Download Defence Against Disease

DEFENSE AGAINST
DISEASE
© 2016 Paul Billiet ODWS
INFECTIOUS DISEASE
Caused by microbes which invade the body and
upset it’s homeostasis
Microbes that cause diseases = pathogens
E.g. viruses, bacteria, fungi, protozoans.
© 2016 Paul Billiet ODWS
Antibiotics
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Only useful against bacteria
Inhibit growth of prokaryote but do not affect
eukaryotes
Viruses use their host cell’s metabolism
Viruses a unaffected by antibiotics.
© 2016 Paul Billiet ODWS
Penecillin
• Alexandre Fleming 1928
• Florey & Chain 1939-1940
© 2016 Paul Billiet ODWS
Fleming
• Plate of staphylococcus
bacteria contaminated by
mould
• The mould inhibited bacterial
growth
• Toxicity tests seemed good on
mice & rabbits
• But the active component
seemed to disappear rapidly
from the blood
• Fleming though it might be
useful as an antiseptic.
© 2016 Paul Billiet ODWS
Mould
colony
Zone of
inhibition
Bacteria
Florey & Chain 1940
• Purified penicillin
• Not an enzyme
• 8 mice injected with a streptococcal
infection
• 4 experimental 4 controls
• 16.5h later the control mice were dead
• Scaled up testing on hundreds of mice.
© 2016 Paul Billiet ODWS
Skin – primary defense
© 2016 Paul Billiet ODWS
www.agen.ufl.edu/.../lect/lect_19/lect_19.htm.
Skin
• Skin consists of the epidermis
• Dead, waterproof layer prevents microbes from
entering the skin
• Continually replaced from below
• Skin flora act as commensals
• Blood clotting seals cuts.
© 2016 Paul Billiet ODWS
Mucus
membranes –
primary
defense
www.lab.anhb.uwa.edu.au/.../Images/sto040pa.jpg
© 2016 Paul Billiet ODWS
Mucus membranes
• Mucus membranes cover the inner compartments
of the body
• Cells being constantly renewed from below
Not waterproof
• These membranes secrete mucus
(mucopolysaccharide), and sugars
• Mucus traps materials in the airways
• A commensal flora grows there too feeding on
the secretions.
© 2016 Paul Billiet ODWS
Other defences
• HCl is secreted from the stomach mucosa = an
anti-microbial agent
• Secretions of lysozyme produced by glands such
as tear and salivary glands.
© 2016 Paul Billiet ODWS
Phagocytic leucocytes
• Leucocytes (white blood cells) can act directly
upon microbes by PHAGOCYTOSIS (Cell
Mediated Immunity)
• Phagocytes recognise and engulf foreign (nonself) material
• Pus forms when large numbers of phagocytes die
from engulfing microbes.
© 2016 Paul Billiet ODWS
Phagocytosis
library.thinkquest.org/.../phagocytosis.gif
Antibodies
• Antibodies are proteins produced by B-cell
lymphocytes
• Antibodies recognise non-self molecules called
antigens
• They call up phagocytes
• They have two or more antigen binding sites
• They are very specific: One antibody recognises
one antigen molecule
• The different binding sites can bind to two or
more cells clumping them together =
AGGLUTINATION.
© 2016 Paul Billiet ODWS
Agglutination
www.vet-lyon.fr/.../ENV_immuno_1A/immun1-04.htm.
Antibodies = immunoglobulins
imgt.cines.fr/.../_UK/PosterIGH/imagesIgH.png
www.science-projects.com/IgG.GIF
© 2016 Paul Billiet ODWS
Antigens
• Antigens are
molecules found on
the surface of non-self
cells
(e.g. microbes
infecting the body or
transplants)
• They are usually
complex molecules
(e.g. glycoproteins).
© 2016 Paul Billiet ODWS
www.okc.cc.ok.us/.../plasmamembrane2.jpg
Antibody production
• Each type of antibody is produced by a specific
lymphocyte B-cell
• B-cells are produced by the red bone marrow
• The body produces a vast range of B-cells
capable of producing different antibody molecules
(cf What is a gene?)
