Host Defenses: The Immune System
Learning Objectives

1. Learn about and describe the interconnecting network of host protection against microbial invasion

a. What generally constitutes the first line of defense
b. What generally constitutes the second line of defense
c. What generally constitutes the third line of defense

2. Define the immune system

a. Name the 4 major subdivisions of this system

i. Define the RES or reticuloendothelial system and the role it plays in immunity
ii. Define the ECF or extracellular fluid and the role it plays in immunity
iii. Describe the role the blood vascular system plays in immunity

1. Describe the differences between the specific and non-specific defenses of the blood

a. Define the two components of the specific immune response and the role they play in immunity
iv. Describe the three function of the lymphatic system in regard to host immunity

2. Name some important sites in the body with lymphoid tissues

3. Learn about and be able to describe the actions of the second line of defense

a. Define Toll-like receptors and the role they play in activating the immune response

b. Define and describe the four symptoms of inflammation
c. Define the role of fever in the immune response

i. What causes fever ii. How does it help protect the body

d. Define Macrophages and Neutrophils (PMN’s), and their role in the body’s immune response
e. Define complement and explain its role in the body’s immune response



We can’t see them. Nevertheless, millions of them are everywhere around us, clinging to us, bent on getting inside of us. If unstopped, they would soon take us over completely.

With life’s beginning, the virus and bacteria wars begin, and they will not end until the last breath is drawn. For months before birth, the fetus is gearing up for battle, producing weapons for the immune system.

“By the age of two or three months, ... weapon manufacturers in the red bone marrow and thymus are working flat out. When the child is ten years old, the human immune system is at its strongest, armed to the teeth. Thereafter, its powers gradually deteriorate.”–The Body Victorious, pages 34-5.

Therefore, our response to viral and bacterial infections, and their destructive ability, is war. It is total war between these disease-carrying alien invaders and our body’s immune system. No quarter asked, none given. Our lives hang in the balance, it is them or us. Usually we win, but not always. The outcome depends on how quickly our immune system is stimulated for the fight.

The immune system is one of the most incredible and complex features of our amazing bodies. The immune system has an incredible ability for dealing with information, for learning and memory, and for creating, storing and using information. It recognizes molecules that have never been in the body before and can differentiate between what belongs there and what doesn’t.

The immune system, which is made up of special cells, proteins, tissues, and organs, defends people against germs and microorganisms every day. In most cases, the immune system does a great job of keeping people healthy and preventing infections. But sometimes problems with the immune system can lead to illness and infection.

The primary functions of a healthy functioning immune system can be summerized as:
1. Surveillance of the body
2. Recognition of foreign material such as pathogens
3. Attack and destrution of foreign invaders

White blood cells formed in the bone marrow are responsible for most of the reactions of the immune system, including antibody production, phagocytosis, and many aspects of inflammation. Lymphoid organs such as the spleen, lymph nodes, and thymus are also intimately involved in these defense mechanisms. Cells of the immune system are able to travel freely among different areas of the body because of the interrelationship between the blood, the lymphatic system, and the reticuloendothelial system. Communication between cells of the immune system is facilitated by the release of chemical messengers such as cytokines. These chemicals stimulate a variety of beneficial responses: They increase blood flow and the migration of white blood cells; they initiate fever; or they destroy virally infected cells. The inflammatory response is a complex reaction to infection that works to fight foreign agents and limit further damage to the body. White blood cells known as phagocytes help to clear foreign organisms from the body. The complement system acts to lyse cells that have been identified as foreign.

Defense Mechanisms of our body

Line of Defense	Innate / Acquired	Specific or Nonspecific	Development of Immunological Memory	Examples
First	Innate	Nonspecific	No	Physical barriers: skin, tears, coughing, sneezing Chemical barriers: low pH, lysozyme, digestive enzymes Genetic barriers: resistance inherent in genetic makeup of host (pathogen cannot invade).
Second	Innate	Nonspecific	No	Phagocytosis, inflammation, fever, interferon
Third	Acquired	Specific	Yes	T lymphocytes, B lymphocytes, antibodies

So what is the first line of defense?



