Non-specific immunity present before exposure to pathogens and effective from birth

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The Innate Immune System

• Non-specific immunity present before exposure to
  pathogens and effective from birth
• External defenses include skin, mucous membranes,
  and secretions
• Internal defenses include phagocytic cells,
  antimicrobial proteins, inflammatory response,
  and natural killer cells
• Recruiting immune cells to sites of infection
• Activation of the complement cascade
• The identification and removal of foreign
  substances
• Activation of the adaptive immune system
• Acting as a physical and chemical barrier to
  infectious agents

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The Adaptive Immune system

• Second line of defense
• Adaptive immune system is usually silent, and can
  be activated to deal with specific pathogens
• Consist mainly of B lymphocytes and T lymphocytes
  
• B Cells Humoral immunity
• T Cells Cell-mediated immunity

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Key Concepts

• Picture slide! Title!

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• Leukocytes
• engulf invading microbes, produce antibodies
• Monocytes
• migrate blood to tissue, develop to macrophages
• Macrophages
• garbage collectors, antigen presenting cells, or
  ferocious killers
• take samples back to the immune system to raise
  the alarm
• Dendritic cells
• specialized antigen-presenting cells that have
  long outgrowths called dendrites
• take samples back to the immune system to raise
  the alarm
• Mast Cells
• Mast cells express MHC class II molecules and can
  participate in antigen presentation
• Neutrophils
• ferocious eaters rapidly engulf invaders coated
  with antibodies and complement, damaged cells or
  cellular debris.
• Do not return to the blood they turn
  into pus cells and die

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Complement Proteins

• aka antimicrobial plasma proteins
• Activated by appearance of foreign organisms
  (marker proteins from invading microbes)
• 20 known types
• Normally in inactive form in circulatory system
• Activated, they serve as messengers
• Proteins aggregate to launch attack on cell
  membranes of fungal/bacterial cells
• Grade 1 ? trigger formation of protective coating
  around invader
• seals/immobilizes cell
• Grade 2 ? then puncture membrane
• water enters, cell swells and bursts
• Grade 3 ? attach to invader
• becomes more susceptible to phagocytosis by
  leukocytes

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B cell (bursa derived cells)

• Produced and matured in the bone marrow
• DNA shuffling for genes of variable portions on
  antibodies lead to 10,000,000,000 types of B
  cells
• Any combination that is self responding is
  weeded out during maturation
• Facilitates humoral response
• Attack by immune system on pathogens outside of
  cells
• Activation Dependent on T cell and antigen
  presentation
• Differentiates into
• Plasma cells
• Mass production of specific antibody
  (2000/second)
• Memory B cells
• Stays for a prolonged period of time for
  reoccurrences of the antigen

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T Cell (Thyroid Cells)

• Produced in the red bone marrow, matures in the
  thymus
• Similar process of gene shuffling occurs for
  variable portions of T cell receptors
• All self responding T cells are weeded out
• Tc cells kill infected cells
• Helper T cells
• Main function is to activate B cells
• Effector T cells
• Memory T cells
• Cytotoxic T cells (Tc)
• Main function is to kill infected cells via
  apoptosis

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Antibodies

• Definition molecules that react with specific
  antigen that induced its synthesis
• Function Opsonization attachment to antigen
• To hinder their activity
• To signal phagocytes towards the antigen
• Immunoglobulins Non membrane bound antibodies d
  antibodies (Ig G,A,M,D,E)
• Constant region
• same throughout the organism, diverse throughout
  individuals for the purpose of self recognition
• Variable region
• same on the membrane on all antibodies of one B
  cell, different for each individual cell
• for the purpose of antigen recognition.
• FC (Fragment crystallization) region
• interacts with FC receptors of phagocytes,
  induces phagocytosis of antigens via binding

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Antigens

• Definition Any substance capable of inducing a
  specific immune response and of reacting with the
  products of that response (antibodies)
• External
• Pathogens
• Internal
• Cancer
• Epitope
• portion of antigen recognized by the immune system

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Inflammatory response

• Triggered by release of chemical signals in
  response to tissue damage
• Dilation and increased permeability of nearby
  capillaries
• promote blood flow to injured site
• helps deliver antimicrobial proteins, clotting
  elements, neutrophils, monocyte-macrophages to
  injured area
• Blood clotting
• increase in local blood supply
• Cause the redness and heat in typical
  inflammation
• blood-engorged capillaries leak fluid into
  neighbouring tissue, causing swelling
• Systemic response severe tissue damage or
  infection, causing body to mount a widespread
  response (eg. fever)
• Septic shock some bacteria can cause
  overwhelming systemic inflammatory response

