1. The Immune System Part 2
In this lecture we will take a closer look at the function of the immune system. 1

2. The Immune System
A system of circulating cells and substances which have the ability to recognize exogenous micro-organisms and endogenous cells which have become neoplastic and attack them.
The system protects the body--self--against these external factors by recognition based on presence of antigen.
To understand the immune system it is important to note that unlike other systems the immune system requires learning function more than structure.
The immune system is a system of circulating cells and substances which have the ability to recognize exgenous micro-organisms and endogenous cells which have become neoplastic and attack them.
The system protects the body against these external factors by recognition based on the presence of an antigen.

3. Cells of the Circulatory System
Since the Immune System is a set of cells, I think that it is important to understand what the big picture looks like. This slide shows the big picture. As you can see, all blood cells are produced from stem cells. Stem cells are located in the bone marrow and differentiate into the cells that you see listed. Obviously there also must be new stem cells produced. Platelets are produced and are involved in the clotting process. Erythrocytes, or red blood cells, are the most common type of cell produced. Everything else besides stem cells, platelets and erythrocytes have something to do with protecting the body against infection. Our focus will be on the lymphoid line which includes Bcells and Tcells. We will also talk about macrophages and some of the granulocytes. Understand that all of these cells from macrophages through T cells are white blood cells.

4. White Blood Cells A. Lymphocytes 1. B-Lymph's 2. T-Lymph's B. Others
1. Neutrophils
2. Basophils
3. Eosonophils
4. Macrophages
Here you see a list of white blood cells or leukocytes. The Lymphocytes we will focus on include B-Lymphs and T-Lymphs. The “B” comes from the term bersa which is a physical structure in birds. The T stands for thymus which is the structure responsible for the development of these cells. Other white blood cells include neutrophils which are involved in fighting infection, basophils, esinophils and macrophages.

5. Organs that Impact Immunity
While we generally do not consider the immune system an anatomical system, there are some structures in the body that are involved in immunity. This picture highlights those structures. Bone marrow is responsible for the production of blood cells. Lymph vessels exist throughout the body. Lymph nodes are concentrations of lymphatic tissue. Lymph nodes swell during infection because we are producing more cells in order to fight the infection. The thymus gland is important in the immune system because it is responsible for the differentiation of T-cells. That is, it transforms cells from a more generic cell, to the more specific T-cell. The other structures noted are structures that have a high concentration of lymphocytic cells.

6. T-Cells Mature in the thymus and are circulated to peripheral tissues
Functions:
1. Killer T-Cells--kill micro-organisms
2. Helper T-Cells--regulate and control the production of lymphokines that signal the plasma cells to produce antibodies
3. Suppressor T-Cells--discourage suppress the production of antibodies
Mature in the thymus and are circulated to peripheral tissues
T-cells are lymphocytes that mature as a result of contact in the thymus gland and are circulated to the peripheral tissue. There are several different types of T-cells. Killer T-Cells produce substances that act directly against microorganisms. Some have the potential to be cytotoxic, that kill these organisms. Helper T-cells are perhaps the most famous T-cells. These are the cells that most people have heard about as a result of HIV education. Helper T-cells function to regulate and control the production of lymphokines. In other words, they regulate and control the function of antibodies that are produced by plasma cells. Suppressor T-cells do the opposite. They discourage or suppress the production of antibodies. As you can see, these cells communicate biochemically by producing substances that regulate function.

7. It is critical to be able to understand this diagram to be able to understand the immune system. It demonstrates how we become immune to the effects of certain microorganisms. It shows how the T-cells and B-cells work. These two cells work in analogous ways. First we will focus on T-cells. Circled on this slide is the induction phase or what you might think of as the primary immune response. Within our body we have T-cells that have been genetically preprogrammed to recognize most if not all of the microorganisms that we are likely to run into in our lives. When exposed to these microorganisms the T-cells react to certain components of that microorganism. These components are called antigens. The T-cell recognizes the fact that the microorganism is foreign. The exposure to the antigen triggers a transformation in these generic T-cells. The T-cell is now transformed into a cell that is designed specifically against that microorganism. This change is known as induction. The newly transformed T-cells then proliferate and mature.

8. Two types of cells are now formed
Two types of cells are now formed. First a memory cell which is what allows you to become immune long term to specific microorganisms. The memory cell is essentially a transformed cell that upon succeeding exposures to the microorganism, can respond quickly because the induction phase does not have to take place again, thus avoiding illness. Sensitized cells are also formed. These cells carry out the functions that we talked about on the previous slide. Effecter cells are killer T-cells. We also have helper cells and suppressor cells. Again note that this is a two stage process. The first stage required transformation, then the second stage is a proliferation of these transformed cells. The first time you are exposed to an antigen you often become sick because the induction phase takes a while. It takes time for the unsensitized T-cells to recognize the microorganism and then transform themselves into cells designed to counter that microorganism. Remember that it is the memory cell that allows us to develop immunity long term.

9. B-Cells Mature in the bone marrow
Genetically coded to recognize outsiders
Transform to fight and then spread
Memory Cells--immunity
Plasma Cells--mature B-cells
Produce antibodies
B-cells are cells that mature in the bone marrow or in the peripheral lymphoid area. These cells are genetically coded to recognize invaders. Once an invader is detected, they transform to fight and then spread. The memory cells allow for immunity. The transformed cells that actually produce antibodies are now called plasma cells. Again the mature B-cells are called plasma cells and they produce the antibodies.

