1. Immune System

2. Immune System
A functional system rather than an organ system in an anatomical sense
Its “structures” are a diverse number of immune cells and molecules that are involved in the immune response.

3. Pathogens
Pathogen = any living organism or virus that is capable of causing disease. Includes:
Bacteria, Viruses, Protozoa, Fungi, some worms
Most don’t result in disease because of our defense system

4. Before antibiotics
Between 1345 – 1350, approx. 25,000,000 people in Europe died from ‘the plague’.
Most people thought it was from breathing ‘bad air’, so treatments included burning nice-smelling incense.
Disease was actually
caused by a bacteria
carried by rats.

5. Before antibiotics
People would either get better on their own, or get worse and die
Ex. 40% of people with pneumonia died
Home ‘cures’
would sometimes
hurt more than
help. Example:
leeches!

6. How antibiotics work against bacteria
Antibiotics take advantage of the differences between prokaryotic and eukaryotic cells
There are many classes of antibiotics each with their own method of destroying bacteria
selectively blocks protein synthesis (aminoglycosides, macrolides, tetracyclines)
some inhibit new cell wall production, blocking their ability to grow and divide (penicillins, cephalosporins), includes amoxicillin, ampicillin, cefalexin
Some damage cell membranes (polymixins)
Some interfere with bacterial enzymes (quinolones, sulfonamides)

7. Immune System: 2 major kinds of defense
First kind is Innate immunity
largely nonspecific, responding to a broad range of microbes.
- external barriers: skin and mucus membranes
- internal barriers: cellular and chemical defenses that defend against microbes that get past the external barrier
(macrophages and other phagocytic cells that ingest and destroy pathogens)

8. Immune System: 2 major kinds of defense
Second kind is Acquired immunity:
Develops after exposure to microbes or other foreign substances
Highly specific
White blood cells (lymphocytes). 2 responses:
Humoral response – cells derived from B-lymphocytes secrete antibodies that bind to microbes and target them for elimination
Cell-mediated response – cytotoxic lymphocytes directly destroy infected body cells, cancer cells, or foreign tissue

9. Overview of innate and cell-mediated responses
Surface barriers
Skin
Mucus membranes
Innate
defenses
Internal defenses
Phagocytes
NK cells
Inflammation
Antimicrobial proteins
Fever
Adaptive
Defenses
(Acquired
Immunity)
Humoral immunity
B cells
Cellular immunity
T cells

10. Ways we prevent pathogens from entering the body
Skin: 2 primary layers:
Dermis (underlayer) has sweat glands, capillaries, sensory receptors, and dermal cells that give strength and structure to skin
Epidermis (top layer) – layer of mostly dead cells. Good barrier because its not truly alive.
Stomach acid: if pathogens
come in with food or liquid,
stomach acid helps to kill
most of them

11. Ways we prevent pathogens from entering the body
Mucus
Pathogens enter in the air we breathe (mouth or nose)
Mucus is produced by cells lining entryways (trachea, nasal passages) to trap incoming pathogens.
The cells that secrete mucus also secrete the enzyme lysozyme which digests bacterial cell walls
Some mucus membranes are lined with cilia, which also help move pathogens up and out

13. What happens when they do get in? (pt.1) Role of phagocytic leukocytes
Leukocytes = white blood cells, many different types, they are the main cells in bloodstream that help fight off pathogens that enter our bodies
- they also provide us with immunity for returning pathogens
Macrophages – large WBC’s that can change their shape and squeeze their way in and out of small blood vessels. They surround invaders and ingest them by phagocytosis.

14. If its “self”? they leave it alone
When a macrophage finds a cell, it determines whether its “self” or “not-self” based on surface protein receptors on the cell
If its “self”? they leave it alone
If its “not-self”? they engulf by phagocytosis and chemically digest it with lysosomes
Non-specific;
just determined
to be “not-self”

15. Macrophages phagocytosing bacteria

18. 4 types of phagocytic leukocytes
1) Macrophages
2) Neutrophils
60-70% of all WBC’s
Attracted to and enter infected tissue, engulfing and destroying microbes there
Self-destruct in only a few days

20. 3) Eosinophils
Critical for defense against multicellular parasites like blood flukes. Instead of engulfing them, they position themselves against the parasite’s body and then discharge destructive enzymes that kill them

21. 4) Dendritic cells
Can ingest by phagocytosis,
But primary role is to stimulate the development of acquired immunity

22. What happens when they do get in? (pt.2) Antibody Production
Antibodies = proteins that we produce in response to a specific type of pathogen
-Y-shaped
Each antibody is different because each type has been produced in response to a different pathogen
Antigens =
foreign substances that
stimulate the production
of antibodies

23. Each type of antibody recognizes one specific antigen
Antibodies have binding sites specifically for those antigens

24. How are antibodies produced
When antigens are found, the body gears up to produce large amounts of antibodies needed
Each type of lymphocyte recognizes one specific antigen and responds by dividing to form clones
These clones then secretes specific antibodies against the antigen

