Adaptive Immunity: Specific Defenses of the Host

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Adaptive Immunity Specific Defenses of the Host

• Chapter 17 Tortora

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Immunity

• Protection against disease (etc)
• The immune system recognizes foreign substances
  and develops an immune response against them.
• Innate or nonspecific immunity seems to have an
  inherited (genetic) component
• Adaptive or specific immunity adapts to a
  particular invader or foreign substance

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Types of acquired immunity

• Acquired immunity can be acquired passively or
  actively
• Active or passive can be acquired naturally or
  artificially
• Naturally acquired active immunity-exposure to
  antigens (you get sick and recover)
• Naturally acquired passive immunity-natural
  transfer of antibodies from mom to child (breast
  feeding and in utero)-this is short lived.

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Immunity continued

• Artificially acquired active-get a vaccination
  which introduces specially prepared antigens into
  the body
• Doesnt cause disease but stimulates your
  reaction
• Artificially acquired passive-introduce
  antibodies into the body
• These are derived from serum so are called
  antisera
• Often inject a horse with antigen and then use
  the horse antibody (spider and snake antivenom)

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Dual nature of the immune system

• First Nobel prize winner was Emil von Behring who
  discovered immunity can be passed from one
  organism to another (now called humoral immunity)
• Scientists later discovered this was due to
  antibodies (1930s)
• Cell mediated immunity is governed by lymphocytes
• Humoral immunity (antibody mediated) involves the
  production of antibody

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Humoral immunity

• B cells or B lymphocytes are responsible for
  antibody production
• This provides resistance to bacteria and viruses
  and bacterial toxins
• B stands for the Bursae of Fabricius
• Antibody or immunoglobulins recognize different
  types of antigen

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Cell mediated Immunity

• Involves T cells (T lymphocytes) that act against
  foreign cells or tissue
• T cells mature in the thymus gland
• Also regulate the activation and proliferation of
  other immune system cells
• Cell mediated immune response is directed against
  bacteria and viruses inside phagocytic cells or
  infected host cells, fungi, protozoa, and
  helminths
• This also causes rejection in implanted tissue

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Antigens and antibody

• Antigen is any foreign substance
• We recognize self and dont attack it (MHC
  antigen)
• Antibody is produced by B cells and combines with
  antigenic determinant or epitopes on the antigen
• Some antigens are small (a molecular weight of
  less than 10,000) and wont trigger a response
  unless attached to a carrier. These small
  antigens are HAPTENS.
• The antibody reacts with the hapten, not the
  carrier.

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Nature of antibody

• Antibodies are proteins made in response to
  antigen that recognize and bind to antigen
• The valence of an antibody is the number of
  antigen binding sites
• Most humans are bivalent
• Antibodies are members of a group of soluble
  proteins called immunoglobulins or Igs.

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Antibody structure

• A bivalent is the simplest structure for an
  antibody so it is referred to as a monomer
• A monomer usually has 4 protein chains
• Two of these are identical light chains (L) and
  two are identical heavy chains (H)
• Light and heavy refer to molecular weights

http//courses.washington.edu/conj/immune/antibody
.htm Citation for picture
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Antibody structure continued

• Variable regions (V) are located at the end of
  the Ys arms
• Their structure reflects the specific antigen
  they recognize, and these are specific to the two
  antigen binding sites (bind to epitopes)
• The stem and lower portion of the Y are the
  constant regions (C)
• These are the same for a particular class of Ig
• There are 5 major types of C regions, giving us 5
  major classes of immunoglobulin
• The Fc regions (on the stem) are important in
  immunological reactions

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Classes of Ig

• IgG-80 of all serum antibody, cross blood vessel
  walls and enter tissue fluids
• Cross placenta to protect fetus
• Protect against circulating bacteria, viruses,
  neutralize toxin, trigger complement, and enhance
  phagocytic cells
• IgM 5-10 of serum antibody and is shaped like a
  pentamer
• First to respond to initial antigen exposure.
  Subsequent exposure results in increased IgG
• Valuable in diagnosis because it is early to
  respond.

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Classes continued

• IgA-5-10 of serum antibody, but most common in
  fluids like saliva and breast milk (helps keep
  baby safe while it develops its own immune
  system)
• Prevent attachment of viruses and/or bacteria to
  mucosal surfaces
• IgD-0.2, found on surface of B cells and act as
  antigen receptors (no known function in serum)
• IgE-0.002 of serum antibody, Fc portion binds to
  mast cells and basophils (allergic reactions),
• Increases during parasite or allergy

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B cells and Humoral immunity

• This antibody mediated immunity is carried out by
  B cells
• HOW?
• B cell exposed to antigen and become activated
• B cells divide and produce clones called plasma
  cells
• Plasma cells produce antibody to that specific
  antigen (say you have measles for instance, it
  wont work against chicken pox)
• Some turn into memory cells so that you can have
  long term immunity to that disease.

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More on B cells

• B cells come from stem cells in bone marrow
  (adult) and liver (fetus)
• Mature B cells are found in spleen and lymph
  nodes
• Recognize antigen by antigen receptors on cell
  surface
• Apoptosis-programmed cell death
• We make 100 million lymphocytes a day, so equal
  number must die. Any that dont encounter
  antigen quickly go through apoptosis

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Activation of antibody producing clones

• Each B cell can only produce an antibody against
  a particular antigen
• A mature B cell can have 100,000 IgM or IgD
  antibody bound to its surface
• When antigen binds to antigen receptor, the B
  cell proliferates into clones that will recognize
  this one antigen (clonal selection)
• Each B cell has the ability to respond to 100
  million antigens thanks to the variable region,
  but once it has responded it can only make clones
  for ONE type.

