Transcript Immunology: Specific Immunity

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
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• The immune system recognizes, responds to,
and remembers molecules that are antigens.
• An antigen:
– Is foreign
– Is large (> 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
Nature of epitopes
Big enough to be noticed.
Specific parts
recognized to
distinguish one
from another.
http://www.automedia.com/NewCarBuyersGuide/photos/2005/Pontiac/Vibe/Wagon/2005_Pontiac_Vibe_ext_1.jpg
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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
Basics of antibodies
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• 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.
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.
http://www.neuro.wustl.edu/neuromuscular/pics/igm.gif
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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/Immunoglobulins
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How DO antibodies help?
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• Antibodies attach to antigens. Period. But…
– Because there are at least 2 binding sites, crossbridges 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.
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
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• 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_Macrophage_C.jpg
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
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• 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.
Immune response-2
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• 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.
Common activation
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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/Bi
ologyPages/A/AntigenPresentation.html#E
xogenous_antigens
Activation of B cells
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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/BiologyPages/T/Th_Lymphokines.gif
T-independent antigens
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Some B cells are
T-independent,
e.g. those that
respond vs.
bacterial PS
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/ClonalSelection.html
Cell mediated immunity
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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/BiologyPages/A/AntigenPresentation.html#endogenous
Summary
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Specificity and memory
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• 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.
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
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• 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.
Hypersensitivities-1
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• 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 baby’s 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-2
Allergies
• 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.
Other views of immunity
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• 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
Active
Active
were acquired by the host thru
Artificial natural
natural means; artificial means
Passive Passive
they were injected.
Artificial natural