Health and Diseases (III) Body Defence P.1

Health and Diseases (III)

Body Defence in Mammals

M

an is living in a world of micro-organisms, many of which are path______and can cause diseases (Pathogens are micro-organisms that can cause diseases.). Many of these micro-organisms either feed on the ti____ or liberate poi_____ substances (toxins), thereby bringing about disease. In destroying tissues and liberating toxic substances, pathogenic micro-organisms change the i______environment and upset the smooth running of the body. Their control by the body's natural defence mechanisms is thus an aspect of hom______.

Pathogen / Disease
virus / AIDS, influenza, poliomyelitis and the common cold,
bacteria / tetanus, typhoid, diphtheria and tuberculosis
unicellular protists / malaria and amoebic dysentery
fungi / Athlete’s foot

Ahealthy individual is able to protect himself from the hostile pathogens by a number of very effective means which are referred to as defence mechanisms. Some of these prevents e____ of pathogens into our body in the first place, while others will fi___against those pathogens that have entered.

Defence mechanisms are thus indispensable for life. Two major types of defence mechanisms are:

  • Non-specific mechanisms are those that combats against any type of pathogens on their invasion.
  • Specific mechanisms(immune responses) refer to those that depends on specific recognition of the invading pathogen for action.

I)Non-specific Mechanisms

These are mechanisms that are

  • present from b and
  • are NOT dependent upon prev exposure to pathogens.
  • are simple in action and are NOT sp against a particular type of pathogen.

1. Mechanical Barriers:

The sk and the mu membranes form a natural physical barrier that prevents the entry of pathogens in the first place. They are referred to as the first line of defence.
Theskin is most effective because of its relatively imp______horny layer (stratum corneum).
The m membrane of the respiratory tractproduce m____ that trap air-borne agents. The mucus are then swept up by the beatingc___ to the throat and is then sw______with saliva.
Thec______of blood at wound not only preventsexcessive bleeding but also blocks the en___ of micro-organisms. /

Health and Diseases (III) Body Defence P.1

2. Chemical Barriers:

Various liquids and chemicals on the surface of our body or inside our body are effective in inhibiting or destroying pathogens. They constitute thechemical barrier mechanisms.

The seb______secretions and sw____ of the skin contains bactericidal and fungicidal fatty acids.

Nasal secretions, saliva, tears, urine and other body fluids contain chemicals capable of inactivating some viruses and tears contain ly______which is active against bacteria.

Secretions from mucous membranes are bactericidal and viricidal.

A___ in the stomach is a powerful sterilizing liquid (gastric juice).

In the vagina, mutualistic bacteria produce lactic a___. This makes the vagina acidic, creating an unfavourable environment for many pathogenic yeasts, bacteria and viruses.

3. Phagocytosis

Pathogens that can escape the mechanical and chemical barriers into our body are first dealt with by white blood cells called phag____. There are two main types of phagocyte:

  • Neutrophils which are cells with an irregular many-lobed nucleus and a granular cytoplasm.
  • Macrophages which are larger cells with a regular horseshoe-shaped nucleus and a non-granular cytoplasm.

Neutro____ are the commonest type of immune cell and make up about 60 % of all white blood cells in the bloodstream. The bone marrow produces 80 million of these cells every minute and their number in______during an infection.

Macrophages develop from another type of white cell in the blood called monocytes which make up only 6 % of the white blood cells. Monocytes are made in the bone marrow and, after circulating in the bloodfor one or two days, they squeeze through the cap______wall and migrate into the tissues where they become macro_____.

The macrophages wander around the tissues collecting up ‘rubbish’, which may be micro-organisms or other for bodies, (in the lungs dust as well as micro-organisms are collected in this manner) or dam or dead cell. They are particularly numerous in the lungs, liver, kidney, spleen and lymph nodes. Although the neutrophils are the first cells to arrive at a site of inf , the longer-lived macrophages take over at any major site.

The eating process is called phagocytosis. It is a non-sp _way of destroying pathogens:

  • Pseudopodia are sent out which eng bacteria to form a phagocytic vesicle or a phagosome
  • Lyso in the phagocytic cell then fuse with the phagosome and discharge their contents into it.
  • The lysozymes are powerful hydrolytic enzymes which di the pathogen and destroy it.
  • After digestion, the residues are disch______ out of the phagocytic cell.

Phagocytosis, however, has a distinct limitation: it does not act against certain bacteria and is not very effective against vir because they hidein____ the body's own cells where they are protected from attack.

4. The Inflammatory Response

At sites of infection, besides the phagocytic action just mentioned, an in______response may also be elicited. This is a more powerful non-specific response to eliminate the pathogens.

  • Due to release of hist______ in the infected area, large number of pha______cells (neutrophils first and macrophages later) are attr to the area from surrounding tissues.
  • At the same time, the blood vessels dil____ and the blood flow to the area increase. The perm______ of the blood vessels also increase, leading to massive flow of fluids out from the blood into the tissues. This causes sw______ in the area.
  • Phagocytic cellsmove out from the b______into the infected tissue, offering extra support to those already there.
/

H , r , s and p , the inflamed area contains numerous b______and phago____, many of which die and form p . Sometimes the inflamed area forms a boil.