• Early on in development the body learns to
recognise the difference between self (belonging
to the body) and non-self (foreign material)
• Only non-self recognising lymphocytes are
retained.
© 2016 Paul Billiet ODWS
The Lymophocyte B-Cell
www.visualsunlimited.com/.../188/188898.jpg
The T-cells
• Macrophages capture
pathogens and present
their antigens to
helper T-cell
lymphocytes
• Helper T-cell
lymphocytes stimulate
the appropriate B-cells
to multiply forming a
clone.
depts.washington.edu/tumorvac/MultiMedia/Imag...
© 2016 Paul Billiet ODWS
Immunisation
• These B-cells produce the antibodies to fight that
particular microbe
• Antibodies are found in the blood plasma
(Humoral Immunity)
• When the infection is overcome memory cells
remain so the immune response is faster the
second time the body is infected (natural
immunity)
• The body can be stimulated into producing the
memory cells by vaccination/immunisation
(artificial immunity).
© 2016 Paul Billiet ODWS
HIV attacks the immune system
• HIV (Human Immunodeficiency Virus) is the virus
that causes AIDS (Acquired Immune Deficiency
Syndrome)
• HIV infects the body through transfer of body
fluids (blood, blood products, semen) or across
the placenta
• HIV infects one type of the T-cell lymphocyte,
helper T-cells.
• Antibody production cannot be stimulated.
© 2016 Paul Billiet ODWS
AIDS
• The immune system fails to respond to an
infection by certain bacteria (e.g. pneumonia) and
fungi (e.g. Candida) which are normally easily
resisted
• The disease may take 8-10 years to reveal itself
• This gives time for several cross infections
• There is no vaccine yet
• Drugs may stop the disease progressing but do
not cure it.
© 2016 Paul Billiet ODWS
THE IMMUNE SYSTEM
Challenge & Response
• Infection = Challenge
• Reaction of immune system = Response
Self & Non-self
• Molecules which belong to the body = Self
• Antigens which are foreign = Non-self
© 2016 Paul Billiet ODWS
THE IMMUNE SYSTEM
Bone marrow
Stem cells
B-cells
© 2016 Paul Billiet ODWS
T-Cells
Macrophages
B-cells
Antigen presented independently
B-cell primed
Helper
TH-cells
Plasma cell clone
Specific antibody
produced
Memory cells
Agglutination of toxins and pathogens
Attraction of macrophages
Activation of complement enzymes in the plasma
© 2016 Paul Billiet ODWS
T-Cells
Thymus gland
Helper
TH-cells
Suppressor
TS-cells
Stimulate specific
B-cell to develop
Switch off immune
response
© 2016 Paul Billiet ODWS
Cytotoxic
TE-cells
Lyse cancer cells
and cells infected
by viruses
Macrophages
Phagocytose
pathogens and present
antigen to T-cell along
with Class II MHC
protein
Helper
TH-cells
Suppressor
TS-cells
© 2016 Paul Billiet ODWS
Cytotoxic
TE-cells
Phagocytosis
Humeral response
Agglutination
• Chemicals in the plasma respond
• For pathogens in the blood stream, lungs, skin and gut.
© 2016 Paul Billiet ODWS
Cell-mediated response
Phagocytosis and cytotoxic cells
• White blood cells directly involved
• For pathogens inside cells (e.g. viruses) and cancerous
cells
• The lymphocyte must recognise both SELF (MHC)
proteins and NON-SELF antigen.
© 2016 Paul Billiet ODWS
Allergies
• An immune response to a substance that is normally
harmless
• Results from the response of a mast cell
• B-cells produce IgE antibodies in response to antigens
• Mast cells are activated by IgE.
Mast cells
• Mast cells are leukocytes that patrol to body cavities
• Mast cells protect against parasite infection
• Mast cells release histamine protein.
© 2016 Paul Billiet ODWS
Histamine
• Histamine provokes increase blood flow to and
permeability of blood vessels in an infected region
(inflammatory response)
• Histamine also increases smooth muscle contraction to
expel parasites.
© 2016 Paul Billiet ODWS