1. The Immune System

2. Cells Recall the cells of the immune system: Granular leukocytes
Neutrophils
Eosinophils
Basophils
Agranular leukocytes
T-cells
B-cells
Monocytes/macrophages

3. “Lines of defense”
While the book tells you that you have 3 lines of defense:
Chemical & physical barriers
Cellular “innate”
Specific/learned
It’s actually much easier and more common to think of 2 types of immune defenses:
Innate immune system
Adaptive immune system

4. Innate immunity Innate immunity refers to: NON-SPECIFIC immunity
Physical barriers: many layers of skin cells, tight junctions of the gut etc.
Non-specific because these keep EVERYTHING out
Chemical barriers: sweat, oil on your skin, mucus, stomach acid, digestive enzymes
Again, no “individual” target…these chemicals hinder everything
Innate immune cells:
Neutrophils, eosinophils, monocytes/macrophages, “natural killer” cells
Immune proteins
Interferons & complement

5. Innate immunity Innate immune cells:
Don’t normally focus on a particular “enemy”
Will destroy/eat anything, as long as:
It is recognized as NOT YOUR OWN, or DOES NOT BELONG HERE
A foreign cell (transplant)
A metaplastic cell (cancer)
These cells destroy ANYTHING
Example: 1 neutrophil from your blood will kill a foreign cell, and can then kill a cancerous cell…it just kills whenever it recognizes something is wrong

6. Innate immunity Innate immunity cells:
“professional eaters” = phagocytes (monocytes/macrophages & neutrophils)
Look for a specific “self” marker
If the target does not express that “self” marker (like your own DNA serial number), the phagocyte will “eat” the cell
Usually a complicated process
Monocytes are big enough that they can eat an entire cell
Neutrophils are more common (most common leukocyte…NOT the most common cell in your blood)
Will tell the target cell to commit suicide…then eat the pieces as the cell dies

7. Phagocytes

8. Innate immunity Innate immunity cells: Natural killer cell (NK cell)
Weird type of cell
Related to T-cells, but not exactly the same
Still a phagocyte (will still eat a target cell)
Uses a 2-signal mechanism
1 = recognize self (looks for “self” marker just like the monocytes & neutrophils)
2 = looks for a “don’t kill me” protein as well
Unlike monocyte or neutrophils, who don’t bother looking for this second marker
“natural killer” because the cell WANTS to kill, and WILL kill unless you “beg” it with the “don’t kill” marker as well

9. Innate immunity The “self” marker:
Known as the “major histocompatibility complex” (MHC) protein
There are 2 types of this protein (MHC1 & MHC2)
EVERY cell in your body must express MHC1
If not, it will be targeted and killed by the innate immune system
MHC1 is also the protein that you “type” when looking for a transplant donor/recipient
Looking for a “close match”
Remember that everyone is different, hence your MHC1 is NOT the same as another persons MHC1

10. Innate immunity Innate immune proteins:
Interferons: “interfere” with viral invasion
Virus = short piece of RNA…not alive
Why antibiotics are useless against the flu (a virus)…antibiotic = “against life”
Virus invades a target cell, takes over the cellular machinery to “copy” itself
Normally results in destruction of the cell
Cell can let other cells know (as well as the immune system) by releasing “interferons”
Interferon = “interfere with virions”
Act to hinder virus from exiting cell
Also act to draw innate immune cells to the infected cell
Also acts to “train” the neighboring cells in how to protect themselves from this virus

11. Innate immunity Innate immune proteins:
Interferons: “interfere” with viral invasion
Why then do we get sick during viral infection?
The interferon system is not perfect
Many virions (virus = the genetic code, virion = particle that holds the virus) can “cheat” this system
The interferon system takes TIME
Remember that this is a protein…coded on your DNA…you have to copy this code onto RNA, export it into the cytoplasm, translate it into protein, and then export the protein out of the cell
During this time, the virus itself is trying to hijack the translation machinery to make copies of itself
Often times, the “sickness” is your innate immune system trying to FIGHT and KILL the cells infected with the virus