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Complement System

• biochemical cascade that attacks surface of
  foreign cells
• contains over 20 different proteins
• named for ability to complement killing of
  pathogens by antibodies
• the major humoural component of innate immune
  system

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Complement System (process)

• Recognition signal triggers rapid killing
  response
• Complement proteins bind to microbe
• Activate protease activity, which in turn
  activates other complement proteins, and etc
• Catalytic cascade amplifies original signal
  through positive feedback
• Cascades result in production of peptides
• Attract immune cells
• Increase vascular permeability
• Coat the surface of a pathogen (marking it for
  destruction)
• Deposition of complement can also kill cells by
  disrupting cell membrane

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B cell (Antigen presentation)

• B cells float freely in the lymph nodes/blood
  stream
• When encountering a pathogen, it will move to
  phagocytose the pathogen
• Antigen presentation (Exogenous)
• Antigen ingested
• Broken down via lysosomes
• Antigen fragments attached to MHC II produced by
  the cell
• MHCII-antigen complex moved to cell membrane
• Helper T cells with the corresponding variable
  portion will attach to the Antigen-MHC II complex

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B cell (Activation and response)

• Activation (Th cell dependent)
• Cytokines released by T cell activates the B cell
• B cell proliferates and differentiation into
  Plasma and Memory B cells
• Plasma cells will produce antibodies
  corresponding to the pathogen, which reduces
  movement and increases phagocytosis rate
• Memory B cells stay around for immunity purposes
• Cytokines released by B cell activates T cell
• T cell proliferates and differentiates into
  effecter and Memory T cells
• Effecter T cell will activate Tc and NK cells
• Memory T cells stay around for immunity purposes

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Kiss, mono
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T cell (cell-mediated response)

• Infected cells will present protein samples on
  MHCI
• Antigen presentation (endogenous)
• Protein sample broken down
• Protein fragment attached to MHCI produced by the
  cell
• MHCI-antigen complex moved to cell membrane
• Cytotoxic T cells will read molecule fragment
  with the help of CD8
• Cell-mediated reponse
• Tc Cells will induce apoptosis in target cell

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MUH HEART! lt/3
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Transplant Rejection

• A process in which a transplant recipient's
  immune system attacks the transplanted organ or
  tissue
• Hyperacute rejection
• Occurs a few minutes after the transplant
• Antigens completely unmatched
• Tissue must be removed right away so the
  recipient does not die.
• Acute rejection
• Any time from the first week to 3 months after
  the transplant
• Everyone has some amount of acute rejection.
• Chronic rejection
• Takes place over many years.
• Body's constant immune response against the new
  organ slowly damages it

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Prevention/Treatment

• Hyperacute rejection
• Removal of the tissue
• Chronic rejection 
• Re-transplant if feasible
• Inhaled cyclosporine being investigated for
  delay/prevention in lung transplants
• Acute rejection 
• Immunosuppressive therapy
• Antibody-based treatments
• Blood transfer
• Marrow transplant

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Exceptions

• Cornea transplants rarely rejected
• Cornea has no blood supply
• Immune cells and antibodies are unable to reach
  cornea to cause rejection
• Transplants from one identical twin to another
  are almost never rejected

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ERMEHGERRRDDD!!
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Autoimmune Diseases

• Immune system loses tolerance for self
• Healthy people have lymphocytes with the ability
  to react against self
• Autoimmune diseases likely arise from some
  failure in immune system regulation
• systemic lupus erythematosus (lupus) generates
  antibodies against self molecules
• Eg. histones and DNA released by normal breakdown
  of body cells
• Skin rashes, fever, arthritis, kidney dysfunction
• rheumatoid arthritis leads to damage and
  inflammation of cartilage and bones of joints
• multiple sclerosis, the most common neurological
  disease in developed countries
• T cells infiltrate central nervous system and
  destroy the myelin sheath
• Serious neurological abnormalities

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Immunity

• Definition The capacity of the immune system to
  respond to a known pathogen (second response)
  more vigorously than the first time (primary
  response), sufficiently enough that few or no
  symptoms show.
• Whats happening Increased efficiency of second
  response is due to increased number of leukocytes
  with corresponding antibodies (memory B and T
  cells)
• Naturally acquired obtained through contact with
  pathogens  
• Artificially acquired obtained via manual
  efforts such as vaccination

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