1. Chp.43 The Immune System

2. Homeostasis and the Immune System
Pathogens invade organisms because they are seeking:
a source of food or water
protection
a place for reproduction
Defense mechanisms evolved to rid the organism of pathogens and return the organism back to its original state.
An immune system protects an organism from pathogens and other foreign material.
It may be useful to go over some terminology with the students:
Homeostasis -- the internal regulation of a system so that its properties remain constant. Homeostasis includes regulation of such things as pH, water, glucose, pathogens, temperature, etc.
Disease -- any abnormal condition in an organism that interferes with its vital physiological processes, caused by pathogenic microorganisms, parasites, unfavorable environmental, genetic, or nutritional factors.
Infectious disease -- a disease that is caused by pathogenic microorganisms that have gained entrance to the body and then multiply and potentially transfer to other organisms.
Pathogen -- an infectious organism or particle that can cause disease in another organism. Pathogens may be lethal.
Immune system -- a defense system that works against invading pathogens and resulting diseases.
The immune system is a method of maintaining homeostasis in an organism. The immune system defends the body against invading pathogens. Point out that the immune system used to be considered a system found only in vertebrates and was not associated with other organisms. It is now recognized that many organisms including sea anemone, fruit flies, and plants also have immune systems.
In this unit, there will be constant references to the evolution of the immune system, cell communication, and homeostasis.
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3. Overview of the Immune System
Parts of the Immune System
1. Innate Immunity
Barrier Defenses
Cellular Response
Chemical Response
2. Adaptive Immunity
Cell Mediated Response
Humoral Response
Emphasize the following
Innate immunity is referred to as nonspecific immunity in the AP Biology Curriculum Framework (see 2.D.4.a). There are two parts to innate immunity including both chemical responses and cellular responses.
-Rapid response
-Cells involved have cell receptors that recognize PAMPS or signature molecules shared by pathogens
-Response involves a variety of phagocytes
-Response can also produce chemical response which includes complementary proteins, antimicrobial proteins
-Response can also include inflammatory response
Emphasize that this is an ancient response that seems to have its origin in cells before plants and animals diverged.
Adaptive Immunity was called specific immunity, and then later it was called by acquired immunity. It is referred to as the “specific immune response” in the AP Biology Curriculum Framework (see 2.D.4.b) It involves two responses, cell mediated response and humoral response. It also requires cells involved in innate immunity to activate adaptive immunity.
-Cell mediated response attacks infected cells
-Humoral response includes the production of antibodies that interacts with the pathogen itself.
-Much slower response
-Recognition of traits specific to particular pathogen, using a vast array of different cells (B cell and T cell lymphocytes) and receptors.

4. Immune System and Innate Immunity
The innate immune system provides the 1st line of defense by:
Activates variety of immune cells to produce molecules that stop the invading pathogens & its resulting disease
providing physical barriers to stop a pathogen
is immediate and utilized by many multicellular organisms.
Point out that most bacteria living on humans are harmless and can even be beneficial. There are approximately five pounds of bacteria living in or on the human body.
The innate immune system was once called the non-specific immune system and there has been an explosion of knowledge in this area.
Graphic
The human body has over 100 trillion bacteria living on it or within it. (~5 lbs. of bacteria living in or on the human body!)

5. Adaptive (Acquired) Immune System
In contrast, an adaptive immune system produces antibodies specific to a pathogen or foreign particle after the pathogen activates B- and T-lymphocytes.
is slower than the innate immune response and it may take days to become effective.
Present only in jawed vertebrates
Graphic
The adaptive immune system used to be called the specific immune system. (emphasis on “adaptive”)
The innate immune system is thought to be an ancient conserved biochemical pathway when compared to the adaptive immune system.
Ask the students what that last fact tells them. Good student answers will address the fact that the innate immune system is thought to constitute an evolutionarily older defense strategy, and is the dominant immune system found in plants, fungi, insects, and in primitive multicellular organisms. (Students may not know that last part!)

