Body Defence

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Body Defence
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• 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.

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1. PREVENTION
secretions
mechanical barriers
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• 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.

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• (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

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• 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

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• 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

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• 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.

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I. INFLAMMATORY RESPONSE
Events during localized infection (a non-specific
mechanism) ? permeability, ? blood flow,
vasodilation
Histamine is released from mast cells
WBCs emerge from blood vessel
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• I. INFLAMMATORY RESPONSE
• When 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)

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• 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.

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To lymph node
To spleen
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• II SPECIFIC IMMUNE RESPONSE
• Lymphocytes 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.

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• 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
• RBCs (blood group substances on membranes)
• grafted cells (cell membrane proteins or
  glyco-proteins)

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• 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.

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• (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.

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• Different types of white blood cells

Stem cell
leucocytes
Granulocytes (polymorphonuclear Leucocytes-PMN)
agranulocytes
lymphocytes
T cell
B cell
Basophil 0-1
Neutrophile 50-70 phagocytic
RBS
Monocyte 2-8
Eosinophil 1-4 Allergic?
platelets
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erythrocytes
Macrophage phagocytic
Mast cell Releases histamine
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• Different types of white blood cells
• 1) 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.

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• 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

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• Development of B T cells
• Both 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

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• 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.

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Primary lymphoid tissues
Secondary lymphoid tissues
/spleen
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• 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!

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antigen processing

T cell response
or
B cell response
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• 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.

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• (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

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antigen
Memory cell
Blast cell
antibodies
OR T-helper cell for T-dependent antigens
Antibody forming cell
Plasma cell
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Primary immune response
Secondary immune response
antigen
B cell
Same antigen
Blast cell
Antibody forming cell
Plasma cell which produce antibodies
Differentiation of B cells
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• 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).

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• 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.

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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.

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• The antibodies can help to destroy antigens in
  three main ways
• 1) Bacterial lysis by antibody

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bacterium
antibodies
Attachment of antibodies
Complement attached to bacterium-antibody complex
A hole is drilled by the complex, resulting in
lysis
Lysis and death
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• The antibodies can help to destroy antigens in
  three main ways
• 1) Bacterial lysis by antibody

2) Enhanced phagocytosis
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Enhanced phagocytosis
coat
Bacterium is slippery Phagocyte cannot grasp it
bacterium
Antibodies attached to coat of bacterium
Since end of antibody has high affinity for
phagocyte, phagocyte can now grasp bacterium
through antibody
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• The antibodies can help to destroy antigens in
  three main ways
• 1) Bacterial lysis by antibody
• 2) Enhanced phagocytosis

3) Certain antibodies can neutralize bacterial
toxins by forming antigen-antibody complexes
which are then phagocytosed. Eosinophils are
especially active in phagocytosing
antigen-antibody complexes.
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• 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.

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Stronger and faster
Latent period
Latent period
Re-injection
1st injection
Secondary response
Primary response
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• 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.

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• (II) Cellular response
• T lymphocytes
•  
• cell divisions and
  differentiation
•  
• cytotoxic T lymphocytes
• and
  memory T lymphocytes
• activated T lymphocytes

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The cell-mediated immune response (CMIR)
Memory cell
Killer T cell (cytotoxic T cell)
Kill antigen directly
lymphokines
antigen
Activated T cell
No antibodies are involved
Activated macrophage kills antigen
monocyte
macrophage
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• 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.

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• 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.

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• (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.

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• Natural Immunity
• 1. Natural passive immunity is important in young
  babies when antibodies in the mothers 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.

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• Artificial Immunity
• 1. 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.

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• 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.

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• 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.

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•  (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.

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• 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 WHOs efforts to eradicate smallpox by
  rigorous immunisation programmes world-wide.

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• 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.

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• (II) TRANSPLANTION
• Grafted 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 recipients immune system will recognise
  transplanted cells as foreign if one or more
  tissue antigens on the donor cells differ from
  those on the recipients own cells.

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• 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.

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• 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.

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• Antibiotics
• Antibiotics 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.

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• Sulphonamides
• Sulphonamides are complex organic ring compounds
  with a powerful antibacterial 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.