Body Defence

BODY DEFENCE MECHANISMS

The body defends itself against physical injuries and invasion by harmful materials and organisms in various ways.

These ways can be divided into PREVENTION and

CURE.

secretions mechanical barriers

1. PREVENTION

1. PREVENTION(a) Against physical injuries(i) Tough outer coating

- keratinised compound squamous epithelium of skin. The skin is thickest in areas where physical injury is most common

e.g. palms of hands, soles of feet.(ii) Adipose tissue - forms a cushion between skin and underlying organs. Some delicate organs, e.g. kidneys, may be further protected by a

coat of fat.(iii) Bones - the delicate haemopoietic (blood forming) tissues are encased in the

shafts of long bones of the limbs and the sternum (red bone marrow). The brain, spinal cord, heart and lungs are also protected by bones.

(b) Against invasion by harmful materials and organisms(i) Intact skin - relatively few chemicals and organisms are able to penetrate intact

skin.(ii) Cilia - beating of cilia on the outer surface of epithelial cells in the

respiratory tract he1ps to prevent harmful dust/bacteria etc. reaching the lungs.

(iii) Secretions - many body secretions contain chemicals which are harmful to

many pathogenic organisms. e.g. gastric juice (pH 2)

tears (from lachrymal glands) mucus - respiratory tract, vagina sebaceous secretions lysozyme in tissue fluid

2 CURE

There are two important mechanisms by which the body can remove harmful materials / organisms once they have entered the body.

These mechanisms are: 

I. INFLAMMATORY RESPONSE

II. SPECIFIC IMMUNE RESPONSE

The inflammatory response is a local response to tissue damage and invasion by harmful materials and/or organisms.

The response is often described as being “non-specific” as the response is much the same regardless of the nature of the issue damage or foreign material/ organisms.

The strength of an inflammatory response does, however, vary according to the severity of an injury.

The inflammatory response can:-  remove dead and damaged body cells-  remove harmful materials and cells

Specific immune responses differ from inflammatory responses in that an immune response is a ‘specific’ response to invasion by harmful materials and/or cells.

Thus a particular immune response will deal specifically with the material or organism which stimulated the response.

Immune responses cannot deal with dead or damaged body cells, however certain cells of the immune system can ‘remember’ a particular harmful material or organism and can react very quickly to a second or subsequent invasion by that substance.

Events during localized infection (a non-specific mechanism): permeability, blood flow, vasodilation

Histamine isreleased frommast cells

WBCs emerge from blood vessel

I. INFLAMMATORY RESPONSE

I. INFLAMMATORY RESPONSEWhen connective tissues and blood vessel walls are damaged by

physical injury or the presence of harmful materials/cells, certain cells respond by liberating a variety of chemicals.

These chemicals have two major functions:(a) Capillary dilation, resulting in increased blood flow in the damage area.(b) Increase in capillary permeability, allowing blood plasma and

neutrophil phagocytes to pass into the surrounding fluid.

(a) and (b) cause the inflamed area to become: (i) red(ii) swollen(iii) warmer than surrounding tissues(iv) painful (due to pressure of increased fluid on local endings)

The phagocytes which have migrated from blood vessels engulf dead and damaged cells, thus cleaning the wound, and also phagocytose harmful materials and organisms.

Once cell debris and ‘foreign’ materials are removed tissue repair can take place.

The inflammatory response is not always sufficient to destroy and remove harmful materials and organisms, and these may migrate from the site of injury to other parts of the body via the blood and lymph.

It is in such situations that a specific immune response occurs.

To lymph node

To spleen

II SPECIFIC IMMUNE RESPONSELymphocytes are the most important cells in immune

responses, although other cells are also involved, such as macrophages.

Lymphocytes are found in the blood (20-25% of white blood cells) and in lymphoid organs such as the bone marrow, thymus, lymph nodes (often called glands) and spleen.

Any substance which is recognized as ‘foreign’ by the body and which can stimulate an immune response is called an ANTIGEN (Ag).

Antigens may be soluble macromolecules, cell surface components or chemicals synthesized by foreign cells.

Commonly encountered antigens include:Bacteria ( components of cell walls and flagellae, toxins)

Viruses ( protein ‘coat’ subunits)

Fungi and protozoa ( cell surface components)

Macromolecules ( especially proteins)

Less frequently encountered antigens include:RBC’s (‘blood group substances’ on membranes)

grafted cells (cell membrane proteins or glyco-proteins)

There are two kinds of immune responses:- ANTIBODY response (or humoral immune response)

- CELLULAR response (or cell-mediated immune response)

In general, ANTIBODY responses deal with bacterial and RBC antigens and possibly fungal and protozoal antigens,

whilst the CELLULAR response deals with viral antigens, grafted cells and possibly fungal and protozoal antigens.

