Immune%20system

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Immune system

• By Zoe Kopp-Weber

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• Over 500 million years ago, the immune system
  first appeared in porifera.
• Based on phagocytic cells only.
• Lampreys, jawless fish, were the first
  vertebrates to have a lymphocyte based immune
  system.
• Jawed fish evolved and B and T cells appeared.

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• Once sharks and other cartilaginous fish evolved,
  the immune system of vertebrates was fully
  formed.
• Really only one noticeable difference between
  shark and mammal immune systems.
• The antibody-encoding systems are arranged in the
  genome a little differently.

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• 3 lines of defense
• First, skin.
• As it is the largest organ of the vertebrate body
• Provides a nearly impenetrable barrier
• Reinforces defense with chemical weapons on the
  surface
• Oil and sweat glands
• Prevents loss of air through evaporation

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• Second, cellular counterattack
• Nonspecific cellular and chemical devices respond
  to infection without identifying invaders
• Central location of collection and distribution
  lymphatic system
• Lymphatic vessels and organs (spleen and thymus
  gland), and lymph nodes

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• Macrophages - ingest microbes by phagocytosis.
• Membrane-bound vacuole with bacterium fuses with
  a lysosome and oxygen free radicals kill the
  microbe
• Supplement phagocytic cells of the liver, spleen
  and bone marrow.

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• Neutrophils
• Kill by phagocytosis but release chemicals that
  kill surrounding bacteria and neutrophils
  themselves.
• Natural killer cells
• Kills cells infected with the viruses by creating
  a hole in the plasma membrane, releasing proteins
  into the membrane, then sending granzymes in to
  initiate cell death (apoptosis)
• Most potent defense against cancer.

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• Third defense, immune response
• Best explained through experiments of Pasteur and
  Jenner
• Edward Jenner studied immunology through smallpox
• Milkmaids whod had cowpox rarely had smallpox
• Tested observation by infection people with
  cowpox, in turn they became immune to smallpox.

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• Why?
• Those injected with cowpox built a defense
  effective against smallpox due to the similar
  surfaces of the diseases.
• Vaccination - injection of harmless microbe to
  develop resistance to a dangerous one.

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• Pasteur studied fowl cholera
• Isolated a culture of diseased bacteria, forgot
  it for two weeks, then injected it into healthy
  birds.
• Birds became slightly sick and recovered
• Later, when injected with large amounts of live
  fowl cholera bacteria, the chickens wouldnt get
  sick.

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• Why?
• Bacteria can illicit imunnity if it doesnt kill
  the animal first.
• Antigen - a molecule that provokes a specific
  immune response
• Large, complex like proteins
• Foreign to body, present on pathogens
• Different parts stimulate different response
• Different parts are antigenic determinant sites

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• Lymphocytes - receptor proteins on surface
  recognize an antigen direct a specific immune
  respose against the antigen/cell carrying the
  antigen.
• B cells - produce proteins called antibodies
• Antibody - protein secreted into blood and other
  body fluids providing humoral immunity
• humor as in a bodily fluid

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• T cells - regulate immune responses of other
  cells and directly attack cells carrying specific
  antigens
• Cell-mediated immunity

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• Specific immune responses protect in 2 ways.
• Acquired immunity (active) - gaining immunity by
  exposure, maybe be getting the disease
• Ex. Chicken pox
• Passive immunity - obtaining antigens from
  another individual
• Ex. Antibodies we receive from our moms
  transferred across the placenta

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• 3 routes of entry by virus/microorganism
• Digestive tract
• Microbes in food killed by saliva while acidic
  stomach and digestive enzymes kill what makes it
  to the intestine.
• Respiratory tract
• Cells lining bronchi secrete mucus trapping air
  microorganisms before reaching the lungs
• Cells with cilia sweep mucous towards the glottis
  where it can be swallowed

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• Urogenital tract
• Acidic urine washes away pathogens from urinary
  tract
• Vaginal secretion are also acidic and prevent
  foreign invasion
• If a pathogen does get by any of these systems,
  the body has other defense mechanisms
• Vomiting, diarrhea, coughing, sneezing, secreted
  mucous.

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• Complement system
• 20 proteins in blood plasma
• Form membrane attack complex
• Forms pore in foreign cell membrane, fluid enters
  and the cell swells and bursts.
• Can amplify inflammatory responses, stimulating
  histamine responses
• Or, phagocytes attracted to infection
• Or, proteins coat microbes so phagocytes may
  attach more readily

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• Interferons
• Alpha and beta
• Made by almost all cells
• Protect normal cells near infected cells,
  preventing viral replication and protein
  assembly.
• Gamma
• Made by lymphocytes and natural killer cells
• Part of immunological defense against infection
  and cancer.

