1. 6.3 and 11.1- Defense against Disease

2. Defense Against Infectious Disease
Essential Idea: The human body has structures and processes that resist the continuous threat of invasion by pathogens.
6.3
Defense Against Infectious Disease
Understandings:
The skin and mucous membranes form a primary defense against pathogens that cause infectious disease
Cuts in the skin are sealed by blood clotting
Clotting factors are released from platelets
The cascade results in the rapid conversion of fibrinogen to fibrin by thrombin
Ingestion of pathogens by phagocytic white blood cells gives non-specific immunity to diseases
Production of antibodies by lymphocytes in response to particular pathogens gives specific immunity
Antibiotics block processes that occur in prokaryotic cells but not in eukaryotic cells
Viruses lack a metabolism and cannot therefore by treated with antibiotics. Some strains of bacteria have evolved with genes confer resistance to antibiotics and some strains of bacteria have multiple resistances
Applications:
Causes and consequences of blood clot formations in coronary arteries
Florey and Chain’s experiments to test penicillin on bacterial infections in time
Effects of HIV on the immune system and methods of transmission

3. Antibody production and vaccination
Essential Idea: Immunity is based on recognition of self and destruction of foreign material.
11.1
Antibody production and vaccination
Understandings:
Every organism has unique molecules on the surface of its cells.
Pathogens can be species-specific although others can cross species barriers.
B lymphocytes are activated by T lymphocytes in mammals.
Activated B cells multiply to form clones of plasma cells and memory cells.
Plasma cells secrete antibodies.
Antibodies aid the destruction of pathogens.
White cells release histamine in response to allergens.
Histamines cause allergic symptoms.
Immunity depends upon the persistence of memory cells.
Vaccines contain antigens that trigger immunity but do not cause the disease.
Fusion of a tumour cell with an antibody-producing plasma cell creates a hybridoma cell.
Monoclonal antibodies are produced by hybridoma cells.
Application:
Smallpox was the first infectious disease of humans to have been eradicated by vaccination.
Monoclonal antibodies to HCG are used in pregnancy test kits.
Antigens on the surface of red blood cells stimulate antibody production in a person with a different blood group.
Skills:
Analysis of epidemiological data related to vaccination programmes.

4. Pathogens
Any living organism or virus that is capable of causing a disease is called a pathogen
Pathogens include:
Viruses
Bacteria
Protozoa
Fungi
Worms

5. Pathogens
Pathogens can be species-specific although others can cross species barriers.
Pathogens have a unique host range (species in which they an cause disease)
Ex. Only humans are susceptible to syphilis, gonorrhea, and measles
Outline the specificity of pathogens.

6. Pathogens
Some pathogens can infect a variety of host species; can cross species barriers
Zoonoses are diseases of other animals that can be transmitted to humans (ex. Rabies)
Outline the specificity of pathogens.

7. Pathogens
A protein to protein match must occur for a cell to recognize another as a host
Pathogen recognizes receptor proteins on host cells
Some of these are even cell-type specific
Ex. HIV only enters and infects white blood cells, the flu virus only infects respiratory cells,
Outline the specificity of pathogens.

8. Self vs. Non-Self
Your immune system is based on recognition of self and destruction of non-self foreign material
Each of your body cells contains the same genetic information and have a common set of cell membrane proteins
Some immune cells are capable of recognizing that set of proteins and consider any cell with those proteins to be “self”
A virus, bacterium, fungus, or even a transplanted organ has different proteins and thus is recognized as “not-self”
Not-self molecules are called “antigens”
Antigens stimulate an immune response
All pathogens have unique antigens
Antigen = antibody generating

9. Self vs. Non-Self RBCs may present antigens
Transfusion of wrong blood type causes an immune response that results in agglutination
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10. Non-Specific immunity (Innate)
Doesn’t matter what the pathogen is or whether the body has encountered the pathogen before

11. Non-specific immunity (Innate)
Barrier defenses
Act as a “wall” to prevent pathogens from infecting the body
Skin - as long as our skin is intact, we are protected from most pathogens entering living tissues

12. Non-Specific immunity (Innate)
Mucous Membranes
Line respiratory and digestive tracts as they are exposed to the outside environment
Cells of mucus membrane produce and secrete a lining of sticky mucus to trap incoming pathogens
Many lined with cilia – move trapped pathogens out of places like your trachea

13. Non-Specific immunity (Innate)
Many barrier defenses also secrete substances to prevent infection
Lysozymes – enzymes in tears that break down bacterial cell walls
Stomach acid – low pH kills many pathogens that may be in your food/drink

14. Non-Specific immunity (Innate)
Inflammatory Response
Triggered by tissue damage
White cells release histamine which triggers dilation of nearby capillaries to help deliver clotting agents and phagocytes to the area and causes fever and increased production of WBCs

