Natural Defence Mechanisms
Learning objective:
• To be able to describe the prevention of
microorganisms gaining access to
living cells
• To be able to describe the role of the
non-specific immune response.
• We are surrounded by microbes in the
air, on the ground and all other
surfaces, and in our food and water.
• The only reason we are still alive is
because humans (and all other
animals) have a very powerful defence
mechanism:
The Immune System.
Possible sites of entry into the
body
• Nose
• Ears
• Eyes
• Mouth
• Genitals
• Cuts in the skin
First line of defence
• The skin
• Sweat and tears
• The digestive tract
• The respiratory tract
The skin
• The outer layer, the epidermis, is 20-30 cells
thick (about as thick as a sheet of paper) and
its cells are toughened by the protein keratin,
forming an impenetrable barrier to invading
microbes
• The next layer, the dermis, is 20-40 times
thicker and provides the main structure for
the skin as well as all the receptor cells,
blood vessels and hairs.
• Cells are constantly being lost from the
surface of the skin (to form dust) and are
replaced by new cells from further down.
Sweat and tears
• These are secreted by glands in the
skin and contain lysozyme enzymes,
which destroy (lyse) bacteria growing
on the surface of the skin by digesting
their peptidoglycan cell walls.
The digestive tract
• This is a potential entry route for
pathogens, but it is protected by
concentrated Hydrochloric acid in the
stomach, which denatures microbial
enzymes and cell surface proteins,
• In the stomach there are also protease
enzymes.
• Saliva also contains lysozymes.
The respiratory tract
• This is protected by sticky mucus secreted
by glands in the bronchi and bronchioles,
which traps microbes and other particles in
inhaled air before they can reach the delicate
alveoli.
• The mucus contains lysozymes, and there
are cilia constantly sweeping the mucus
upwards to the throat, where it is swallowed
so that the microbes are killed by the
stomach acid.
Say hello to the friendly
bacteria….
• The human body is home to billions of bacterial
cells
• These may be known as the natural microbiota, the
normal flora, the commensal flora (because they
have a non-harmful or commensal relationship with
their host) or even the "friendly bacteria".
• There are more bacteria cells in a human than there
are human cells.
• These commensal bacteria colonise the skin,
mouth, lower digestive tract, respiratory tract and
vagina, and they help prevent infection by outcompeting pathogenic microbes for food and
space.
The core’s been breached
Captain
• So what happens if this first line of
defence is broken?
• Enter…..
The parts of the immune system are spread all
over the body. They include:
Lymph nodes
in neck
Lymph nodes
in armpits
thymus
spleen
Lymph nodes
in groin
• The lymph and blood vessels transport pathogens and
leukocytes all over the body.
• The lymph nodes contain millions of phagocyte and
lymphocyte cells, which identify and remove
pathogens from lymph.
• The spleen also contains millions of phagocyte and
lymphocyte cells, which identify and remove
pathogens from blood.
• Blood stem cells are differentiated into T-lymphocytes
in the thymus. Once in the thymus they are activated.
These activated or COMPETENT T-lymphocytes pass
to the lymph nodes and spleen
Leukocytes
• Leukocytes are white blood cells that defend
the body from the invasion of microbes
• Leukocytes are derived from stem cells,
which are produced in huge numbers in the
bone marrow
• These stem cells differentiate to form all
types of blood cell, from platelets, red blood
cells to the dozens of different kinds of
leukocytes.
• Leukocytes fall into four categories.
White
blood cells
(leukocytes)
Phagocytes
Granulocytes
For
inflammation
T Lymphocytes
For cell
mediated
immunity
B Lymphocytes
For antibody
mediated
immunity
For
phagocytosis
Macrophages
Neutrophils
Monocytes
Mast cells
Eosinophils
Basophils
Helper T cells
Killer T cells
Memory T cells
B cells
Plasma B cells
Memory B cells
Non specific
immune system
Specific
immune system
Non specific immune system
• The phagocytes and the granulocytes form
the non-specific immune system, which kills
pathogens quickly and indiscriminately.
• Although effective, it does not lead to
immunity to a disease as it does not "learn
from experience".
• Granulocytes initiate the inflammatory
response
• Phagocytes kill bacteria by phagocytosis.
Inflammatory response
• The inflammatory response is a localised response to
injury or infection.
• The granulocyte cells and the affected cells release
chemicals, including histamines and prostaglandins.
• These chemicals cause:
– vaso-dilation to increase the flow of blood to the area
(so the area turns red);
– capillary leakage so that phagocytes and granulocytes
can enter the local tissue fluid (so the area swells);
– sensory neurone impulses (so the area is tender or
painful);
– blood clotting to seal a wound (so a scab is formed).
– The dead pathogens and phagocytes, together with
excess tissue fluid, are release as pus.
– The chemicals also help to stimulate the specific
immune response
Feeling hot?
– Pyrexia is caused by pyrogen chemicals, which
include some of the inflammation chemicals as
well as bacterial endotoxins.
– These stimulate the hypothalamus of the brain to
increase the body's temperature from 37°C up to
39°C. This helps the immune system and inhibits
growth of some pathogenic bacteria.
Phagocytes
• Phagocytes are large, irregularly-shaped
leukocyte cells that remove bacteria, viruses,
cellular debris and dust particles.
• Phagocytosis is carried out by both neutrophils
and macrophages, the only difference is the
location of their action.
• Neutrophils circulate in the blood, while
macrophages are found in lymph, tissue fluid,
lungs and other spaces, where they kill microbes
before they enter the blood.
Non specific immune response
• Cells under attack produce histamine.
• Pathogens release chemicals.
• These both attract phagocytes
(chemotaxis).
• Pathogens may be covered in marker
antibodies (from B lymphocytes). This
stimulates phagocytes to attack as they
have receptor proteins which recognise
antibody molecules and attach to them.
Phagocytosis
• The phagocytes are constantly changing
shape, and they flow over microbes,
surrounding and ingesting them through the
process of phagocytosis to form a
phagosome.
• The phagosome then fuses with lysosomes small vesicle containing lysozymes, which
are released into the phagosome, killing and
digesting the microbe.
The bacteria will
be attracted to
the membrane of
the neutrophil
Phagocytosis. The
neutrophil will
engulf the bacteria.
Once in the neutrophil,
lysosomes (vesicles
containing digestive
enzymes) will form and
make their way towards
the phagosome
containing the bacteria.
The lysosomes
will fuse with the
phagosome.
Now the bacteria
will be killed and
digested by
enzymes.
Macrophages
• Macrophages make proteins that act in
two ways:
• By making pores in their cell
membranes and can also inhibit viral
reproduction inside cells.
• Or by the proteins sticking to the
outside of the bacteria to make them
more appealing for the phagocytes to
eat.
Complement System.
• This comprises more than 20 different
proteins, which kill microbes by making
pores in their cell membranes and can
also inhibit viral reproduction inside
cells.
• They are also involved in activating
other parts of the immune system.
Question
•
Macrophages are a type of white blood cell
involved in protecting against disease. One
of their functions is to release substances
called pyrogens which cause a fever to
develop.
(a) Give two ways in which macrophages
protect against disease, other than by
producing pyrogens. (2 marks)
1. phagocytosis / engulf and digest (allow
ingest, destroy, inactivate);
2. antigen presenting;
» 2 marks