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• Inflammatory response - localized, nonspecific
  response to infection
• Injured cells release chemical alarm singals
• I.e., histamine which dilates local blood
  vessels, increasing blood flow and making area
  warm.
• Also increase permeability of capillaries, tissue
  swelling

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• Phagocytes go from blood to extracellular fluid
  to attack
• Neutrophils spill chemicals killing nearby
  bacteria and other cells
• Pus - dead/dying pathogens, tissues cells,
  neutrophils
• Monocytes engulf pathogens and dead cells

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• Temperature response
• Macrophages release interleukin-1
• Carried by blood to brain, direct neurons in
  hypothalamus to raise body temp.
• Fever
• Stimulates phagocytosis
• Spleen and liver store iron, reducing bacteria
• Temperatures 103 degrees F and up, dangerous
• Temperatures above 105 degrees F, fatal
• Denature enzymes

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• Cells of specific immune system
• Leukocytes - white blood cells
• Neutrophils, monocytes (phagocytic)
• Lymphocytes, T cells and B cells
• T cells - originate from bone marrow to thymus
• Indentify pathogens by their antigens

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• 4 principal T cells
• Helper T cells - initiate immune response
• Memory T cells - provide quick response to
  angtigen
• cell poisoning T cells - lyse the infected
  cells
• Suppressor T cells - terminate immune response

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• B cells, however, mature in bone marrow
• Released to circulate in blood and lymph
• Recognize particular foreign antigens
• Divide rapidly
• Differentiate into plasma and memory cells
• Plasma cells stick to antigens, flagging them for
  destruction

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• Initiating immune response (example via
  influenza)
• After viruses avoid first two lines of defense,
  macrophages initiate immune defense and inspect
  cell surfaces.
• Most vertebrate cell surfaces have glyco (or MHC)
  proteins produced by MHC genes
• Major histocompatibility proteins
• Genes are polymorphic (many forms)

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• MHC proteins serve as self markers due to
  individuality like fingerprints.
• This allows immune system to distinguish between
  foreign cells self-versus-nonself recognition
• Antigen-presenting cells - cells that partially
  digest antigens, process and move them to surface
  of plasma membrane
• Then complexed with MHC proteins so T cells can
  recognize them.

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• T Cells Cell-Mediated Immune Response
• Macrophages secrete interleukin-1 when processing
  foreign antigens
• Stimulating cell division and activating T cells,
  helper T cells secrete cytokines
• Cytokines are regulatory molecules, lymphokines
  are secreted by lymphocytes
• Cytokine is named according to biological
  activity but names can be misleading because of
  their different actions.
• Interleukin followed by number to determine.

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• Helper T cells also secrete interleukin-2,
  activating cytotoxic T cells and B cells
• Cytotoxic T cells destroy infected cells if they
  display the foreign antigen with their MHC
  proteins
• Also will attack any foreign MHC-I
• This causes problems like graft rejection with
  transplanted tissues
• The closer individuals are related, the less MHC
  proteins will vary, more likely tissues will be
  tolerated
• Drug cyclosporin deactivates cytotoxic T cells

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• Tumors have surface antigens that can stimulate
  immune destruction
• Initiate attack mostly by cytotoxic T cells and
  natural killer cells
• Immunological surveillance - proposed in 70s,
  described role of immune system in fighting
  cancer
• Human interferons by genetically engineered
  bacteria made large amounts of substances for
  experimental treatment. Useful with certain
  cancers.

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• B Cells the Humoral Immune Response
• Unlike T cells, these bind to free antigens as
  well.
• Antigen particles enter by endocytosis and are
  processed by B cells
• Helper T cells recognize specific antigen, bind
  to B cell and release interleukin-2 so the B cell
  divides.

