Immunology: Specific Immunity

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Immunology Specific Immunity

• Immunity not being susceptible to disease
• Types of immunity
• Innate you have it from birth.
• Species as humans, immune to diseases of many
  other creatures
• Genetic presence/absence of receptors
• Non-specific host defenses Macrophages, etc.
• Acquired after exposure, your body remembers
  specific invader.

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Nature of antigens

• The immune system recognizes, responds to, and
  remembers molecules that are antigens.
• An antigen
• Is foreign
• Is large (gt 5000 MW)
• Is molecularly complex.
• Not all of a large foreign molecule is
  recognized.
• The specific part of an antigen recognized by an
  antibody or receptor is called an epitope.
• A molecule that is too small to be an antigen
  without piggy-backing onto another is a hapten

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Nature of epitopes
Big enough to be noticed.
Specific parts recognized to distinguish one from
another.
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Dual Nature of the immune system

• Humoral and cell mediated
• Humoral refers to body fluids
• Specifically antibodies protein molecules
  dissolved in blood, body fluids, and secretions.
• B lymphocytes are the source of antibodies
• Cell mediated refers to the direct involvement of
  cells to attack an infection
• T lymphocytes either kill cells directly or
  recruit macrophages to kill cells directly
• T helper cells help B T cells thru direct
  contact

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Basics of antibodies

• Protein molecules produced by activated B cells
• Belong to class of proteins called
  immunoglobulins (Ig), a subclass of globulins.
• Y-shaped molecule with hinges
• Ends include variable regions where antigen
  binding occurs.
• Antibodies made by a single B cell are all the
  same, differ from those made by another in
  variable region.

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Basic Antibody structure

• Molecule undergoes shape change upon binding to
  antigen.
• Classic lock key like an enzyme.

Heavy chain
Fc end binds to host cells.
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Nature of antibodies
Ends attach to antigens. Two ends means can
attach to 2 different antigens at the same time.
Fc end attaches to molecules on host cell
surface a handle for host.
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The Antibodies

• IgG most abundant in blood and body fluids
  single Y shaped molecule, remains in circulation
  for long time.
• IgM 5 Y-shaped units linked together, first type
  of antibody made in an immune response.

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The Antibodies-2

• IgA present in large quantities in body
  secretions a dimer (2 Y-shaped units, tail to
  tail), helps protect mucous membranes.
• IgE single Y shaped unit, in small quantities,
  found bound to mast cells attached by Fc end,
  involved in allergies (mast cells release
  histamine).
• IgD The receptor for antigen normally found on
  the surface of B cells if it is shed into
  bloodstream, looks a lot like an IgG antibody.
  In very small amounts.
• Useful site http//www.webmd.com/a-to-z-guides/Im
  munoglobulins

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How DO antibodies help?

• Antibodies attach to antigens. Period. But
• Because there are at least 2 binding sites,
  cross-bridges form, linking antigens together in
  clumps.
• Attaching covers up critical sites on the
  antigens.
• Agglutination Aby links cells, viruses together
  to make clumps that attract macrophages.
• Precipitation toxin molecules come out of
  solution, can be cleared out.
• Neutralization toxins, viruses no longer active.
• Because critical binding site is covered.

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Crosslinking by antibodies

• Antibodies have at least 2 combining sites can
  react with different antigens at the same time to
  form a clump.
• Soluble antigens clump is too big, becomes
  insoluble precipitation.
• Insoluble antigens clump settles out
  agglutination.

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Neutralization

• Toxin (or virus) cannot bind to receptor on cell
  surface because antibody physically blocks access.

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How DO antibodies help?-2

• Opsonization an opsonin is something that
  promotes phagocytosis.
• By making antigens into clumps.
• By providing a handle (Fc end of antibody tp
  which the phagocyte can bind).
• Complement fixation
• Antibody binds to antigen, antibody changes shape
• Shape change activates complement
• Activated complement leads to increased
  inflammation, opsonization, and cell lysis.

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Opsonization
Antibodies provide a handle (Fc end) for
phagocytes to grab onto to improve phagocytosis.
Clumped cells are bigger, easier to grab than
single cells
http//content.luxology.com/modo/201/img/modo201_M
acrophage_C.jpg
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Lysis function of complement
Antibody binding to antigen on bacterial cell
surface activates first component of complement.
Complement cascade one protein activates another.
Complement components assemble to create hole
punch cell lysis.
http//people.eku.edu/ritchisong/complement2.gif
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The Immune response

• An immune response is what the immune system does
  when confronted by an antigen.
• An immune response is an elaborate interplay
  between antigen, non-specific defenses, and B and
  T lymphocytes.
• The process involves direct contact (cells,
  molecules bind to receptors on cell surfaces) and
  cytokines (messenger molecules) that also bind to
  receptors on cell surfaces.