6. Evolution of the Immune System
Ancestral amoebas performed phagocytosis (the cellular ingestion & digestion of bacteria and other foreign substances) to obtain food.
It would be advantageous for these ancestral amoeba to be able to distinguish between self and non-self when ingesting other cells.
The interaction between receptors and signature molecules could provide this distinction mechanism.
Point out to students that amoebas and immune system phagocytes are very similar. They both move with pseudopods (students may or may not have this prior knowledge and be familiar with amoebas). Both of these cells utilize phagocytosis and destroy other cells.
The ancestor to the amoeba lived in a freshwater environment. Phagocytosis allowed it to ingest other cells and extract nutrients from them. If the ancestral amoeba could not distinguish between other amoeba cells and foreign cells (other than amoeba), it is possible that amoeba cells could have completely disappeared.
It was advantageous for amoebas to distinguish between self and non-self cells. The best way to do this is by way of receptors and signature molecules.
Signature molecules are identifying molecules that are unique to a particular group of organisms. For example, cellulose is a signature molecule for plants, chitin is a signature molecule for certain fungi, muramic acid or murein is a signature molecule for bacteria (not Archaea), and double-stranded (DS) RNA is a signature molecule for certain RNA viruses. This list is not exhaustive. Signature molecules would have allowed the amoeba to distinguish between another amoeba and a foreign cell or potential food.
Graphic-

7. Recall: General Cell Communication
Graphic-Campbell
Point out that the immune system is involved in cell communication. There are three features of cell communication as shown in the diagram.
Reception occurs between a membrane receptor and a signaling molecule or, in this case, a signature molecule on the pathogen.
Once reception occurs, the receptor activates a signal transduction pathway.
The final result of the signal transduction pathway is some sort of cellular response. In the case of ancestral amoeba, it is assumed that the response was phagocytosis. Explain to students how this mechanism could also be used by multicellular organisms to defend the body against pathogens.
Q: Propose a cell communication mechanism that ancestral amoeba may have used to distinguish between foreign cells and other amoeba cells.
A: The ancestral amoeba probably had several receptors for different signal or signature molecules of foreign cells. If a receptor was activated, it then engaged a transduction pathway that resulted in phagocytosis of the attached cell. If a cell did not attach, it may have been another amoeba and would be ignored.

8. Cell Communication and Immune System
Example of receptors and various signature molecules.
Explain how this part of the immune system is an example of cell communication.
List all the observations you can make about this diagram.
Graphic Campbell
Point out the following:
The receptor is unique and will attach only to signal molecules. The signal molecules or signature molecules for a group of pathogens are also called pathogen-associated molecular patterns (PAMPs).
For example only one receptor might be needed for bacteria because bacteria have cell walls made of murein or muramic acid. If a bacterium with the cell wall made of murein attaches to the receptor, it is recognized as a foreign object.
Once the PAMP attached to the receptor, then a certain transduction pathway was activated resulting in a response that would aid in eliminating the pathogen.
TLR stands for Toll-like-receptor. These are similar to the Toll receptor found in Drosophila. The Toll receptor was discovered by Christiane Nüsslein-Volhard of the Max Planck Institute in Tübingen in 1985 in looking at Drosophila larva. Her comment about an odd looking larva was “Das war ja toll” meaning “That was weird”. The gene responsible for the oddity was coined the Toll gene and the gene product was called the Toll receptor. While important in the development of larva, later it was discovered this receptor was important in the innate immune response.
Many proteins have been identified that are similar in structure and function to the Toll receptor and are hence called Toll-like-receptors or TLR.
For example:
TLR4 receptor for a lipopolysaccharide found in gram-negative bacteria
TLR5 receptor for protein flagellin found in bacteria
TLR3 receptor DS RNA found in certain RNA viruses
TLR9 receptor for unmethylated DNA found in DNA viruses and bacteria
These are all molecules that would NOT be found in the host organism and are foreign to the host organism.
Answer to the diagram explanation. The diagram is an example of cell communication. The parts are the following:
Stimulus-PAMP such as flagellin or ds RNA
Receptors-TLR receptors unique for a certain foreign PAMP
Transduction Pathway- promoting or aiding in an immune response such as the inflammatory response
Response-Inflammatory response
Observations may include
Receptors are proteins.
Receptors are found in the membrane.
Receptors are also found in the vesicles but inserted in the membrane.
Receptors activate a transduction pathway.
There are different type of stimuli and each one has a unique receptor.

