In This Lesson:
Immunology
(Lesson 3 of 3)
Today is Tuesday,
February 16th, 2016
Pre-Class:
How many “tiers” does the
immune system have?
(take a guess)
Also, what’s the best way to
make your immune system
more effective?
Today’s Agenda
• The Immune System
– Including all three levels of response.
• Antibodies
• Immunity
• Where is this in my book?
– Chapter 43.
By the end of this lesson…
• You should be able to narrate the immune
response to a pathogen with details for each
of the three levels.
• You should be able to distinguish between five
general types of white blood cells with detail
given to the four main types of lymphocytes.
• You should be able to describe the five classes
of immunoglobulins.
Perspective
• This is the part where I try to give you guys
inspiration or motivation to learn.
• I’ll be honest with you – and this is not a joke – to
me this is one of the most beautiful things in
biology.
• Think about it – we’ve learned about evolution
and all the amazing ways organisms have
developed to become more efficient at life.
• Now we look at a part of the body that has had,
by far, the most intense selective pressures for
the longest evolutionary time.
Perspective
• Now you’re going to witness conflict on a
molecular scale.
• Quite literally, this is a battle for resources
between an invader and the body.
• Watch as cells interact with one another with one
“side” trying to outdo the other and exploit
weaknesses.
• The best part? Nothing is actually conscious.
• It’s nothing short of brilliant. It’s nothing short of
amazing.
The Germ Theory
• Today, we’re well aware of germs.
• We know that things we can’t see can hurt us.
• However, there was a time when the idea of a
microscopic pathogen was laughable.
• It’s the 1860s.
• Enter Louis Pasteur.
The Germ Theory
• Louis Pasteur (same dude as the
pasteurization process) takes on a
centuries-old debate about the nature
of disease.
• He shows that disease is caused by
bacteria through:
– Breakdown of tissue.
– Toxin release.
• Further, disease can be transmitted by:
–
–
–
–
–
Air
Water
Food
Contact
Invertebrates (especially insects)
Louis Pasteur
The Germ Theory
• So the Germ Theory is born.
– The Germ Theory simply states that microscopic
organisms are capable of causing disease.
– So, no more is it “the vapors” making women ill.
http://www.broadsheet.ie/wp-content/uploads/2011/06/mlady.gif
Fast forward to 1890…
• Robert Koch, considered the father of
modern bacteriology, puts forth Koch’s
Postulates to connect a pathogen to a
disease.
• A researcher must:
– Find the same pathogen in all diseased
organisms.
– Isolate and grow the pathogen in a lab.
– Sicken healthy animals with the pathogen.
– Isolate the same pathogen from the newlyinfected organism and grow it again.
Robert Koch
http://upload.wikimedia.org/wikipedia/commons/thumb/8/8d/RobertKoch_cropped.jpg/190px-RobertKoch_cropped.jpg
Koch’s Postulates
Disease Transmission
• With the Germ Theory comes five modes of disease
transmission:
– Direct contact
• Example: Infectious mononucleosis, chlamydia.
– Indirect contact
• A surface that transfers disease – like a doorknob a sick person
touches that infects someone else – is a fomite.
• Example: The common cold.
– Aerosol [large water/mist droplet]
• Example: Respiratory viruses.
– Airborne [small droplet]
• Example: Measles, tuberculosis, chicken pox, smallpox.
– Vector [other organism or food]
• A vector is another organism that transfers a disease.
• Example: E. coli, listeria, bubonic plague.
http://phprimer.afmc.ca/Part3-PracticeImprovingHealth/Chapter11InfectiousDiseaseControl/Modesandcontroloftransmission
Case-in-Point: Typhoid Mary
• This is Mary Mallon (1869-1938), better known
as “Typhoid Mary.”
– Let me tell you why she doesn’t look happy.
• She carried typhoid fever but was completely
asymptomatic.
• She also happened to work as a private cook for
families. Whoops.
– Because of her job, she continuously made people ill.
• Over the course of her career she infected 51 and is linked
to at least 3 deaths, but possibly up to 50.
• She is also quoted to have said she did not understand the
purpose of hand washing and refused to give up her job
as a cook.
– She was forcibly quarantined by the City of New York
twice and died after almost 30 years in isolation.
