Transcript T Cells

Lymphatic & Immune Systems
Lymphatic System
Reabsorbs about 15% of
fluid filtered by blood
capillaries & returns it to
blood
Provides immunity &
protection from foreign
cells & matter in the
body
Absorbs dietary lipids in
small intestine &
transports them to
blood
p 809
Lymph = fluid in lymphatic vessels
• Usually clear, colorless fluid
• Originates in lymphatic capillaries
p 810
Lymphatic Vessels
Histology similar to veins
•Thinner walls
•More valves
Flow of Lymph
Like venous; low pressure
& speed
Primary driving force is
rhythmic contractions of
vessels
Assisted by Milking &
“Thoracic pump”
p 811
p 813
p 813
Lymph Nodes
In-line filters that
cleanse the lymph as it
passes through
Reticular fibers act as a
filter and delay
microbes & debris
Macrophages &
reticular cells remove
about 99% of impurities
from lymph
p 817
p 817
Lymphatic Cells
Natural killer (NK) = lymphocytes that
attack & destroy bacteria, transplanted
cells, & host cells that are cancerous or
viral-infected
Provide immune surveillance
T lymphocytes = mature in thymus &
provide cell-mediated immunity
B lymphocytes = mature in bone marrow &
provide antibody-mediated immunity
Lymphatic Cells
Macrophages = develop
from monocytes into large
highly phagocytic cells
that destroy foreign matter
and dead tissues & cells
Act as antigen-presenting
cells (APCs) by breaking
down foreign matter &
displaying parts of it on
their cell membrane
Lymphatic Cells
Dendritic cells = APCs that engulf foreign
matter by endocytosis
Located in epidermis (Langerhans cells),
mucous membranes, & lymphatic organs
Reticular cells = act as APCs in thymus
Form blood-thymus barrier that isolates
lymphocytes from blood-borne antigens
Produce hormones that promote
development & actions of T cells
Lymphatic Tissues
Lymphatic Nodules = dense masses of
lymphocytes & macrophages
Some appear temporarily to fight infections
Permanent nodules are found in;
• Lymph nodes
• Tonsils
• Appendix
• Ileum of Sm. Intestine (Peyer’s Patches)
Red Bone Marrow
Source of all blood cells which enter the
blood through sinusoids
Site where
B lymphocytes mature
p 814
Thymus
•Site where T lymphocytes mature
•Shrinks to small size in adults
•Secretes hormones that stimulate development
and activities of T lymphocytes
p 815
Tonsils.
Patches of lymphatic tissue that guard entrances
to the pharynx
Surface has deep pits called crypts that help trap
foreign materials
p 819
Spleen:
Largest lymphatic organ
Acts as in-line filter for blood, with reticular fibers
as filter and macrophages to ingest microbes &
foreign material
“Erythrocyte graveyard” where worn out RBCs are
phagocytized by macrophages
p 819
Nonspecific Defenses
Protection against a wide range of
pathogens
Pathogens = anything capable of causing
disease
• Bacteria
• Viruses
• Toxic chemicals
• Radiation
Nonspecific Defenses
•
•
•
•
•
•
•
External Barriers
Leukocytes & Macrophages
Immunological Surveillance
Interferons
Complement System
Inflammatory Response
Fever
External Barriers
Skin
Mucous Membranes
Secretions;
Tears, saliva, urine, vaginal secretions,
perspiration
Lysozymes = antibacterial enzymes that
breakdown cell walls
Stomach acid
Leukocytes & Macrophages
Neutrophils
Phagocytosis, plus
Lysozymes release enzymes that trigger the
respiratory burst, which produces;
Superoxide (O2-)
Hydrogen peroxide (H2O2)
Hypochlorite (HClO)
All highly toxic, so form a killing zone, that
kills many bacteria & neutrophils
Eosinophils
Phagocytosis
Release toxic chemicals
Particularly effective against allergens &
parasites
Basophils
Secrete histamine (vasodilator)
Secrete heparin (anticoagulant)
Stimulated by Eosinophils
Monocytes
Leave blood and become macrophages
• Wandering (Free) macrophages
• Fixed macrophages
Includes;
• Dendritic cells
• Microglia
• Alveolar macrophages
• Hepatic macrophages (Kuppfer’s cells)
Interferons
Small proteins
Released from viral-infected cells & bind to
receptors on surface of nearby cells
causing them to make antiviral proteins
that prevent viral replication, thereby
protecting those cells
Act as cell to cell signals to stimulate
activities of macrophages and NK cells
Complement System
Group of 30 or more
proteins
Important role in both
Specific and
Nonspecific defenses
p 823
Membrane Attack Complex
p 824
Immune Surveillance
Natural Killer (NK) Cells patrol body looking
to find & destroy bacteria, transplanted cells,
viral-infected cells, & cancer cells.