9. Evolution and Immunity
Toll-like receptor
(TLR) pathways comparison for plants, invertebrates and vertebrates
There is DNA evidence that Toll pathway existed prior to the divergence of plants and animals. While the previous slide showed the inflammatory response was activated in that particular cell, there are various types of immune responses that can occur. For example, one transduction pathway can result in the activation of transcription factors that activate genes that synthesize “players” participating in the immune response.
Point out to the students that the fact that these pathways and receptors are similar to one another, suggests an evolutionary relationship between plants, invertebrates, and vertebrates.
Students need to know:
There are receptors, and these receptors attach to a PAMP (signature molecules found on the pathogen and not the host).
Once the PAMP is attached it activates some sort of transduction pathway.
The response of the transduction pathway is associated with aiding an immune response. For example, it may result in the production of transcription factors. The transcription factors will activate genes involved in an immune response.
They need to know this is considered to be an ancient pathway that has been conserved and passed down through time.
Differences exist due to the accumulation of various mutations. Accumulated mutations somehow enhanced the function of the proteins. Mutations that were detrimental were probably not passed on. Students do not need to know the actual names or pathways of an individual type of cell.
Students do not need to know the names of the proteins or pathways shown in the diagram.
Graphic-
List any similarities that you observe among the 3 pathways.
If this pathway was once in an ancestral cell, explain why the differences exist between the three organisms.

10. Innate Immunity (Nonspecific Immunity) and the
First Line of Defense
Innate Immunity (Nonspecific Immunity) and the
Innate Immunity-Activated immediately upon exposure to pathogen and is the same response for each exposure.
First line of Defense: Integument System-
Skin and mucous membranes provide a physical barrier to entry of pathogens. Skin contains keratin, a structural protein that helps form that barrier. Mucus helps trap pathogens.
Skin's fatty acids and secretion from tears, sweat and oil glands are toxic to bacteria.
Natural bacterial fauna can outcompete many pathogen.
Your are born with your Innate Immunity and it does not require exposure to the disease to activate it. First line of defense-This defense works to keep the pathogen out of the body.
Integumentary System-
Skin & mucous membranes line entire body (mucous membranes line every opening into the body) - skin contains keratin which is a structural protein that helps form a physical barrier to the entry of pathogens; Mucous membranes produce mucus that helps trap foreign particles. The numerous cell layers in both help provide a barrier, as well.
Skin's fatty acids and secretion from sweat and oil glands are toxic to bacteria. Some of the secretions contain lysozyme which can break down cell walls of many bacterial cells. Also the secretions keep the pH of the skin ranges from 3-5 which is too acidic for many bacteria.
Mucous membranes secrete mucous that traps and allows for the removal of invading pathogen
The skin also has a natural fauna of bacteria that can outcompete most pathogens.

11. Body Passages and Innate Immunity
Trachea lined with ciliated cells and cells that secrete mucus.
Esophagus leads to stomach with a pH of 1-2 (acidic) which kills most pathogens
Urinary tract has lower pH (again acidic) and is flushed with urine.
Tear ducts with lysozymes.
Reproductive tract also has a lower pH (acidic once more).
Body passages-
Trachea has mucus produced by the respiratory system. This mucus traps particles and the cilia sweep it out of the tube (to the back of the throat where it is swallowed into the stomach and destroyed by the acid). The orange cells produce mucus that that traps microorganisms that enter. The yellow cells are ciliated which beat in unison to expel mucus and trapped microorganisms upward to pharynx.
Esophagus leads to stomach with pH of 1-2 which kills most invading pathogens. No matter how hard you wash an apple, you still swallow thousands of microorganisms.
All openings into the body are lined with mucous producing membranes. SO anything that enters the human body has to either cross the skin or a mucous membrane.
The lower pH of the urinary and reproductive tract help prevent the entry of pathogens.