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• This divison produces long-lived memory and
  short-lived plasma B cells
• Plasma cells produce antibodies
• Antibodies are proteins called immunoglobulins
  (Ig), divided into subclasses
• IgM - first one secreted in primary response,
  allowing antigen-containing particles to stick
• IgG - secreted during secondary response, major
  form in blood plasma
• IgD - receptors for antigens on B cells
• IgA - major form in saliva , mucus, breast milk
• IgE - promotes release of histamine (sometimes
  resulting in allergies)

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• Antibodies dont kill pathogens directly, but
  activate the complement system and target the
  pathogen for attack by phagocytic cells.
• Antibodies are made up of 2 identical short
  polypeptides (light chains) and 2 identical long
  polypeptides (heavy chains) forming a Y-shaped
  molecule

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• Stem is formed by constant regions of heavy
  chains
• Most variation occurs in the variable regions of
  each arm.
• Variable amino acid sequences causes specificity
  of antibodies for antigens that reside in the arms

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• How can B cells detect millions of foreign cells?
• Somatic DNA arrangement - when an antibody is
  assembled, different sequences of DNA form a
  composite gene
• More sequences generated by the shifting of the
  reading frame during transcription and mistakes
  during replications as lymphocytes divide.

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• Somatic mutation - mutations that change amino
  acid sequences in a somatic cell
• 19 million different possible antibodies without
  the possibility of mutations, 200 million with.

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• Immunological Tolerance - acceptance of self
  cells
• Colonial deletion/suppression
• Embryo, fetus, newborns lymphocyte clones have
  receptors for self antigens that are eliminated
  or suppressed as they mature. Cells learn to
  identify self antigens.
• Only clones that survive are those directed
  against foreign cells
• Sometimes B or T cells recognize their own
  tissues as antigens
• Autoimmune disease

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• The first time the body encounters a pathogen,
  few B and T cells recognize its antigens
• Binding of the antigen to its receptor causes
  division and produces a clone (colonal selection)
• Primary immune response - a person is sick
  because few cells can make an immune response so
  the response is weak

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• Clones of memory cells develop after the primary
  response so should a second infection come, the
  response is stronger (secondary immune response)
• Memory cells can survive for decades
• Reason vaccines are effective

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• Blood type indicates the class of antigens found
  on the red blood cell surface
• Tolerance to those of own antigens (I.e., type B
  to B antigens)
• Should they be mixed, cells clump which can cause
  inflammation and organ damage.

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• Rh-positive allele is more comon
• In the case of Rh-negative mothers, they arent
  exposed to the Rh antigen of the fetus during
  pregnancy
• During birth, exposure may occur and mother may
  produce antibodies against it
• These can cross the placenta in future
  pregnancies and cause hemolysis of Rh-positive
  cells of the fetus
• Baby is born anemic with erythrblastosis fetalis

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• Monoclonal antibodies - exhibit specificity for
  one antigenic determinant
• Hybridoma - secretes identical, monoclonal
  antibodies
• Modern pregnancy tests covered with monoclonal
  antibodies produced against a pregnancy hormone.
• Antigen is present, reaction (agglutination)
  occurs.

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• AIDS
• The retrovirus (HIV) mounts an attack on CD4 T
  cells (helper and inducer), leaving the immune
  system open to any foreign antigen
• CD4 T cells make up 60-80 of circulating T
  cells but HIV cells replicate before dying and
  infect entire population
• HIV causes these cells to also secrete a
  suppressing factor that blocks other T cells from
  attacking the HIV antigen
• Finally, blocks transcription of MHC genes so
  recognition and destruction of infected cells is
  hindered.

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• Renders person defenseless from infection
• AZT inhibits the enzyme needed for the virus to
  produce DNA
• Mutation rates are high, however, so its
  difficult to make an effective vaccine

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• Antigen shifting - to mutate frequently so the
  nature of surface antigens vary
• Process of evolution by natural selection
• Happens with African sleeping sickness and
  influenza
• New vaccine based on DNA may help by injecting a
  gene from the pathogen that doesnt change,
  fragments sticking to cell membrane and marking
  it for destruction.

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• Autoimmune diseases - produced by failure of the
  immune system to recongize and tolerate self
  antigens
• Self antigen may be hidden until exposure later
  occurs
• Systemic lupus erythematosus
• Antibodies to nucleoproteins made
• Immune attack triggers inflammation and organ
  damage. Must be suppressed through
  corticosteroids and drugs like aspirin

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• Allergy
• Immediate hypersensitivity - abnormal B cell
  response to allergen produces symptoms quickly
• Delayed hypersensitivity - abnormal T cell
  response produces symptons within 48 hours after
  exposure

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• Immediate results from IgE antibodies. Allergen
  binds to mast cells and basophils when exposed
  and histamine is secreted
• Excessive release causes anaphylactic shock, a
  uncontrollable fall in blood pressure
• Delayed results from secretion of lymphokines,
  must be treated with corticosteroids.