The Immune Response

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The Immune Response
• Inside your body there
is an amazing
protection mechanism
called the immune
system. It is designed
to defend you against
millions of bacteria,
microbes, viruses,
toxins and parasites
that would love to
invade your body
Functions of the immune system
• Primary function: defense; resist pathogens, foreign bodies
and abnormal cells
• Immunity acquired by:
– natural infection
– vaccination
• When it fails:
– congenital immunodeficiency diseases
– immunocompromise
– DEATH
Pathogen: a disease causing
organism
Pathogens
1)
2)
3)
4)
5)
Bacteria
Viruses
Protozoans
Fungi
Parasitic worms
E coli bacteria
Bacillus anthracis
Bacteria vs. Viruses
• First organisms on
earth
• Most species on earth
• Living cells
• Prokaryotic (simpler:
no nucleus, circular
DNA)
• A virus is a different
breed altogether.
• A virus is not really
alive.
• A virus particle is
nothing but a
fragment of DNA in
a protective coat.
• The virus comes in contact with a cell, attaches itself
to the cell wall and injects its DNA (and perhaps a
few enzymes) into the cell.
• The DNA uses the machinery inside the living cell to
reproduce new virus particles. Eventually the
hijacked cell dies and bursts, freeing the new virus
particles; or the viral particles may bud off of the cell
so it remains alive. In either case, the cell is a factory
for the virus.
The Lytic
Cycle
Bacterial antibiotic resistance
How does it happen?
1. Spontaneous mutation
Bacterial antibiotic resistance
How does it happen?
1. Spontaneous mutation
2 Plasmid transfer
Bacterial antibiotic resistance
How does it happen?
1. Spontaneous mutation
2. Plasmid transfer
3. Sex
Types of WBCs
Can be classified based
on the appearance of
granules when viewed
under the light
microscope.
1. Granulocytes
1
•
–
Contain visible granules.
Includes:
•
•
•
2.
Basophils
Eosinophils
Neutrophils
Agranulocytes
–
Do not contain visible
granules. Includes:
•
•
Lymphocytes
Monocytes
2
WBC Circulation and Movement
• Use the bloodstream
mainly to travel from
organ to organ or to
quickly go to areas of
invasion/injury.
• Characteristics of
circulating WBCs:
– Capable of amoeboid movement
• What role might this play in WBC function?
– They can migrate out of the bloodstream by squeezing thru
endothelial cells (this process is called diapedesis)
– They are attracted to specific chemical stimuli. This is known
as positive chemotaxis and allows WBCs to converge on
pathogens and damaged tissues
Agranulocytes Lymphocytes
• 20-30% of circulating leukocytes
• Slightly larger than RBCs. In blood
smears, you typically only see a thin
halo of cytoplasm around a
relatively large nucleus.
• Continuously migrate from the
bloodstream thru peripheral tissues
and back into the bloodstream.
• Circulating lymphocytes are only a minute fraction of the total # in the
body. Most are in other connective tissues and in lymphatic organs.
• Circulating blood contains 3 classes:
– T cells: defend against foreign cells and tissues and coordinate the immune
response
– B cells: produce and distribute antibodies that attack foreign materials
Agranulocytes Monocytes
• 2-8% of circulating WBCs
• Almost twice as big as an RBC
• Nucleus is large and tends to be
oval or kidney-shaped
• Individual monocytes use the
bloodstream as a highway, staying
in circulation for only about 24hrs
before entering peripheral tissues
to become a tissue macrophage, an
aggressive phagocyte.
Granulocytes Basophils
• >1% of circulating leukocytes
• Smaller than neutrophils and
eosinophils, only about 8-10µm in
diameter.
• Contain granules that appear deep
purple or blue
• Basophils migrate to injury sites
and discharge the contents of their
granules – histamine (a
vasodilator and increaser of
capillary permeability) and
heparin (an anticoagulant). This
enhances the local inflammation
initiated by mast cells and attracts
other WBCs
Granulocytes Eosinophils
• 2-4% of circulating WBCs
• Similar in size to neutrophils but have
reddish-orange staining granules (Eos is the
Greek goddess of dawn) and a bilobed
nucleus.
• Move into tissues after several hours and
survive from minutes to days.
• They will phagocytize antibody-coated
bacteria, protozoa, and cellular debris, but
their main method of attack is the exocytosis
of toxic compounds onto the surface of their
target.
• Important defenders against large, multicellular parasites such as flukes or parasitic
worms. They  in # dramatically during a
parasitic infection.
• Also sensitive to allergens and  in # during
allergic reactions as well.
Granulocytes Neutrophils
• 50-70% of circulating WBCs
• Cytoplasm is packed with pale
(“neutral colored”) granules that
contain bactericidal compounds
• Mature neutrophils have a
segmented nucleus. They are a.k.a
polymorphonuclear leukocytes.
• About 12µm in diameter.
• Highly mobile and generally the
first WBCs to arrive at an injury
site.
• Specialize in attacking and
digesting bacteria that have been
“marked” for destruction.
• Survive in the bloodstream for
only about 10hrs
Types of acquired immunity
• Active immunity
• stimulated by immunizations (infection or
vaccination)
• immune response plays an active role in the
generation of response
• takes time for it to be generated
• memory; next time, response will be faster
Types of acquired immunity
• Passive immunity
• passive transfer of antibodies or cells
• no active effort in the part of the immune
response
• example: antibodies against venoms
• works fast
• no memory
Types of acquired immunity
• Humoral immunity
• mediated by antibodies produced by plasma cells
(B cells)
• can be transferred
•
http://www.msjensen.gen.umn.edu/webanatomy/wa_lymphatic_immunology/wa_lymph_antibody_mov.html
• Cellular immunity
• mediated by T cells
• T cells produce cytokines which activate other
cells such as macrophages to effectively deal with
antigen
•
http://www.msjensen.gen.umn.edu/webanatomy/wa_lymphatic_immunology/wa_lymph_cytotox_mov.html
Primary and secondary
immune response
• Primary
• after antigen recognition, there is lag phase of 35 days -activation phase
• first antibody to be produced is IgM
• IgG is produced next
• levels of antibody peak between days 20-30
• antibody levels decrease, antigen is cleared
Primary and secondary
immune response
• Secondary
• immune response is quicker
• antibodies peak 2-5 days (activation phase is
short)
• higher magnitude response
• longer duration
• predominantly IgG
Features of the specific immune
system
• Self-regulation
• decreases with time because of antigen disappearance
• Discrimination of self-non-self
• response to FOREIGN antigens
• remains unresponsive to self antigens via
TOLERANCE; breakdown of tolerance leads to
autoimmune diseases
Major Histocompatability
Complex
 Protein markers that occur on surface of all body
cells
 Interact with cytotoxic T cells
 Different for individual--only the same in identical
twins
 Used to distinguish self from nonself
 This ability to distinguish self happens early in life
by T-cell in the Thymus
 This is the reason organ donors have to closely
match recipients
MHC Complex
How do diseases act as agents
that promote natural selection?
• Influenza of 1918--can be compared to the plague
in terms of its devastation
• Changed WWI and killed more than the war
Population of NY city with respect to immunity to the 1918 flu
1890’s
Natural immunity to the 1918 flu
No natural immunity to the 1918 flu
Population of NY city with respect to immunity to the 1918 flu
1890’s
1918 Flu
Survivors of 1918 flu
Their children
Population of NY city with respect to immunity to the 1918 flu
(assuming no immigration)
1890’s
1990’s
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