In actuality there are several types of barriers that protect organisms from infection, including mechanical, chemical and biological barriers. The immune system consists of three overlapping lines of defense, the first two of which provide nonspecific protection against anything seen as being foreign to the body. The first line of defense consists of barriers to foreign objects, while the second is responsible for protecting the body once foreign matter has entered. The third is more unique and is in relation to how the genetic makeup of an individual predisposes that individual to be more vulnerable to some pathogens and immune to others.

Physical Barriers of an Organisms Body
The waxy cuticle of many leaves, the exoskeleton of insects, the shells and membranes of externally deposited eggs, and skin are examples of the mechanical barriers that are the first line of defense against infection. However, as organisms cannot be completely sealed against their environments, other systems act to protect body openings such as the lungs, intestines, and the genitourinary tract. In the lungs, coughing and sneezing mechanically eject pathogens and other irritants from the respiratory tract. The flushing action of tears and urine, also mechanically expels pathogens, while mucus secreted by the respiratory and gastrointestinal tract serves to trap and entangle microorganisms.

Chemical Defenses
Chemical barriers also protect against infection. The skin and respiratory tract secrete antimicrobial peptides such as the β defensins. Enzymes such as lysozome and phospholipase A2 in saliva, tears, and breast milk are also antibacterials. Vaginal secretions serve as a chemical barrier following menarche, when they become slightly acidic, while semen contains defensins and zinc to kill pathogens. In the stomach, gastric acid and proteases serve as powerful chemical defenses against ingested pathogens.
Within the genitourinary and gastrointestinal tracts, commensal flora serve as biological barriers by competing with pathogenic bacteria for food and space and, in some cases, by changing the conditions in their environment, such as pH or available iron. This reduces the probability that pathogens will be able to reach sufficient numbers to cause illness. However, since most antibiotics non-specifically target bacteria and do not affect fungi, oral antibiotics can lead to an “overgrowth” of fungi and cause conditions such as a vaginal candidiasi (a yeast infection). There is good evidence that re-introduction of probiotic flora, such as pure cultures of the lactobacilli normally found in unpasteurized yogurt, helps restore a healthy balance of microbial populations in intestinal infections in children and encouraging preliminary data in studies on bacterial gastroenteritis, inflammatory bowel diseases, urinary tract infection and post-surgical infections.

Genetic Defenses
Some pathogens have such specificity that the genetic makeup of a person could be enough to make them immune to those pathogens. Viruses are an excellent example as they attach themselves to a specific host receptor, if the host doesn't have the receptor the virus needs, then there is nothing to attach too and thus is not infected. Another example of a genetic defense is an individual that carries the gene for sickle-cell anemia are resistant to aquiring malaira. This also holds true for susceptibility to tuberculosis, leprosy, and some systemic fungal infections, if the individual has a gene that provides a resistance to them.

Test yourself: What is the first line of defense? What are examples of it? Is it innate or acquired? Nonspecific or specific? Why is the skin considered a defense against microbes? What are some examples of physical or anatomical barriers at the body’s surface? How does the ciliary escalator guard the respiratory tract against microorganisms? What are the nonspecific chemical defenses of the skin and eyes? What is the chemical defense found in tears and saliva, and how does it protect against bacteria? What do skin cells secrete that acts as an antimicrobe? How does this chemical work? How are the stomach, intestines, semen, and vagina inhibitory to pathogens?


