11 Immune System (Simple)

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THE IMMUNE SYSTEM

Stem Cell

Lymphoid Stem Cell Myeloid Progenitor

B Cell T Cell Natural Neutrophil Eosinophil Monocytes


Killer

Cytotoxic Helper Suppressor Basophil Mast Cell

Plasma
Plasma Mast Cell
Cell
Cell
Immune System “Players”: Major Cells

• Stem Cell: an undifferentiated cell whose


daughter cells may differentiate into two
different cells
• Lymphoid Stem Cell: white blood cell (WBC) of
the immune system that is part of the lymph
system
• Myeloid Progenitor: makes platelets, red
blood cells and some WBCs
Immune System “Players”: Lymphoid Cells

• B Cells: A lymphocyte that matures in the


bone marrow and carries out humoral
immune response. B Cells have membrane
bound antigen receptors.
– Plasma Cell: (Activated by B Cells) Secrete
antibodies to eliminate certain antigens
– Memory Cell: (Activated by B Cells) Remember
antigen that caused its formation
Plasma Cell
The orange part is the endoplasmic reticulum that
manufactures, modifies and transports proteins, or antibodies.
The cells nucleus is redish-brown and the dark brown dots are
mitochondria which provide the cell with energy.
Immune System “Players”: Lymphoid Cells

• T Cells: A lymphocyte that matures in the thymus and


functions in cell mediated response.
– TC (Cytotoxic) Cells: Kill infected cells and cancer cells
– TH (Helper) Cells: Secrete Cytokines, molecules that are
released by one cell as a regulator of a neighboring cell ( B and
T cells)
– TS(Suppressor) Cells: Probably turn off immune system when
antigen is gone.
• Memory T Cells: Cells that fight certain previously
exposed infections faster and stronger than the first
time.
T Cell in Action
Cytotoxic T Cell (orange) killing a cancer cell (purple).
Immune System “Players”: Lymphoid Cells

• Natural Killer Cells (NK Cells):


Cells that destroy a body’s
infected cells, especially the
ones that harbor viruses, and
aberrant cells, which can form
tumors.
– “Shake hands” with cell
– If cell has no recognizable MHC
(identification), then the NK kills it
– Attack the membrane of target cell
causing it to lysis
Immune System “Players”: Myeloid
Progenitor Cells
• Phagocyte Cells: WBCs that ingest invading
particles
– Eosinophils
• 1.5% WBCs
• Limited phagocytic activity, but contain enzymes within
cytoplasmic granules
• Destroy parasites by positioning themselves on walls and
releasing enzymes
– Neotrophils
• 60-70% of WBCs
• Can leave blood and enter infected tissues to destroy
microbes, then self destruct
• Live only a few days
Immune System “Players”: Myeloid
Progenitor Cells
• Phagocyte Cells: WBCs that ingest invading
particles
– Eosinophils
• 1.5% WBCs
• Limited phagocytic activity, but contain enzymes within
cytoplasmic granules
• Destroy parasites by positioning themselves on walls and
releasing enzymes
– Neotrophils
• 60-70% of WBCs
• Can leave blood and enter infected tissues to destroy
microbes, then self destruct
• Live only a few days
Parasite

Eosinophil:
Above showing the granules
which release enzymes and the
size. To the right showing a
eosinophil attacking a parasite.
Neutophil:
Leaving the blood to migrate into a tissue and a Neutrophil animation
Immune System “Players”: Myeloid
Progenitor Cells
• Monocytes
– 5% WBCs
– Very effective phagocytic defense
– Monocytes develop into macrophages (big eaters) after
migrating into a tissue
– Have amoeboid cells that pull in microbes which are then
destroyed (by enzymes and reactive oxygen) with
macrophages
– Some macrophages reside permanently in organs and
connective tissue (many reside in lymph nodes and the spleen)
– Macrophages secrete hormones called cytokines that call for
immune system cells and activate cells involved in tissue repair
Immune System “Players”: Myeloid
Progenitor Cells
• Basophils and Mast Cells
– Contain the chemical histamine which aids in the
inflammatory response
– When these cells are injured in connective tissue,
histamine is released
– This triggers vasodilation and makes the capillaries
“leaky”
Monocyte ready to
defend against Vasodilation by
antigens histamines released
by basophils and mast
cells
Substances
COMPLEMENT
LYSOZYME
Body tissue

INTERFERON
Alfha, beta, gamma
Substances
HISTAMINE
INTERLEUKINS contained in basophils and mast cells

MHC This can be used as a Chemical signal


biochemical fingerprint
to each individual.
Substances
PROSTAGLANDINS
Helps cause local
vessel dilation.

