Immunology sheet # 1

Immunology
In this course we are going to talk about the immune system of the human body, as we know Humans live in a hostile environment, containing many pathogens trying to make use of our bodies for their own benefit causing infection (the growth of organisms in our bodies trying to survive at our own expense), that's why we must have a system to protect us from all the organisms, pathogens, toxins and any other harmful substances, and that is the function of "The Immune System".
An important property of the immune system(since it is capable of killing) is the ability to differentiate foreign bodies from our own normal cells. So when the body encounters a foreign substance an immune response is established that lasts for a certain necessary time and then has to be switched off.
Abnormalities in the immune response may be encountered and will ultimately lead to diseases, which can be classified into 3 categories and those are:
1)Immunodeficiency: if there is no good immune response, when the cells or chemicals in the immune system are incapable of fighting the infectious disease.
[Immune response is inadequate].
2)Auto immunity: when the immune system's ability to differentiate is compromised and therefore starts attacking and destroying our own cells and tissues, by producing cells or antibodies that attack the normal cells causing autoimmune diseases. [Immune response is mis-guided].
3) Hypersensitivity: here the immune response is normal but it lasts for a prolonged period of time or is directed towards things that are trivial (unimportant), and the net result is destruction of the surrounding normal tissues and causing inflammation, for example some people establish an immune response and produce antibodies toward pollens which normally does not induce a response. [Immune response is normal but prolonged and sometimes misdirected].

Now we are going to talk about the immune system guiding these responses which consists of Cells and Tissues.
Tissues of the Immune System
*Primary immune tissues:
-The site of production and maturation of cells
- Consists of:
The Bone marrow: where all the cells of the immune system are produced.
Thymus: the site of production of T cells.
*Secondary immune tissues:
-After the cells are produced and matured within the primary lymphoid tissue(primary immune tissue) , they leave it and circulate in the blood to reach other tissues in the body where they settle and wait to encounter foreign bodies so they can do their job in eliminating them, and those are known as the secondary lymphoid tissues.
-Consists of:
Spleen
Lymph nodes
MALT (Mucosal-asssociated Lymphoid Tissue): present in the mucosa of the GI and respiratory tract, which are scattered patches of lymphoid tissue that does not look like lymph nodes because they are not surrounded by a capsule.
-So there is nothing that comes into our bodies without passing through these secondary lymphoid tissue, for example anything that penetrates the skin will be drained through the lymphatics to the lymph nodes(axillary, inguinal or cervical) depending on location of the invading foreign body on the outer skin. On the other hand the spleen controls the blood, anything that goes through the blood will have to pass through the spleen and thus will be captured there. Also the MALT has an important role in eliminating the foreign bodies attacking the mucosa of the GI and respiratory tracks which are exposed to the outer environment.
So the secondary lymphoid tissues harbor all the mature cells of the immune system and act as the soldiers of our body, ready to deal with the invaders.



Cells of the Immune System

The mother of all the cells of the immune system is the stem cell found in the bone marrow, which gives 2 lineages: Myeloid and Lymphoid.
The myeloid line gives rise to a number of cells:
Granulocytes (Eosinophils, Neutrophils, Basophils, and mast cells) and the Macrophages.
Eosinophils
-Named so because it takes up the eosin dye in H&E sections due to its basic components.
-Appears pink or bright red.
-The main component of its granules is "The major basic protein" which is a potent anti parasitic agent.
-An increase in the number of Eosinophils in the blood (Eosinophilia) is associated with parasitic infections or allergic reactions.
-Cells of the immune system usually have certain molecules on their surface (receptors) that are responsible for the interaction between one cell and another and between cells and outer molecules, there is around 200-300 different types of these receptors found on the different types of cells, and are usually called by their functional name , for example receptors for the immunoglobulins are called Fc receptors, and if they attach complement components then they are called Complement receptors.
There's also what is called the CD System (Clusters of Differentiation), which are receptors on the surface of the cells and are -as indicated by their name- defined by clusters of antibodies, and their presence is determined by the degree of differentiation of the cells (a cell not containing a CD molecule may acquire it after differentiation), for example an X antibody will attach to the cell only if it contains X receptor. For instance the CD4 receptor is present on the surface of T-lymphocytes (mainly the helper T-lymphocytes) and Macrophages, so if if we apply CD4 antibodies to an unknown population of cells and those antibodies cluster to the cells, then this indicates that those cells may be either T-lymphocytes or Macrophages.

