Immune System Quiz

The Question - QUIZ
An important defense against disease in vertebrate animals is the ability to eliminate, inactivate, or destroy foreign substances and organisms. Explain how the immune system achieves all of the following.
1) Provides an immediate nonspecific immune response
2) Activates T and B cells in response to an infection
3) Responds to a later exposure to the same infectious agent
4) Distinguishes self from nonself

General Idea --- What is immune system:

I. The purpose of the immune system is to keep infectious microorganisms, such as certain bacteria, viruses, and fungi, out of the body, and to destroy any infectious microorganisms that do invade the body. The immune system is made up of a complex and vital network of cells and organs that protect the body from infection.

II. The organs involved with the immune system are called the lymphoid organs, which affect growth, development, and the release of lymphocytes (a certain type of white blood cell). The blood vessels and lymphatic vessels are important parts of the lymphoid organs, because they carry the lymphocytes to and from different areas in the body. Each lymphoid organ plays a role in the production and activation of lymphocytes. 

Lymphoid organs include:

• adenoids (two glands located at the back of the nasal passage)
• appendix (a small tube that is connected to the large intestine)
• blood vessels (the arteries, veins, and capillaries through which blood flows)
• bone marrow (the soft, fatty tissue found in bone cavities)
• lymph nodes (small organs shaped like beans, which are located throughout the body and connect via the lymphatic vessels)
• lymphatic vessels (a network of channels throughout the body that carries lymphocytes to the lymphoid organs and bloodstream)
• Peyer's patches (lymphoid tissue in the small intestine)
• spleen (a fist-sized organ located in the abdominal cavity)
• thymus (two lobes that join in front of the trachea behind the breast bone)
• tonsils (two oval masses in the back of the throat)

Lymphoid organs

1. Provides an immediate nonspecific response

For immune system, there are physical, chemical and cellualr defenses against foreign invasions, such as viruses, bacteria, and other agents of disease. During the early stages of an infection, there is an inflammatory repsonse (aka nonspecific response)

• Non-specific attack
• Phagocytes active ("eat" pathogen)

Nonspecific Response is our second line of defense. it provides us immediate defense against pathogen infection. It does noe target a speicific cell. The elements of the non-specific immune system include anatomical barriers, secretory molecules and cellular components. Among the mechanical anatomical barriers are the skin and internal epithelial layers, the movement of the intestines and the oscillation of broncho-pulmonary cilia. Associated with these protective surfaces are chemical and biological agents.

Anatomical barriers to infections
The epithelial surfaces form a physical barrier that is very impermeable to most infectious agents. Thus, the skin acts as our first line of defense against invading organisms. Also, movement due to cilia or peristalsis helps to keep air passages and the gastrointestinal tract free from microorganisms. The flushing action of tears and saliva helps prevent infection of the eyes and mouth as fatty acids in sweat inhibit the growth of bacteria, and lysozyme and phospholipase found in tears, saliva and nasal secretions can break down the cell wall of bacteria and destabilize bacterial membranes. The trapping effect of mucus that lines the respiratory and gastrointestinal tract helps protect the lungs and digestive systems from infection. 

B. Humoral barriers to infection
The anatomical barriers are very effective in preventing colonization of tissues by microorganisms. However, when there is damage to tissues the anatomical barriers are breached and infection may occur. Once infectious agents have penetrated tissues, acute inflammation defense mechanism would then kick in. Humoral factors play an important role in inflammation, which is characterized by edema and the recruitment of phagocytic cells. These humoral factors are found in serum or they are formed at the site of infection.