15. Allergies
Inflammatory response occurs in response to non- threatening foreign substances (allergens)
Usually localized, but in extreme cases cause the response throughout the body (anaphylactic shock)
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16. Non-Specific immunity (Innate)
Phagocytic white blood cells
Recognize non-self (non-specific), engulf and destroy
All phagocytes typically contain many lysosome organelles in order to help chemically digest whatever has been engulfed
Macrophages are the most common type

18. Blood clotting
Cuts in the skin are sealed by blood clotting to prevent blood loss and prevent pathogens from entering the body
Circulating in the blood are platelets and molecules called plasma proteins
2 of these plasma proteins, prothrombin and fibrinogen are inactive until bleeding occurs

19. Blood clotting
Platelets are formed in the bone marrow when very large blood cells are broken down into fragments
Platelets do not have a nucleus and only have a life span of 8 – 10 days

20. Blood clotting When a small blood vessel is damaged:
The damaged cells of the blood vessel release chemicals that stimulate platelets to adhere to the damaged area
Then other platelets begin adhering to those platelets
This begins to form a plug for damaged area
To strengthen the plug, the damaged tissue and platelets release chemicals called clotting factors which convert prothrombin into thrombin

21. Blood clotting
Thrombin is an active enzyme which catalyzes the conversion of the soluble fibrinogen into relatively insoluble fibrin
The appropriately named fibrin is a fibrous protein which forms a mesh-like network that helps to stabilize the platelet plug
More and more cellular debris becomes trapped in the fibrin mesh and soon a stable clot has formed preventing both further blood loss and entry of pathogens

23. Blood clotting
Problems can arise in patients with Coronary Heart Disease when clotting occurs in the coronary arteries
Clots form, blocking the flow of blood in the coronary arteries, depriving the hear muscle of oxygen, killing the cells of the heart

24. Specific immunity (Adaptive)
The adaptive immune system is coordinated by lymphocytes, a class of leukocyte (white blood cells), and results in the production of antibodies.
Antibodies are protein molecules that we produce in response to a specific type of antigen
Each antibody is a protein that is Y shaped. At the end of each of the forks of the Y is a binding site where the antibody attaches itself to an antigen

25. Specific immunity (Adaptive)
Because the antigen is a protein on the surface of a pathogen, the antibody thus becomes attached to the pathogen
Most pathogens have several different antigens on their surface and therefore may trigger the production of many different types of antibody
Even though each type of antibody is different and specific for just one type of antigen, antibodies as a group of molecules are amazingly similar to each other

26. Specific immunity (Adaptive)

28. Specific immunity (Adaptive)
The leucocytes that produce antibodies are called B lymphocytes or B cells
Each person has many different type of B lymphocytes which produce a specific antibody
Gene regulation and alternative splicing allow millions of different antibodies to be made

29. Specific immunity (Adaptive)
Each type of B lymphocyte or B cell is capable of synthesizing and secreting a specific antibody which binds to a specific antigen
The problem is that you cannot have enough of each type of B cell for the amount of antibody secretion that may be needed at various times
Leucocytes represent 1% of all the cells in your bloodstream, so no one type of B lymphocyte is found in high numbers
Your body has cellular communication methods which lead to the cloning of the appropriate B cell type to synthesize and secrete the required antibody type to combat a specific antigen when needed

30. Immune Response
The first type of leukocyte to encounter a pathogen is usually a macrophage, which will phagocytize the pathogen (this is non-specific)
The macrophage will partially digest the pathogen, and then display pieces of the pathogen on its cell membrane – this is called “antigen presentation”

31. Immune Response
The macrophage presents the antigen to another type of lymphocyte called a Helper T cell
Helper T cells recognize the antigen and are “activated”

32. Immune Response
Helper T cells in turn activate the proper B cells that can make antibodies to that antigen
An activated B cell will undergo mitosis (make clones of itself = proliferation)
These clones will differentiate into two type of cells
Plasma cells secrete antibodies in large quantities
Memory B cells are long lasting cells which will circulate in the blood stream waiting for subsequent infections by the same pathogen

34. Immunity Primary – first exposure to an antigen
Secondary – same antigen encountered again later, faster and greater
Starts with memory B cells
Immunity is dependent upon the persistence of memory cells

35. Vaccines
Expose body to antigens so that memory cells are made without causing disease

36. Vaccines Several Forms
Live unattenuated (expose to actual disease – rare, ex. Use cowpox to prevent smallpox)
Live attenuated – weakened/altered (ex. MMR, chicken pox)
Killed/inactivated – need boosters (ex. Cholera, pertussis)

37. Vaccines
Smallpox was the first infectious disease of humans to have been eradicated by vaccination
Discovered by Edward Jenner – observed that milkmaids did not get smallpox
Took cowpox puss from an infected milkmaid and gave it to an 8 year old boy – boy did not get sick when exposed to smallpox
Last known case occurred in Somalia in 1977, declared eradicated by the WHO in 1980

39. Vaccines
Herd Immunity - If most of the people in a community have been immunized and are protected from an infectious agent, the chance of a susceptible (i.e. unimmunized) individual contacting an infected individual is so low that the susceptible person is not likely to become infected.

