Biology (Immunological Basics)

GREASE THOSE WHEELS ( BIOLOGY )

#1 IMMUNOLOGICAL BASICS

Lets start with my fav: biology and a topic which can be one of the most difficult yet crucial part of your AS Level and beyond - immunology.

Following is the checklist for this topic from the 2010 Biology Syllabus...

• recognise phagocytes and lymphocytes under the light microscope;
• describe the origin, maturation and mode of action of phagocytes;
• explain the meaning of the term immune response, making reference to the terms antigen, self and non-self;
• distinguish between B- and T-lymphocytes in their mode of action in fighting infection, and describe their origin and functions;
• explain the role of memory cells in long-term immunity;
• relate the molecular structure of antibodies to their functions;

These are the points which examiners\question setters at Cambridge assume that you know very well so we will cover each aspect in detail...

a) recognise phagocytes and lymphocytes under the light microscope;

The following micrographs show as to how different types of phagocytes and lymphocytes look under the microscope. These type of photomicrographs are frequent in paper 31,32 as well as 21,22 so look at them well...

The cell with the lobed nucleus [in the centre] is a neutrophill; a type of a phagocyte.

The cell with a horseshoe-shaped nucleus is a monocyte; from the family of phagocytes.

The cell with a uniformly circular nucleus is a lymphocyte; it can either by a B-lymphocyte or T-lymphocyte. Notice its size; which roughly equals that of a RBC.

The comparatively huge cell cell in the centre is a plasma cell; it is formed upon differentiation [something close to specialization] of B-lymphocytes during an immune response.

Thats it for the first part.

b) describe the origin, maturation and mode of action of phagocytes;
Monocytes and Neutrophils are formed in the bone marrow by stem cells. Monocytes leave the bone marrow before being fully functional and attain maturity in the blood stream. After 40-60 hours of circulation by a mature monocyte, it settles in the tissue and increases in size slightly, now a macrophage [e.g, the alveolar macrophage in the alveoli]. On the other hand neutrophils do not leave bone marrow until maturity. 

All three types of phagocytes share the same job,i.e, phagocytosis [killing by engulfing]. The mechanism is described below...

1. Chemotaxis , i.e, the process by which cells are attracted to the bacteria. It may be by the materials released by the bacteria or opsonization , and opsonin is a type of antibody that renders bacteria more susceptible to phagocytosis [which may be by coating of the outer membrane of bacteria], or by agglutination [via agglutinins which 'clump' together bacteria].
2. Attachment , the phagocyte and bacteria attach together.
3. Endocytosis , the formation of false feet [ pseudopodia ] or a simple invagination of the cell membrane that results in the foreign body being engulfed.
4. Vacuole Formation , upon engulfment a phagocytic vacuole/phagosome forms around the bacteria/foreign body.
5. Killing/Lysis , this can be done by Hydrogen Peroxide or other lysins. Remember hydrogen peroxide production requires O 2 so the lysis of bacteria or other engulfed components is a very much aerobic process. And also the contraction of certain contractile proteins, microfilaments is responsible for the changes in orientation of the cell membrane associated with vacuole formation and endocytosis so this process also requires energy .
6. Digestion , lysosomes [vacuoles containing 50+ hydrolytic enzymes in an acidic media] attach to the phagosomes and release their contents inside them. Subsequent digestion reduces the bacteria to useful amino acids , respiratory substrates [glucose etc] which are taken up by cell for future use.

Phagocytosis going on...

c) explain the meaning of the term immune response, making reference to the terms antigen, self and non-self;

An immune response is a our body's reaction to an antigen which a marker molecule in the cell surface membrane of foreign bodies that sets off an immune response.

The discrimination between self and non-self cells is an integral part of our immune system. This distinguishing is possible by the presence of glycoproteins or other types of recognition molecules . Our body functions normally when no abnormal recognition protein/molecule is encountered by our immune system but when foreign particles exhibiting recognition proteins that our not normally found in our body are encountered then our body's defense mechanism starts rolling, i.e, an immune response is initiated. This can be a product of two scenarios:

• Tissue Transplant leading to tissue rejection because the donor can never have the same recognition proteins as the acceptor. Thats why, following up a tissue transplant, the acceptors are usually at prescriptions that suppress their immune system from starting an immune response.
• Invasion of Bacteria and other foreign particles

d) distinguish between B- and T-lymphocytes in their mode of action in fighting infection, and describe their origin and functions;

The lymphocytes are the backbone of our immune system without them our immune system would be of no use. Moreover the two main types of lymphocytes, the T and B lymphocytes are interdependent thats why a person infected by the AIDS virus has a severely depleted immune system due to the destruction of T-Lymphocytes.

