1. IMMUNITY

2. Immunity Immunity: ability of an organism to resist disease.
Homeostasis: the tendency of the body to maintain stability while continually adjusting to conditions that are optimal for survival.
Homeostatic mechanisms are necessary for the body to regain its balance when disease or injury occurs and to maintain that balance if it is to remain healthy.
Antigen: any substance that elicits an immune response.
Antibodies: made in response to specific antigens; can inactivate the antigen that triggered the antibody formation.

3. The Body Fights Back: 2 Ways
Surface Barriers Keep Intruders Out
Prevents entry of antigens inside our body
Skin, Mucosa
Response Against Antigens:
Cell Mediated Immunity: Cell activates itself to defend against the attack
Humoral Immunity: Cell produces antibodies carried in blood to combat the intrusion
Slide 4 Picture1: (bottom)
ANTIBODY RESPONSE IMAGE: in the antibody (or humoral) arm of the the acquired immune response, the destruction of invaders is done by antibodies (proteins called immunolglobulins), shown as brick red "Y" shaped molecules at right of picture. Invading microorganisms are shown at top as golden ovoids. They are engulfed (phagocytosed) by a macrophage (green cell at top). The macrophage then presents antigens to a (purple) Helper T-Cell which in turn activates a B-Cell causing it to divide and differentiate into Plasma Cells (large bluish cells at lower left). Plasma cells have a great deal of rough endoplasmic reticulum and are devoted to protein synthesis (of antibodies). The antibodies that are released lock onto their corresponding antigens and lead to the inactivation or destruction of the invader. A dendritic cell is shown at upper left.
Picture 2: (top)
CELL MEDIATED IMAGE: in the cellular immune response, the destruction of infected or altered cells is done by Cytotoxix T-Cells, shown as purple spikey cells arcing at left of picture. The cell targeted for destruction is shown as a large green sphere at the bottom of the picture. This cell crumples and disintegrates and the cytotoxic cell leaves to attack further target cells. Antigen presentation is shown at the top of the picture where a green macrophage presents viral antigens to a helper T-Cell. The Helper T-Cell then releases cytokines that activate the cytotoxic T-Cells. A dendritic cell is shown at upper left.

4. Declaring War on Invaders
The Antigen The Enemy Invader
Usually a bacteria or virus
Comes in many different forms and attacks the body

5. The Warriors The Macrophage Body's Radar
Type of cell normally present in the blood
Detects the enemy

6. The Warriors The T-Helper Cell Communication Link
Communication Link Between the body's macrophages and B-cells
A subtype of lymphocyte that activates macrophages and B cells. Does not directly inactivate antigens.
They are called T cells because they original in the thymus (but later migrate to all lymph nodes. In children, the thymus is a huge gland in the neck; later is shrinks. In HIV infections, towards the end of infection, T helper cells become inactive, leading to a breakdown of immunity in general, leading to AIDS (acquired immunity deficiency syndrome).

7. T-Cells in Action
Virus
Virus
Virus
When a macrophage ingests a viral particle (blue blobs), it presents the antigen (green arrow) of the virus on its outer surface. Then, a T-cell with the correct t-cell receptor (yellow y-shaped structure) can bind to the viral antigen on the surface of the macrophage. This activates the T-cell. The activated T-cell can then assist in the immune response.

8. The Warriors The B-Cell The War Factory
Produces antibodies custom tailored for the type of enemy antigen

9. B-Cells in Action
Virus

10. The Warriors Antibodies Antigen Busters Complement Support Troops
Designed to seek and destroy the specific enemy antigen
Complement Support Troops
Assists the antibodies to neutralize the enemy antigen
Complement is actually a system of about 20 blood-borne proteins that can be recruited during an immune response to help inactivate antigens. The system is not specific for specific antigens, but it “complements” the action of specific antibodies.

11. Humoral Immunity Structure of antibodies (Y-shaped proteins)
Since antibodies circulate through the humours (body fluids), the protection afforded by B cells is called humoral immunity.
Structure of antibodies (Y-shaped proteins)
The variable portion is created to be a specific match to a specific antigen. The rest of the protein is non-active, just serving to “carry” the active portion of the molecule.

12. So what does an antibody do?
Binds to molecules (antigens) on the surface of invading organism.
Inactivates or renders the microorganism susceptible to destruction by the immune system.

13. The War
Immune Complex: When antibodies and complement attack the antigen, an immune complex is formed.
Polymorph : Disposal Unit. Detects the immune complexes and removes them
T-Suppressor Cell: Another Communication Link Signals to the B-cell to stop making antibodies once the antigen has been destroyed

14. Antigens: chemicals (usually proteins) that trigger an immune response
Antigens: chemicals (usually proteins) that trigger an immune response. Sources of antigens include infections agents and other sources (such as food, plant pollen, etc.) that expose the body to proteins that are different from (foreign) to those in the body. The animal and human body react to foreign substances (antigens such as viruses and bacteria) with two kinds of response. The humoral (body fluid) response is for B cell lymphocytes to make antibodies. The second response type is for T-cell lymphocytes to release chemicals such as “cytokines” that indirectly kill cells bearing foreign antigens.

15. Review 1 What is the enemy called that invades the cell?
What keeps intruders out?
What are the two kinds of immunity?
Pathogen, the portion of the pathogen which causes an immune response is known as an antigen
Surface Barriers, like skin
Cell-mediated and Humoral

16. Surface Barriers or Mucosal Immunity
Skin
Cilia
Tears, Saliva, Urine.
Sticky mucus
Stomach:
Hydrochloric Acid
Then why do certain bacteria cause food poisoning? They are resistant to hydrochloric acid. But it does kill many other kinds of organisms. The digestive tract also destroys most proteins, which is why you can’t treat genetic diseases by eating synthetic proteins that are made to compensate for defective proteins caused by the genetic disorder.