The Second Line of Defense.
Organisms that manage to penetrate the body's first line of defense then encounter another hurdle: the body's nonspecific immune system. The term nonspecific means that this line of defense goes into operation whenever any kind of foreign material enters the body. The immune systems of animals have developed the ability to tell the difference between its own cells, that is, cells produced by the body, and any other kind of material. The foreign matter might be another kind of organism, such as a bacterium or virus; cells from another animal; or inanimate matter, such as coal dust, pollen, cigarette smoke, or asbestosis fibers. Anything that causes an immune response in an animal is said to be an antigen.
Identification of foreign particles as "not-me" cells is made by a group of white blood cells known lymphocytes. Lymphocytes search out antigens in the bloodstream and destroy them by phagocytosis. Phagocytosis is the process by which one cell surrounds a second cell and engulfs it. Once the foreign cell has been swallowed up by the lymphocyte, it is digested by enzymes released from the lymphocyte.
The invasion of antigens can also produce an inflammatory response. Suppose you cut your finger on a tin can. The cut soon becomes red, swollen, and warm. These signs are evidence of the inflammatory response. Injured tissues send out signals to immune system cells, which quickly migrate to the injured area. These immune cells perform different functions. Some destroy bacteria by phagocytosis. Others release enzymes that kill the bacteria. Still other cells release a substance called histamine. Histamine causes blood vessels to dilate (become wider), thus increasing blood flow to the area. All of these activities promote healing in the injured tissue.
Allergic reactions are examples of an inappropriate inflammatory response. When a person is allergic to pollen, the body's immune system is reacting to pollen (a harmless substance) as if it were a bacterium and an immune response is prompted. When pollen is inhaled, it stimulates an inflammatory response in the nasal cavity and sinuses. Histamine is released, which dilates blood vessels and causes large amounts of mucous to be produced, leading to a "runny nose." In addition, histamine stimulates the release of tears and is responsible for the watery eyes and nasal congestion typical of allergies.
To combat these reactions, many people take drugs that deactivate histamine. These drugs, called antihistamines, are available over the counter and by prescription. Some allergic reactions result in the production of large amounts of histamine, which impairs breathing and necessitates prompt emergency care. People prone to these extreme allergic reactions must carry a special syringe with epinephrine (adrenalin), a drug that quickly counteracts this severe respiratory reaction.

Test yourself: What is the 2nd line of defense? What are examples of it? Is it innate or acquired? Nonspecific or specific?


Question: Why and how does an allergic reaction occurs in the nasal cavity.




The Third Line of Defense

The body's third line of defense against invasion by foreign organisms is the specific immune system. The specific immune system consists of two kinds of lymphocytes known as T lymphocytes and B lymphocytes. The two kinds of cells are sometimes known simply as T cells and B cells. Both kinds of cells are produced in bone marrow. T cells then migrate to the thymus (which gives them the T in their names), where they mature. No one knows where B cells mature. T cells and B cells differ from nonspecific lymphocytes in that they attack only very specific antigens. For example, the blood and lymph of humans have T cell lymphocytes that specifically target the chicken pox virus, T cell lymphocytes that target the diphtheria virus, and so on. When T cell lymphocytes specific for the chicken pox virus encounters a body cell infected with this virus, the T cell multiplies rapidly and destroys the invading virus.
Two kinds of T cells exist: killer T cells and helper T cells. Killer T cells go directly to the target antigen and attack it. Helper T cells have many different functions, including to help in the development of B cells. Another function is to stimulate the formation of other T cells and the release of various chemicals that aid in the destruction of antigens.

Helper T cells have an especially crucial role in the immune system. Thus, any disease that destroys helper T cells has a devastating effect on the immune system as a whole. HIV (human immunodeficiency virus, which causes AIDS [acquired immunodeficiency syndrome]), for example, infects and kills helper T cells, thus disabling the immune system and leaving the body helpless to stave off infection.

Memory cells. After an invader has been destroyed, some T cells remain behind. These cells are called memory cells. Memory cells give an animal immunity to future attacks by the original invader. Once a person has had chicken pox, memory cells are created. If the person is later exposed to the chicken pox virus again, the virus is quickly destroyed. This secondary immune response, involving memory cells, is much faster than the primary immune response.
The procedure known as vaccination makes use of the above process. Vaccination is the process by which a killed microorganism (or parts thereof) are injected into a person's bloodstream. The presence of these particles prompts the formation of memory cells without a person's having to actually develop the disease.
the third and final line of defense- acquired specific immunity is the product of a dual system the the B and T lymphocytes are composed of. During fetal development the lymphocytes undergo a selective process that specializes the for reacting only to onr specific antigen. During this time Immunocompetence, the ability of the body to react with myriad foreign substances, develops. An infant is born with the theoretical potential to acquire millions of different immunities.

B cells and the antibody response. When helper T cells recognize the presence of an invading antigen, they stimulate B cells in the blood and lymph to start reproducing. As the B cells reproduce, they also undergo a change in structure and become known as plasma cells. Those plasma cells then begin to secrete compounds known as antibodies. Antibodies are chemicals released by B cells that attach themselves to the surface of an antigen. The presence of an antibody helps other cells in the immune system recognize the antigen and mark it for destruction.