CLOTTING PROTEINS
Blood clotting 
Substances ANTIBODY
PYROGENS Specific protein
produced by
specialized
lymphocytes.

ANTIGEN
Molecule that sets the
body’s thermostat at a
higher temperature.
Process: Fighting an Infection
1. Chemotaxis
• When the epithelium of the skin is damaged,
chemicals are sent into the bloodstream by the
invading bacteria and tissues
– These molecules, called chemokines, attract phagocytic
cells to the infected area

• Chemotaxis is the process of


phagocytic cells migrating to
the source of the chemical
attractant
2. Vasodilation
• When the chemokines are released, vasodilation,
the widening of the arteries, also occurs
– Increases the blood flow to the infected area, carrying
the needed white blood cells
– Causes the redness and heat as the white blood cells
work to cure the infection
Inflammation:

1.redness
2.pain
3.swelling
4.heat
3. Diapedesis
• When the white blood
cells get to the infected
area in the bloodstream,
they undergo the process
of diapedesis
• The cells move through the
epithelium of the
capillaries and into the
surrounding interstitial
fluid to destroy the
invaders
• When the white 3. Diapedesis
blood cells get to the
infected area in the
bloodstream, they
undergo the process
of diapedesis
• The cells move
through the
epithelium of the
capillaries and into
the surrounding
interstitial fluid to
destroy the invaders
2.
2. chemokines
chemokines sensed
sensed by
by
1. neutrophils/monocytes
neutrophils/monocytes
1. damaged
damaged
cell
cell releases
releases
chemokines
chemokines
3.
3. monocytes
monocytes squeeze
squeeze
out
out of
of capillaries
capillaries
(diapedesis)
(diapedesis)

4.
4. monocytes
monocytes (and/or
(and/or
macrophages)
macrophages) start
start to
to
engulf
engulf pathogen
pathogen
(phagocytosis)
(phagocytosis)
4. Phagocytosis
• When the phagocytic cells get to the
invaders, they go through the process of
phagocytosis to finally eliminate the
bacteria
4. Phagocytosis
• When the
phagocytic cells
get to the
invaders, they go
through the
process of
phagocytosis to
finally eliminate
the bacteria
• The Pseudopodia on the macrophages attach
to polysaccharides on the microbes surface to
pull it in.
• Once the microbe is in the cell, the lysosome
comes to destroy it
• The lysosome in the cell can kill the microbe in
one of two ways:
1) Generating toxic forms of oxygen
2) Releasing enzymes that digest microbial components
Clotting Cascade
• When the skin’s
epithelium is damaged,
a series of reactions
occur to stop the
bleeding
• The cascade follows two
pathways: extrinsic and
intrinsic and then
finishes in the final http://www.hopkinsmedicine.org/hemato
common pathway logy/Coagulation.swf
Edema
-Definition: large amount of fluid beneath the skin; swelling
-Homeostasis maintains the amount of interstitial fluid around the body
- Too much fluid causes swelling as well as poor removal of fluid
How it starts--
Leaky Capillaries
Two types of pressure measured in the capillaries:
- hydrostatic pressure: causes water to filter into
surrounding tissues
- oncotic pressure: pulls water back into the vessel
from the tissues
Together the two pressures maintain homeostasis of fluid
levels in the body
Most leakage occurs in the capillaries due to
there semi-permeable membrane
Factors that increase leakage of fluid
1. increase of hydrostatic pressure in vessel
2. decrease of oncotic pressure in vessel
3. increase in vessel wall permeability
Humoral Immunity
What is it?
Transformation of B-cells into plasma cells that can then produce and secrete antibodies
B-cells =
-created in the bone marrow
-circulate through blood and lymph
-changes into a clone of plasma cells to secret a specific antibody
-also can change into a clone of memory cells to make antibodies after first encounters
1st Antigen Exposure
- Antigen is engulfed by macrophage
-Macrophage stimulates Helper T-Cell
-Helper T-Cells stimulate B-Cells and Cytotoxic T-Cells
-B-Cells turn into plasma and memory cells
-Plasma cells secret antibodies into blood; memory b-cells are “stored”
until their specific antigen shows up again (2nd exposure)
-Cytotoxic t-cells turn into active cytotoxic t-cells and memory t-cells
- Cytotoxic t-cells go and kill the antigen; memory t-cells are also stored
until their specific antigen shows up again (2nd exposure)
Cellular Immunity
What is it?
Ability for antibodies to recognize a foreign organism, known as antigens,
and destroy it
Advantage
Allows for a person’s body to destroy of antigen faster before the antigen,
which could be harmful to a person, causes damage