12. Second Line of Defense Phagocytes and the Chemicals Released
Second Line of Defense-Activation of phagocytes (leukocytes/white blood cells)
Made in the red bone marrow.
Found in connective tissue, tissue lining organs, lymph nodes and circulating in the blood.
Second Line of Defense-Activation of leukocytes which are phagocytes.
Terminology
Leukocytes-are white blood cells.
Two types:
Phagocytes- are white blood cells that phagocytize (engulf or “eat”) pathogens.
Lymphocytes-are white blood cells that are involved in the adaptive immune response. They are not phagocytes. T cells help activate B cells and kill infected body cells. B cells produce antibodies. Natural killer cells aid in disposing of infected cells.
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13. Plant Defenses
Plants, like animals, must defend against pathogens and herbivores with:
physical barriers
secondary metabolites
immune responses
Emphasize that plants, unlike animals, cannot escape potential consumers. Unlike many animals (echinoderms and flatworms are some notable exceptions), plants have the ability to regenerate or replace parts.
Ask students to suggest strategies for defense. Possible suggestions follow:
An epidermis with a waxy cuticle making it more difficult for bacteria and fungi to penetrate into the inner body of the plant. Thorns and spines that discourage herbivores from eating parts of a plant.
Secondary metabolites that can make herbivores ill or poison them.
An immune response that includes apoptosis (cell suicide) of infected cells (also called the hypersensitivity response) and release of chemical signals to protect the rest of the healthy plant.

14. Coevolution of Herbivores and Plants
Certain herbivores and plants have coevolved with one another.
Let students propose may have happened. Prod them along an evolutionary pathway…
While this metabolite may have been harmful at first, there may have been a butterfly with a mutation that allowed it to sequester the metabolite, break it down, and utilize the by-products.
Graphic-
This butterfly can breakdown the secondary metabolite produced by the passion vine and use a nitrogen by-product in protein metabolism.

15. Immunity and Invertebrates -- Physical Barriers
Examples of innate immunity in Drosophila:
First line of defense is the exoskeleton made of chitin.
Chitin also lines the digestive tract.
The enzyme lysozyme found in the gut breaks down the cell walls of bacteria.
Emphasize that having the gut lined with chitin confers a physical barrier to large pathogens like bacteria. Lysozyme is the enzyme that is found in tears, saliva, and milk. Lysozyme breaks down the cell walls of bacterial cells.
Hemocytes phagocytize microbes like macrophages and amoebas.
Graphic-

16. Innate Immunity
If the pathogen escapes the digestive tract, it will be in a fluid called hemolymph.
Moving throughout the hemolymph are hemocytes.
Some hemocytes can destroy pathogens by phagocytosis.
Emphasize:
Insects are invertebrates like mollusks and echinoderms. They also have an open circulatory system with fluid flowing through large cavities. The fluid is called hemolymph with cells (hemocytes) circulating through the cavities. These hemocytes have the ability to do phagocytosis. They engulf microbes as a part of the immune system.
Arthropods are the most successful animal phylum. They are found virtually in every niche. They are exposed to a great variety of pathogens. It is not surprising that invertebrates have an immune system to defend themselves.
Graphic Campbell

