THE IMMUNE SYSTEM

IMMUNE OVERVIEW

A good way to start understanding the immune system is to liken it to a castle. A castle, like our bodies, is a fortress. A castle has three lines of defense:

• First, A moat and drawbridge. The first line of defense in our bodies are physical and chemical barriers - our skin, stomach acids, mucous, tears, vaginal opening, of which the last three mostly produce lysozyme to destroy harmful incoming pathogens.
• Second, Sentries and archers who stand on the castle wall. In our bodies the second line of defense is non-specific immune responses - marcrophages, neutrophils, interferons, and complement proteins. This line of defense also includes fever and inflammatory response as nonspecific defenses.
• Third, Soldiers within the castle.Our third line of defense is specific immune responses - T Cells and B Cells. There are many types of each which work like a close knit team to destroy pathogens.

If pathogens (invaders) try and succeed in penetrating the first line of defense, then the second line of defense is ready to act. If both the first and second line of defense fail, then the third line of defense will act. It is when all three lines of defense are breached that we get sick and are subject to disease.
So what we are trying to say is that the immune system is a set of mechanisms of defense, protecting an organism from infection by identifying and attacking pathogens. This is a difficult task, since pathogens range from viruses to parasitic worms and must be detected with absolute specificity as they are "hidden" amongst normal cells and tissues. Pathogens are also constantly changing themselves to avoid detection and successfully infect and destroy their hosts.

The immune system is a complex system that is responsible for protecting us against infections and foreign substances. There are three lines of defense: the first is to keep invaders out (through skin, mucus membranes, etc), the second line of defense consists of non-specific ways to defend against pathogens that have broken through the first line of defense (such as with inflammatory response and fever). The third line of defense is mounted against specific pathogens that are causing disease (B cells produce antibodies against bacteria or viruses in the extracellular fluid, while T cells kill cells that have become infected). The immune system is closely tied to the lymphatic system, with B and T lymphocytes being found primarily within lymph nodes. Tonsils and the thymus gland are also considered lymph organs and are involved in immunity. We often don't realize how effective the immune system is until it fails or malfunctions, such as when the lymphocytes are attacked by HIV in an AIDS patient.


Harmful Organisms Viruses

• Viruses are non-living particles consisting of protein and nucleic acid that infect cells in biological organisms. They can reproduce only by invading and taking over other cells as they lack the cellular machinery for self reproduction. A virus is about ten times smaller than a bacteria. Some viruses you will recognize are: influenza, herpes, measles, and the common cold. Some viruses are particularly dangerous because they can undergo a period of latency, during which they are hidden in the cell and do not reproduce. Influenza and HIV are examples of viruses that frequently mutate, thus making it nearly impossible to achieve a long-lasting immunity.

Bacteria

• Bacteria can be deadly. They are the major cause of preventable infections and death. Some well known illnesses are caused by bacteria: staph infections, strep infections, tuberculosis, food poisoning, tetanus, leprosy, and pneumonia. Because bacterial cells are different from human cells, compounds can be found that can kill specific bacterial targets while leaving the human patient unharmed. Antibacterial agents can be successful in wiping out a bacterial infection. The problem with antibiotics is that many strains of bacteria are growing resistant to them. Plus, our bodies are not getting the chance to develop immunity to certain bacteria. It may be better to use probiotics (new supplements that promote the growth of healthy and helpful bacteria) rather than depend on antibiotics so much.

Protozoans

• The protozoans are mostly eukaryotic unicellular organisms with organelles and a nucleus.
• Malaria is the most dangerous disease caused by protozoans and is endemic in about 50% of the populations on Earth. Two to four million people die each year from malaria, a million of these are under the age of five. Malaria is caused by one of the Plasmodium species of mosquitoes.

Fungi

• Fungi are more like animals and humans than they are like bacteria because of their eukaryotic cells. Though they produce large, visible colonies on old bread, molds and yeasts are in the category of microscopic fungi. Yeasts are one-celled and reproduce by budding. Molds exist as cell chains, called hyphae.
• Mycoses are diseases caused by fungi. Because of the similarity between human cells and fungal cells, it has been difficult for scientists to design antibiotics that are effective against fungi and do not harm humans. Some of the diseases caused by fungi are: tineas, vaginal infection (candidiasis), and histoplasmosis.