41. VACCINES ARE SAFE AND THEY WORK!!!

43. Antibiotics
Medications that block cellular processes in prokaryotic cells but not eukaryotic cells
DNA replication, transcription, translation, ribosome function and cell wall formation
Ineffective against viruses because they do not have a metabolism (no processes to block) and they utilize our cells’ metabolism to reproduce so anything to inhibit them would also harm our cells
Can block protein synthesis in bacteria but not eukaryotes, or inhibit new cell wall production blocking reproduction

44. Antibiotics First discovered by Alexander Fleming in 1929
Studying Staphylocoocus bacteria
Noticed some older samples had mold (specifically a fungus called Penicillium notatum) growing on them that killed the surrounding bacteria
Purified a substance from the mold and named it penicillin
Penicillin did not harm human cells
Fungi and bacteria compete for resources, so fungi release substances to kill bacteria to eliminate competition for food

45. Antibiotics Florey and Chain did further experiments with penicillin
Isolated it in a stable form
Were working fast to get medicine to troops in WWII – would not meet today’s standards
Broad-spectrum antibiotics – work on a wide range of bacterial infections
Over 4000 antibiotics found, only 50 shown to be safe for human use

46. Antibiotic Resistance
The overuse and misuse of antibiotics has led to strains of bacteria that are resistant to (cannot be killed by) some antibiotics
Driven by natural selection
Remember – mutations are random
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48. Antibiotic Resistance
Especially a problem if a strain of bacteria develops resistance to multiple types of antibiotics
MRSA - methicillin-resistant Staphylococcus aureus
MDR-TB - multidrug-resistant tuberculosis
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49. HIV
Human immunodeficiency virus (HIV) is a virus that eventually results in the set of symptoms collectively called acquired immune deficiency syndrome (AIDS)
In the early stages of infection, the body is capable of making antibodies to the virus – if those antibodies are detected in the blood, that indicated an individual is HIV positive
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50. HIV HIV specifically recognizes and infects Helper T cells
Without Helper T cells, B cells are not activated and antibodies are not produced
Results in death from secondary infections, many of which would not make a healthy individual sick
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51. HIV HIV is transmitted from person to person by body fluids
This includes body fluid exchanges during sex and ill-advised practice of reusing unsterile syringe needles for legal or illegal drug injections
More than a few people became HIV positive from blood transfusions
Today, at least in countries with reasonable medical care, blood is routinely tested for the presence of blood-born diseases and immediately destroyed if pathogens are found
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52. Polyclonal Antibodies
A primary immune response by an organism is called polyclonal response because pathogens have multiple antigens (poly)
Each of the protein types can cause an immune response and thus several different kinds of antibodies are produced and several different kinds of memory cells remain after infection
Once a polyclonal immune response has occurred, it is very difficult to separate the different kinds of antibody that have been produced
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53. Monoclonal Antibodies
“Pure” antibodies (of only one type)
Must be produced in a lab in a multistep process
Injection of an antigen into a lab animal such as a mouse
Animal given time to go through a primary immune response (polyclonal)
Spleen of lab animal is ‘harvested’ in order to gain access to B cells making antibodies to the antigen
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54. Monoclonal Antibodies
Two problems exist at this point of procedure:
Keeping B cell types alive for an extended period of time
Identification of the B cell type that produces the antibody which recognized the desired antigen
B cells are kept alive by fusing them with cancerous cells
When grown together, a few of the cells fuse together and become cell called hybridoma
Have characteristics of both cells
Produce antibodies of particular type and are long lived (cells are virtually immortal when kept in suitable environment)
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55. Monoclonal Antibodies
Use ELISA (enzyme-linked immunosorbent assay) to identify which containers hold a pure colony of B cells which are producing the desired antibody
Result is a population of hybridoma cells that produce monoclonal antibodies and are basically immortal
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56. Monoclonal Antibodies
Monoclonal antibodies have a variety of diagnostic uses, including pregnancy test kits
Early in pregnancy, the embryo produces a hormone called human chorionic gonadotrophin (HCG)
HCG from the embryo can be found in the blood and urine of the mother
Hybridoma cells can be used to create anti-HCG antibodies which are chemically bonded to an enzyme which catalyzes a color change when the antibody encounters HCG molecules
ONLY embryos produce HCG

57. Monoclonal Antibodies
There is an increasing use of monoclonal antibodies for medical treatment as well as for diagnosis
When body cells become cancerous, they begin to produce cancer cell-specific antigens on their cell membranes
One possible treatment for cancer is to produce monoclonal antibodies that target the cancer-cell antigens
The monoclonal antibody could be chemically modified to carry with it a toxin specific for this type of cancer cell
Advantage would be to target the caner cell directly