(a) Development of immune responsiveness(i) Lymphocytes develop in the bone marrow from haemopoietic

precursor cells.

(ii) Some lymphocytes nature fully in the bone marrow to become B lymphocytes (B cells).

(iii)Other, immature, lymphocytes pass from the bone marrow to the thymus where they mature into T lymphocytes (T cells).

(iv)Both B and T cells pass to the lymph nodes and spleen via the blood stream.

(N.B. Lymph nodes and spleen can be regarded as a complex organization of three types of cell involved in the initiation of the immune reaction - lymphocytes, plasma cells and phagocytic cells of the mono-nuclear phagocyte system.

Different types of white blood cells

RBS plateletsT cell B cell

33%Monocyte2-8%

Neutrophile50-70%phagocytic

Basophil0-1% Eosinophil

1-4%Allergic?

Macrophagephagocytic Mast cell

Releases histamine

Granulocytes(polymorphonuclearLeucocytes-PMN)

agranulocytes

lymphocytes

erythrocytes

leucocytes

Stem cell

Different types of white blood cells1) Granulocytes (polymorphonuclear leucocytes or cells)- White blood cells that possess GRANULES in their cytoplasm,

with nuclei & a few days of life span,- a) Neutrophils: - the most abundant PMN, an important PHAGOCYTIC cell for

NON-SPECIFIC body defence; - amoeboid, can leave blood vessels & enter into tissue. b) Eosinophils: quite rare, functions uncertain but probably phagocytic &

associated with hypersensitivity & allergic reactions. c) Basophils: - smallest number, NON-PHAGOCYTIC but becomes MAST

CELLS when entered tissues; - contains HISTAMINES which when released, will cause vaso-

dilation, increased blood flow, increased permeability of blood vessels & outflow of cells.

2) Agranulocytes (no granules in the cytoplasm)a) lymphocytes (33%):

B CELLS & T CELLS which are small cells with large nucleus;

b) monocytes (2-8%):

Phagocytic, becomes macrophage in tissues & have kidney-shaped nucleus

**Development of B & T cellsBoth B & T cells originate from a stem cell in

haemopoietic tissues (yolk sac & liver in foetus; bone marrow in adults).

Some migrate via blood to the thymus & develop into T cells/lymphocytes.

These T cells then migrate to lymph nodes & spleens where most of them reside and be ready for specific immure responses.

Thymus, being an important organ for the differentiation of stem cells into specific lymphocytes, is called the PRIMARY LYMPHOID TISSUE while lymph nodes & spleen where the mature immunocompetent cells lie are called SECONDARY LYMPHOID TISSUES

In birds, some stem cells migrate from haemopoietic tissues to an organ called Bursa of Fabricius and develop into B cells/lymphocytes.

The B cells then migrate to the lymph nodes & spleen and reside there for specific immune responses.

The bursa equivalent for mammals is unknown. The bone marrow is thought to be a likely place.

When B & T cells arrive at the secondary lymphoid organs (lymph nodes & spleen), they settle in separate specific areas.

There are specific T & B areas in these organs.

Primary lymphoid tissues

Secondary lymphoid tissues

/spleen

The secondary lymphoid organs are the places where B & T cells accumulate.

It is also the place where pathogens in blood & lymph are caught.

It is in these places that pathogens stimulate the B & T cells and TURN ON specific immune responses.

Most specific responses take place at these sites. They are therefore the battle grounds for specific mechanisms!

or

**

**antigen processing

T cell response

B cell response

STIMULATION OF SPECIFIC RESPONSES

When pathogens reach the lymph node or spleen, they may be first processed 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.

(b) Reaction of lymphocytes to antigen (i) In the lymph nodes or spleen the antigen stimulates B

and / or T lymphocytes as follows:

(ii) ( I ) Humoral response:

Blastcell

Memory cellantigen

Antibody forming cell

Plasma cell

antibodiesOR T-helper cell for T-dependent antigens

antigen

B cell

Blast cell

Antibody forming cellPlasma cell which produce antibodies

Same antigen

Primary immune response

Secondary immune response

Differentiation of B cells

The characteristics of the humoral response is that B cells are involved & the process results in the production of ANTIBODIES specific for the antigen.