Diagnosis
Infectious diseases are diagnosed by laboratory techniques such as microscopy and culture. Since many bacteria have no color, scientists have developed special staining procedures to more accurately diagnose.

• Culture

Bacteria and fungi can be identified by growing them on plates until colonies are visible. Viruses are cultured on eggs or live cells.

• Antibiotic sensitivity

After colonies of bacteria are grown on plates, discs are placed on the plates that contain different antibiotics. Bacteria will not grow around the most effective antibiotic.

• Tests for viruses

Since viruses are too small to be seen with a light microscope, viral infections can be diagnosed indirectly by their effects on cells. Some viruses cause changes to the surface of cultured cells, causing them to stick together.

Immunization
While some infectious diseases are common and can occur many times in the same person, others can only occur once in a lifetime thanks to the immune system and it's ability to remember the organism and prevent following infections. To avoid an epidemic of a grave disease such as polio, before the disease can be acquired, an immunization can create a man-made "memory".

• Active immunization

A person receives an injection (vaccine) that contains dead or harmless living forms of an organism. The vaccine stimulates the immune system to produce antibodies and memorize the organism. If there is a later exposure to this organism and subsequent infection, the antibodies will stop the infection.

• Passive immunization

Blood containing antibodies is taken from animals or humans who have recently had an infection. Blood serum is made that contains the antibodies, and then injected into the person. The antibodies either attack an infection that is present or provide short-term protection.

• Genetically engineered viruses

Genetic engineering is a technique that alters or changes the DNA of a plant or animal by inserting new genetic information from another organism. After these organisms replicate, vaccines and hormones are made that can help fight disease.

• Hepatitis B vaccine

The gene of the surface antigen of Hepatitis B virus is implanted into the DNA of a single bacterium. The bacteria produces viral antigens which are then implanted to stimulate the immune system.

DEFENSES AGAINST INFECTION

Innate Defense – first line of defense

Physical and chemical barriers are the body's first line of defense.
Physical or Mechanical barriers

• Skin

One of the bodies first line of defenses against bacteria and other harmful organisms is the skin. Our skin is a barrier which stops infection from entering the body. Millions of microorganisms live harmlessly on the skin and in the air around us. Sebaceous glands in the skin produce sweat and sebum, which, combined help to protect the skin. Both substances contain antiseptic properties, of lysozome is the main property. Although our skin is a good defense, it isn’t perfect. The skin itself can also become infected by bacteria, viruses, fungi or tiny parasites. Some examples of these are: boils, impetigo; ringworm, athletes foot; cold sore, wart, verucca; and scabies.

• Mucus membranes

Another very important first line of defense is our mucus membranes. The mucous membranes (or mucosae; singular: mucosa) line various body cavities that are exposed to the external environment and internal organs. It is at several places continuous with skin: at the nostrils, the lips, the ears, the genital area, and the anus. The nose and mouth serve as passageways for air going to and from the lungs. As we inhale and exhale, the mucus membranes that line these passageways warm and humidify the air. It has been said that there is more bacteria contained in a human mouth than the the sum of all the people that have ever lived on the earth. Mucus membranes serve different functions, however, their more important job is to secrete mucus that traps bacteria and other foreign debris that irritates the lining of the respiratory tract. This mucus is produced and stored in the sinuses by other mucus membranes. We get congested when there is excessive fluid in the sinus cavities. This is a result of an increase in mucus secretions, as well as an increase in the amount of fluids that passes across the blood vessels of the mucus membranes that line the nose and sinus. There are also many chemicals, such as pesticides and anthrax that are absorbed through the skin. All mucous membranes are ciliated. Cilia are thin, tail-like projections extending approximately 5–10 micrometers outwards from the cell body. Their main function is to move things across their surface.

• Mucociliary escalator

The mucociliary clearance of the respiratory tract is an important defense mechanism against foreign debris and inhaled pathogens. The cilia that lines the upper and lower airways are lined with a thin layer of mucus. These beat rapidly to propel particles that are trapped in the mucus layer to the pharynx. Defective mucociliary clearance predisposes our respiratory tracts to recurrent infections. These cilial defects may be either congenital or acquired by infection, toxins or drugs.

Chemical Defenses

• Tears, saliva

Tears and saliva contain lysozyme, an antiseptic enzyme that attacks cell walls of bacteria and breaks them down.