12. Innate immunity Innate immune proteins:
Complement: group of 20 proteins
Made by liver
Always in the blood
Complement protein #3 (C3) is the key player
Travels through the blood looking for protein/carbohydrate
Once it finds the target, it will cling to it,
Then, it will cut itself in half
Cutting then triggers the “conglomeration” of the rest of the complement proteins
The “target” is a group of proteins that your body DOES NOT make
More common on bacteria

13. Innate immunity Innate immune proteins:
Complement: group of 20 proteins
The cells of your body all have the SAME DNA
Hence, the proteins and carbohydrates on their cell membranes are the same
The particular protein/carbohydrate that C-3 (complement #3) looks for is the same in every cell in your body…but different in someone else
Once the 20 complement proteins come together:
Form a pore (a hole) in the plasma membrane
Attacked cell cannot control loss of cytosol, cannot control electro-chemical gradient across plasma membrane, cannot control OSMOLARITY

14. Innate immunity Innate immune proteins:
Complement: group of 20 proteins
Remember the short lifespan of C-3?
Only lasts about 2-5 minutes
This is how you can transfuse blood from a donor to a recipient, BUT, you cannot simply transfer it directly
If you hooked a line up from the donor’s arm to the recipients arm, the donor’s complement system would attack the recipient
In your body, the cells of your body produce another group of “complement control” proteins to limit their destructive activity

15. Innate immunity Innate immune proteins: Remember DNA
Everyone is different, hence your DNA is different
This means that your complement is slightly different
Your own complement will see another body as foreign and try to attack it
Complement is a very destructive defense that doesn’t care what it kills
It also works VERY FAST: initial xenotransplants were tested by transplanting pig hearts into baboons
Even though the two animals had been “matched” as donors, the baboon complement system turned the hearts into “jelly” in a few hours

16. Innate immunity Innate immune response in action:
Whenever the innate immune system acts, it shows a number of characteristics
Redness (more blood getting to the site of action)
Heat (increased heat = higher metabolic activity…remember what happens when you break ATP?)
FEVER (whole body temperature elevation)
Swelling (because more blood is flowing)
Pain (usually because of the swelling, damage etc.)
All of these actions occur very quickly (pinch yourself hard and watch)

17. Specific/acquired immunity
In contrast to the non-specific immune system, you also have a specific or “adaptive” immune system
Where the innate immune system just attacks, the adaptive immune system “LEARNS”, then it attacks (hence, this branch of the immune system takes longer to respond)
System requires lymphocytes (agranular leukocytes)
A lot of life forms don’t have an adaptive immune system…they get by with innate immunity

18. Specific/acquired immunity
Cells of the specific immune system:
T-lymphocytes (T-cells):
T-helper cells = central player…the antigen recognizer
T-effector (cytotoxic T-cell) = the killer
T-memory = long-term “memory” of how to respond to the antigen next time
B-lymphocytes (B-cells):
Secrete antibody after they learn to make it from the antigen-presenting cell,
T-helper cell will tell the B-cell to make more antibody when you are exposed to the antigen again

19. Specific/acquired immunity
Key term: antigen
Antigen = something that will trigger the specific immune response
Not simply an MHC molecule to tell the immune system if this is “self” or not
Can be a protein, membrane lipid, nucleic acid…almost anything
An antigen will trigger the production of an ANTIBODY
This antibody is another protein, made by the acquired immune system
Antibody specifically recognizes ONLY that antigen

20. Specific/acquired immunity
Antibody & immunity:
When you say you are immune to something, what you are really saying is: “you have antibodies that recognize that something”
These antibodies are made by the specific/acquired immune system after it learns about the target
In essence, you “acquire” antibodies by “learning”
Much like you “acquire” knowledge by studying