10. Macrophages Mature in the bone marrow-- circulate throughout the body
Some become fixed to specific tissues
ex. Histocytes (connective tissue) Kupffers cells (liver)
All are functionally similar in that they engulf and destroy foreign material.
Are essential in processing antigens
Macrophages are large phagocytic cells that circulate through the body. They also become fixed to specific tissues. They engulf foreign material and process the antigen. This processing of the antigen is important because it allows the T-cells and B-cells to recognize the presence of the antigenic or foreign material.

11. Here you see that process graphically
Here you see that process graphically. Again this is parallel to process undergone by the T-cells. In this case we see unsensitized B-cells being presented with an antigen by the macrophages. We also see the fact that the T helper cell stimulates these unsensitized B-cells to become transformed.

12. The transformed B-cells then become two types
The transformed B-cells then become two types. Again we have memory cells, the cells that allow us to develop long term immunity. Mature B-cells that produce antibodies, as we discussed before, are called plasma cells. Whether or not a particular microorganism triggers B-cell immunity or T-cell immunity depends on the nature of that organism. Some disease creating agents trigger B-cell immunity and some trigger T-cell immunity and some also trigger both.

13. Antibodies & Antigens
Antibody--Serum proteins produced by plasma cells that bind with antigens and induce cell lysis.
Antigen--Any substance capable of eliciting an immune response--usually large protein, polysaccharide, or lipid molecules contained in/on cell walls of certain organisms.
* Every antibody is unique to the antigen it is reacting to
It is important that you take a good look at these definitions because students often confuse antibodies and antigens. When you read the definitions, think about what they are actually talking about. Antibodies are literally serum proteins produced by plasma cells that bind with antigens and induce cell lysis. In other words antibodies are products produced by transformed B-cells that attack microorganisms. Antibodies are the chemicals that try to destroy the invading microorganism. The antigen, on the other hand, is actually part of the microorganism. It is a piece of the virus or bacteria. The antigen is what the body recognizes as foreign. As the definition says, it is any substance that is capable of eliciting an immune response; anything in the body that triggers the processes that we have been talking about. Usually antigens are either proteins, polysaccharides which are sugars, or lipid molecules that are in the cell walls or some other part of the microorganism. Every antibody is unique to the antigen to which it is reacting. In other words, the antigen-antibody reactions are specific which is why we become immune to some diseases and not others. These reactions are dependant upon the recognition of the antigen by the immune system.

14. Antigen-Antibody Binding Results In..
1. Inflammation - histamine release increases delivery of T-cells & macrophages causes infection in the capillaries to leak
2. Chemotaxis -movement of macrophages to area signals phagocytes to come to the bacteria through releasing chemicals that attract them to the area and marking what does not belong.
During these reactions, the antibody is produced and literally binds with the antigen. The antibody biochemically reacts with the antigen on the microorganism. This binding causes several effects. First, something that you are familiar with, is inflammation. This is why a cut that is infected becomes red and tender. Inflammation is caused by histamine release. This is not necessarily a bad thing because the inflammation is a result of the increased blood flow to the area. This blood flow allows for the B-cells T-cells and macrophages to be delivered to the site of the infection. Chemotaxis: when antibodies and antigens bind, they attract macrophages to the area. The binding releases chemical signals that tell the microphage to come to devour the bacteria.

15. Antigen-Antibody Binding Results In..
3. Agglutination- clumping
4. Opsonization- macrophage binding
5. Cytolysis- cell destruction
Antigen-antibody complexing tends to cause agglutination or clumping of the affected material. If microorganisms are stuck together they are more easily dealt with by the body. Another result of antigen-antibody binding is opsonization. The biochemical processes that occur form a hook for the macrophage which makes it easier for the macrophage to latch onto the microorganism. Finally, antigen-antibody binding can result in cytolysis which is destruction of the organism.

16. Terms related to immunity:
1. Non-self--
2. Memory--
3. Specificity--
To review, there are three important concepts when thinking about immunity. First, the concept of non-self. This could be any material that is antigenic or in other words any material that the body recognizes is not supposed to be there. Second is memory. This is the idea that to some microorganisms we develop long-term immunity which is a function of the memory cells. The third concept is specificity. This is the idea that immunity is very specific to the particular antigen contained on the microorganism.

17. To review, these charts show the pattern or antibody response that occurs the first time a person encounters an organism, verses succeeding times the organism is encountered if this microorganism is one that we develop long term immunity to. A good example would be chicken pox. Imagine, on the graph on the left at place where the arrow is pointing, that this could be your first exposure to chicken pox. There is a period of time before the body is able to produce new antibodies, and the immune response is not very large. This lag time between exposure and the immune response is the time where the person will develop the illness. The time on the graph around 2 weeks is when the individual begins to resolve the symptoms. The graph on the right shows what will happen when a person is subsequently exposed to the same antigen. As you can see, the immune response is built up very quickly and the response is large. When we are exposed to chicken pox after the initial exposure, our body mounts a large response so that we do not get sick. This is why we say that we can generally only get chicken pox once in a lifetime.