• Stomach acids

Glands in the stomach lining produce hydrocloric acid. This acid kills most invading organisms that are swallowed and take up residence there.

Non-specific responses to infection - 2nd line of defense

We are born with built in nonspecific defenses that all respond in the same way to invading pathogens. The outermost defense our body has is our skin. The sebaceous glands produce sweat and sebum, which contain ANTISEPTIC properties which protect. This bacteria-killing substance called LYZOSOME is also found in tears and saliva. Acidic urine in the urinary tract and friendly bacteria in the genital tract prevent the multiplying of harmful organisms in these areas. Most invading organisms in the stomach are killed by gland production of hydrochloric acid. These are a few examples of how the outer defenses protect us. All outer defenses work together as the body's first line of defense.

Inflammatory response: Any break in the skin will allow bacteria to enter the body. These foreign microbes will cause swelling and reddening at the site of injury. This reaction by the body is called an inflammatory reaction or inflammatory response.

• Swelling, redness (errythema), heat, and pain

Inflammation is characterized by the following quintet: swelling (tumor), redness (rubor), heat (calor), pain (dolor) and dysfunction of the organs involved (functio laesa). When an injury occurs, a capillary and several tissue cells are apt to rupture, releasing histamine and kinins. These cause the capillaries to dilate, become more permeable, and leak fluid into these tissues. Dilation and fluid leaking into the tissues causes swelling, redness, and heat. The swelling and kinins stimulate nerve endings, causing pain. If there has been a break in the skin due to the injury, invading microbes may enter. A common cause of inflammation after surgery is serous fluid. This is a mixture of plamsa, lymph and interstitial fluids .seeping from the damaged cells and vessels. If enough serous fluid accumulates a mass called a seroma may form. Treatment of a seroma may involve the removal of the fluid with a needle into a syringe, a process called aspiration.

• Phagocytosis by neutrophils and macrophages

In the event of a break in the skin, neutrophils, monocytes (and macrophages) arrive and attempt to engulf and destroy the invaders. Phagocytosis is receptor-mediated event, which ensures that only unwanted particles are ingested. Stimulated macrophages can bring about an explosive increase in the number of leukocytes by producing Colony Stimulating Factors (CSFs). The CSFs pass by way of the blood to the bone marrow, where they stimulate the production and the release of white blood cells (WBCs), primarily neutrophils. Lymphocytes in nearby lymph nodes produce specific antibodies to attack the microbes. During the conflict, some neutrophils die and become mixed with dead tissue, bacteria, living white cells, etc. This thick yellow-white fluid is called pus. When a person has an illness, an examination of the numbers and types of WBC's in their blood can be very useful.

The primary cells of the immune system are the leukocytes or white blood cells(WBC). Most leukocytes are much larger then red blood cells, but they are not nearly as numerous. A microliter of whole blood contains about 5 million red blood cells but only about 7000 leukocytes.
One functional group of leukocytes is the phagocytes, WBC that engulf and ingest their targets by phagocytosis. This group includes the neutrophils, macrophages, monocytes (which are macrophage precursors), and eosinophils. A second functional group is the cytotoxic cells, so named because they kill the cells they attack. This group includes eosinophils and some types of lymphocytes.

• Eosinophils fight parasites and contribute to allergic reactions. They account for only 1-3% of all leukocytes. The life span of a typical eosinophil in the blood is about 6-12 hours. Eosinophils are known to attach to large parasites and release substances from their granules that damage or kill the parasite. Eosinophils also participate in allergic reactions, by contributing to inflammation and tissue damage by releasing toxic enzymes.
• Basophils (mast cells) release histamine and other chemicals. They also release mediators that contribute to inflammation. The granules contain histamine, heparin(an anticoagulant), cytokines, and other chemicals involved in allergic and immune responses.
• Neutrophils "eat" bacteria and release cytokines. Neutrophils are the most abundant WBC, 50-70% of the total. Neutrophils, like other leukocytes are formed in the bone marrow. They are easily identified by a segmented neucleus. They are phagocytic cells that typically ingest and kill bacteria. Most neutrophils remain in the blood but can leave the circulation if attracted to an extravascular site of damage or infection.
• Monocytes are the precursor cells of tissue macrophages. Monocytes are not that common in the blood 1-6% of WBC. Once out of the blood, monocytes enlarge and differentiate into macrophages. Some tissue macrophages patrol the tissues, creeping along by amoeboid motion. Others find a location and remain fixed in place. Macrophages are the primary scavengers within tissues. Macrophages also remove larger particles, such as old RBC and dead neutrophils. Macrophages play an important role in the development of acquired immunity. After they ingest and digest molecular or cellular antigens, fragments of processed antigen are inserted into the macrophage membrane as part of surface protein complexes.
• Lymphocytes are the key cells that mediate the acquired immune response of the body. Only about 5% of lyphocytes are found in circulation. They constitute 20-30% of all WBC. Most lymphocytes are found in lymphoid tissues, where they are more likely to encounter invaders. By one estimate,the adult body contains a trillion lymphocytes at any one time. (B cells and T cells)