21. Specific/acquired immunity
Acquired immunity needs the innate immune system
Somehow, you have to “present” antigen to teach the T-cells & B-cells that make up the acquired immune system
Innate immune cells often do this by:
Ingesting the target,
Presenting pieces of that target to the acquired immune cells (immature cells that are learning)
Uses the MHC2 molecule…it acts as a “cup” to hold pieces of the target

22. Specific/acquired immunity
Innate immune cells therefore act as “antigen presenting cells”
Present antigen that is stuck on MHC2 molecule for the adaptive immune system to “see”
They usually learn from an MHC2 molecule (although MHC1 molecule can do this as well)
Other cells throughout can do the same thing
In lymph nodes, you have special “antigen presenting cells” that take up antigen and present it to immature “learning” cells

24. Specific/acquired immunity
Antigen-presenting cell presents antigen to the immature (T-helper cell)
This occurs in lymph node & thymus
Where immature lymphocytes go to “mature” / learn
As they learn, they are watched by the antigen presenting cell
If they learn incorrectly, or learn something that is too close to “self”, they are “killed” and not permitted to leave the lymph node/thymus
Why?
If you chop up a foreign cell, there is a chance that a part of it will be very similar to YOURSELF
If this happens, you don’t want to risk your immune system learning to recognize this as an enemy

25. Specific/acquired immunity
How it works (in short):
Antigen-presenting cell shows its antigens to T-helper cell
T-helper will then recruit immature T-cells to teach them what to look for
T-killer cells
B-cells (to make antibodies)
After this, you have immunity
You’ve acquired immunity against that antigen

26. Specific/acquired immunity
How long it takes:
This process takes much longer than the innate immune system
First have to recognize and ingest the antigen
Then, have to present antigen
Now, have to present antigen to immature lymphocytes
Have to “train” immature lymphocytes to recognize
Have to “grow” or increase the number of those cells
Whole process usually takes 2-4 weeks
Remember the tetanus example?

27. Specific/acquired immunity
In the lymph nodes/thymus, lymphocytes learn
They can only recognize 1 target
For every antigen, you have 1 lymphocyte
It will divide when needed (clone itself)
This is why you want to expose yourself to as much as possible when young
When you are young, your adaptive immune system is quickly trying to learn EVERYTHING
Once you stop “learning”, all you can do is “re-arrange” what you know
Hence, as adults, all we can do with our specific immune system is “modify” what it already knows to “adapt” to new enemies

28. Antibodies After you have B-cells that produce antibodies,
Antibodies will “clump” around their target
Clumped antibodies are a target for the innate phagocyte cells (monocytes, neutrophils)
Antibodies also can “mask” or “cover” the antigen so that it cannot act/work
If it is a toxin, you can “cover” it so that it can’t interact with its target…again, the innate phagocytes will then eat that “clump”

29. Adaptive activity & suppression
Since antibodies and learning take a large amount of energy, you don’t want it always active
When you “learn” it, you quickly develop/grow a large number of cells that specifically target that target
AFTER the infection/exposure, the immune system then tries to “limit” those cells
Tells many of them to die
After the infection, you reduce the number of T-killer and B-cells that were grown to specifically deal with that infection
You don’t kill all of them, you keep a small number handy for the next time

30. Adaptive activity & suppression
The B-cells are reduced in number, but they still make and release antibody (they just release less)
Next time, these antibodies will clump if you are exposed to the antigen again
Starts the process again
T-helper recognizes clumped antibodies
NOW, T-helper does not have to “train” a new group of T-killer cells or B-cells…
T-helper only has to “wake up” those cells from the first time

31. Adaptive activity & suppression
In subsequent exposures, your adaptive immune system works faster
It already knows how to respond,
All it has to do now is rapidly increase the immune cells that already know how to kill and/or make antibodies against this antigen