• It appears that Salmonella typhi may hide in white
blood cells called macrophages.
http://upload.wikimedia.org/wikipedia/commons/e/eb/Mary_Mallon_%28Typhoid_Mary%29.jpg
Mary Mallon
Immune System
• So along with the advancement of
bacteriology, science also began to turn its
attention to immunology (how your body
defends itself).
• What’s your body’s first line of defense? The
first “line” of the immune system?
– The “boundaries” of your body.
Infection
• Thus, the points of entry for a pathogen
include:
– Digestive system
– Respiratory system
– Urogenital tract
– Breaks in skin (including cuts, eyes, ears…)
• Infection can then spread via:
– The circulatory system
– The lymphatic system
Let’s Introduce The Boundaries…
• …with a video:
– The Simpsons – Three Stooges Syndrome
Lines of Defense
Summary Slide
• 1st Line: Barriers
– Skin, mucus membranes, secretions.
• 2nd Line: Non-Specific
– Broad, internal defense.
– Known as the innate response.
• 3rd Line: Specific
– Acquired immunity specific to the pathogen.
– Known as the adaptive/acquired response.
First Line of Defense: External
Examples
• The trachea/windpipe is lined with
cells that have cilia (to sweep out
pathogens) and mucus (to stop
them).
• Tears and saliva “wash” pathogens
away and have lysozymes (enzymes
that damage bacterial cell walls).
• Sweat (pH 3-5) and stomach acid
(pH 2) denature proteins.
Infection
• Once a pathogen enters your body, it’s up to your
immune system to fight it off.
• After all, you’re a nice environment for a pathogen.
– You’re warm.
– You’re packed with nutrients.
– You don’t even have cell walls!
• Pathogens can then circulate via…the circulatory
system.
• Luckily, you have an alternate circulatory system for
the immune system called the lymphatic system.
The Lymphatic System
Production of Red/White Blood Cells
Inflammatory
Response
Fight Parasites
Become
Macrophages
Short-lived
Phagocytes
(most white
blood cells)
Second Line of Defense: Internal
• White blood cells, broadly
known as leukocytes, are
actually several different cells.
• Furthermore, they have
equivalents that exist within
tissues that don’t circulate but
play similar roles.
• There’s also other stuff that
floats around, plus the blood
“liquid” itself.
• Here’s a guide…
Mast Cell
Neutrophil
Macrophage Natural Killer Cell
Blood Plasma and Blood Serum
• Blood plasma is the liquid in blood, not
including the blood cells.
– It includes clotting factors like fibrinogens.
• Blood serum does not include fibrinogens.
Blood Components
• Fibrinogens
– Proteins that help in clotting.
• Platelets
– Cells that help in clotting.
• Erythrocytes
– Red blood cells [RBC] – carry oxygen.
– 4.8-5.2 million RBC per milliliter of human blood.
• Leukocytes
– White blood cells [WBC] – immune system.
– 4000-10,000 WBC per milliliter of human blood.
– Five major classes.
http://bme.virginia.edu/ley/leukocytes.html
The Five Types of Leukocytes
1. Neutrophils (40%-75% of WBC)
– Live for about three days.
– Find their way to infection site by chemoattractants.
– Ingest and destroy bacteria.
• Neutrophil Chases S. aureus video
2. Eosinophils (1%-6% of WBC)
– Live for weeks.
– Move to infection site via chemoattractants and kill
bacteria.
– Defend against multicellular invaders (like worms).
http://bme.virginia.edu/ley/leukocytes.html
The Five Types of Leukocytes
3. Basophils (<1% of WBC)
– Play a role in inflammatory reactions.
4. Monocytes/Macrophages (2%-10% of WBC)
– Monocytes mature into macrophages.
– “Big eater” cells with long (months-years) life
spans.
– May circulate or may remain in an organ.
– Process and display antigens (more later).
http://bme.virginia.edu/ley/leukocytes.html
The Five Types of Leukocytes
5. Lymphocytes (20%-45% of WBC)
– B lymphocytes (B cells) have immunoglobulins
(antibodies) on their surfaces to detect foreign cells, after
which they turn into plasma cells and secrete antibodies.
– T lymphocytes (T cells) help with cell-mediated immune
response – essentially immune responses on the level of
cells and not involving antibodies.
– Natural killer cells (NK cells) destroy cells infected by
viruses or that have become cancerous.
• Note: B & T lymphocytes are the only WBC
mentioned that DO NOT take part in the innate
response.