Now back to the eosinophils, on its surface there is a receptor that is specific to only one type of antibodies which is the IgE. When the body develops an immune response against a parasitic infection, the body tends to produce IgE which has receptors for it on the eosinophils. Now the IgE binds to the parasite and later on the eosinophils come and bind to the IgE through its receptor, and this reaction results in pouring of the Basic protein from the eosinophil to the parasite which will actually result in killing of the parasite. This mechanism is different than that of the neutrophils that are phagocytic cells(engulf bacteria), and that is due to the large size of the parasites which render it resistant to phagocytosis.

IgE may also be produced in allergic reactions, and people who have a tendancy more than others to develop allergic reactions are called atopic, and those usually produce IgE to antigens that are not really parasites such as pollens. Almost 10% of the population are atopic, and this is usually more in developed countries(US and Europe) and less in developing countries.

Neutrophils:
(or Polymorphonuclear leukocytes)
-Nucleus is segmented (two or three segments)
-Granules are neutral (neither blue nor pink)
-Constitutes about 60% of the WBCs
-Their life time is relatively short, only for a few days then they die, but they are continuously replaced.
-Is a phagocytic cell engulfing the foreign materials in the human body.
-Neutrophils recognize certain materials(sugars or proteins) present on the surface of bacteria and attach itself to it, such as mannose sugar which is present only on bacteria and this binds to mannose binding protein on the surface of neutrophils causing the bacteria to be engulfed. The engulfed bacteria is now contained in certain vesicles called "phagosomes", these bind to "lysosomes" which are the granules of the neutrophil containing hydrolytic enzymes, this fusion results in the the formation of a "phagolysosome" and killing of the bacteria by the hydrolytic enzymes.

-After that the cell will die and release the granules to the outside causing some tissue damage. So there is now dead bacteria, WBCs which are the dead neutrophils, dead tissue and debris around the site of infection, all of which results in the formation of pus, such infection is known as pyogenic and is usually caused by Gram +ve bacteria. Because they contain peptidoglycan in their cell wall they attract neutrophils and result in the formation of pus.

Basophils & Mast Cells:
-They come from a common origin, but they do not give rise to each other.
-Basophils are present in the blood, while mast cells are present in the connective tissue
-They are stuffed with granules that are usually blue in color because they are acidic and take up the Hematoxylin dye in H&E staining.
-The granules contain mainly Histamin, and whenever these cells degranulate due to different stimuli, they release histamine which is a potent mediator for inflammation (causing vasodilatation, increase vascular permeability, and increase irritation to nerve endings).
-Mast cells in turn may also have a role in the allergic response, due to the presence of IgE receptors on its surface just like the eosinophil, the difference is that the IgE binds to the surface of the mast cell before attaching to the antigen itself, thus most of the IgE in our bodies are attached to mast cells.
-When a certain antigen gains access to our bodies, it will attach to the IgE and usually one antigen links to two antibodies and this causes the release of histamine from mast cells.
So Eosinophils and Mast cells both have a role in allergic and hypersensitivity reactions…
Note: Type 1 hypersensitivity reaction called "Immediate type hypersensitivity" is mediated by IgE already attached to the mast cells, that's why it is quick developing symptoms of the allergic reaction within 10-15 minutes from the time of exposure to the antigen.


Macrophages:
-Is a phagocytic cell that can recognize foreign material and engulf it.
-It differs than the Neutrophil in that it doesn't die after engulfing the bacteria, but it takes up the bacteria and breaks it down through the action of hydrolytic enzymes present in the phagolysosome and then takes part of this bacteria and sprays them on its surface. Actually, this presentation on its surface is for the benefit of some other cells of the lymphoid tissue which are the lymphocytes, that need to recognize antigens that are present on the surface of macrophages that's why macrophages are called Antigen-presenting cells(APCs).
-Macrophages are originated from monocytes which comes out from the bone marrow and circulate in the blood and then distribute itself in the different tissues of the body.
Macrophages in the liver  Kuppfer cells
Macrophages in the bone  Osteoclast
Macrophages in the nervous system  Microglial cells



That's all for today !!
Good Luck




Tala Mazahreh
Lec # 1 Immunology
Sunday 28/11/2010