Table 2. Physico-chemical barriers to infections
System/Organ	Active component	Effector Mechanism
Skin	Squamous cells; Sweat	Desquamation; flushing, organic acids
GI tract	Columnar cells	Peristalsis, low pH, bile acid, flushing, thiocyanate
Lung	Tracheal cilia	Mucocialiary elevator, surfactant
Nasopharynx and eye	Mucus, saliva, tears	Flushing, lysozyme
Circulation and lymphoid organs	Phagocytic cells NK cells and K-cell LAK	Phagocytosis and intracellular killing Direct and antibody dependent cytolysis IL2-activated cytolysis
Serum	Lactoferrin and Transferrin	Iron binding
	Interferons	Antiviral proteins
	TNF-alpha	antiviral, phagocyte activation
	Lysozyme	Peptidoglycan hydrolysis
	Fibronectin	Opsonization and phagocytosis
	Complement	Opsonization, enhanced phagocytosis, inflammation

C. Cells for nonspecific response 

Phagocytes - cells which "eat" foreign material to destroy them
Phagocytes are formed from stem cells in bone marrow (stem cells are undifferentiated WBC's) 

Neutrophil- phagocytize bacteria. Polymorphonuclear cells are recruited to the site of infection where they phagocytose invading organisms and kill them intracellularly. In addition, PMNs contribute to collateral tissue damage that occurs during inflammation.
Eosinophils - secrete enzymes to kill parasitic worms among other pathogins. Eosinophils have proteins in granules that are effective in killing certain parasites.  

Macrophage - "big eaters" phagocytize just about anything. Tissue macrophagesand newly recruited monocytes, which differentiate into macrophages, also function in phagocytosis and intracellular killing of microorganisms. In addition, macrophages are capable of extracellular killing of infected or altered self target cells. Furthermore, macrophages contribute to tissue repair and act as antigen-presenting cells, which are required for the induction of specific immune responses.
Natural killer (NK) and lymphokine activated killer (LAK) cells – NK and LAK cells can nonspecifically kill virus infected and tumor cells. These cells are not part of the inflammatory response but they are important in nonspecific immunity to viral infections and tumor surveillance. 

Macrophage destroying bacterial cells

2. Activates T and B cells in response to an infection
T cells (Helper T cells and Cytotoxic T cells)
T cells arise from stem cells in the bone marrow, and then travel to the thymus where the differentiate and mature. At maturity, they acquire receptors for self markers (MHC molecules) and for antigen-specific receptors. They are then released into the blood as "virgin" T cells.
T cells ignore other cells with MHC molecules and they ignore free-floating antigens. However, they will bind with a antigen-presenting macrophage (a macrophage possessing a MHC-antigen complex). This binding promotes rapid cell division and differentiation into effector and memory cells (all with receptors for the antigen).
Effector helper T cells secrete interlukins (stimulate both T and B cells to divide and differentiate).
Effector cytotoxic T cells recognize infected cells with the MHC-antigen complex. They then destroy the cell with perforans (enzymes which perforate the cell membrane, allowing cytoplasm to leak out) and other toxins which attack organelles and DNA.

B cells and Antibodies
B cells also arise from stem cells in the bone marrow. As they develop and mature, they start synthesizing a single type of antibody.
Antibodies are proteins which recognize antigens.
The virgin B cell produces antibodies which move to the cell surface and stick out.
The B cell floats in the blood when it encounters the specific antigen it becomes primed for replication.
The B cell must receive an interleukin signal from a helper T cell which has already become activated by a macrophage with a MHC-antigen complex. This promotes rapid cell division.
The B cell population then differentiates into effector and memory B cells.
The effector B cells then produce a staggering amount of free-floating antibodies.
When these free-floating antibodies encounter an antigen, they tag it for destruction by phagocytes and complementary proteins.

*ADAPTIVE immunity = highly specific for a particular pathogen / antigen.

Antigen presenting cells present foreign antigen on their surface.