17. Toll Receptor The Toll receptor recognizes signature molecules.
This activates signal transduction pathways, often producing transcription factors.
These transcription factors activate genes needed to synthesize anti-microbial peptides for destruction or deactivation of pathogens.
Emphasize:
Over 10 Toll receptors have been identified in Drosphila. Each different TOLL binds with signature molecules (PAMPs) unique to a group of pathogens. This allows a few receptors to respond to a great number of pathogens. For example all Gram-negative bacteria or all fungi.
The response is immediate.
The response is not long lasting like the adaptive immune response.
Q: Ask students to identify structures or processes that confirm is an example of cell communication. A:
There is a signal (PAMP)
There is a receptor (Toll)
There is transduction pathway
There is a response (immune response)
Graphic

18. Evidence
These flies were engineered so that the immune cells expressed a green fluorescent protein when the innate immune system was activated.
Q: Why was it important to stab a fly with sterile needle?
A: It is used as a control to make sure that simply the act of stabbing the fly did NOT cause the innate immune response to be activated.
Graphic
The top fly was inoculated with bacteria and the one below was “stabbed” with a sterile needle (no injection of bacteria). The top fly’s immune system was activated while the bottom fly’s was not.

19. Natural Killer Cell (not a phagocyte)
Natural killer cells can detect infected cells and cancerous cells due to changes in plasma proteins of the cells.
They secrete chemicals into the infected cells and kill them or puncture the infected cell’s membrane.
Natural killer cells are leukocytes that roam the body contacting cells looking for infected cells by viruses and/or cancer cells. Eukaryotic cells are transformed when infected by viruses and cancer cells are also transformed by changes. These changes include changes in the surface proteins. Natural killer cell (in the foreground) is killing a cancer cell by punching holes in the plasma membrane. Water will rush in and lyse the cell. 19 19

20. Phagocytes and Chemical Response
Phagocytes can also activate chemical responses like the inflammatory response and the production of antimicrobial peptides. 20

21. Interferons
The transduction pathway activates antiviral genes to produce proteins that will protect the cell against viral infection. IMPORTANT: Interferon will not protect the infected cell but interferon protects neighboring cells from viral infection.
Interferon is used as a treatment for chronic viral hepatitis C and viral hepatitis B.
The term interferon comes from the action of the substance interfering with viral reproduction.
Graphic
Interferons are proteins made by virus-infected cells. They are secreted and transported to neighboring cells to prevent viral infection from the infected cell. 21 21

22. Histamine Release and Inflammatory Response
Histamine is released by mast cells and basophil cells which are attracted to an injury site. When the skin is penetrated, cells are ruptured releasing chemical signals to attract the mast and basophil cells. These cells release histamine.
This illustrates the inflammatory response that is most important. Explain the diagram and make sure that all the students understand the parts each cell is contributing to this process. 22 22

23. Inflammatory Response
Increases capillary permeability. The area becomes swollen, red, temperature increases from the increased blood flow.
Phagocytes leave the capillary bed because they are attracted histamine and other signals.
Phagocytes clean up pathogens and cell debris.
The four classic signs of inflammation are heat, redness, swelling and pain. Ask students to use the diagram to explain how/why each of these symptoms result, as well as the benefits of inflammation.
When the skin is penetrated, cells are ruptured. The ruptured cells release chemical signals to attract mast and basophil cells to the site. The mast and basophils then cells release histamine.
Histamine increases capillary permeability. The area becomes swollen as fluids leave the capillary beds to the injured area. Nerve endings become tender.
Phagocytes come to the injured area via the circulatory system. The phagocytes (first to arrive are neutrophils and then sometime later macrophages) leave the capillary beds to the injured area.
They clean up pathogens and cellular debris.
Some phagocytes die in cleaning up the site forming pus. 23 23

24. Homeostasis and Inflammatory Response
Inflammation continues as long as the triggers (pathogens) are present.
When phagocytes complete their job by removing the pathogens, macrophages begin to secrete substances that-
Suppress inflammation
Promote tissue repair
If the stimulus persists, then the inflammation continues. Continued inflammation is called chronic inflammation and is not normal. Chronic inflammation causes diseases such as asthma, Crohn’s disease, rheumatoid arthritis, atherosclerosis, diabetes and cancer.
Graphic

