1. Defense against infectious disease
Topics 6.3 and 11.1

2. Assessment Statements
6.3.1 Define pathogen.
6.3.2 Explain why antibiotics are effective against bacteria but not against viruses.
6.3.3 Outline the role of skin and mucous membranes in defence against pathogens.
6.3.4 Outline how phagocytic leucocytes ingest pathogens in the blood and in body tissues.
6.3.5 Distinguish between antigens and antibodies.
6.3.6 Explain antibody production.
6.3.7 Outline the effects of HIV on the immune system.
6.3.8 Discuss the cause, transmission and social implications of AIDS.

3. Pathogen
Any living organism or virus that is capable of causing a disease
Include:
Viruses
Bacteria
Protozoa
Fungi
Worms
Exposure to vast majority does not result in disease
Why not?

4. Why are antibiotics effective against bacteria but not against viruses?
Bacteria background
Prokaryotic
Different kind of protein synthesis
Cell wall
Antibiotics are chemicals which take advantage of differences between prokaryotic and eukaryotic cells
Categories:
Selectively blocks protein synthesis
Inhibits the production of a new cell wall, thus blocking their ability to grow and divide
Virus background
Make use of our body cells’ metabolism
Any chemical that could inhibit this would also damage our cells

5. Role of skin Barrier to infection Two layers
Dermis (sweat glands, capillaries, sensory receptors and dermal cells which give structure and strength to the skin)
Epidermis (constantly being replaced as underlying dermal cells dies and are moved upwards)
As long as are skin stays intact, we are protected from most pathogens entering living tissue

6. Role of stomach acid
Kills most of ingested particles

7. Role of mucus Area with mucous membrane What it is and does Trachea
Tube which carries air to and from the lungs
Nasal passages
Tubes which allow air to enter the nose and then the trachea
Urethra
Tube which carries urine from bladder to the outside
Vagina
Reproductive tract leading from uterus to the outside

8. Role of phagocytic leukocytes
A.k.a. white blood cells
Found in bloodstream
Macrophage
Type which gets involved early in the process of fighting off a pathogen
Large wbcs that are able to change their cellular shape to surround an invader and take it through the process of phagocytosis
Often referred to as amoeboid motion
Can squeeze in and out of small blood vessels

9. When a macrophage meets a cell
Recognizes ‘self’ cells from ‘not-self’
Recognition based on the protein molecules that make up part of the surface of all cells and viruses
If the proteins are ‘self’, then the cell is left alone
If the proteins are ‘not-self’, the macrophage engulfs the invader by phagocytosis
Lysosomes within the macrophage chemically digest whatever has been engulfed
Type of response is non-specific b/c the identity of the pathogen has not been determined at this point

10. Antibodies
Protein molecules that we produce in response to a specific type of pathogen
Each type of antibody is different
Each pathogen is made up of either cells with cell membranes or, in the case of a virus, a protein coat
Cellular invaders have proteins called antigens that are embedded into their outer surface
Most pathogens have several different antigens on their surface and therefore may trigger the production of many different types of antibodies

11. Each antibody is a protein that is Y shaped
At the end of each of the forks of the Y is a binding site
The binding site is where the antibody attaches itself to an antigen
b/c the antigen is a protein on the surface of a pathogen, the antibody thus becomes attached to the pathogen

13. Typical immune response
A specific antigen type is identified (e.g. a particular cold virus)
A specific B lymphocyte (leukocytes that produce antibodies) is identified that can produce an antibody which will bind to the antigen.
The B lymphocyte and several identical B lymphocytes clone themselves to rapidly increase the number of the same type of B lymphocytes
Newly formed ‘army’ begins antibody production

14. Video
Newly released antibodies circulate in the bloodstream and eventually find their antigen match
Using various mechanisms, the antibodies help eliminate the pathogen
bind themselves directly to the pathogen, which cuts off the pathogen's ties with other cells in the body
bind and cover the pathogen so phagocytic cells can recognize it
Some of the cloned antibody-producing lymphocytes remain in the bloodstream and give immunity from a second infection by the same pathogen. They are called memory cells.

