  • Heat
  • Pain + Loss of function
  • Presence of neutrophils (PMNs)
• Innate Immunity - Inflammation at site of infection

  1. Vasodilation & increased capillary permeability
  2. Histamine & kinins
  3. Infiltration of plasma and cells
  4. Neutrophils (PMNs), lymphocytes
  5. Proteins (complement, antibodies)
  6. Localization mechanism
  7. Coagulation
  8. Kinins
  9. Repair by fibroblasts

  
• Chronic inflammation:

  • Results from persistent irritation
  • TB, burns, infected prosthetics, autoimmune disease, DM
  • Prominent mononuclear cell involvement & greater tissue destruction
  • Lesions, exudates
• Inflammation is the initial "911 call"; the non-specific response to various irritants.
• The 4 major characteristics of innate immunity are:

  1. Pathogen pattern recognition along with anatomical/physical barriers
  2. Does not require an adaptive response
  3. Cellular components
  4. Phagocytes (macrophages, neutrophils (PMNs), granulocytes (release of inflammatory substances: histamine, prostaglandins, leukotrienes)
  5. Humoral components
  6. Bioactive molecules in serum & secretions
  7. Cell-associated signaling molecules
  8. Respond to microbial antigens
• All the body's surfaces are sites of microbial infection & shedding.
• Mechanical, chemical, and microbiological barriers prevent bacteria from crossing epithelia and colonizing tissues.
• Defensin


  Any member of a large family of antimicrobial peptides that a penetrate microbial membranes and disrupt their integrity through number of ways. They are present at epithelial surfaces and in neutrophil granules.
• PAMP


  Pathogen Associated Microbial Pattern
• Phagocytes have specific cell-surface proteins that detect microbial products and signal macrophage activation.

  
• Complement proteins (that act as a cascade) can recognize some bacterial structures and facilitate phagocytosis. They are made by the liver and act as a "tag".

  
• • Toll-Like Receptors are a family of 10 cell-surface proteins that act as receptors for different microbial products.
  • TLRs all trigger a common pathway of intracellular signaling that is shared by the receptor for cytokine IL-1.
  • TLRs are found on macrophages, mast cells, NK cells, and B cells.
• Passive Immunity Characteristics

  • Therapeutic transfer of specific effectors
  • Rapid onset, short duration
  • No memory
  • Acquired naturally or artificially
  • Subsequent exposure may result in adverse reactions
• Lymphocytes develop and differentiate under the control of 2 primary lymphoid tissues, thymus & bone marrow.