25. Fever Inflammatory response is often accompanied by fever.
Some cytokines stimulate the brain to make prostaglandins. These prostaglandins stimulate the hypothalamus to a new temperature set point. The signals the hypothalamus sends out then:
Constrict blood vessels in the skin
Contract skeletal muscles
Increase heart rate and respiration
Is fever good or bad?
Fever increases circulation and also increases enzyme activity and metabolism. Another benefit of fever is that some pathogens reproduce slower at a higher temperature.
If the temperature is too high, the body responds by sweating and opening up blood vessels in the skin. Temperatures above 105o F can cause serious damage to the brain.
Also point out that not all people are “average”. Ask students what the “average” human body temperature is. They should respond 98.6F or 37 C. HOWEVER it is not uncommon for someone’s healthy body temperature to be 97F which means a fever of 99 F is indeed troublesome for that individual!

26. Adaptive Immunity (Specific Immunity) Third Line of Defense
Develops after exposure to pathogens
Involves very specific response to pathogens
Much slower than innate immunity
Requires support of innate immunity to function
Two parts:
humoral immunity
cell mediated immunity
Updated Information:
There has been an explosion regarding emerging new information about the workings of the immune system. It is important that AP biology teachers keep current by obtaining new editions of university first year biology texts. Publishers will send you a “review copy” if you fill out their on-line form. Even the framework is outdated when it comes to certain terminology. Make your students aware of this and familiar with both the old and new terminology since AP test questions are often in development for two years and circulation on AP exams for far longer!
Outdated Terminology
Specific immunity or specific immune system is now referred to in all the new text books as adaptive immunity or the adaptive immune system. (Reece/Campbell, Raven and Johnson, Starr and Taggart, Hillis, & Solmon and Berg). The framework refers to the specific immune system rather than the adaptive immune system. Additionally, for a short while the specific immune system was called the acquired immune system. This was prior to the term adaptive immune system coming into our vocabulary.
Nonspecific immunity or nonspecific immune system is referred to in new text books as innate immunity or the innate immune system. (This was addressed in the second power point of this series.)
Virgin B and T cells are now called naïve B and T cells.
MHC receptors are now call T cell receptors.
Examine the EK 2.D.4.b and EK 2.D.4.b .1:
2.D.4.b
Mammals use specific immune responses triggered by natural or artificial agents that disrupt dynamic homeostasis.
Evidence of student learning is a demonstrated understanding of each of the following:
 1. The mammalian immune system includes two types of specific responses: cell mediated and humoral.
This might give one the impression that only mammals possess an adaptive immune system. This EK is misleading as the adaptive immune system (specific immune system,) so far, has been found in all jawed animals. Cartilage fish do have lymphoid tissue (primitive compared to mammals) and do synthesize T cells. Jawless vertebrates such a hagfish and lampreys do not have an adaptive immune system. 26 26

27. Lymphocytes—Specialized Cells
Adaptive Immunity
Lymphocytes—Specialized Cells
B cells- are synthesized and mature in the red bone marrow
T cells- are synthesize in bone marrow but mature in the thymus
Immature B and T cells are virtually indistinguishable.
There are two types of lymphocytes involved in the adaptive (specific) immune response, B cells and T cells. When immature, the two cells are indistinguishable. Both originate in the red bone marrow.
Naïve lymphocytes are those that have not been exposed to a matching antigen. Each lymphocyte is programmed to match a particular antigen to be activated. Until that match occurs and the lymphocyte is activated, it is termed a naive lymphocyte.
T cells mature in the thymus and have a large number of ribosomes. The thymus gland is located just above the heart. As an infant, the thymus is large but as time passes on, the thymus gland begins to shrink in size until adulthood. Adults retain their thymus but it is smaller in size than the thymus gland in infancy. There are different populations of T cells; including cytotoxic T cells, helper T cells, and memory T cells. T cells function in the cell-mediated response and are also important in the humoral response. (Humoral immunity is so named because it involves substances found in the humours, or body fluids.)
Different types of T cells
Naive T cells are those T cells that have not be activated or presented a matching antigen.
Helper T cells (TH) activate the B cells in the humoral response
Cytotoxic T cells (TC) destroy infected body cells
Memory T cells (TM) are long lived T cells that have been initiated to a particular pathogen and kept in reserve. They are easily activated if the pathogen invades once again.
Effector cells are lymphocytes that have been selected and transformed to “fight” a pathogen.
B cells mature in red bone marrow and have a large amount of rough E.R. They are important in the humoral response production of antibodies, which is why they need so much rough ER.
Types of B cells
Naïve B cells are B cells that have not been activated or presented a matching antigen
Plasma B cells are activated B cells that produce copious amounts of free floating antibodies.
Memory B cells are long lived B cells that have been initiated to a particular pathogen and are kept in reserve. They are easily activated if the pathogen invades once again.
The cell on the left is an immature lymphocyte. The middle cell is a mature B cell with extensive E.R. The cell on the right is a mature T cell with its extensive amount of ribosomes.
Graphic 27