15. How HIV damages the immune system
Human immunodeficiency virus (HIV) is the virus that eventually results in the set of symptoms collectively called acquired immune deficiency syndrome (AIDS)
All viruses must find a type of cell in the body that matches their own proteins in a complementary way
Helper-T cell is a communicator cell that HIV infects
HIV has a latency period that may be several years long

16. Helper-T cells communicate which cells need to undergo cloning process and begin antibody production
When the helper-T cells begin to die, the communication ceases and antibodies do not get produced
At this stage, the individual no longer fights off pathogens as they did before and the symptoms of AIDS start to appear

17. Issues related to AIDS
Hard to find a vaccine or cure b/c it ‘hides away’ for years
It is waiting for some chemical signal to become active
It also mutates very quickly
The body’s immune responses or vaccines may not even recognize HIV after it has mutated several times
Initially it was difficult to get funding due to the association of HIV with sexual activity and drug abuse

18. HIV is transmitted person to person by body fluids
Enzyme-linked immunosorbent assays (ELISA) are often used to detect the presence or absence of a particular protein
Newly infected people will initially produce antibodies against HIV
ELISA detects them
HIV is transmitted person to person by body fluids
Blood is now routinely tested for the presence of blood-borne diseases and immediately destroyed if pathogens are found

19. Originally labeled as a disease affecting homosexuals and drug abusers
Now know that it is rapidly spreading by heterosexual encounters
Those diagnosed may be discriminated
The Ray Brothers
Until a cure is found, we continue to lengthen the life-span of those infected and to educate people on how to decrease their risk of exposure to HIV
Vaccine trial

20. Defence against infectious disease
Topic 11.1

21. Assessment Statements
Describe the process of blood clotting.
Outline the principle of challenge and response, clonal selection and memory cells as the basis of immunity.
Define active and passive immunity.
Explain antibody production.
Describe the production of monoclonal antibodies and their use in diagnosis and in treatment.
Explain the principle of vaccination.
Discuss the benefits and dangers of vaccination.

22. Why does blood clot?
When small blood vessels get broken, blood escapes from the closed circulatory system
Our bodies create a clot which ‘seals’ the damaged blood vessels preventing excessive blood loss and helping to prevent pathogens from entering the body
Prothrombin and fibrinogen are plasma proteins which circulate in the blood
Platelets are cell fragments which also circulate

23. Blood clotting sequence
Blood vessel is damaged
Damaged cells release chemicals which stimulate platelets to adhere to the damaged area
Other platelets begin adhering to those platelets
To strengthen the plug, the damaged tissue and platelets release chemicals called clotting factors which convert prothrombin into thrombin
Thrombin is an active enzyme which catalyses the conversion of soluble fibrinogen into the relatively insoluble fibrin
Fibrin is a fibrous protein which forms a mesh-like network that helps to stabilize the platelet plug
More cellular debris gets trapped in the fibrin mesh and soon a stable clot has formed preventing both further blood loss and entry of pathogens

25. Hemophilia Inherited blood disorder which is sex-linked Most are male
People born with hemophilia have little or no clotting factor

26. Antibody production
The bloodstream contains many different types of B lymphocytes or B cells
Each type is capable of synthesizing and secreting a specific antibody which binds to a specific antigen
Problem: there isn’t enough room to have enough of each type of B cell for the amount of antibody secretion that may be needed at various times
Leukocytes represent roughly 1% of all the cells in your bloodstream
Cellular communication methods lead the cloning of the appropriate B cell type for antibody synthesis when needed

27. Macrophage encounters a foreign antigen and engulfs the possible pathogen by phagocytosis
Antigens of the invader are displayed on the cell membrane of the macrophage – this is known as antigen presentation
Leukocytes known as helper-T cells chemically recognize the antigen being presented and become activated
Helper-T cells chemically communicate with the specific B cell type (which has also come in contact with the antigens) that is able to produce the antibody needed
animation