The various non-specific mechanisms normally provide quite a good defence for the body and many invading pathogens are destroyed by them and consequently not able to penetrate deep enough into the body to cause disease. However, in some cases, these mechanisms are not powerful enough to stop the invading pathogen at the site of infection. In such situations the pathogenscontinue to replicate locally and increase in number. Eventually they entered the lymph and blood. Those in the lymph will reach l nodes and those in b______will reach thespl and li At these places the pathogens will meet the fixed Phagocytic cells there. Some of the pathogens will be destroyed by these cells. The remaining ones, however, will multiply and turn on the s______immune responses of the body (specific mechanisms).

II)Specific Mechanisms

There are four major characteristics of specific mechanisms: spe______, di______, me______and self-tol______.

It can recognize specific molecules and produce molecules and cells to match up with and counteract each one of them;

The immune system displays enormous diversity of immune cells and antibodies;

It is able to remember previous exposure to an antigen and a second encounter will be met with a much stronger response;

It can distinguish between "self" and "non-self molecules and normally launch attack on non-self particles only.

A)Basic Definition

  • Pathogens are micro-organisms that can cause d . Pathogens often have anti on their cell surfaces.
  • Antigens are usuallydefinedas

Substances, living or non-l , pathogenic or non-p , that can stimulate a specific im response.

More precisely, an antigen is a substance that specifically combines with ananti .

Antigen usually takes the form of a protein or glycoprotein (protein with short chain poly ) structure on the surface of microbial organisms or other tissue cells

(s antigens) or as a free molecule.

Antigens may not be living path______. Large chemical molecules can also be antigenic and stimulate specific responses. (examples of antigens: Kidney issues, Red Blood cells, bacteria, viruses, foreign proteins, pollen grains, drugs, pollutants.)

  • An antibody is a prot molecule (immunoglob____) produced by an animalin response tothe presence of foreign substance -- antigenfor which it has a high affi____.

B)The Mammalian Immune System

There are two specific mechanisms: theH______Immune Response (HIR) and the Cell-m______Immune Response (CMIR). The mammalian immune system comprises:

  • bone marrow- with precursors (st___ cells) of blood cells
  • blood and lymph- where located various types of w____ blood cells are important for specific defence
  • lymphoid tissues- thymus, bone marrow (primary- where lym______are produced)

lymph nodes and spleen (secondary-- where they develop to maturity)

a)Formation of blood cells

All blood cells arise from common ancestral cells called st cells found in the bone m .

The stem cells develop into :
r__ blood cells,
plate___,
W____ Blood cells / Leukocytes
White Blood cells can be classified into two major groups :
Granulocytes
have granules in their cytoplasm
have lobed nucleus
Agranulocytes
no granules in their cytoplasm
kidney-shaped nucleus /

i)Different types of White Blood Cells (leukocytes)

1) Granulocytes (also called PMNs -- polymorphonuclear leukocytes)

White cells that possess gran____ in their cytoplasm are referred to as granulocytes. They all have lo___ nuclei. They have a short life span (few days).

  • Neutrophils: (50-70%) - the most abundant type of PMN.

An important phag______cell for non-specific body defence.

Actively amoeboid, capable of loco______.

Can leave blood ves and enter into tissue by squeezing between cells of the capillary wall.

  • Eosinophils: (1-4%) - quite rare. Functions ill-defined. Associated with hypersensitivity and allergic reaction.
  • Basophils: (0-1%) Non-phagocytic. Becomes mast cells when entered tissues. Contains hist_____ which when released, will cause vaso______, increase blood flow, increased perm______of blood vessels and outflow of phagocytic cells.

2) Agranulocytes

These are cells with no granules in the cytoplasm. There are two types :

  • Lymphocytes(33%) : B and T cells are chiefly responsible for the sp immune responses.

___cells (for HIR). ___cells (for CMIR).

  • Monocytes (2-8%): phagocytic, become macro______in tissues.

b)Development of B and T cells

Both B and T cellsoriginate from stem cells in bone marrow. Some migrate via blood to the thymus and develop into T cells / lymphocytes. These T cells then migrate to lymph nodes and spleenswhere most of them reside and be ready for specific immune responses.

The lymph n___ and sp____ are where B and T cells accumulate. It is also the place where pathogens in blood and lymph are caught.
Pathogens stim____ the B and T cells and turn on sp_____ immune responses. Most specific responses take place at these sites. They are therefore the battle grounds for specific mechanisms!
Lymph nodes
The lymph nodes are alsocalled 'glands' which sometimessw up when we are suffering from an infection. They are widely distributed in the body, particularly the groin and armpits. Each lymph node consists of a network of delicate f through which lymph filters through. Lymph is a colourless fluid, derived from the blood. Itis brought to the node by a lymph vessel and drained away from it by another lymph vessel. The latter leads ultimately to a vein in the neck where the lymph rejoins the bloodstream.
The lymph nodes contain phag macrophages which remove pathogens and foreign particles from the lymph. These phagocytes are mainly fixed to the fibrous network though they can move out of the lymph node to nearby tissues. /