Types of WBC’s
(antibodies) 
Cellular vs. Humoral Immunity

-Humoral immunity is the first stage the builds the


memory b-cells for cellular immunity.
-Cellular immunity depends on the cells that are
made during b-cell and cytotoxic t-cell
transformation into memory cells
-Memory cells are formed with specific antibody
receptors that bind to a specific antigen
Clonal Selection
Definition
-The selection of a lymphocyte by an antigen which activates the
lymphocyte stimulating it to divide and diferentiate.
Two Types:
1. Effector cells
--plasma cells--make antibodies--short lived
2. Memory cells
--long lived

White blood cells fighting a


antigen
the antibody (Ab) protein
hypervariable
region
(hundreds of
billions of
possible shapes)

constant region
(same for all
antibody
molecules)
(aka Fc region)
a simpler way to show the antibody molecule

hypervariable region (hundreds of


billions of possible shapes)

constant region (same for all antibody


molecules)
(also called Fc region)
• Ab are incredibly SPECIFIC
• each one will bind ONLY to its matching antigen.
• this shows 14 different antibody molecules.
• in reality there would be MANY BILLIONS of
different antibodies.
antigens (Ag)
• any foreign object that our immune
system can react with
• protein, virus, bacterial cell, toxic
molecule, pollen grain, polysaccharide,
etc
• here, there are 8 shown
• in reality there are hundreds of billions
• any ONE bacterial cell might have
hundreds or thousands of antigenic
proteins on its surface
• Antigens and Antibodies must make an EXACT MATCH
• if they don’t match – no triggering, no sticking
• if they DO match – they stick together strongly
• if they DO match – triggers something to happen

• what DOES happen when they match?


another way to show the
antibody molecule...

http://www.nwfsc.noaa.gov/hab/habs_toxins/marine_biotoxins/detection/elisa.html
• B cells make antibodies
• each B cell makes ONE
type of antibody
• but it makes a lot of
them
B cell • it sticks those Ab on its
surface, with the “red”
end facing out
• if any “red” antigen
comes around, it will be
“caught” by the surface
Ab
• if any “red” antigen
comes around, it will be
“caught” by the surface
Ab
• NO OTHER antigen will
B cell be caught
• this “primes” the B cell
• B cell matures into
plasma cell
• plasma cell pumps out
its specific antibody
• plasma cell also
replicates
• all daughter cells also
pump out “red”
antibody
• plasma cell also replicates
• all daughter cells also pump
out “red” antibody
this is a B cell which
produces “red” Ab

B cell

here’s an even simpler diagram showing a B cell with


“red” antibodies
recall there would be
millions of different B
cells circulating
each would have its own
Ab projecting from its
surface
Lymphocytes
-White blood cells
-Built with specific, unique antibodies on their surface
-Antibodies are proteins that bind with antigens to neutralize it
Because of cellular immunity, the body knows which white blood
cell carries the specific antibody to “battle” the antigen
Advantage:
having the specific antibody that neutralizes the antigen is
helpful because the antibody can “battle” and destroy antigens
quickly and easily

WBC vs. RBC 


Features
Features
Specifity

In the first line of Defense the immune system remains non-specific.


Elements of the immune system active at this point:
• Mucous
• Skin
• Secretions (skin & mucous membranes)
Second Lind of Defense-
It still remains non-specific, as the natural response occur.
• Inflammatory Response (w/histamine)
• Phagocytic WBC’s (ingestion of invading cells)
• Neutrophils are attracted to damaged cells
• Monocytes release macrophages
• Natural killer cells are released
• Antomicrobial Proteins complement the system and directly attack
microbes or impede reproduction
Third Line of Defense is where the immune system is specific.
Lymphocytes come into play:
B Lympho’s
T Lympho’s
__ membrane bound antigen receptors
Also Antigens, which are antibody generator
At this point there is clonol selection where the selection of a
lymphocyte by an antigen activates the lymphocyte stimulating it to
divide and differentiate.

Memory Cells

There are memory cells, which are created after antigen


receptors and antigen molecules (B cells) and this end up
being antibody molecules. These consist of memory cells and
plasma cells.

The memory cells make it possible for the body to recognize


viruses that have already entered the body once before.
Self/ non-self recognition

The main function of the immune system is distinguishing self from non-self. The
essence of immunological response is a two part system: recognition and
destruction. The pathogens or foreign bodies that trigger the immune system are
called antigens. Antibodies is the structure which mostly recognizes foreign bodies.
They go throughout the body “shaking hands” with the other cells to make sure
they know each other and to see if anything is wrong with the cells of the body.

Diversity

In the immune system there must be a diverse amount of lymphocyte receptors


to ensure that at least a few lymphocytes can bind to any given pathogen. This diversity
is created from inherited gene segments or libraries.
Memory
cell
THANK YOU!

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