28. Cell cloning
When a helper-T cell activates a specific B cell, the activated B cell type begins a series of cell division known as cell cloning
Types
Antibody-secreting plasma cells – secrete antibodies immediately and help to fight off the primary infection
Memory cells – do no secrete antibodies during the primary infection, but are long-lived cells which remain circulating in the bloodstream waiting for a subsequent infection

29. Principles of true immunity
Challenge and response
Immune system challenged by an antigen during 1st infection in order to develop an immunity
Macrophages, helper-T cells, B cells
Clonal selection
Identification of plasma B cells
Multiple cell divisions to build up #s of same cell
Memory cells
Provide long-term immunity

30. Types of immunity Active Passive
Always leads to the production of memory cells
Provides long-term immunity
Passive
When an organism acquires antibodies which were produced in another organism
Only the organism which produces the antibodies has the memory cells
Mother to fetus through placenta
From mother’s colostrum
Injection of antibodies in antisera (antivenoms produced for treatment of poisonous snake and spider bites)

31. Polyclonal antibodies
Primary immune response
Pathogen is being recognized as many antigens and not just one
Each of the protein types can cause an immune response and thus several different kinds of plasma B cells undergo clonal selection, so several different kinds of antibodies are produced and several different kinds of memory cells remain after the infection
It is difficult to separate the different kinds of antibody that have been produced

32. Monoclonal antibodies
Researchers have developed a clever and unique procedure for forming many antibodies, all of the same type
Procedure:
Inject an antigen into a laboratory animal
Animal is given time to go through a primary immune response
Response is polyclonal
Spleen is harvested to gain access to many blood cells
B cells kept alive by fusing them with cancerous (myeloma) cells
When B cells and myeloma cells are grown together a few of the cells fuse together and become a cell called a hybridoma

33. These hybrid cells produce antibodies of a particular type and they are very long lived (as are all cancer cells)
Individual hybridomas transferred and cultured in separate containers
Each container is tested for the presence of a particular antibody by use of the ELISA test
Enzyme-linked immunosorbent assay test identifies which containers hold a pure colony of B cells which are producing the type of antibody desired
These cells are cultured for a very long period of time
animation

35. Uses of monoclonal antibodies
Diagnosis
Pregnancy testing which detects human chorionic gonadotrophin (HCG)
Anti-HCG antibodies are chemically bonded to an enzyme which catalyses a color change when the antibody encounters HCG molecules
Treatment
Monoclonal antibodies that target the cancer-cell antigens
Antibody could be chemically modified to carry with it a toxin specific for this type of cancer
Antibody could contain a radioisotope for pin-point radiation therapy

36. How does a vaccine result in immunity?
One cannot be immune to a pathogen before being exposed to it at least once
For many diseases, vaccines have been developed that act as the first exposure to the pathogen
Vaccine is developed by weakening a pathogen and then injecting the pathogen into the body
Methods:
Selecting a weak strain
Heating the pathogen
Chemical treatment of pathogen
Infection is not prevented, but the secondary immune response is quicker and more intense than the primary response

37. Benefits and dangers of vaccination
Possible total elimination of the disease (ex. Smallpox)
Prior to 1999, many vaccines contained thimerosal, a mercury-based preservative. Mercury has been shown to be a neurotoxin.
Decrease in spread of epidemics and pandemics
Perception exists that multiple vaccines given to children in a relatively short period of time may ‘overload’ their immune system
Preventative medicine is typically the most cost-effective approach to healthcare
Anecdotal evidence suggested that MMR vaccine may have a link the onset of autism (no support from clinical studies)
Each vaccinated individual benefits b/c the full symptoms of the disease do not have to be experienced in order to gain immunity
Cases have been reported of vaccines leading to allergic reactions and autoimmune responses