• Antigen is recognized by T and B cells.
• Cytotoxic T cells kill infected cells.
• Helper T cells Activate Macrophages, T and B cells.
• B cells produce AntiBodies.
• AntiBodies bind to antigens and bring about: 
• Neutralization: pathogen can’t adhere to host cell
• Opsonization: makes it easier for phagocytosis
• Complement activation: kills infected cell by punching holes in cell membrane.
• Memory cells are made that are much more efficient (does NOT need T cell activation) in proliferating and making antibodies in case the same infection strikes in the future.
• Memory cells allow the body to mount a greater, and more sustained response against the same pathogen during secondary response.

3. Responds to a later exposure to the same infectious agent
Immune memory --- when an antigen makes contact for the first time with cells of the humoral immune system, B lymphocytes that are producers of specific immunoglobulins against that antigen multiply and in days synthesize their antibodies. This is called primary response. Some of these specific B lymphocytes remain in the circulation for a long time, sometimes during the entire life of the individual, and they become the memory cells of the immune system. T cells can also produce memory cells with an even longer life span than B memory cells. When the body is exposed in the future to the same antigen, B and T memory cells help the immune system to activate much faster, and the production of antibodies will be faster and more intense since the immune system is already prepared to react against that antigen. This is called the secondary response. 

Examples of this phenomenon could be chicken pox and cancer. As we known, if a person had chicken pox before, that person is most likely never getting chicken pox again. The same goes for who had the immunization of chicken pox. Also, when fighting cancer, our immune system undergoes the same mechanism. When one's body is exposeed to cancerous cells, one's immune system would remember these cancerous cells and recognize these cells next time. However, if one happens to develop cancer, one's imuune system is probably being worn out.  

4. Distinguishes self from nonself

One of the most essential abilities of the immune response is the ability to distinguish between "self" and "non-self." Every cell in one's body carries the same set of distinctive surface proteins that distinguish one as "self." Normally one's immune cells do not attack one's own body tissues, which all carry the same pattern of self-markers; rather, one's immune system coexists peaceably with one's other body cells in a state known as self-tolerance. This set of unique markers on human cells is called the major histocompatibility complex (MHC). There are two classes: MHC Class I proteins, which are on all cells, and MHC Class II proteins, which are only on certain specialized cells.

Any non-self substance capable of triggering an immune response is known as an antigen. An antigen can be a whole non-self cell, a bacterium, a virus, an MHC marker protein or even a portion of a protein from a foreign organism. The distinctive markers on antigens that trigger an immune response are called epitopes. When tissues or cells from another individual enter your body carrying such antigenic non-self epitopes, your immune cells react. This explains why transplanted tissues may be rejected as foreign and why antibodies will bind to them.

Every cell in one's body is covered with these MHC self-marker proteins, and--except for identical twins--individuals carry different sets. MHC marker proteins are as distinct as blood types and come in two categories--MHC Class I: humans bear 6 markers out of 200 possible variations; and MHC Class II: humans display 8 out of about 230 possibilities ( National Cancer Institute 2014).

Summary
Immunity can be either natural or artificial, innate or acquired=adaptive, and either active or passive.
Active natural (contact with infection): develops slowly, is long term, and antigen specific.
Active artificial (immunization): develops slowly, lasts for several years, and is specific to the antigen for which the immunization was given.
Passive natural (transplacental = mother to child): develops immediately, is temporary, and affects all antigens to which the mother has immunity.
Passive artificial (injection of gamma globulin): develops immediately, is temporary, and affects all antigens to which the donor has immunity. 

Sources from:
Mr. Kevin Quick, Lecture at The Webb Schools, 2014.
http://thelifeofapremed.tumblr.com/post/56690250816/leukocytes-macrophages-neutrophils-mast-cells
http://pathmicro.med.sc.edu/ghaffar/innate.htm
http://www.cancer.gov/cancertopics/understandingcancer/immunesystem/AllPages
http://www.uic.edu/classes/bios/bios100/lecturesf04am/lect23.htm
http://www.course-notes.org/Biology/Outlines/Chapter_43_The_Immune_System 

http://en.wikipedia.org/wiki/Polyclonal_B_cell_response