Today!
Learning Goal:To be able to describe the nature of physical and chemical
barriers in plants and animals (including humans) to invading pathogens.
1. How does a pathogen cause disease?
2. What natural barriers do humans have to prevent pathogens from
causing disease?
3. What does ‘non-specific’ or ‘innate’ immunity refer to?
Microbes rule
Microbes (bacteria/fungi/single celled
organisms) ruled the planet for about 2.8
billion years before multicellular organisms
arose.
They live literally everywhere.
In the ocean, 1 million bacterial cells per ml of
water.
In a gram of soil, you’ll find 1 billion bacterial
cells.
The weight of all the microbes on the planet
outweighs all plant life on the planet… and a
trillion bacterial cells weighs just under a gram.
That gram of S. dysenteriae would be
enough to give every human on the planet
dysentery.
Microbes rule
So how are we not being infected all the time?
The immune system
‘Immunity’ comes from the latin term for being
‘free of burden’.
It is the ability for a host to resist infection.
Two types of immunity:- Nonspecific immune
response (innate or natural)- Specific
immune response (acquired or
adaptive)
Non specific immunity
Non specific immunity is the bodies first line of defence against invading
pathogens. It includes:
Skin
Mucus
Some enzymes
White blood cells (leukocytes)- macrophages- dendritic cells
Inflammation
Natural Killer cells
Microbiota
First line of defense: Skin
The skin is made of thick, tough, closely
packed together cells called keratinocytes
The skin is a barrier to penetration.
Continuous shedding of the outer layer of
skin removes many microorganisms from
attachment.
Salty (not conducive to growth -bad for
microbes)
Acidic (low pH – bad for microbes)
Dry (always bad for microbes)
Lysozyme (enzymes that break up
bacterial cells)
Sebum/oil/lipid production
First line of defence: Other Barriers
Mucous membranes:
Mucous provides another physical barrier
to infection.
Sneezing and coughing prevents
pathogens from getting to the lungs.
The acidic environment of the stomach
kills most pathogens
First line of Defence:Microbiological
barriers
There is another layer to your innate immune system
that we haven’t talked about.
The first line of defence includes, chemical, physical
and microbiological barriers.
This includes your microbiome. The individual
profile of bacteria you have in your gut and URT, and
Genitourinary tract.
This is why antibiotics can cause thrush sometimes.
The host bacteria out compete pathogens for access
to cell receptors, and access to nutrients.
[Link]
Second line of defence: Phagocytes
The immune system produces a
variety of cells which originate as stem
cells in the bone marrow.
These cells have roles both in the
innate immune response, and the
specific immune response.
How do you tell? If they change in
response to a pathogen, then theyare
adaptive. If they act regardless of
specificity, they are innate.
Second line of defence: Phagocytes
Phagocyte comes from the greek:
Phagein – to eat, Kytos – cell.
They make up a variety of cells which
have an initial response to invading
“non – self” pathogens.
Self: proteins or “antigens” which
are part of the host’s own makeup
Non-self: antigens that are not on
host cells, but on cells that have come
from outside the host organism (e.g.
glycoproteins/lipids on bacterial cells)
Self and non-self
Every cell (human/bacterial/otherwise) has protein
(glycoprotein/glycolipid) markers on the plasma membrane
which act as ‘antigens’
Antigens are literally “molecules that generate antibodies”.
Self cells have proteins on their outer membrane called MHC
proteins. (Major Histocompatibility Complex)
Most cells display MHC1 molecules on their membranes. These
are recognised as self by the immune system of the host.
The specific shape of these MHC1 proteins let the body know
they are self cells.
Some cells of the immune system have MHC2 protein and play
a role in signalling other cells of the immune system.
[Link]
Second line of defence: Phagocytes
Phagocytes recognise non-self
markers on pathogens, and engulf
(eat) them through endocytosis.
They then will be delivered to a
lysosome (an organelle containing
digestive enzymes and proteases)
The pathogen will be broken apart,
and it’s antigens will be repackaged to
be displayed on the membrane of the
macrophage (we will see why when
we talk about acquired immunity).
Today!
Learning Goal:To be able to describe the role of the lymphatic system in
innate immune response:
1. What MHC markers are present in humans, and what is their function?
2. What natural barriers do humans have to prevent pathogens from
causing disease?