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Immune response-2

• Certain cells such as macrophages encounter and
  process the antigen (chopping it up).
• They display it on the cell surface for other
  cells to interact with. Macrophage Antigen
  Presenting cell (APC).
• Display is attached to MHC (major
  histocompatibility complex), your molecular UPC
  code.
• Stimulation of cells by binding usually results
  in release of cytokines which tell a cell 2
  things
• Get activated multiply.

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Common activation
Macrophage which has encountered antigen
processes it, display it with MHCII protein on
surface. Via T cell receptor and CD4, T helper
cell binds to this. APC secretes Il-1 which
activates the T helper cell.
http//users.rcn.com/jkimball.ma.ultranet/BiologyP
ages/A/AntigenPresentation.htmlExogenous_antigens
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Activation of B cells
Requires 2 signals B cell binds to specific
antigen. T-helper cells bind to B cells and
release Il-4 which activates B cell. It becomes
plasma cell and cranks out antibodies.
http//users.rcn.com/jkimball.ma.ultranet/BiologyP
ages/T/Th_Lymphokines.gif
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T-independent antigens
Some B cells are T-independent, e.g. those that
respond vs. bacterial PS
http//users.rcn.com/jkimball.ma.ultranet/BiologyP
ages/C/ClonalSelection.html
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Cell mediated immunity
CD8 T cells (cytotoxic cells) are activated by
the release of Il-2 from T helper cells. CD8
cells recognize antigens on the surface of
infected cells, attach to these cells and secrete
perforins
Perforins punch holes into the infected cells,
killing them.
http//users.rcn.com/jkimball.ma.ultranet/BiologyP
ages/A/AntigenPresentation.htmlendogenous
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Summary
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Specificity and memory

• In all cases, the response to an antigen is
  carried out only by those T cells and B cells
  which are programmed to react to that antigen,
  that is, have a surface receptor with the proper
  fit to react with that antigen.
• Both B cells and T cells, when stimulated to
  multiply, produce memory cells which are long
  lived. These are the cells that allow the quick
  response when the antigen is encountered at a
  later time.

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Memory and antibody titer
Upon first exposure to antigen, accumulation of
antibody is slow. Memory cells make for a
quicker, larger response afterwards.
This is the basis for booster shots.
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Vaccines

• From vaccus, Latin for cow, from Ed Jenner
  using cowpox to immunize.
• Live attenuated vaccine
• Pathogen grown to make it weak, used alive.
• Killed/inactivated vaccine
• Destroyed with formalin, weaker immune response
• Subunit/conjugate/engineered
• A portion of pathogen used, often combined with
  another molecule for effectiveness antigen may
  be produced through genetic engineering.

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Hypersensitivities-1

• Inappropriate immune responses
• Type II are cytotoxic reactions like the Rh
  factor problem and bad blood transfusions.
• Rh is one of many blood groups, like ABO
• An Rh fetus in an Rh- mother means she gets
  immunized by babys blood cells, makes Aby.
• Second pregnancy, fetal RBCs are attacked.
• Solution give Rho-gam during 1st pregnancy.
• Type III are immune complex disorders, where too
  many agn-aby clumps cause inflammation.

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Hypersensitivities-2Allergies

• Type I are immediate type, in which antigen binds
  to IgE on mast cells, histamine released.
• Histamine smooth muscle contraction,
  vasodilation.
• Results in asthma, diarrhea, shock depending on
  where antigen enters body. Ex. Bee sting.
• Type IV are delayed type, T cell produces various
  cytokines which affect macrophages.
• The bar fight scenario come, stay, get angry.
• Angry macrophages cause much tissue damage.
• Ex. Poison ivy urushiol-coated cells killed.

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Other views of immunity

• 2 x 2 matrix Immunity is either active or
  passive either natural or artificial.
• Active means that host is making his own
  antibodies passive means the antibodies came
  from someone else.
• Natural means the antibodies
• were acquired by the host thru
• natural means artificial means
• they were injected.

Active Artificial Active natural
Passive Artificial Passivenatural