The Bodys Defense

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Immunity

• The Bodys Defense

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Introduction

• All animals must have a way of defending
  themselves against pathogenic organisms such as
  bacteria and viruses.
• We must also protect our self from abnormal cells
  like cancer
• 3 Lines of defense have evolved to protect us

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The Front Line

• Intact skin is a barrier that cannot normally be
  penetrated by bacteria or viruses, but small
  abrasion may allow them in.
• mucous membranes that line the digestive,
  respiratory, and genitourinary tracts bar the
  entry of potentially harmful microbes
• Not Just Physical Barriers secretions from
  sebaceous and sweat glands give the skin a pH
  ranging from 3 to 5, which is acidic enough to
  prevent colonization by many microbes
• inhibited by the washing action of saliva, tears,
  and mucous secretions that continually bathe the
  exposed epithelium.
• All these secretions contain antimicrobial
  proteins

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Front Line Cont

• Mucus traps many invaders but what about those
  present in food or water, or those in swallowed
  mucus, they must contend with the highly acidic
  environment of the stomach
• virus hepatitis A, can survive gastric acidity
• What if They get Through????
• Second Line which depends mainly on
  phagocytosis, the ingestion of invading organisms
  by certain types of white cells
• phagocytic cells called neutrophils constitute
  about 60-70 of all white blood cells
  (leukocytes
• Cells damaged by invading microbes release
  chemical signals that attract neutrophils from
  the blood Chemotaxis
• neutrophils enter the infected tissue, engulfing
  and destroying microbes there average life span
  is only a few days

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Second Line--Nonspecific

• Monocytes, about 5 of leukocytes, provide an
  even more effective phagocytic defense
• they migrate into tissues and develop into
  macrophages large, long-lived phagocytes
• Picture 1st Slide
• Once inside lysosomes break down the invaders by
  generating toxic forms of oxygen or enzymes
• microbes that have evolved mechanisms for evading
  phagocytic destruction.
• Some bacteria have outer capsules to which a
  macrophage cannot attach
• Mycobacterium tuberculosis, are readily engulfed
  but are resistant to lysosomal destruction and
  can even reproduce inside a macrophage

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Cont.

• macrophages migrate throughout the body, while
  others reside permanently in certain tissues,
  including the lung, liver, kidney, connective
  tissue, brain, and especially in lymph nodes and
  the spleen.
• Interstitial fluid, perhaps containing pathogens,
  is taken up by lymphatic capillaries, and flows
  as lymph, eventually returning to the blood
  circulatory system.
• Along the way, lymph must pass through numerous
  lymph nodes, where any pathogens present
  encounter macrophages and lymphocytes
• Eosinophils, about 1.5 of all leukocytes,
  contribute to defense against large parasitic
  invaders, such as the blood fluke
• position themselves against the external wall of
  a parasite and discharge destructive enzymes from
  cytoplasmic granules

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Cont

• Natural killer (NK) cells do not attack
  microorganisms directly, destroy virus-infected
  body cellsLike Nuclear weapons
• Also attack deformed body cells that could become
  cancer---they destroy a cells membrane causing it
  to lyse
• Damage to tissue by a physical injury or by the
  entry of microorganisms triggers a localized
  inflammatory response.
• chemical signals of the inflamatory response is
  histamine. Histamine is released by circulating
  leucocytes called basophils and by mast cells in
  connective tissue
• triggers both dilation and increased permeability
  of nearby capillaries.

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Immune Response Example
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Inflammation
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Cont

• Chemical Defense interferons- are proteins that
  are secreted by viral infected cells that bond to
  healthy cells and prevent virus from bonding.
  Defensins or complement are proteins produced by
  neutrophils that when activated can punch holes
  in infected cells literally blowing them up.
  Collectins- are proteins that recognize foreign
  structure or sugar arrangement and stick
• Fever Hypothalmus heat regulation can be reset
  by pyrogens (secreted by white blood cells)
• High temperatures inhibit the release of iron and
  zinc from liver and spleen needed by bacteria
• Fever also increases the speed of tissue repair

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Nonspecific Summary

• To summarize the nonspecific defense systems, the
  first line of defense, the skin and mucous
  membranes, prevents most microbes from entering
  the body.
• The second line of defense uses phagocytes,
  natural killer cells, inflammation, and
  antimicrobial proteins to defend against microbes
  that have managed to enter the body.
• These two lines of defense are nonspecific in
  that they do not distinguish among pathogens

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Specific 3rd Line of Defense

• Like snipers in the military they have a specific
  target
• lymphocytes, the key cells of the immune system -
  the bodys third line of defense
• Lymphocytes generate efficient and selective
  immune responses
• Antigen specific recognizes and acts against
  particular foreign substances
• Systemic not restricted to the initial
  infection site
• Has memory recognizes and mounts a stronger
  attack on previously encountered pathogens
• Distinguish self from non-selfCan be
  Problematic!!
• 2 main types of lymphocytes B lymphocytes (B
  cells) and T lymphocytes (T cells).

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Cont.