More on Phagocytic WBC
• Phagocytic WBC recognize markers
(antigens) on pathogens that are
not found normally in the body.
• In response, they engulf and
phagocytize the invader, often
either attacking it with toxins or
trapping it in a vesicle and fusing it
with the lysosome for digestion.
– Video! [Amoeba eats two
Paramecia]
More on Phagocytic WBC
• Key: When a white blood cell phagocytizes a
pathogen during the innate response, it will
present a digested part of the pathogen on
the OUTSIDE of itself.
• This is going to be important later on.
Review: Phagocytosis
• Recall that phagocytosis (cell
eating) is a way for cells to ingest
large molecules or, more
appropriate to this lesson,
microbes.
– FYI, microbes are microorganisms, yo.
• As seen in the image to the right, a
WBC is about as close to a
nightmare as a bacterium could
have.
More on the Inflammatory Response
• Damage to a tissue will trigger a local
inflammatory response.
• Under the skin, basophils (and tissue-bound
equivalents called mast cells) release histamine.
– Histamine is a molecule derived from the amino acid
histidine and causes the inflammatory response.
– As you might guess, this happens a lot for allergies
and antihistamines like Benadryl® act to control the
molecule.
• Side note: Anaphylaxis is an extreme allergic reaction due
to an abundance of.
More on the Inflammatory Response
• Key: As a result of the histamine
release, capillaries dilate (expand)
and become more “leaky.”
– Blood supply to the area increases.
– Clots can more easily form.
• You experience this as redness,
swelling, and heat at the site.
• You may also experience a fever.
Mast Cell
Case-in-Point: Tissue Damage
At the bacteria-coated splinter site, a mast cell (which is like a tissuebound basophil) releases histamines that draw in phagocytic cells and
swell the local blood vessels/skin while bacteria are eaten.
Case-in-Point: Fever
• If the local response is not enough, the activated
macrophages trigger the hypothalamus (in the
brain) to raise overall body temperature.
• The higher temperature may help to:
– Inhibit bacterial growth.
• E. coli, for example, grow best at 37°C or 98.6°F.
– Stimulate phagocytosis.
– Repair tissues faster.
– Reduce blood iron levels.
• Turns out iron is like bacterio-’roids for growth.
Case-in-Point: Survival of the Sickest
• [Excerpt]
• Note: When the text reads “…acute phase
response…” it’s talking about the innate
response.
Aside: Allergies
• An allergic reaction is, simply, an overreaction
on the part of the body’s immune system to
something that’s not really pathogenic.
– Peanuts aren’t exactly a toxin, right?
• Allergens stimulate a release of histamine.
• Coughing, runny noses, and swelling are side
effects of your immune system’s various
attempts to rid the body of the perceived
invader.
About NK Cells
• Natural killer cells destroy
infected cells by releasing a
protein called perforin.
– Guess what it does?
– Perforates the cell!
• Perforin protein fuses with the
membrane and punctures it,
allowing fluid to come in until
the cell lyses (bursts).
– Remember apoptosis?
Vesicle
with
perforin
ECM
Membrane
Cytoplasm
Other Antimicrobial Proteins
• Interferons are proteins that are released by an
infected cell.
• When neighboring cells receive the interferon
signal, they make substances that prevent viral
replication.
– Think of it like an early warning sign…sort of a, “Don’t
come near me, I’m not feeling well” message.
– FYI, this is all still part of the innate response.
Third Line of Defense: Internal/Specific
• This is the last line of defense.
• Don’t let that fool you…
• …it’s powerful.
http://www.thomasvan.com/wp-content/files/rohan-army-return-of-the-king.jpg
Third Line of Defense: Internal/Specific
• This is where the big guns come
out…
• …the lymphocytes.
– These cells are straight gangsta.
– Note that natural killer cells are
lymphocytes but come into play
during the innate response.
• This is a specific response that is
more coordinated than anything
in the prior waves of defense.
– Remember, it’s the adaptive or
acquired immune response.
Wait a sec…
• How does a pathogen even get to this point?
• One example is provided by, as your book
explains, Mycobacterium tuberculosis, which
causes…tuberculosis.
• It still gets eaten by macrophages but doesn’t
die and instead grows even more inside the
macrophage.
Antigens
• Lymphocytes respond most strongly to antigens on
other cells.