28. Adaptive Immunity and Primary Lymphatic Tissue
All lymphocytes originate in the red bone marrow. T cells then migrate to, and mature in, the thymus.
B cells remain in the marrow to mature.
Lymphocytes, like the phagocytes, originate in the red bone marrow. They are descendants of lymphoid stem cells rather than the myloid stem cells that give rise to the red blood cells, platelets, and phagocytes. Refer back to the innate immune system information regarding the origin of cells of the immune system.
Graphic and Campbell 28 28

29. 4 Characteristics of Adaptive Immunity
Self/Nonself Recognition - T cells and B cells have the ability to recognize one’s own cells versus a pathogen (invader).
Specificity - Lymphocytes are tailored to combat specific antigens due to the great diversity of B cells and T cells.
Diversity - There are potentially billions of different antigen receptors on B cells and T cells that recognize billions of different antigens.
Memory - Immune system is capable of “remembering” a pathogen once exposed.
Emphasize that the memory characteristic will be discussed after going over the primary immune response of the cell mediated and humoral responses. Both cell mediated and humoral immunity have a “memory” to quickly respond to a second exposure to a certain pathogen.

30. Adaptive Immune System: Two Components
Adaptive Immune System (Specific Immune System): Cell Mediated Immunity
Adaptive Immune System: Two Components
Cell Mediated Immunity- Specialized T cells recognize and destroy infected body cells and cancer cells.
Humoral Immunity- Selected B cells produce copious amounts of antibodies to fight pathogens.
Graphic

31. The body cell is tagged as infected.
Cell Mediated Immunity- Specialized T cells Matching T Cells with Infected Cells
The body cell is tagged as infected.
Selected cytotoxic cell recognizes the infected body cell and attaches to the cell.
This body cell is identified as infected because of the MHC I is tagged with the bits and pieces of the pathogen. 31

32. Cytotoxic Cells Destroy Infected Cells
Once attached, the cytotoxic cell secretes perforin which makes pores in the membrane of the infected cell.
The cytotoxic cell also secretes granzymes which cause the infected cell to die.
Once the cytotoxic cell has completed its job, the cytotoxic cell can continue searching other infected cells.
Cytotoxic cells can also kill cancer cells because cancer cells change and produce new proteins. Some of these new proteins combine with MHC I proteins and appear on the surface of the cancer cell. Cytotoxic cells recognize these cells as foreign and destroy it. Every once in a while the cells will escape the cytotoxic-T-cell because the MHC I protein has also changed. There is no longer a dual match. T cells do not recognize the cancer cell as foreign. The cancer cells continue to replicate or metastasize.
The granzymes induce apoptosis once they enter the infected cell. 32

33. Cytotoxic Cells Destroy Infected Cells
This is another rendition of how a cytotoxic cell kills in infected cell. Below is a cytotoxic cell (orange) killing a cancer cell (purple) 33 33