• granulocytes- leukocytes which have lobed nuleus
• Neutrophils- distinguished by their lobed nuclei and bu their fine, pale lavendar granules, released by bone marrow, make up 55-90% of circulating leukocytes
• Eosinophils- stain orange to red granules and bilobed nucleus, more numerous in the bone marrow and the spleen, only 1-3& of the WBC count, used for the immune system sometimes, granules contain perioxidase, lysozome, and other digestive enzymes, also involved in inflammatory and allergic reactions
• basophils-pale stained, constricted nuclei and very psominet dark blue to black granules. share morphologicals and functional similarities with mast cells

Test yourself:
What is the 3rd line of defense? What are examples of it?
Is it innate or acquired? Nonspecific or specific?

The four major subdivisions of the immune system are:

1. Reticuloendothelial system (RES)
2. Extracellular fluid (ECF)
3 The Blood Stream
4. The Lymphatic system

For effective immune responsiveness, the activities in one fluid compartment must be conveyed to other compartments. At this level, clusters of tissue cells are in direct contact with the reticuloendothelial system and the extracellular fluid. Other compartments or vessels that penetrate at this level are blood and lymphatic capillaries. This close association allows cells and chemicals that originate in the RES and ECF to seep or migrate into the blood and lymphatics; any products of a lymphatic reaction can be transmitted directly into the blood through the connection between these two systems; and certain cells and chemicals originating in the blood can move throught the vessel walls into the extracellular spaces and migrate into the lymphatic system. This means that regardless of which compartment is first exposed to a pathogen, in immune reaction in any one of them will eventually be communicated to the others at the microscopic level. As a result, no cell in the body is far removed from competent immune protection, no matter how isolated.

The Reticuloendothelial system (RES)



Extracellular Fluid

in biology, body fluid that is not contained in cells. It is found in blood, in lymph, in body cavities lined with serous (moisture-exuding) membrane, in the cavities and channels of the brain and spinal cord, and in muscular and other body tissues. It differs from intracellular fluid (fluid within the cells) in that it generally has a high concentration of sodium and low concentration of potassium, while intracellular fluid is high in potassium and low in sodium. The fluid is often secreted by cells to provide a constant environment for cellular operations.

The Blood Stream

The blood stream contains whole blood, which consists of plasma and blood cells (red blood cells and white blood cells).

• Plasma consists of 92% water, metabolic proteins, globulins, clotting factors, hormones and all other chemicals and gases to support normal physiological functions.
  
• Serum is a clear fluid that is essentially the same as plasma except that it does not contain any clotting factors. It is often used in immune testing and therapy
  
• Buffy Coat is a thin layer of off-white material (contains the white blood cells).
  

The production of blood cells, known as hematopoiesis or hemopoiesis, begins early in embryonic development in the yolk sac (an embryonic membrane). Later it is taken over by the liver and lymphatic organs, and it is finally assumed entirely and permanently by the red bone marrow. Although much of a newborn's red marrow is devoted to hemopoietic function, the active marrow sites gradually recede, and by the age of 4 years, only the ribs, sternum, pelvic girdle, flat bones of the skull and spinal column, and proximal portions of the humerus and femur are devoted to blood cell production.

The relatively short life of blood cells demands a rapid turnover that is continuous throughout a human lifespan. The primary precursor of new blood cells is a pool of undifferentiated cells called pluripotential stem cells maintained in the marrow. During development, these stem cells proliferate and differentiate--meaning that immature or unspecialized cells develop the specialized form and function of mature cells. The primary lines of cells that arise from this process produce red blood cells (RBC's), white blood cells (WBC's, or Leukocytes), and platelets (thrombocytes). The white blood cell lines are programmed to develop into several secondary lines of cells during the final process of differentiation. These committed lines of WBC's are largely responsible for immune function.

Test yourself: What is the circulatory system composed of? What does whole blood consists of? What is hematopoiesis, and where is it occur? What three types of cells arise when stem cells differentiate? What two groups are leukocytes divided into? How else are these groups distinguished from each other?



