Chapter 26/27

• Innate Immunity


  Inborn pre-existing host defenses against a broad range of pathogens
• Adaptive Immunity (Acquired Immunity)


  Immunity that occurs after exposure to an antigen (piece of a specific pathogen). Typically triggered when a pathogen evades the innate immune system
• Natural Host Resistance


  • Normal Microbiota helps host resist pathogens, particularly on the skin and in the gut (competitive exclusion) – not part of immune system
  • The ability of microbes to cause disease varies between species
• Infection site and tissue specificity

  • Different pathogens invade different tissues
  • Routes of infection are crucial (e.g., tetanus is in wounds, while Salmonella is ingested, not vice versa)
• Lymphatic system


  A separate circulatory system that drains lymph fluid from extravascular tissues
• Blood


  Pumped through arteries and capillaries and returns from the body through veins
• Leukocytes (white blood cells)


  Pass from blood into the lymphatic system in capillary beds
• Lymph nodes


  Contain high concentrations of lymphocytes and phagocytes
• Leukocytes


  Nucleated white blood cells
• Lymphocytes


  Specialized leukocytes involved exclusively in adaptive immune response
• B cells


  Originate and mature in bone marrow
• T cells


  Originate in bone marrow but mature in thymus
• Bone marrow and thymus


  Primary lymphoid organs
• Myeloid cells


  Derived from a myeloid precursor cell
• Myeloid cells


  • Antigen-presenting cells (APCs) engulf, process, and present antibodies to lymphocytes
  • Granulocytes contain toxins or enzymes that are released to kill target cells
• Lymphoid stem cells


  Produce T cells, B cells and NK cells
• T cell receptors (TCR's)


  Unique protein that interacts with a single antigen
• Antibodies or immunoglobulins (Ig's)


  Unique protein that interacts with a single antigen
• Tissue damage by invading pathogen triggers the recruitment of a large number of phagocytes


  1. Tissue damage and chemokine release

  2. Resident leukocytes and damaged cells release cytokines, or chemical mediators, that allow communication between white blood cells

  3. Release of cytokines and chemokines (chemotactic cytokines) causes the specific migration of macrophages and neutrophils to the area as they leave circulation (extravasation)
• Pathogen-associated molecular patterns (PAMP)

  Pathogens have structures and molecules not found in or on host cells (e.g., peptidoglycan, flagellin, dsRNA)
• Pattern recognition receptors


  Leukocytes have membrane bound or soluble proteins that recognize PAMPs
• Signal transduction in phagocytes

  1. Upon encountering a pathogen associated molecular pattern, Toll-like receptors (TLR) will send a signal to the nucleus

  2. Upon activation of TLRs, a leukocyte will start a phosphorylation cascade to transmit the activation signal to the nucleus, activating transcription factors to turn on genes in response to the activation signal
• Phagosome


  Membrane bound vesicle that holds engulfed bacteria
• Phagolysosome


  Formed when phagocytic host cell fuses lysosomes with the phagosome
• Reactive oxygen intermediates


  Toxic substances produced by phagocytes to kill bacteria within a phagolysosome
• Inflammation


  A nonspecific reaction to noxious stimuli, resulting in redness, swelling, pain, and heat localized at site of infection, sometimes becomes systemic
• Cytokines and chemokines


  Attract leukocytes to a site of inflammation
• Interleukin-1 (IL-1)


  Cytokine that causes the host's body temperature to rise, causing a fever
• Pyrogens


  Fever-causing cytokines
• Prostaglandin


  Involved in the release of pyrogens that cause fever
• Transferrins


  Proteins that sequester iron, keeping it away from pathogens and limiting their growth
• Septic shock


  Widespread (systemic) inflammation can lead to shock as the increased vascular permeability decreases a host's blood pressure, which can cause damage to multiple organs at the same time
• LPS


  Gram-negative bacteria contain this, which triggers a proinflammatory cytokine response from leukocytes as their Toll-like receptors are activated, leading to a cytokine storm which can be fatal
• Complement system (C')


  A set of circulating, inactive proteins that are sequentially activated in response to a pathogen
• Natural killer (NK) cells

  Cytotoxic lymphocytes that recognize cells that DO NOT display Major Histocompatibility Complex I (MHC I) proteins
• Granzyme


  Enzyme that induces programmed cell death (apoptosis)
• Perforin


  Pokes holes in (perforates) the target membrane
• Interferons


  Small cytokine proteins produced by virally infected cells that prevent viral replication by stimulating the production of antiviral proteins in uninfected cells
• Specificity


  Of antigen–antibody reaction is dependent on lymphocyte cell receptors interacting with individual pathogen
• T cell selection and tolerance

  1. Precursor T cells travel from the bone marrow to the thymus, where they mature and are put under both positive and negative selective pressure

  2. Positive selection: T cells that recognize MHC peptides are retained

  3. Negative selection: T cells that pass the positive selection and strongly bind to self-antigens are selected against

  4. Clonal deletions: More than 99 percent of T cells that enter the thymus do not survive the selection process

  5. Remaining T cells react strongly with foreign antigens