– An antigen is anything that causes an immune response.
– In this case, these are unique protein markers (“cellular name
tags”).
• “But don’t macrophages respond to antigens too?” says
the thoughtful student?
• “Yep, but those cells only distinguish ‘self’ from
‘foreign,’” says the icy-hearted teacher.
– Even pollen and transplanted tissue comes with antigens.
Antigens
• B lymphocytes (or B cells) recognize intact
pathogens.
– These are pathogens in the blood or lymphatic system,
thus they provide a humoral response.
• So this is an active defense to stop infection in body fluid.
• T lymphocytes (or T cells) recognize antigen
fragments.
– These come from pathogens that have already entered
cells, thus they provide a cellular response (also known
as the cell-mediated response).
• So this is a damage-control step.
More About B & T Cells
• B cells mature in bone marrow.
• T cells mature in the thymus
(an immune system organ at
the top of the chest).
• During maturation, cells
“learn” which antigens are
which and are destroyed if
they attack body cells.
– Millions of these cells are
produced, each one recognizing
a different antigen.
More About B Cells
• Recall that B cells are the ones that provide the
blood and lymph response.
• In response to a pathogen, B cells copy
themselves into two cell types:
– Plasma cells immediately produce a ton of
antibodies for the short term.
– Memory cells provide long-term immunity,
recognizing that same antigen long into the future.
• Coughvaccinemechanismcough.
Antigens and Antibodies
• As you may recall from our blood type
discussion, an antigen generates an immune
response.
– Antigens are often cell membrane marker
proteins, but technically even a splinter could
count as an antigen.
– Antigen = Stimulus
• An antibody is a free-floating protein that
binds to a particular antigen.
– Antibody = Response
Antigens and Antibodies
• An antigen has on it a region that makes it unique.
– That region is called an epitope or antigenic
determinant, since the actual antigen can be quite large.
Antigens and Antibodies
• Antibodies take the shape of a Y (kinda) and are
considered multi-chain glycoproteins.
• They have a variable binding region which is different
on each antibody – different so that they can match
particular antigens’ epitopes.
• They bind to and “handcuff” antigens.
Antibodies and B Cells
• So, when an antigen invades the body, a B
lymphocyte (B cell) will bind to it to recognize the
epitope.
• Similarly, if a cell is invaded, a T lymphocyte (T
cell) will bind to the antigen fragments.
• How does a B cell or a T cell recognize antigens?
– It has hundreds of thousands of antigen receptors.
• An antigen receptor is just like an antibody, except it’s
attached to the lymphocyte membrane.
Antigen Receptors
More on this one later…
Clonal Selection
• So the body has many, many different B/T cells
floating around in it, just waiting for virtually any
kind of antigen.
• Once it arrives, the body can rapidly start
producing antibodies since one of those
lymphocytes just has to have the right antigen
receptor.
– The ability of the body to fight infections without
having encountered an antigen yet (based on having
so many circulating B/T cells) is called clonal
selection.
The Overall B Cell Response
• An antigen enters the body.
• B cells recognize the antigen by binding to it with
their antigen receptors.
• Once bonded, B cells become activated, produce a
bunch of clones through mitosis, mature into
plasma cells, and release a buttload of antibodies.
– Antibodies are blood/lymph-soluble versions of those
antigen receptors.
• Some B cells stick around as memory cells.
– T cells are a little different and don’t release
antibodies…hold for now.
Antibody Structure
• Antibodies have four chains:
– Light (L) chain (two identical chainz)
– Heavy (H) chain (two identical
chainz that are twice as long as the
light chains)
• The ends of the light and heavy
chains – the antigen binding sites
shown in yellow – are made of
highly variable sequences of amino
acids.
Heavy Chain
s
s
s
s
s
s
s
s
s
s
– Thus, these are also called the
variable (V) regions.
• Constant regions are shown in purple. Light Chain
• The chains are held together by
disulfide bridges.
Heavy Chain
s
s
s
s s
s s
s
s
s
s
s
s
s
s
s
s
s
s
s
s
s
s
s
s
s
Light Chain
A little more molecularly accurate…
Light Chains
Antigen-Binding Site
Heavy Chains
Antigen-Binding Site
B Cells and Antibodies
• The variable regions have around 100 amino acids.
– No two B cells are likely to secrete antibodies with the
same variable region.
