Today is Wednesday,February 21st, 2018

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?

Guided Reading!

In This Lesson:Immunology

(Lesson 3 of 3)

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 newly-

infected organism and grow it again.http://upload.wikimedia.org/wikipedia/commons/thumb/8/8d/RobertKoch_cropped.jpg/190px-RobertKoch_cropped.jpg

Robert Koch

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, like your skin, for

example.

Infection

• Thus, the points of entry for a pathogen include:– Breaks in skin (including cuts, eyes, ears…)– Digestive system– Respiratory system– Urogenital tract

• 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 DefenseSummary Slide

• 1st Line: Barriers– Skin, mucus membranes, secretions.

• 2nd Line: Non-Specific– Response 2A

• Broad, internal defense.• Known as the innate response.

• 3rd Line: Specific– Response 2B

• Acquired immunity specific to the pathogen.• Known as the adaptive/acquired response.

First Line of Defense: ExternalExamples

• 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

Short-lived Phagocytes (most white blood cells)Become

Macrophages

Second Line of Defense: InternalThink of this like 2A (happens concurrently with adaptive/acquired)

• 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

Macrophage

Neutrophil

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.

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 histamine and immune cells.

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 tissue-bound 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?

ECM

Cytoplasm

Vesicle with

perforin

Membrane

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/SpecificThink of this like 2B (happens concurrently with the innate response)

• 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/SpecificThink of this like 2B (happens concurrently with the innate response)

• 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.

Memory B

Cell

B Cell Mechanism

Here’s a B Cell.

Notice it has a bunch of different antigen receptors on

the membrane.

We’re in the bloodstream, by the way…

Here’s a pathogen. Let’s call it……Bubonic plague (Yersinia pestis).

Antigen

Epitope

Antigen Recognition!Gasp!

The B Cell divides into Plasma B Cells and

Memory B Cells.

The Plasma B Cells spew out antibodies.

Plasma B Cell

B Cell

Antigen ReceptorsMore 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 Details• 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.– Thus, these are also called the variable

(V) regions.• Constant regions are shown in purple.

• The chains are held together by disulfide bridges.

sss

s

ss

ss

ss

ss

ss

ss

ss

ss

s

ss

ss

s

ss

ss

ss

ss

ss

Light Chain Light Chain

Heavy Chain Heavy 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 #notonthetest

• 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

Weeks0 2 4 6

IgM IgG

Exposuretoantigen

Antib

ody

leve

ls

Antibody Classes

Class H chain L chain Subunitsmg/mL

(how common in serum)

IgM Mu Kappa or Lambda

5 sets of2 H, 2 L 0.5-3

IgG Gamma Kappa or Lambda 2 H, 2 L 6-13

IgA Alpha Kappa or Lambda

2 sets of2 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

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 beat-down 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 PhasesSummary 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.– 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.

ECM

Bacterial Cytoplasm

Complement Proteins

Cellular Lesion

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://www.intechopen.com/source/html/41621/media/f9.jpghttp://img.webmd.com/dtmcms/live/webmd/consumer_assets/site_images/articles/health_tools/rheumatoid_arthritis_overview_slideshow/PRinc_rm_x-ray_of_rheumatoid_arthritis.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/AIDSFinal 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 for 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 (helper) T cells.

• The inflammatory T cells help 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: A Tale of Two Diseases

• Think it can’t get any weirder?• When toxo infects mice, it makes them less

afraid of cats.– Infected mice move around out in the open

instead of up against walls and sometimes even are attracted (!) to cat smells.

• This allows the parasite to complete its life cycle, as it can only reproduce in cats.

• Parasites Practicing Mind Control article

Closure

• CrashCourse – Your Immune System – Natural Born Killer

• Immunity POGIL•