White Blood Cells (Leukocytes)

Types of Leukocytes

Granulocytes

Neutrophils:
- Neutrophils are the most common type of white blood cell, comprising about 50-70% of all white blood cells.
- They are phagocytic, meaning that they can ingest other cells, though they do not survive the act.
- Neutrophils are the first immune cells to arrive at a site of infection, through a process known as chemotaxis.
- Though neutrophils are short lived, with a half-life of four to ten hours when not activated and immediate death upon ingesting a pathogen, they are plentiful and responsible for the bulk of an immune response.
- They are the main component of pus and responsible for its whitish color.
- Neutrophils are present in the bloodstream until signaled to a site of infection by chemical cues in the body.
- They are fast acting, arriving at the site of infection within an hour.
- Before ingesting invasive bacteria, neutrophils can release a net of fibers called a neutrophil extracellular trap (NET), which serves to trap and kill microbes outside of the cell.
- When neutrophils ingest microbes, they release a number of proteins in primary, secondary, and tertiary granules that help kill the bacteria. They also release superoxide, which becomes converted into hypochlorous acid, or chlorine bleach, which is theorized to play a part in killing microbes as well.
- Since neutrophils are such an important part of the immune response, a lowered neutrophil count results in a compromised immune system.

Eosinophils:
- An eosinophil is a type of white blood cell involved in immune system responses.
- These cells also appear to play a role in allergies and asthma when the body produces too many of them and they overreact to a perceived problem in the body, because they release substances which can be toxic.
- The eosinophil cell is named for a type of acidic dye.
- The ability to thrive in acidic environments is important for an eosinophil, as it allows the cell to reach many areas of the body.
- Eosinophils may also be referred to as acidophiles in some regions of the world, reflecting their acid-loving nature, although this terminology is not usual.
- Normally, eosinophils make up around one to six percent of the white blood cells in the body.
- They are produced in the bone marrow.
- They are part of a group of white blood cells known as granulocytes, because they are filled with small granules of material which they can release at the site of an infection or inflammatory reaction. Essentially, granulocytes are like mobile responders with their own tool kits which they can utilize to address an emerging medical problem quickly.
- An eosinophil can respond to bacterial, parasitic, and viral infections anywhere in the body, and the cells can also deal with ongoing inflammatory processes such as those caused by underlying infections or excessive immune responses.
- Typically, concentrations of these cells in the blood increase when someone is battling infection.
- When eosinophils flock to an area like the gut to respond to an infection and then flood the area with various compounds, they can cause irritation, inflammation, and other problems.
- In allergic responses, eosinophils overreact to an allergen, causing problems like skin irritation and difficulty breathing.
- Eosinpenia, in which there are too few, can be the result of steroid use or Cushing's Syndrome.

Basophils:
- Basophils are also a type of white blood cell.
- These cells are extremely rare, making up less than one percent of the white blood cells in the body at any given time.
- They are also not very well understood, despite the best efforts of researchers interested in the components of the blood.
- The granules seen in basophils contain pieces of information relevant to the immune system, and compounds which the immune system utilizes when it responds to an infection or inflammation.
- Basophils can release histamine and heparin to respond to a suspected infection.
- Release of the granules is known as degranulation.
- The name “basophil” is a reference to the fact that these cells take dyes and stains very readily, turning a vivid purple when stained with the base dyes used to prepare specimens for study and identification.
- Staining makes basophils easier to see, because they stand out from a blood sample, although the stain obscures the internal structures of the cell.
- Each basophil has a two-lobed nucleus, surrounded by the tiny granules it carries.
- Basophils originate in the bone marrow, where they are created by stem cells.
- They circulate throughout the body in the blood stream, with the ability to pass into various tissues as needed.
- When an infectious agent is detected by the immune system, basophils respond, along with numerous other types of white blood cells.
- Researchers believe that in addition to helping at the site of an infection, these cells also help the body develop immunities by storing information which can be used by the T cells.
- Normal basophil counts can vary, depending on the patient and the situation.
- In a healthy person, the count is typically very low.
- In someone with an active infection or allergic response, the number of basophils in the blood can climb, betraying the presence of an infection.
- High basophil levels have also been observed in people with asthma, which may be due to the chronic lung inflammations experienced by many asthma sufferers.

Questions:
Which WBC is the most common, is phagocyctic, and are fast acting in response to an infection?
Which WBC when found in a healthy person is very low, releases histamine and heparin, and will degranulates?
Which WBC plays a role in asthma and allergies?

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Agranulocytes
T lymphocytes:
- Also called T cell, a type of lymphocyte which is involved in the function of the immune system.
- T cells can bind to various cells in the body to kill off infected cells and attack antigens which could cause someone to get sick.
- A decline in the level of T cells can indicate that someone is suffering from a disease which causes immune suppression, or that someone is taking medications which suppress the functions of the immune system, as is done to prepare for organ transplants.