– V regions recognize epitopes.
• The other parts of the antibody are known as the
constant (C) regions.
– Humans have two different light chain C regions:
• κ (kappa) and λ (lambda)
– Humans have five different heavy chain C regions:
• µ (mu), γ (gamma), α (alpha), δ (delta), and ε (epsilon)
– C regions trigger a response.
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/AntigenReceptors.html
Five Heavy Chain C Regions
• Here’s the important part: the five different
heavy chain regions made by humans gives
rise to five different antibody classes.
– In this case, antibodies are being referred to by
their alternative name, immunoglobulin.
Five Heavy-Chain C Regions
#toomanywordsononeslide
• IgM: First immune response, activate complement proteins.
– Presence of IgM indicates a current infection.
• Four subclasses.
• IgG: Second immune response, promote phagocytosis, and
can cross placenta.
– Most abundant of the circulating antibodies.
• IgA: Released in sweat and other secretions.
– Prevents attachment of pathogens to epithelial (surface) cells.
• Two subclasses.
• IgE: Trigger allergic reactions and bind with basophils/mast
cells.
– Promote release of histamine.
• IgD: Uh? No one really knows yet.
– May help B cells mature into antibody-spewing plasma cells.
Immunoglobulin Memory Device
•
•
•
•
•
IgM: Meets the pathogen (appears first).
IgG: Given to you (crosses placenta).
IgA: Atop your skin. (released in sweat/secretions)
IgE: Enflames. (allergic/inflammatory reactions)
IgD: Don’t know?
Antibody Classes
Exposure
to
antigen
Antibody levels
IgM
0
IgG
2
4
Weeks
6
Antibody Classes
Class
mg/mL
H chain
L chain
Subunits
IgM
Mu
Kappa or
Lambda
5 sets of
2 H, 2 L
0.5-3
IgG
Gamma
Kappa or
Lambda
2 H, 2 L
6-13
Alpha
Kappa or
Lambda
2 sets of
2 H, 2 L
0.6-3
IgE
Epsilon
Kappa or
Lambda
2 H, 2 L
<0.0004
IgD
Delta
Kappa or
Lambda
2 H, 2 L
<0.14
IgA
(how common
in serum)
Pause.
• Wait a second.
• How in the world can B
cells make so many
different antigen receptors
and thus so many different
kinds of antibodies?
• In short:
– Rearrangement of DNA.
• Chromosome 14 has the
gene segments for those
antibody regions.
Pause again.
• You have a bunch of antibodies. So?
• Antibodies help end infections in one of four main
ways:
– Blocking binding sites on the outside of viruses and
bacteria. (neutralization)
– Marking pathogens for digestion (opsonization).
– Agglutination (clumping) of microbes to encourage
phagocytosis.
• This explains why antigens are Y-shaped – picture next slide.
• Remember this from blood typing?
– Making antigens insoluble.
– Activating complement proteins – IgM molecules.
Antibody Action
Memory Cells
• After an infection has occurred and is winding
down, some cells stick around even after the
immunoglobulin in the blood decreases.
– These are called memory cells.
– When memory cells are reactivated following a
repeat infection, they’re called effector cells.
http://askabiologist.asu.edu/memory-b-cell
Memory Cells
• Generally, it can take around 15 days to build an
appropriate level of antibodies following a new
infection (a 1° infection and a primary immune
response).
• Memory cells will generate enough antibodies to
fight off a repeat infection (a 2° infection and a
secondary immune response) in 5 days.
• Future infections may be eliminated so quickly
you don’t even notice you’re sick.
– It could be happening right now!
http://askabiologist.asu.edu/memory-b-cell
Memory Cells
http://askabiologist.asu.edu/memory-b-cell
Memory Cells
• Are you thinking what I’m thinking?
– Vaccines!
• Yep, this is how vaccines work.
– Introduce a weak antigen.
– The body generates an immune response and
memory cells.
– The body becomes immune.
• Both B and T cells generate memory cells.
– And speaking of…
Am I missing something?
• We’ve left T cells behind for a little bit.
• Remember that B cells are responsible for the
humoral response, that is, they take out
antigens still in the blood or lymph.
• T cells, however, present the cellular response
and are responsible for dealing with cells that
have already been infected.
MHC
• At the Philadelphia Zoo, an MHC is a
Madagascar Hissing Cockroach.