Lymph Nodes are small oval shaped structures located along the lymphatic vessels. Lymph nodes act as filters, with an internal honeycomb of connective tissue filled with lymphocytes that collect and destroy bacteria and viruses. They are divided into compartments, each packed with B lymphocytes and a sinus. As lymph flows through the sinuses, it is filtered by macrophages whose function is to engulf pathogens and debris. Also present in the sinuses are T lymphocytes, whose functions are to fight infections and attack cancer cells. Lymph nodes are in each cavity of the body except the dorsal cavity. Physicians can often detect the body’s reaction to infection by feeling for swollen, tender lymph nodes under the arm pits and in the neck, because when the body is fighting an infection, these lymphocytes multiply rapidly and produce a characteristic swelling of the lymph nodes.

Tonsils are often the first organs to encounter pathogens and antigens that come into the body by mouth or nose.

Peyer’s patches, located in the wall of the intestine and the appendix, attached to the cecum of the large intestine, intercept pathogens that come into the body through the intestinal tract.

Interferon (IFNs) are naturally occurring glycoproteins involved in non-specific immune responses. Interferons do just as their name states they "interfere" with viral growth. Interferons are initiated from a cell that has been infected by a virus. When a cell has been infected by a virus the virus will then cause the cell to make viral nucleic acid. This nucleic acid acts as a signal and it causes the cell to realize that it has been infected with a virus. So the cell will start making and sending out interferons. The IFN's that the cell sends out go to nearby healthy cells and warns them of a virus. The healthy cells then start intracellular changes that help the cells to be more resistant to the virus.



Complement System

Complement is activated by antigen-antibody complexes and causes holes to form in the plasma membrane of foreign microbes or cells (lysis). The complement system is considered a nonspecific defense, but it can be activated against specific microbes that have been marked with antibodies. Hemolytic transfusion reactions are caused by complement activation after a person expresses antibodies against the antigens found on the inappropriately donated blood. Hemolytic Disease of the Newborn (HDN) is due to maternal antibodies against the Rh factor crossing the placenta, binding to the baby's red blood cells, and stimulating the baby's own complement system to lyse its red blood cells.
Interferon in response to viral infection Interferon (IFNs) are naturally occurring glycoproteins involved in non-specific immune responses. Interferons do just as their name states they "interfere" with viral growth. Interferons are initiated from a cell that has been infected by a virus. When a cell has been infected by a virus the virus will then cause the cell to make viral nucleic acid. This nucleic acid acts as a signal and it causes the cell to realize that it has been infected with a virus. So the cell will start making and sending out interferons. The IFN's that the cell sends out go to nearby healthy cells and warns them of a virus. The healthy cells then start intracellular changes that help the cells to be more resistant to the virus.

Adaptive Defense (Specific Defense--third line of defense)
This part of the immune system directly targets invading microbes. Our specific immune defenses respond to antigens. An antigen is a protein (or polysaccharide) molecule, typically on the cell membrane, that the body recognizes as non-self. They are found on microbes, foreign cells, or on cancer cells. Normally our immune system does not respond to our own antigens (if it does, then this is an autoimmune disease). Sometimes we develop an immune response to a harmless antigen, such as pollen or cat dander (this is an allergic response).

Lymphocytes Specific Immunity is dependent upon two types of lymphocytes, the B cells and the T cells. Their names are based on where in the body they mature. B cells mature in the bone marrow, and T cells mature in the thymus gland. In comparison, both B and T cells can recognize and target antigen-bearing cells, although they go about this in different ways. B and T cell lymphocytes are capable of recognizing an antigen because they have specific receptor molecules on their surface which exactly fit individual antigens (like a lock and a key). Any B or T cell can only respond to one type of antigen. The body does not know ahead of time which antigens it will encounter, but rather makes receptor sites for a huge number of possible antigens. It is estimated that for the million or so antigens we encounter in our lifetime we have an equal number of specific lymphocytes for each possible antigen.