• antigen elicits an immune response is by
  activating B cells to secrete proteins called
  antibodies-- Humoral Immunity
• Each antigen has a particular molecular shape and
  stimulates certain B cells to secrete antibodies
  that interact specifically with it
• B and T cells recognize specific antigens through
  their plasma membrane-bound antigen receptors
• single T or B lymphocyte bears about 100,000
  receptors for antigen, all with exactly the same
  specificity
• Although it encounters a large repertoire of B
  cells and T cells, a microorganism interacts only
  with lymphocytes bearing receptors specific for
  its various antigenic molecules

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Cont

• selection of a lymphocyte by one of the
  microbes antigens activates the lymphocyte,
  stimulating it to divide and differentiate, and
  eventually, producing two clones of cells
• Plasma cells which produce antibodies specific to
  the antigen that activated it and memory cells
  that are long lived and have receptors specific
  to that antigen---Called Clonal selection
• secrete about 2,000 antibody molecules per second
  over the cells 4- to 5-day life span
• This 1st encounter is called the Primary Immune
  Response
• You are sick while the response develops, but
  once antibodies have been produced it is all
  over---unless the invading organism change its
  surface receptors???

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Cont.

• second exposure to the same antigen at some later
  time elicits the secondary immune
  responsestronger then the 1st
• response is faster (only 2 to 7 days), of greater
  magnitude, and more prolonged
• immune systems capacity to generate secondary
  immune responses is called immunological
  memorythe basis of the flu shot

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Immune Response--Overview
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Cell Mediated Immunity

• B cells and T cells mature in the bone marrow and
  thymus, their antigen receptors are tested for
  potential self-reactivity
• lymphocytes bearing receptors specific for
  molecules already present in the body are
  rendered nonfunctional or destroyed by apoptosis,
  leaving only lymphocytes that react to foreign
  molecules--- failures of self-tolerance can lead
  to autoimmune diseases
• T cells do have a crucial interaction with one
  important group of native molecules whereas
  B-Cells do not
• collections of cell surface glycoproteins encoded
  by a family of genes called the major
  histocompatibility complex (MHC) mark body cells
  as self

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Cont

• Class I MHC molecules are found on almost all
  nucleated cells - that is, on almost every cell.
• Class II MHC molecules are restricted to a few
  specialized cell types, including macrophages, B
  cells, activated T cells, and those inside the
  thymus
• numerous possible alleles for each class I and
  class II MHC gene it is unlikely that any two
  people, except identical twins, will have exactly
  the same set of MHC molecules---Think transplant
• MHC Molecules are antigen presenters
• 2 main types of T cells, and each responds to one
  class of MCH molecule.
• Cytotoxic T cells (TC) have antigen receptors
  that bind to protein fragments displayed by the
  bodys class I MHC molecules.
• Helper T cells (TH) have receptors that bind to
  peptides displayed by the bodys class II MCH
  molecules

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Antigen Presentation
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Review

• immune responses of B and T lymphocytes exhibit 4
  things that characterize the immune system as a
  whole specificity, diversity, memory, and the
  ability to distinguish self from nonself

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What Are Antibodies and What can They DO

• Y shaped proteins that are completely specific
  and have many uses for immunity and science. Also
  known as immunoglobulin (Igs)
• 5 main types made of 4 amino acids chains linked
  by di-sulfide bonds.

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Here They Are
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Getting Immunity
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Sounds Perfect---What About Malfunctions

• Malfunctions effects range from the minor
  inconvenience of some allergies to the serious
  and often fatal consequences of certain
  autoimmune and immunodeficiency diseases
• Allergies Many small molecules (called haptens
  or incomplete antigens) are not antigenic, but
  link up with our own proteins
• The immune system may recognize and respond to a
  protein-hapten combination
• The immune response is harmful rather than
  protective because it attacks our own cells

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Cont

• anaphylactic shock, a life threatening reaction
  to injected or ingested allergens.
• Anaphylactic shock results when widespread mast
  cell rupturing triggers abrupt dilation of
  peripheral blood vessels, causing a precipitous
  drop in blood pressure.
• Death may occur within minutesCaused when the
  body produces IgE antibodies.
• What if You Do Not Know Who You Are
• Autoimmunity

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Autoimmune Diseases

• systemic lupus erythematosus (lupus), the immune
  system generates antibodies against all sorts of
  self molecules, including histamines.
• Lupus is characterized by skin rashes, fever,
  arthritis, and kidney dysfunction.
• Rheumatoid arthritis leads to damage and painful
  inflammation of the cartilage and bone of joints.
• In insulin-dependent diabetes mellitus, the
  insulin-producing beta cells of the pancreas are
  the targets of autoimmune cell-mediated
  responses.
• Multiple sclerosis (MS) is the most common
  chronic neurological disease in developed
  countries-- T cells reactive against myelin
  infiltrate the central nervous system and destroy
  the myelin of neurons.

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SCID

• severe combined immunodeficiency (SCID), both
  branches of the immune system fail to function.
• For individuals with this disease, long-term
  survival requires a bone marrow transplant that
  will continue to supply functional lymphocytes
• Have cured In Lab Trials using Stem Cells
• WOW!!!!!!!!!!!!!!!!!!!!!!!!!!!!

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References

• Jack Brown M.S. Biology
• Shier,David, Jackie Butler, Ricki Lewis Holes
  Human Anatomy and Physiology 10th edition 2004
  McGraw-Hill
• Marieb, Elaine Essentials of Human Anatomy and
  Physiology 7th edition. 2003 Pearson Education
  Inc Benjamin Cummings pub.
• Microsoft Encarta Encyclopedia 2004
• Starr and Taggart The Unity and Diversity of
  Life 10th edition 2004 Thomson Brookes/Cole
• Campbell and Reece Biology 6th edition 2002
  Benjamin Cummings.
• Raven and Johnson Holt Biology 2004 Holt,
  Rinehart and Winston.