– Remember that Animal of the Week?
• In immunology, MHC is the major
histocompatibility complex.
– And it is beautiful.
Major Histocompatibility Complex
• Here’s a great example of the MHC in action,
courtesy the wonderful J Kimball Biology pages
online.
• Suppose you get the flu.
• An influenza virion invades a cell and starts
reproducing.
• B cells can’t destroy the little bugger since it’s
already ducked into a cellular shelter.
• However, the infected cell contains the molecular
version of a kindergarten tattle-tale.
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/B/B_and_Tcells.html
Major Histocompatibility Complex
• Histocompatibility proteins constantly bring
proteins made inside the cell to the outside of
the cell and display them to the extracellular
matrix.
• Each cell displays a mosaic of all kinds of
proteins it is using on its outside – this is the
major histocompatibility complex.
– In other words, the MHC is the entire complex of
proteins on the outside of the cell.
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/B/B_and_Tcells.html
Major Histocompatibility Complex
• An infected cell will display an antigenic
peptide from a pathogen it has
digested.
– It’s the cellular equivalent of a red flag or
a “wanted” poster.
• The nearest T cell, as we’ll soon learn,
notices the marker and lays a beatdown on that cell.
• Outside of infections, the MHC explains
why transplanted organs are sometimes
rejected.
– FYI: The MHC is genetically determined
with multiple allele/polygenic
inheritance.
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/HLA.html#class_II
T Cells
• There are two main types of T
cells, discussed here in short
and next in detail:
– Helper T Cells (CD4+ Cells)
• These alert the immune system of
an infection by initiating the
humoral and cellular responses.
– Killer T Cells (CD8+ Cells)
• These destroy infected cells.
• Note: The CD4/CD8 thing comes
from the transmembrane
proteins they express.
Helper T Cells
• Helper T cells respond either to infected cells or to
macrophages that have eaten something infectious.
• They do two main things for the body:
1. Release cytokines (in this case, lymphokines) – attractant
molecules that draw in other WBC.
• See the root word? “kine-” like “kinesis” or “kinetic?”
• This action results in a “walling-off” of the infected area, leading to
redness, or an abscess, or a rash like from poison ivy.
• Remember earlier when I said phagocytic WBC will present their
catch on the outside of their cells? They’re showing it to helper T
cells.
2. Bind to B cells and stimulate them to turn into plasma cell
clones.
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/B/B_and_Tcells.html
Aside: MHC Classes
• Technically, CD4+ cells (helper T cells) respond
to a subset of MHC molecules called class II
histocompatibility molecules which are
generally only presented by certain cells,
mostly immune system cells.
– Class I histocompatibility molecules are made by
nearly all cells.
• Like many topics in biology, there’s always
more to know…
Killer T Cells
• Killer T cells (or cytotoxic T lymphocytes) release
perforin to destroy infected cells.
• FYI: Killer T cells are different from natural killer
cells, which are part of the innate response.
Cytotoxic T
Cell
Animation!
The Overall T Cell Response
• Either an infected cell or a macrophage presents
an antigen to the helper T cell.
• The helper T cell activates a killer T cell and/or B
cells.
– Killer T cells destroy infected cells.
– B cells start releasing antibodies.
• New note: Interleukins are proteins responsible
for the signaling between white blood cells –
mainly lymphocytes – that coordinates this
response.
White Blood Cell Recruitment Phases
Summary Slide
• 1st Line of Defense: External
– No white blood cells used.
• 2nd Line of Defense: Internal (innate/non-specific)
– Inflammatory response (possible).
– Neutrophils, macrophages, basophils, eosinophils, natural
killer cells.
• 3rd Line of Defense: Internal/Specific
(acquired/adaptive)
– Lymphocytes*.
• *Not including natural killer cells.
Summary Animation
• Immune Response
Aside: Bionic Macrophages?
• T cells sometimes join with B cells to promote
inflammation (and pathogen death).
– Helpers, killer T cells, and inflammatory T cells…
• In the words of Carl Zimmer in Parasite Rex:
– “[T cells] lock onto the antigen displayed on the
macrophage's MHC. That locking acts like a trigger, turning
the macrophage into a more violent killer, spraying more
poisons. At the same time, the inflammatory T cells help
make the cut swell far more than the macrophages can
manage on their own. The inflammatory T cells also kill off
tired old macrophages and spur the production of new ones
to devour their elder cousins. They're like battle-hungry
generals: they're good to have around in a war but can't be
allowed to get out of control.”