- These cells originate in the bone marrow, working their way into a gland called the thymus, where they mature.
- The "T" in "T cell" comes from "thymus."
- In the thymus, the cells differentiate into different types of T cells such as helper cells, natural killer cells, regulatory cells, and cytotoxic cells.
- These cells in turn travel through the bloodstream to look for signs of unwanted invaders, at which point the cells swing into action to neutralize or destroy the invaders they have identified.
- Another important event occurs in the thymus when T cells mature. The thymus goes through a process known as “negative selection,” in which T cells which could trigger autoimmune responses are allowed to die off. This is designed to prevent the immune system from attacking the body by accident.
- Sometimes this process goes awry, causing autoimmune conditions.
- A T cell can do all sorts of things, depending on which type it is.
- Some bind to cells and kill them if the cells have become infected, while others store the memory of specific antigens so that the body can respond quickly if these antigens are identified.
- Helper T cells identify situations in which an immune system response is needed, and trigger the release of various signals to the rest of the body.
- Regulatory T cells mop up in the aftermath of an infection, taking care to remove cells which have developed autoimmune responses.
- In individuals with suspected immune conditions, a doctor may request a test which is designed to count the T cells and to identify numbers of particular types. CD4 cells, for example, are a kind of T cell which decline radically in patients with HIV.
- In people of normal health, the CD4 count is usually above 1,000, while AIDS patients have 200 or fewer CD4 cells in their blood tests.

Question:
What cell (T Cell or B Cell) will undergo transformation to a plasma cell?
Where does the T Cell originates?

B lymphocytes:
- A type of lymphocyte that is the basis for the body's humoral immune system since it produces and secretes immunoglobulins (antibodies) in response to antigens.
- B-lymphocytes, also called B-cells, represent about 5–15% of the circulating lymphoid pool and are classically defined by the presence of endogenously produced immunoglobulins.
- Like all blood cells, B-lymphocytes develop in the bone marrow and then migrate to any of various parts of the body via the bloodstream.
- When an antigen (a particular foreign protein, such as a substance on the surface of a bacterium) is encountered by the immune system, certain B-lymphocytes are stimulated to enlarge and undergo cell division, transforming into cells called plasma cells.
- The plasma cells secrete into the blood vast numbers of tailor-made immunoglobulins that attach to the antigen on the surface of the microorganism.

B-cell acute lymphocytic leukemia is a type of leukemia (blood cancer) in which too many B-cell lymphoblasts (immature white blood cells) are found in the blood and bone marrow. It is the most common type of acute lymphoblastic leukemia (ALL). Also called precursor B-lymphoblastic leukemia and B-cell acute lymphoblastic leukemia.

B-cell lymphoma is a type of cancer that forms in B cells. B-cell lymphomas usually occur in adults and may be either indolent (slow-growing) or aggressive (fast-growing). There are many different types of B-cell lymphomas, and prognosis and treatment depend on the type and stage of cancer.
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Question:
When an antigen is encountered by the immune system, the ( ) undergoes transformation into cells called ( ).

Monocytes:
- Depending on a patient's level of health, monocytes make up between one and three percent of the total white blood cells in the body.
- They can be counted as part of a blood test, and changes in their levels can indicate changes in a patient's health.
- As a general rule, a low monocyte count is a good sign, and a high count indicates that a problem is present.

- These cells are also made in the bone marrow, and they spread through the body in one to three days.
- They can develop into either dendritic cells or macrophages.
- Dendritic cells belong to a group of cells known as antigen presenting cells, because they acquire antigens and show them to T cells so that the T cells learn to recognize dangerous antigens.
- Dendritic cells typically present antigens to T cells before they are fully developed, so that the T cell can respond appropriately after it has been shown an antigen.
- Macrophages are cells which eat other cells.
- Classically, they attack any foreign material, such as a bacteria or virus, consuming it so that it cannot hurt the body and preserving an antigen so that the body will be able to recognize the foreign material in the future.
- Macrophages can also eat cells in the body which have been infected by a pathogen, to curb the spread of the pathogen and keep the body healthy.
- Levels of monocytes in the blood tend to rise when someone has an infection, because more of these cells are needed to fight it.
- Monocytes can also increase in response to stress and other factors.
- The normal levels of monocytes can vary widely, making it important for patients to discuss the results of blood tests with doctors, rather than trying to puzzle them out on their own. Because many things can cause a high value, having a high count is not necessarily a cause for major concern.