25. How are antibodies produced
A B-cell´s recognition of a target structure quickly leads to the production of numerous antibodies ready to attack this target. Memory cells ensure a quick response in case the target reappears at a later time. B-cells which don’t recognize the target (here the cells 1 and n), don’t produce antibodies

27. Immune Response animation

28. Immune Response A macrophage discovers an antigen
When it determines it to be “not-self”, it engulfs it by phagocytosis, but pieces are purposely left on the cell membrane of the macrophage
Helper T cells chemically recognize the antigen being presented and become activated
Helper T cells then chemically communicate with (activate) the specific B cell that is able to produce the antibody needed

29. Immune Response
(B lymphocytes are the leukocytes that produce antibodies)
B cells are activated to clone themselves by mitosis to make many more of themselves
- (antibody-secreting plasma cells and memory cells)
The newly formed ‘army’ begins antibody production
Antibodies circulate in the blood until they find their antigen match
Antibodies destroy the pathogens
Some of the cloned lymphocytes stay in bloodstream and give immunity from a second infection by the same pathogen. (they are called memory cells)

31. HIV
HIV infects cells in the immune system, specifically helper T cells
Once helper T cells are destroyed, there is no longer communication between cells and antibodies are not produced, so the individual cant fight off pathogens
HIV can be dormant in host cells for years before becoming active
Once active, secondary infections occur, and symptoms of AIDS begin to appear

32. Issues related to AIDS
What are some cultural and economic reasons for differences in the prevalence of AIDS?

33. Principles of Immunity
Challenge and response: The immune system must be challenged by an antigen during the first infection in order to develop an immunity.
All the cellular events (involving macrophages, helper-T cells, and B cells) are part of the response which leads to immunity to this pathogen

34. Principles of Immunity
Clonal selection: when B cells encounter a specific antigen to which their antibody binds, they multiply many times to form clones.
Memory cells: These are the cells that provide long-term immunity. You must experience a pathogen once in order to produce these and be truly immune.

35. Active vs. Passive Immunity
Active immunity: Immunity due to the production of antibodies after the body’s immune cells have been stimulated by antigens.
Passive immunity: when one organism acquires antibodies which were produced in another organism.
Only the organism which produced the antibodies has the memory cells and so has long-term immunity. Getting antibodies from somewhere else acts only short-term.

36. Examples of Passive Immunity
Antibodies passed from mother to fetus through the placenta
Antibodies passed from mother to baby through the colostrum. Colostrum is the breast milk produced in late pregnancy and first few days after birth; high antibody concentration.
Injection of antibodies in antisera. Ex. antivenom if you’ve been bitten by a poisonous snake

37. Production of monoclonal antibodies
Process by which large quantities of antibodies (targeted against a particular antigen) can be produced
A mouse (or other laboratory animal) is injected with a specific antigen
Then the animal is given time to go through an
immune response
The mouse’s body will
stimulate the production of
antibodies against the
antigen

38. Production of monoclonal antibodies
The spleen is taken out as a source of many B cells
B cells are fused with tumor (cancer) cells to produce hybridomas

39. Production of monoclonal antibodies
Each hybridoma proliferates and produces mass quantities of antibodies called monoclonal antibodies

41. Uses of monoclonal antibodies: Diagnosis
One common use: pregnancy testing.
Early in pregnancy, the embryo starts to produce a hormone called HCG (Human Chorionic Gonadotrophin).
Only pregnant women would have this hormone which shows up in blood and urine.
Hybridomas are produced by injecting a mouse with HCG, the B cells produced secrete antibodies which recognize HCG as an antigen. These anti-HCG antibodies are bonded to an enzyme which shows a color change when the antibody encounters HCG.
why pregnancy tests change color when positive

42. Uses of monoclonal antibodies: Treatment
Cancer cells produce cancer-cell specific antigens on their cell membranes
One possible treatment for cancer is to produced monoclonal antibodies that target those antigens
Big advantage is that they target the cancer cells directly

43. Vaccination
A vaccine is developed by weakening a virus by heating it or chemically treating it, then injecting it into the body
The body will recognize it as ‘not-self’ and the primary immune response takes place (including formation of memory B cells for quick response if needed later)

44. Note that a second infection of the same pathogen results in a faster response with more antibodies produced

45. Benefits of vaccination
Possible total elimination of the disease, as has occurred with smallpox
Decrease in spread of pandemics (worldwide infections) and endemics (local infections). Increased international travel has made this very important: an infection started on one side of the world could be on other side of the world in < 1 day
Preventative medicine is cheaper than treating diseases
Prevention of harmful side-effects of diseases

46. Dangers of vaccination
Possible toxic effects of mercury; prior to 1999, a mercury-based preservative was used
Multiple vaccines in a short period of time may ‘overload’ the immune system
Possible links to autism (?)