B Cells Produce Antibodies
B cell lymphocytes are responsible for antibody-mediated immunity (humoral immunity). They produce antibodies, which are proteins that bind with and neutralize specific antigens. Antibodies do not directly kill bacteria, but mark them for destruction. When antibodies bind to viruses they can prevent the viruses from infecting cells. When antibodies bind to toxins they can neutralize the toxin (why we get immunized against the tetanus toxin). Humoral immunity works best fighting against target viruses, bacteria, and foreign molecules that are soluble in blood and lymph before the bacteria or viruses have entered into cells (extracellular bacteria and extracellular viruses).
B cells produce two different types of cells:

• plasma cells
• memory cells

Questions


1. The immune system is divided into..
a. Three groups; First, Second, and third lines of defense.
b. Two groups; General immunity and specific immunity
c. Two groups; nonspecific and specific
d. all of the above

2. Which is not part of the first line of defense.
a. Protects portals of entry.
b. antibodies
c. Saliva, and tear
d. Nasal hairs

3. What causes Whooping cough?
a. High levels of lactic acid
b. damaged cilia
c. dieing cells filled with keratin
d. too much MHC

4. Which is NOT a characteristic of the Lymphatic system?
a. acts as a drain
b. protects against foreign material
c. provides an auxiliary route for the return of extracellular fluid to the circulatory system
d. sinuses lymph nodes and spleen

5. Lymph is...
a. a plasma like liquid carried by lymphatic circulation
b. made up of pyrogens
c. a protein that ingests and eliminates foreign material
d. a secondary response that is produced in response to viruses, RNA, Immune products, and various antigens.

6. When neutrophils and macrophages squeeze out of capillaries to fight off infection it is called:
a. phagocytosis
b. hemolysis
c. interleukin
d. diapedesis
e. folliculitis

7. During a great battle between your WBC's and an aggressive microbe, an inflammatory response has been initiated. Redness and edema has kicked in what else does the body do to protect itself?
a. Histamine cause vasodilation
b. Hypothalmus raises the thermostat
c. Neutrophils engulf and destroy the microbe
d. Living and dead WBC and bacteria accumulate
e. All of the above

8. Specificity and memory are associated with which body defense mechanism?
a. inflammatory response
b. phagocytosis by macrophages and neutrophils
c. interferon
d. T cell and B cell responses
e. anatomical barriers in the body

9. ___________ is an additional chemical defense found in tears and saliva.
a. T lymphocytes
b. saline
c. lysozyme
d. EFC

10. A phagocytic white blood cell is best described as "large eater"is called a ______.
a. Macrophage
b. Mast cell
c. Plasma cell
d. T-cell
e. None of the above

11. During a secondary immune response,
a. antibodies are made quickly and in great amounts.
b. antibody production lasts longer than in a primary response
c. antibodies of the IgG class are produced.
d. lymphocyte clones are believed to develop.
e. all of these apply

12.Which of these cell types aids the activation of T lymphocytes by antigens?
a. macrophages
b. neutrophils
c. mast cells
d. natural killer cells

13. A mother passing antibodies to her baby through breast milk would be considered what type of immunity?
a. Passive immunity
b. Artificial immunity
c. Active Immunity
d. Kentucky Fried Chicken

14. Which of the following would Not be considered an autoimmune disease?
a. Systemic Lupus Erythematosus
b. Multiple Sclerosis
c. Rheumatoid Arthritis
d. Herpes Simplex Virus

15. Mycoses is caused by
a. Fungi
b. Bacteria
c. Protozoans
d. none of the above

16. If you are experiencing rhinitis what is wrong with you
a. You are having trouble bending your knee
b. Unable to hear
c. Runny nose
d. Stuffy nose

17. Antibodies prepared from a clone of cells derived from a single B cell are called
______antibodies.
a. allergen
b. inerferon
c. monclonal
d. a and b

18. The bubble boy had what immune deficiency?
a. SCID
b. SSGC
c. GCG
d. ABC

19. The 1st vaccine was for
a. small pox
b. chicken pox
c. measles
d. mumps