About…Antimicrobial Proteins?
• Your blood also contains
antimicrobial proteins that
function in the same way NK
cells and T cells do.
ECM
Cellular Lesion
– These proteins are part of the
complement system.
• ~20 proteins in the blood
plasma activate one another
and perforate pathogens
through a membrane attack
complex.
Bacterial
Cytoplasm
Complement
Proteins
The Complement System
• Typically, the presence of an
antibody will start the cascade,
making this part of the
acquired immune response.
– It’s a little weird, but the
complement system is often
among the first (chronological)
defenses after a pathogen has
entered the body.
– It IS specific to the antigen, can
be aided by B cells, and cannot
kill “self” cells.
– Remember that the waves
aren’t exactly lined up
chronologically, but are
organized by specificity.
http://www.niaid.nih.gov/topics/immunesystem/immunecells/Pages/complementSystem.aspx
Autoimmune Diseases
• These occur when the immune system attacks the
body’s own cells. Some examples:
– Lupus occurs when antibodies against a person’s own
proteins are released as normal cells breakdown.
• Oddly, 9 out of 10 sufferers of lupus are women.
– Rheumatoid arthritis occurs when antibodies damage
cartilage and bone.
– Diabetes occurs when beta-islet cells of the pancreas are
destroyed.
– Multiple Sclerosis occurs when T cells attack nerves in
the brain.
Rheumatoid Arthritis
http://img.webmd.com/dtmcms/live/webmd/consumer_assets/site_images/articles/health_tools/rheumatoid_arthritis_overview_slideshow/P
Rinc_rm_x-ray_of_rheumatoid_arthritis.jpg
http://www.intechopen.com/source/html/41621/media/f9.jpg
A Different Kind of “Immune Disease”
• Here’s a strange one:
• Multiple myeloma is when a cell secreting
antibodies (plasma cell) becomes cancerous.
• As a result, the cell(s) start releasing tons of a
certain kind of antibody into the blood/lymph.
– This can interfere with kidney function, among
other things.
Closure: Pus
• Pus is a substance
composed of dead white
blood cells, usually after
they’ve defeated a
pathogen.
– Pus is mostly neutrophils.
• Ever hear of an abscess?
– That’s pus building up in an
enclosed space.
http://www.englishforpharmacists.com/matchingpairs/imagesjmatch/bl/microbiology1/pus.jpg
Closure
• Earlier in the year, we spent some time talking
about cell communication and the endocrine
system.
– Remember that?
– Hormones, ligands, signal transduction pathways?
• Keep in mind, much of what you just learned
about immunology is also cell communication.
– T cells presenting antigens to B cells, the MHC, et
cetera…
Closure: Immunity
• Hopefully you’re realized that your immune
system does a great job keeping you feeling well,
but it needs practice to be at its best.
• Practice can come in the form of actually getting
sick (ugh) or a vaccine, if possible.
• Active immunity is the immunity you build up in
this way – from active pathogens.
• Passive immunity comes from yo’ mama, as in it
was given to you at birth.
– Passive immunity will keep you alive long enough to
get your own immune system started.
– Remember IgA antibodies?
Closure: HIV/AIDS
• Unfortunately, an exploration of HIV’s
mechanism is probably also a good way to
recap the immune system, as it provides an
excellent example of how it can be
compromised.
• Remember that HIV is the actual virus –
Human Immunodeficiency Virus – while AIDS
is the resulting condition – Acquired
Immunodeficiency Syndrome.
Closure: HIV/AIDS
• Technically there are two variants:
– HIV-1, which is the one that’s everywhere.
– HIV-2, which is mainly in West Africa.
• In its general form, HIV infects helper T cells
(CD4+ cells).
• As a retrovirus, it reverse-transcribes RNA to
DNA, which is then added to the genome of
the host cell via an enzyme called integrase.
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/AIDS.html
Closure: HIV/AIDS
• At first, virus levels in the blood become very high.
– The early phase – within two weeks.
• Then, virus levels drop and antibodies rise.
– Helper T cells are repeatedly killed and replaced.
– The antibody presence is how HIV is tested.
– The middle phase – months to years.
• Finally, helper T cell levels decline rapidly.