THE PRIMARY RESPONSE (elicited when an antigen entered into the body for the FIRST TIME):

When an antigen reaches the lymph node/spleen, it will stimulate the appropriate B cell there which is specific to it.

Some antigens cannot turn on the B cell directly, they need the presence of T cells & these antigens are called T-dependent antigens (in contrast to T-independent antigens).

The stimulated B cell will then differentiate & multiply into BLAST CELLS.

These in turn proliferate & differentiate into ANTI-BODY FORMING CELLS and then plasma cells which are very efficient in producing ANTI-BODIES which can then act on the antigen.

Receptor sites for antigens

High affinity for PMNs, macrophage

The antibodies are Y-shaped structures which are also called IMMJJNOGLOBULINS as they are protein molecules.

The top ends of the “Y” are specific to the particular antigen & can therefore bind to it.

The antibodies can help to destroy antigens in three main ways:

1) Bacterial lysis by antibody

bacterium

antibodies

Attachment of antibodies

Complement attached to bacterium-antibody complex

A hole is drilled by the complex, resulting in lysis

Lysis and death

The antibodies can help to destroy antigens in three main ways:

1) Bacterial lysis by antibody

2) Enhanced phagocytosis

Enhanced phagocytosis:

coat Bacterium is “slippery”Phagocyte cannot grasp it

Antibodies attached to coat of bacterium

Since end of antibody has highaffinity for phagocyte,phagocyte can now grasp bacterium through antibody

bacterium

The antibodies can help to destroy antigens in three main ways:

1) Bacterial lysis by antibody

2) Enhanced phagocytosis3) Certain antibodies can neutralize bacterial toxins by

forming antigen-antibody complexes which are then phagocytosed.

Eosinophils are especially active in phagocytosing antigen-antibody complexes.

SECONDARY RESPONSE:Memory B lymphocytes are long-lived cells which

remain dormant in lymphoid tissues for many months or years, until the antigen which stimulated their production is encountered again.

If and when this occurs the memory B Lymphocytes respond immediately to antigen by dividing and differentiating into more plasma cells and memory B lymphocytes.

Latent period

1st injection

Primary response

Re-injection

Latent period

Secondary response

Stronger and faster

Compared with the original, or primary response to antigen the secondary immune response is:

- larger

- faster

- longer lasting, as once stimulated, the memory cells continue to divide for months or years.

(II) Cellular response

T lymphocytes

 

cell divisions and differentiation

 

cytotoxic T lymphocytes

and + ‘memory’ T lymphocytes

activated T lymphocytes

antigen

Memory cell

Killer T cell (cytotoxic T cell)

Kill antigen directly

lymphokines

macrophage

Activated T cell

monocyte

Activatedmacrophagekills antigen

*No antibodies are involved

The cell-mediated immune response (CMIR)

Cytotoxic T lymphocytes - these migrate (if necessary) to the site of the

antigen, which is normally a cell with antigen on its surface.

- The cytotoxic T cells are capable of killing cells with antigen on their surfaces.

- These ‘target’ cells then lyse and the fragments are phagocytosed.

- As ‘in the antibody response, cytotoxic T cells have a particular specificity, only reacting with cells bearing the antigen which stimulated their production.

Activated T lymphocytes

- these liberate chemicals called lymphokines.

The lymphokines then activate the macrophages into activated macrophages which are highly efficient in eating and killing the antigens.

Memory T lymphocytes are very similar to memory B lymphocytes, except that subsequent stimulation by antigen results in rapid production of more cytotoxic T lymphocytes and memory T lymphocytes.

The same graph showing primary and secondary responses applies except that the y axis becomes ‘number of cytotoxic T lymphocytes’.

(I) IMMUNITY ANY IHM1UNITSATOIN

Immunity of the body refers to “all those physiologic mechanisms that endow the animal with the capacity to recognize materials as foreign to itself and to neutralize, eliminate, or metabolize them with or without injury to its own tissues”.

Immunity to a disease may be acquired naturally or artificially.

Natural Immunity1. Natural passive immunity is important in young babies

when antibodies in the mother’s blood diffuse across the placenta before birth.

Maternal antibodies are also present in breast milk.

As antibodies are catabolised in a few months the protective effect is short-lived.

2. Natural active immunity results from infection with a pathogen, resulting in the individual producing his own antibodies etc.

If the disease has a long incubation period then both primary and secondary responses occur, resulting long-term immunity, e.g. mumps, chicken pox.