Test yourself.
What are monocyctes, what are they function, and whats the role they play in the immune system?

The Lymph System



The lymphatic system consists of organs, ducts, and nodes. It transports a water clear fluid called lymph. This fluid distributes immune cells and other factors throughout the body. It also interacts with the blood circulatory system to drain fluid from cells and tissues. The lymphatic system contains immune cells called lymphocytes, which protect the body against antigens (viruses, bacteria, etc.) that invade the body.

Main Functions

• To collect and return interstitial fluid, including plasma protein to the blood, and thus help maintain fluid balance
  
• To defend the body against disease by producing lymphocytes
  
• To absorb lipids from the intestine and transport them to the blood
  

Lymph Organs: include the bone marrow, lymph nodes, spleen, and thymus. Precursor cells in the bone marrow produce lymphocytes. B-lymphocytes (B-cells) mature in the bone marrow. T-lymphocytes (T-cells) mature in the thymus gland. Besides providing a home for lymphocytes (B-cells and T-cells), the ducts of the lymphatic system provide transportation for proteins, fats, and other substances in a medium called lymph.
Lymph Nodes: Human lymph nodes are bean-shaped and range in size from a few millimeters to about 1-2 cm in their normal state. They may become enlarged due to a tumor or infection. White blood cells are located within honeycomb structures of the lymph nodes. Lymph nodes are enlarged when the body is infected due to enhanced production of some cells and division of activated T and B cells. In some cases they may feel enlarged due to past infections; although one may be healthy, one may still feel them residually enlarged.
Lymph means clear water and it is basically the fluid and protein that has been squeezed out of the blood (i.e. blood plasma). The lymph is drained from the tissue in microscopic blind-ended vessels called lymph capillaries. These lymph capillaries are very permeable, and because they are not pressurized the lymph fluid can drain easily from the tissue into the lymph capillaries. As with the blood network the lymph vessels form a network throughout the body, unlike the blood the lymph system is a one-way street draining lymph from the tissue and returning it to the blood.

Test yourself:
What are the three main functions of the Lymphatic system?

Secondary lymphatic tissues control the quality of immune responses. Differences among the various lymphatic tissues significantly affect the form of immunity and relate to how antigens (bacteria, virus, fungus, etc.) are acquired by these organs.

• Lymph nodes are filters of lymph
  
• The spleen is a filter of blood
  
• Mucosal associated lymphatic tissues acquire antigens by transcytosis to lymphoid tissue from the external environment across specialized follicle-associated epithelial cells.
  

The Second Line of Defense

• Recognition
  
• Inflammation
  
• Phagocytosis
  
• Interferon
  
• Complement
  

Recognition--How the Immune system recognizes foreign pathogens

Without an efficient means of recognizing foreign pathogens, the formidable power of the immune system would be wasted. Although it was apparent that the immune system was certainly capable of recognizing pathogens, the exact manner in whic hit did so remained a mystery. Recently, however, a collection of protein receptors was found residing on the surface of the immune system's earliest responding cells (macrophages, dendritic cells). The proteins, termed Toll-like receptors, or TLRs, dwell within the cell membrane of the phagocytes with one end of the receptor exposed to the extracellular environment, while the other end of the protein resides within the cytoplasm of the cell. When a foreign molecule is detected by one TLR, it immediately dimerizes, or joins with a second TLR, and relays a signal that a foreign molecule has been detected, to the inside of the cell. Within the cell, the activated receptor induces the production of a variety of chemicals, including interleukins 1 and 8, which stimulate the (nonspecific)inflammatory response, and interleukins 6 and 12, which promote the (specific) activity of B and T cells.

Currently, ten TLRs are known to exist in humans, with each receptor having the ability to recognize an esential constituent of a pathogenic microbe, such as the lipopolysaccharide component of gram-negative cell walls or double-stranded RNA molecules, such as that seen in West Nile virus. These pathpogen-specific molecules, called PAMPs are described in the section on phagocytosis. Because these components are shared among many pathogens, only a small number of TLRs is needed to recognize an astonishing variety of microbes.

Characteristics of Toll-like Receptors