– The late phase – typically less than a year. This is the part
called AIDS and virus levels rise again.
– Opportunistic infections by other pathogens or cancer kill
the patient.
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/A/AIDS.html
Closure: HIV/AIDS
Final Points
• HIV is most commonly found in blood and semen, as well
as breast milk.
• Transmission, therefore, occurs when blood can be
transferred – even through needle use or transfusions – or
when semen comes in contact with dendritic cells.
– Dendritic cells are a sort of para-immune cell.
– They are found at non-skin surfaces of the body, like in the
adenoids/tonsils in the mouth or the GI tract.
– They also constantly take in antigens to present them to the
immune system and to T-cells.
• Hence, the high levels of HIV in IV drug user and
homosexual communities.
– But those ARE NOT the only susceptible groups of people.
Closure: HIV/AIDS and Rhinovirus
• Both HIV and the common cold (often linked
to rhinovirus) are difficult targets vaccines
because they mutate so often.
• For example, HIV mutates so frequently
(about once per replication) that over one day
an infected person can produce 1,000,000,000
different copies of the virus.
– So there’s no way to make a set of memory B-cells
that’s effective.
– But there’s hope!
Closure: HIV/AIDS
• TED: Seth Berkley – HIV and Influenza – The
Vaccine Strategy
• Scientists announce anti-HIV agent so
powerful it can work in a vaccine article
Closure: A Tale of Two Diseases
• Note to students: This won’t be on any test
(including the AP Test).
• However, it’s so incredibly interesting I feel a
need to regale you with this here story.
• Sit back, kick your feet up, and enjoy.
Closure: A Tale of Two Diseases
• We’ve already established how AIDS is a
condition marked by the death of T cells.
– Keep that in mind for later.
• On the other hand, there’s a parasite known as
Toxoplasma gondii (“toxo” for short), and it’s a
protozoan (basically a protist).
• Approximately 1 out of every 3 people in the
world are infected with it and, according to Carl
Zimmer, regions of Europe may have 100%
infection rates.
– People aren’t necessarily symptomatic, though.
Closure: A Tale of Two Diseases
• Toxo’s parasitic cycle exists between cats and
their prey.
– Cat poop releases toxo eggs, eggs are eaten by other
animals, toxo matures in those animals, those
animals are eaten by cats.
– Repeat.
• Also, sound familiar?
http://stream1.gifsoup.com/view1/4865936/anchorman-cat-poop-o.gif
Closure: A Tale of Two Diseases
• People get toxo by accidentally ingesting a tiny bit
of soil or by eating an infected animal.
– Toxo invades all kinds of cells and reproduces up to
128 individuals inside them, then bursts out and
repeats the process.
– Then it stops.
• Huh?
– Toxo eventually reaches a point where it nearly stops
reproduction and all individuals “hide out” in
protective shells known as cysts.
• They’ll break out once they’re inside a cat again.
• For humans, the reproductive cycle can result in,
at worst, a feeling of having a flu.
Closure: A Tale of Two Diseases
• Here’s where it gets weird.
• As you know, parasites that kill their hosts are not
very successful parasites.
• To keep itself in check, toxo actually stimulates its
host’s immune system, promoting the generation
of inflammatory T cells.
• The inflammatory T cells kill all parasites not
hiding inside those cysts.
– Thus, they never “over-reproduce” and kill the host.
• Actually, this is starting to sound like that lemmings myth.
Closure: A Tale of Two Diseases
• So, now for the final part of the story.
• First, pregnant women are often advised (to their
surprise) not to clean cat litter boxes. Why?
– Because they may pick up the parasite.
– The parasite may find its way into the fetus.
– When toxo attempts to recruit inflammatory T cells to
keep itself from reproducing too much…nothing
happens.
• Fetuses don’t have a developed-enough immune system.
• Thus, miscarriage. And more toxo around.
Closure: A Tale of Two Diseases
• Second, where does AIDS come in?
• Toxo is unfortunately a major opportunistic
killer of HIV-positive individuals.
• Once again, like in a fetus, there are no T cells
to prevent over-reproduction of the parasite.
• Most toxo damage occurs in the brain, and
instead of a mild flu feeling, victims often fall
into delirium and potentially die.
Closure
• CrashCourse – Your Immune System – Natural
Born Killer
• Immunity POGIL
• 