Artificial Immunity1. Artificial passive immunity involves an injection of

‘ready-made’ antibodies, usually obtained from animals immunised with the antigen.

The immunity is short-lived (3-6 months) as the antibodies are catabolised, however this is a good method of immunisation if instant immunity is required.

2. Artificial active immunity involves the introduction of killed or non-virulent strains of disease-causing organisms into the body.

Humoral and/or cellular responses then take place.

Generally at least two doses of antigen are given at suitable intervals, so that the secondary immune response is stimulated.

There are three main types of bacterial and viral antigen preparations in current use:

(a) Toxoids

Soluble toxins of bacteria such as diphtheria and tetanus, modified and made less toxic by adding formalin or gentle-beating.

Treatment destroys the toxic parts of the antigen molecule, leaving the antigenic sites unchanged.

(b) Killed organisms

Cultured organisms killed by heat, UV light or chemicals, e.g. whooping cough (pertussis), poliomyelitis (Salk), cholera, typhoid.

 (c) Live, “attenuated” organisms

Vaccines made from strains of organisms that have lost their virulence.

The emergence of an attenuated strain is a combination of science and luck

e.g. BCG - a virulent strain of Mycobacterium tuberculosis was grown in a medium containing bile salts which resulted in the production of an attenuated strain - Bacillus Calmette - Guerin (1908).

Other examples of vaccines prepared from attenuated organisms are poliomyelitis (Sabin), measles, rubella, yellow fever.

Virtually all countries tog have a Standard immnunisation schedule for babies and children.

There is no doubt that childhood immunisation has had a dramatic effect on the incidence of many - often fatal - viral and bacterial diseases, many of which are virtually unheard of in Hong Kong today.

Perhaps the greatest success story is the result of the WHO’s efforts to eradicate smallpox by rigorous immunisation programmes world-wide.

At present considerable efforts are being made to develop vaccines for the prevention of protozoal diseases such as malaria, trypanosomiasis and schistosomiasis, these diseases being common causes of illness and death in developing countries.

The reason why no, successful vaccines have been developed so far seems to be that protozoan pathogens have evolved a variety of complex mechanisms for evading the immune responses of their human hosts.

Additionally there are a number of bacterial and viral diseases for which vaccines are not yet available, either because the killed organisms are not antigenic or because a safe (non-virulent) strain of a particular organism has not yet beep developed, e.g. viral hepatitis – new and better vaccines are not available.

(II) TRANSPLANTIONGrafted skin and transplanted organs such as kidneys may be

rejected by the recipient - unless the donor is an identical twin or possibly a sibling.

The rejection mechanism is basically a cellular immune response against ‘foreign antigens’ on the membranes of the transplanted cells.

On virtually all our cells, except RBCs and the cornea, are genetically-coded glyco-proteins called transplantation antigens or histo-compatibility antigens.

In a population possibly one hundred or more of these antigens exist, but one individual only possesses eight of these.

The number of combinations is therefore enormous! The recipient’s immune system will recognise transplanted cells as

foreign if one or more tissue antigens on the donor cells differ from those on the recipient’s own cells.

Fortunately it is now possible to ‘type’ the cells of potential donors and recipients in the laboratory for the most important of these antigens.

A good ‘tissue-match’ between donor and recipient (i.e. most or all antigens the same) indicates that the transplant has a good chance of survival and vice-versa.

DRUGS

In the broadest sense, a drug is any chemical that can effect an alteration in the function or structure of living tissue.

As commonly used, the word ‘drugs’ implies medicinal chemicals - those substances that, in carefully regulated doses, produce desirable changes in the human body, counteracting disease or relieving distress.

AntibioticsAntibiotics refer to drugs obtained from

microorganisms, and are often used to kill other microorganisms.

They may be anti-bacterial and/or anti -fungal.

One of the best known antibiotics is penicillin, which acts on growing bacteria, killing them and preventing their growth.

However, its precise mode of action is unknown, as is the case with the majority of antibiotics.

SulphonamidesSulphonamides are complex organic ring compounds

with a powerful anti bacterial action. The sulphonamides are similar in their chemical

structure to para-aminobenzoic acid, an essential metabolite in the reproduction of certain bacteria.

They are believed to compete with para-aminobenzoic acid for the active site of an enzyme.

In this way, though they do not actually kill the active site of an enzyme.

In this way, though they do not actually kill the bacteria, they stop them reproducing.