3. What is the difference between first and second line immune defence?
Second line of defence: Phagocytes
There are a variety of different phagocytes:
Neutrophils: circulate in blood and act phagocytose any bacterial pathogens they
encounter.
Eosinophils: Move from the blood into tissue and play a role in defending against
parasites. Also increased during allergic reactions.
Monocytes: Once they leave the bone marrow, they mature into the largest
phagocytes called [Link] are called on by componentsof
the Specific immune system.
Mast cells and Basophils: involved in inflammatory responses and allergic
responses
Dendritic cells: present in skin and mucous,digest and present antigens to
the specificimmune system
[Link]
Second line of defence: Phagocytes
There are a variety of different phagocytes:
Natural Killer Cells:
Are large, non phagocytic cells that can destroy host cells.
They recognise both viral infected cells, and cells that are malignant (cancerous
tumour forming cells)
They can detect antibodies (adaptive)
They can also just detect host cells whichare missing MHC1 molecules (stressed
cells that are infected or cancerous)
Does not engulf cells, but releases granzymes which kill the host cell.
[Link]
Second line of defence:
Complement
The complement cascade is a number of proteins which bind to pathogens and
increase the binding of the next protein.
They do two things1. Opsonisation: opsonisation basically means marking
a pathogen for destruction. Macrophages and other cells recognise
complement proteins, bind to them, and engulf the pathogen.2. Lysis: When
the whole complement cascade is bound to a cellular pathogen it forms a ‘plug’
or hole in the membrane, which leads to the intracellularpressure bursting the
cell.
Second line of defence: Cytokines and
Interferon
Cytokines are proteins released by most
cells of the immune system, and have a
variety of roles.
They can be stimulated by viral,
bacterial, parasitic infection, or even
cancer, inflammation, or the action of
other cells of the immune system.
They have a variety of functions, but
generally involve signalling in the
immune system.
Inteferons are cytokines produced in
response to viral infection and interfere
in viral reproduction in the host cell.
Second line of defence: Inflammation
- Inflammation is an increase of blood
supply to an area that has encountered
pathogens.
- The release of histamine by mast
cells and basophils increases the
permeability of the vascular tissue
- Therefore, circulating phagocytes
(neutrophils) move into the area (via
normal blood circulation) and then
move out into the affected tissue.
- Phagocytes in the area then produce
more histamine, which attracts more
phagocytes to wound.
The lymphatic system:
The lymphatic system functions as a sort
of filter for the circulatory systems and the
tissue.
We know that capillaries form networks
across tissue where there is a diffusion of
gasses, proteins and other material.
Lymphatic capillaries pick up all the stuff
that doesn’t get absorbed back into the
blood.
It essentially removes all the extrafluid and
proteins from tissues.
The lymphatic system:
The lymphatic system is separated into
primary tissue, and secondary
tissue.
The Primary tissue is where B-cells
and T-cells develop and mature. I.e. The
Bone marrow, and the Thymus.
The Secondary tissue is where B-
cells and T-cells are introduced to antigen
to proliferate and be selected. E.g. Lymph
nodes, vessels, spleen etc.
Lymph is forced through the lymph
vessels by muscular contractions (not
heart).
Lymph vessels have valves and mean that
lymph only flows in one direction.
Lymph is then filtered (all pathogen
removed) at lymph nodes.
The lymphatic system:
Important cells of the immune systemare
involved in the lymphatic system.
The lymphatic system moves dendritic cells to
the site of infection to become APC
Lymphocytes include B-cells, T-cellsand NK cells
Lymphocytes all start life as immature
undifferentiated cells in the bone marrow.
The Bone marrow and the Thymusare really
important in allowing the lymphocytes to
develop recognition ofself and non-self.
T-cells mature in the Thymus, B-Cells mature in
the Bone marrow.
The lymphatic system:
Lymphedema occurs when the lymphatic
system (in particular the lymph nodes) are
blocked or damaged.
Lymph fluid accumulates and causes
swelling
Lymph nodes can swell up during an
infection due to the large volume of fluid,
white blood cells, and pathogenic antigens
being filtere.
Immunology so far:
First Line: Skin, mucous, enzymes, sebum, lysozymes, tears
Second Line:Phagocytes, Complement, NK cells, Cytokines, Interferon,
Inflammation, Fever
Elicits responses which stimulate the Third Line: Specific immunity:
Lymphatic system, Lymphocytes, B-Cells, T-Cells, NK cells.