17. Analogy Suppose the classroom is a body. All students are cells.
Rats are Antigens.
Doors and Windows prevent them from entering - Surface Barriers.
Some of you Tough ones (T-cells) will capture the rodents - Cell-mediated Immunity.
Some of you Brainiacs (B-cells) will call pest control (Antibodies) to capture the rodents – Humoral Immunity.

18. The Ultimate Battlefield : Blood
BLOOD: It is the place where the antigen and the antibody/T-cells collide.
Blood cells= RBCs + WBCs + Platelets.

19. Normal Blood Cell Count
Type of Cell
Men
Women
RBC
5-6 billion cells per Liter of Blood
4-5 billion cells per Liter of Blood
WBC
4-11 billion cells per Liter of Blood
Platelets
billion cells per Liter of Blood
Type of Cell
Increase
Decrease
RBC
Erythrocytosis
Anemia
WBC
Leucocytosis
Leucopenia
Lymphocyte
Lymphocytosis
Lymphocytopenia
Platelets
Thrombocytosis
Thrombocytopenia
The suffix, “cytosis” means increase in number of cells. The suffix “penia” means insufficient or not enough.

20. The Cells in Blood
*Lymphocyte not shown. Looks like a monocyte, except nucleus mostly fills the cell and does not have a notch in it.
Source: National Library of Medicine

21. The Role of Neutrophils
When a wound occurs, neutrophils migrate out of blood to rush to the wound and phagocytize (“eat”) the bacteria. This is what pus is made of.
BUT, recent research shows that neutrophils can harbor a blood-borne parasite, without killing it. When the neutrophil dies, it releases the parasite and helps it spread into its real target, macrophages (Science. 321 (2008): ). It’s like the Trojan horse story in ancient Greece.
“old” neutrophil surrounded by red blood cells

22. The Role of Monocytes Eosinophils Turn into Macrophages
Attack Internal Parasites
Note the notch in the nucleus. Otherwise, it looks like a lymphocyte.
Note the red granules in the cytoplasm.

23. The Role of Macrophages
Enter tissue and engulf and then digest cellular debris and microbes
Note the irregular cell membrane. These are the largest blood cell, but they migrate out of blood into damaged tissue.

24. The Role of Platelets Blood Clotting
They can clump together to form clots. No role in immunity.

25. Review 2 What do Macrophages do? Where is the “Ultimate Battlefield?”
What do Platelets do?
1 Enter tissue and engulf and then digest cellular debris and microbes
2 The Blood
3 Clot the Blood

26. Leukocytosis
Leukocytosis: white blood cell count increased above the normal range.
It is not a disorder or a disease, but a sign of illness.
It occurs in response to a wide variety of conditions, including
viral, bacterial, fungal, or parasitic infection
cancer
Hemorrhage (internal bleeding)
exposure to certain medications or chemicals including steroids.

27. Leukopenia
Leukopenia: a decrease in the number of circulating white blood cells in the blood.
As white blood cells get “used up” during infection, leucopenia can place patients at higher risk for infection.
Causes:
Influenza, typhus, malaria, HIV, tuberculosis, dengue, Rickettsial infections, enlargement of the spleen and folate deficiencies.
chemotherapy, radiation therapy, leukemia , myelofibrosis and anemia.
many common medications like minocyclen.

28. HIV (Human Immunodeficiency Virus)
HIV infection causes AIDS (Acquired ImmunoDeficiency Syndrome).
AIDS causes the immune system to fail, leading to life-threatening opportunistic infections.
Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or breast milk.
The four major routes of transmission are
unprotected sexual intercourse,
contaminated needles
breast milk
transmission from an infected mother to her baby at birth.
What’s the difference between HIV and AIDS? One is the name of the virus; the other describes the eventual effect of the disease.

29. AIDS (Acquired ImmunoDeficiency Syndrome)
Virus infects vital cells such as helper T cells and macrophages.
When T cell numbers decline below a critical level, cell-mediated immunity is lost, and infections with a variety of opportunistic microbes appear.
Typically, resistance is lost early on to oral Candida species and to Mycobacterium tuberculosis, which causes oral candidiasis (thrush) and tuberculosis.

30. Cell-mediated immunity
It is an immune response that does not involve antibodies, but rather the cells act as the killers themselves.
It protects the body by:
Activating antigen-specific T-cells that destroy infected cells.
Activating macrophages that destroy intracellular pathogens.
Activating NK (Natural Killer) cells that release a protein that kills the target cells

31. Review 3 What is Leukopenia and what does it cause?
What immune response does not involve antibodies?
Reduced white blood cell count, causes a higher risk of infection
Cell-mediated immunity

32. Immune System Research
How do they test for antibodies?

33. ELISA TEST
Remove blood cells and use the fluid (serum) to test for presence of antibody.
Place target sample on a support
Add serum that has antibody against antigen being tested for. Antibody, if present, binds the antigen.
Add a second antibody (that was separately developed to react with the antibody/antigen complex in step B) binds it to the complex. Second antibody was also prepared with an enzyme attached to it.
This new complex is made visible by reacting it with an enzyme that converts it to a colored compound that you can see.
ELISA tests make it possible to see and quantify the presence of antiboides in body fluids.
Courtesy The Howard Hughes Medical Institute: The Virtual Immunology Laboratory. Students can actually run a computer simulation of the test by obtaining the CD from the HHMI. The disk is free to teachers and is called The Virtual Lab Series. Other simulations on the disk include a bacterial ID lab, a cardiology lab, a neurophysiology lab, and a transgenic fly lab.