Both of these cells originate in the stem cells of the bone marrow . While the B-cells mature in the bone marrow, the T-cells move as precursors [non-functional form] to the thymus gland where they mature and T-lymphocytes which are over reactive and can cause harm to the body's own cells are also destroyed here.

B-Lymphocytes

B-Lymphocytes can differentiate into Memory Cells and Plasma Cells. The former acts as an immunological memory of the antigen in question after the body is exposed to it for the first time and has countered it and remains in the blood stream for months or even years to initiate a more severe secondary immune response when that antigen is encountered again. While plasma cell s are there to produce antibodies against a specific antigen and thus have a more developed and extended Rough Endoplasmic Reticulum and Golgi Body.

T-Lymphocytes

The are of two main types; Helper Cells and Cytotoxic Cells. T- Helper Cells sells act like assistants to the immune system, when they come across an immune cell such as a Dendritic Cell or Macrophage displaying {on their cell membrane like war trophies, after they have destroyed an antigen bearing cell =)] an antigen which they are also specific to, they form a temporary bond at the T-Cell Receptor (TCR) which can be thought of as a binding site on an enzyme and release chemicals called cytokines which simulate other immune system cells like Macrophages and Lymphocytes to take action against the intruder. This simulation can be done in the form of B-Lymphocytes activation and differentiation to produce plasma cells.While Cytotoxic Cells exclusively scan the cell membranes of the bodies' own cells for changes in the Major Histocompatibility Complex [it can be thought of as a genomic region in a cell responsible for protein synthesis and displaying of the proteins encoded inside the cell on the cell surface membrane], malignant growth [as in cancer], cell invasion by viruses and other intercellular parasites alter the MHC of the cell [i.e other/more types of proteins will started to get synthesized] and thus Cytotoxic Cells act on it and destroy the cell as a whole.

Now Lets See These Two Types of Lymphocytes Working Together

There are two routes that an immune response can follow we will briefly outline both of them...The first one is a simpler Humoral Response ...

A non-activated B-cell has several antigen binding sites attached to its cell membrane ----> A complementary antigen attaches to it ----> It is digested by the B-Cell while its antigen is displayed on the cell membrane of the B-Cell ----> T-Helper cell recognizes the antigen and binds to it ----> Cytokines are secreted by the THC ----> Cytokines lead to a subsequent B-cell activation and differentiation and also the activation of T-Cytotoxix cells ----> Plasma Cells produced by this process secrete antibodies that bind to the antigens to which they are specific ----> The intruder is destroyed.

The other one is a bit more complex Cell-Mediated Response...

T-Helper Cell binds to an antigen displayed on the cell membrane of an Antigen Displaying Cell (Macrophages, Dendritic etc) ----> Cytokines are secreted which activate B-Cells and the Cytotoxic Cells ----> Antibodies are secreted by plasma cells; Cytotoxic cells destroy altered self cells.

e) relate the molecular structure of antibodies to their functions;

The image on the write shows a typical 'Y-shaped' antibody (also called Immunoglobulins) structure. They are proteins that are utilized by the immune system to detect and neutralize foreign objects. They consist of a light chains (the two smaller ones) and the heavy chains (the two central ones) which both have a variable region (specific to every different type of antibody) at the tips with an antigen-binding site (shown in yellow). The heavier chains and the heavy and light chains are linked together by disulfide linkages which are a type of covalent bonds that are formed upon the oxidation of thiol groups [-SH2] that are left over from the cysteine molecules. They are very important to the functioning of the antibody because most of its functions are carried out in an extracellular aqueous environment which attacks both the other available alternatives, ionic bonds and hydrogen bonding so the preservation of an antibody's structure is critical to its proper functioning and the disulfide linkages ensure just that.

Some of the important antibody functions are listed below...

• Opsonization; the stimulation of other immune cells (like Macrophages) to engulf a foreign particle.
• Agglutination; the clumping together or precipitation of antigen-bearing material.
• Lysis; breakdown of an antigen bearing particle.
• Detoxification; the neutralization of harmful substances produced by foreign particles.

Whewww!! That took some long time typing...hope you grasp the points well!!! =)