34. Adaptive Immune System (Specific Immune System): Humoral Immunity
Selected B cells produce copious amounts of antibodies that interact with antigens found on pathogens.
Needs the support of helper T cells.
The graphic on the left is a naïve B cell and the one on a right is a transformed B cell or plasma cell producing antibodies.
Graphic 34

35. Adaptive Immune System: Humoral Immunity
An antigen is any material that stimulates selected B cells to produce copious amounts of antibodies.
Antigens include bacterial cell walls, viral parts, flagella, etc.
An epitope is the part of an antigen to which the antibody attaches. An antigen can have more than one epitope or type of epitope.
Point out that any one antigen can have a number of different epitopes to which different antibodies can attach. Epitopes are also called antigenic determinants. In the illustration, the antigen shown has three different epitopes or antigenic determinants.
Antigens can be proteins or carbohydrates but not lipids.
Point out the clumping ability of antibodies by possessing two receptor sites.
Graphic Campbell. 35

36. This illustrates how out of thousands of different naïve B cells, only the one with the correct receptor site is selected and cloned.
This process is sometimes called “clonal selection.” 36

37. Antibodies Can Inactivate Antigens
Antibodies (AB) are also called immunoglobulins (Igs). There are different classes of AB or Igs. (Students are not responsible for the different classes of AB or Igs).
AB or Igs can be isolated from the blood serum. Blood serum is the liquid that remains when all blood cells and blood clotting factors are removed from the blood. Serum contains water, electrolytes, nutrients, antibodies, and other non-clotting proteins.
How AB work:
Neutralization: AB will coat the epitopes so that the pathogen cannot interact with the receptor sites of cells. Also in certain cases the “tail” of the AB is constant and can attach to a receptor site on a macrophage causing the macrophage to literally roll over and engulf the pathogen. This process is called opsonization (loosely translates as “make tasty”) and is illustrated on slide 13.
Agglutination: AB bind to several AG clumping them together so phagocytes can devour them.
Precipitation: AB will attach to soluble AG so that it will precipitate out and can be easily engulfed (phagocytosis).
Certain interaction with AB and AG trigger complement system, the complement proteins cause holes in invading cells, water rushes in, and the cell bursts.
Graphic Campbell 37 37

38. This is a summary of the humoral response.
The first exposure to a specific antigen represents the primary immune response
During this time, effector B cells called plasma cells are generated, and T cells are activated to their effector forms.
Effector cells with regard to the immune system are those B and T cells that have been activated and are in the process of defending the body from pathogens. Effector cells include plasma B cells, activated helper T cells, cytotoxic T cells. They do not include naïve B and T cells or memory B and T cells.
Memory B and T cells are made and stored in lymphatic tissue during the primary immune response.
A subsequent exposure to that same antigen activates a secondary immune response.
Graphic Campbell 38 38

39. Secondary Immune Response
Memory B cells and T cells are selected for when exposure to a subsequent pathogen occurs and the memory cells are a match for the antigen.
Memory B cells and T cells quickly reproduce, making plasma B cells, helper T cells and cytotoxic T cells (effector cells).
Plasma B cells begin to make AB and cytotoxic T cells begin to destroy infected cells. 39

40. Secondary Immune Response
Memory cells live for many years. If there is a subsequent exposure to the AG, the B and T memory cells are selected for and begin to synthesize plasma B cells, cytotoxic T cells, and helper T cells.
The graph shows that it may take two weeks from the initial exposure for plasma cells to be at their maximum production level producing AB.
Look at the response by inoculating the person with a second antigen. This demonstrates that the exaggerated response to the second exposure of antigen A is due that the fact that it is not due second first time exposure to an antigen.
Upon subsequent exposure though it only take two days to be at the same AB production level that it took the first exposure two weeks to attain.
In only seven days the number of antibodies in the blood stream is 100 times the amount produced by the primary response.
This is because of rapid activation memory cells B and T cells. 40