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Antigen/antibody complex

• B cells usually require the help of a helper T
  cell
• An antigen that requires the helper T cells for
  antibody production is called a T-dependent
  antigen
• B cell contacts the antigen and is processed
  inside the B cell
• Fragments of the antigen combine with MHC and are
  displayed on the B cell surface.
• The T cell comes in contact with the antigenic
  fragment/MHC presented on the B cell and
  activates the T cell
• The T cell produces cytokines that in turn
  activate the B cell to produce clones, some of
  which become the plasma cell.

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Antigen-antibody binding and results

• Antigen/antibody complex is formed quickly
• Binding targets the antigen for phagocytosis or
  complement
• Agglutination is clumping of antigens to make
  them easier for phagocytes to digest
• Neutralization-IgG antibodies inactivate viruses
  by blocking their attachment to a host
• Opsonization-antigen is covered by antibody to
  aid in ingestion/digestion by phagocytic cells
• IgG and IgM trigger complement

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T cells and Cell mediated Immunity

• The chemical messengers of immune cells are
  called cytokines
• These chemical messengers allow the cells to
  communicate with each other
• There are 60 different cytokines identified to
  date
• Some cytokines help the communication between
  leukocytes and are called interleukins
• There are 18 of these (IL-1, IL-2 etc) (see table
  17.3)
• Another group is called chemokines that help
  induce leukocytes to migrate into infected areas.

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Cellular components of immunity

• T cells are the key component
• They develop from stem cells in bone marrow and
  mature in the thymus gland
• After maturation they migrate to lymphoid organs
• T cells respond to specific antigen, multiply as
  clones into effector T cells, and destroy the
  invader

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Types of T cells

• Helper T-have central role in immune response,
  these activate macrophages and help form
  cytotoxic T cells
• Cytotoxic T destroy target cells on contact by
  producing perforin that lysis a bacterial or
  viral infected cells
• Delayed hypersensitivity T involved in allergic
  reactions and tissue rejection,
• Suppressor T are involved in stopping the
  reaction once the danger is passed. (Now called
  regulatory T cells).
• Another way to classify T cells is by the type of
  surface receptor called CD (clusters of
  differentiation)
• Two are CD4 and CD8.

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Nonspecific cellular components

• Natural killer cells or NK cells -lymphocytes
  that can destroy other cells, especially tumor
  cells and other viral infected cells
• Activated macrophages are stimulated macrophages
  that have been activated by the cytokines
  produced by helper T cells
• These macrophages can be activated by digesting
  antigen too.
• Macrophages often act as antigen presenting cells
  (APCs)
• This is identified by the T cells

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Interrelationship between cell mediated and
humoral immunity

• Antibody production depends on macrophages and T
  cells (T dependent antigen)
• 1. antigen is ingested and presented by the APC
• 2. The helper T cells reacts with this
  MHC-antigen complex
• 3. This activates the T cell and it begins to
  proliferate and produce cytokines.
• 4. The cytokines activate macrophages, CD8 cells,
  and natural killer cells

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continued

• 5. IL-2 influences a B cell to differentiate into
  a plasma cell that produces antibody
• Sometimes antigen can stimulate B cells directly
  without the help of T cells. This is called T
  independent antigen
• In this case the antigen reacts directly with the
  B cell receptors.
• This is usually weaker

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Immunological memory

• Intensity of the antibody mediated humoral
  response is reflected by antibody titer
• This is the amount of antibody in the serum after
  infection has been cleared
• There is no detectable titer in the serum for 4-7
  days (initial infection)
• IgG peaks in 10-17 days, and titer increases
• This is the primary response
• If you are exposed again, the memory response
  peaks in 2-7 days and is much greater!

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When the immune system goes haywire!

• Hypersensitivity-antigenic response beyond the
  normal response due to previous exposure
  (sensitization) by an allergen
• 4 types
• Type I-anaphylatic reactions
• Type II cytotoxic reactions
• Type III-Immune complex reactions
• Type IV-delayed cell mediated (delayed
  hypersensitivity)
• http//www.cehs.siu.edu/fix/medmicro/hyper.htm

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Type I

• Occur quickly (2-30 minutes) after exposure
• May be localized or systemic
• Localized reactions include hives, hay fever,
  asthma
• Systemic includes shock and breathing difficulty
  (death can result)
• Over reactive IgE ( you inherit the sensitivity
  but may have a completely different allergy)

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Type II

• Involve activation of complement by IgG or IgM
  antibodies within an antigenic cell
• This causes lysis of the cell
• Common type II reactions are transfusion
  reactions (ABO blood group)
• Erthryoblastosis fetalis or hemolytic disease of
  the newborn (Rh negative mom has a second Rh
  positive baby, the second baby is likely to
  develop this)

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Type III

• Form when certain ratios of antigen and antibody
  occur
• Usually involves IgG
• IF there is a slight excess of antigen, the
  soluble complex that forms is small and escape
  phagocytosis
• It this happens the complex may become trapped in
  the basement membrane beneath cells, activating
  complement and inflammation
• Neutrophils enter and release enzymes that can
  damage the cells within 2-8 hours.
• An example is glomerulonephritis which damages
  kidney glomeruli causing kidney failure
• Another is serum sickness following injection of
  antitoxin produced by an animal

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Type IV

• Caused by T cells
• Delay may be a day or more
• Include allergic contact dermatitis (allergic to
  latex)
• T B tine test