32. Active vs. Passive immunity
You can get antibodies or “train” your adaptive immune system by:
Allowing yourself to be invaded/exposed
Infection
Providing “parts” of a target
Vaccinations = chopped up pieces of the target you need to attack
Body will develop antibodies based on these small pieces
Your mother gave you some of her antibodies and antigens when she breast fed you
You can also “augment” your antibody array by acquiring foreign antibodies
Remember the Tetanus example? The “vaccination” usually has antibodies as well

33. Active vs. Passive immunity
Whereas your own antibody production will last for life, getting an antibody from another person/animal will not last long
Tetanus antibodies (when they vaccinate you) will only last a few days
Innate immune system will gobble them up and get rid of them

34. Tolerance & allergies
You don’t want your immune system to attack EVERYTHING
It would take up too much energy
It would pre-occupy your metabolism
You therefore try to “tolerate” many things that are potential antigens
Tolerance = immune system is “suppressed” from developing a response
Allergy = inappropriate immune response to something that should be tolerated

35. Tolerance & allergies Seasonal allergies
Hay fever, pollen allergies etc. are all potential antigens
Exposure to these potential allergens should be “tolerated”
However, sometimes adaptive immune system does not tolerate these antigens, and develops a response to them
Runny nose, itchy watery eyes = innate immune system functions (increase blood flow to site of ‘invasion/exposure) triggered by the adaptive immune system
Antibodies will clump, triggering innate phagocyte cells to enter…they are in blood, so you increase blood flow to that region

36. Tolerance & allergies Anaphylaxis
Extreme inappropriate immune response
Often dietary antigens
Because your digestive system has over ½ of your total immune system, it is constantly being exposed to antigens
Since there are so many immune cells, the response is magnified in your gut

37. Tolerance & allergies Allergy medications:
Anti-histamine = blocks histamine receptor on target cell
Histamine is released by basophils (innate immune system) and mast cells (adaptive immune cell “sentry”)
Allergy = inappropriate immune response
Whenever you trigger an immune response, you need increased blood flow (to deliver the immune cells)
Histamine helps to increase the blood flow because it relaxes blood vessels (makes the bigger = vasodilation)
Anti-histamine = block this increase in blood vessel size, thereby hindering influx of immune cells

38. Tolerance & allergies
Hindering the effects of histamine = reducing blood flow
There is normal blood flow, just not the INCREASED volume that would be present
Reduces immune cell influx into the tissue
Reduces volume of plasma leaking from capillary bed (tears, runny nose)

39. Tolerance & allergies
Allergy is a nice example of the ENTIRE immune system working (inappropriately)
Normally “tolerant” of the antigen (dust, pollen etc.)
Adaptive immune system somehow learns to respond to this potential antigen and is permitted to “leave” the “school” and show others
Once you are exposed to the antigen again, the response is much faster
Antibodies clump around the antigen
Redness, heat, swelling, pain = innate immune system attracted by the antibodies to “eat”
Increase blood flow to the region to increase number of innate immune cells to deal with “invader”

40. Tolerance & allergies
Recall Celiac’s disease: wheat gluten enteropathy
Remember wheat gluten (gliadin) is very resistant to digestion & denaturation
Normally, this intact protein is “tolerated” by the immune system
It knows that this is not a toxin or an invader
Celiac’s disease = intolerance of this protein
Intestinal epithelial cells will endocytose gluten & present it “stuck” onto their MHC1 molecules
Adaptive immune system then learns to mount a response to this protein
Next time patient ingests gluten, it will be presented on the MCH1 molecule again, but immune system will only “see” the antigen, and not the “self”

41. Tolerance & allergies Lactose intolerance is not correct:
Lactose = glucose-galactose “dimer” of carbohydrate
Must be digested into glucose AND galactose (separate monomers) by lactase
The lactose intolerance = reduced or no expression of the lactase enzyme
Cannot digest lactose
What kind of diarrhea is this?
Should really be called “lactase deficiency” rather than lactose intolerance