C)Stimulation of Specific Responses

When pathogens reach the lymph node or spleen, they may first be pro by the macrophages at these sites (antigen processing).
The processed antigens may then stimulate either the T or B cells (or both in some cases) and turn on the CMIR or HIR respectively.
Sometimes, pathogens need not go through “antigen processing” and can stimulate B and T cells directly. /

a)Humoral Immune Response (HIR)

Some antigens will turn on the humoral response. e.g. bacteria, pollen, animal fur, red blood cells etc. The characteristics of the HIR is thatB cells are involved and the process results in the production of anti specific for the antigen.

i)ThePrimary Response

A primary response is the response that is elicited when an antigen entered into the body for the first time. Any subsequent entry by the s antigen will cause a different response that is called a sec______response.

  • When the antigen reach the lymph node / spleen, it will stimulate the appr ___ B cell there which is specific to it.
  • Some antigens cannot turn on the B cell directly, they need the presence of T cells and these antigens are called T-______antigens. Those which do not require T cells for stimulating B cells are called T-independent antigens.
  • Thestimulated B cells will thendifferentiate and multiply into antibody forming cells –pl cells which are very efficient in producing anti______(Ab).
  • The specificantibodies can then act on the specificantigen / pathogen.
  • Some stimulated B cells become long living ‘ m cells ’.

ii)Secondary Response

Some activated B cells will turn into small memory cells.
  • These have a l life span and remains for a long time in the blood circulation.
  • They can be turned on more easily and vigorously on the body's n exposure to the same antigen.
  • Thus, if the antigen invades the body a second time, the memory cell will quickly becomes act , and lead to formation of anti_____-producing cells and antibodies very quickly.
/

This is called a Secondary Response which has Four characteristics:-

a shorter l___ period.

a sh______increase and

a h______level of antibodies produced.

the high antibody level stays I______in the body.

The response is highly sp______for the antigen. Another antigen cannot elicit a secondary response.

As a result of the more ef______secondary response, the level of antibody is built up very q_____ and the pathogens are destroyed so rapidly thatonly mild or no symptoms appear. This is called im .

Antibodies
They areY-shaped structures which are also calledimmuno as they areprotein molecules. The two top ends of the “Y” arespecific to the particular antigen and can therefore bind to it.
  • Lysis
Attach to the pathogen (e.g. bacterium) and cause lysis of bacterial cell wall. Consequently, water and salts inside the antigen (bacterium) leak out and the bacterium is killed.
  • Enhanced phagocytosis
Antibody attaches to the antigen (e.g. bacterium), making the antigen easier to be eaten by phagocytes.

  • Neutralize bacterial toxins
bacterial toxins (a harmful substance secreted by bacterium) are neutralized by the formation of antigen-antibody complexes which are then phagocytosed.
Antibodies have a short l spanand are soon metabolized if not used. As the antibody produced is used up, its level in blooddecl_____.

Q.Vaccination is often given in multiple doses, separated by several weeks or even months. Why do you suppose the doses are spread out over such a long period rather than given in a single dose? 5m

Q.What particular organelles do you suppose to be well-developed or especially abundant in the clones of the activated B cells (plasma cells) ?

Reference Reading : Clonal Selection Theory (by Macfarlane Burnet -- a Nobel Prize winner)
This theory explains the mechanism whereby lymphocytes can be induced to synthesize antibodies of the correct specificity for the antigen that triggered the immune response. The theory assumes that there is a great diversity of lymphocytes (more than ten million different clones of B cells) at birth, genetically programmed to produce antibodies of all different specificity. When an antigen arrives, only those relatively few lymphocytes with specificity for the antigen are triggered to proliferate and form a lot more cells (clones). Thus the antigen selects lymphocytes of correct specificity to respond. This theory is quite generally accepted. It could also apply to the cell-mediated type of immune response.
How does each B lymphocyte recognise its unique antigen? The B cell carries on its surface the same kind of antibodies that it is capable of producing. These surface antibodies act as receptors. When an appropriate antigen comes along, it is recognised by the matching clone, which then divides rapidly to make thousands more identical B cells (clones), all secreting that particular antibodies that bind to that antigen into the blood and lymph.

b)The Cell-Mediated Immune Response (CMIR)

Instead of stimulating the body to produce antibodies, some antigens (e.g. certain bacteria, viruses, foreign cells like skin, kidney etc.) turn on the CMIR.

i)Primary Response

When such an antigen enters the blood and eventually the spleen and lymph nodes, it will stimulate the T cellsspecific to the antigen to respond. The T cells may respond in either one of the following ways:-

  • the stimulated T cell may become aKiller T cell which can kill the antigen directly.
  • Alternatively, the stimulated T cell may become an Activated T cell which liberate chemicals called Lymphokines. The lymphokines then acti____ the macrophages in the spleen and lymph nodes into activated macrophages which are highly efficient in eating and killing the antigen. The effector in this mechanism is therefore the Activated Macro .