p 824
Inflammation
Inflammation is a local defensive response
to injury, like trauma or infection
Purposes;
1. Limit spread of pathogens & eventually
destroy them
2. Remove debris of damaged tissue
3. Start tissue repair
Words ending in itis denote inflammation of
that tissue (arthritis, dermatitis, etc)
Signs = heat, redness, swelling, pain
Inflammation
Vasodilation triggered by histamine & other
chemicals released from basophils, mast
cells & damaged cells (flow=heat, redness)
These chemicals also cause Increased Blood
Vessel Permeability as intercellular clefts
widen & allow increased filtration of;
• Fluids (swelling)
• Leukocytes
• Proteins (complement, antibodies, clotting
factors)
Neutrophil Behavior
Margination = loose
adhesion to vessel wall
Diapedesis = crawl thru
gaps between cells
Chemotaxis = move
toward chemical signals
from damaged cells
Phagocytosis = engulf
and digest foreign cells
& molecules
p 826
Neutrophils release signaling molecules to
attract more phagocytes (neutrophils &
macrophages) through chemotaxis
Macrophages engulf & destroy pathogens,
and casualties, like tissue cells &
neutrophils
Macrophages secrete colony-stimulating
factors, that trigger increased production
of more leukocytes (reinforcements)
What remains is Pus which is the dead
cells, tissue debris & fluid that are
eventually absorbed
Pain receptors are stimulated by;
1. Direct injury
2. Pressure from edema
3. Chemicals released by damaged cells
(like prostaglandins & bradykinin) and
bacterial toxins
Fever
Fever is an abnormal increase in body temp due to
hypothalamus raising the set point for body temp.
Pyrogen (fever-causing agent) = interleukin-1, that
triggers hypothalamus release of prostaglandin E
(PGE) which raises set point for temp
p 827
Specific Immunity
Specific immunity is directed at
one and only one specific pathogen
An initial exposure to a pathogen will
create a memory
When exposed again to the same
pathogen the body reacts so quickly
that there is no noticeable illness.
Specific Immunity
Cellular (cell-mediated) immunity =
lymphocytes directly attack & destroy
foreign cells or diseased host cells where
Pathogen is inside human cells
Intracellular Viruses, Bacteria,
Protozoans, & Yeast
Cells of Transplanted Tissue & Cancer Cells
Specific Immunity
Humoral (antibody-mediated) immunity =
antibodies tag or mark the pathogen for
destruction by other mechanisms
Indirect attack by antibodies,
instead of immune cells directly
Extracellular Viruses, Bacteria,
Protozoans, & Yeast
Molecular (noncellular) pathogens
like, toxins, venoms and allergens
Antigens
Antigen = any molecule that triggers an
immune response, normally proteins,
polysaccharides, glycoproteins, &
glycolipids
Antigenic Determinant Sites (epitopes)
= portions of the exposed surface of the antigen
that actually make it an antigen, (trigger an
immune response)
= sites where antibodies bind
Immune system must distinguish between;
Self vs. Nonself molecules
Haptens
•
•
•
•
Too small to be an antigen
Bind host macromolecule = then antigenic
Second exposure may not require binding
Include many allergens;
• Cosmetics
• Detergents
• Industrial chemicals
• Poison ivy
• Animal dander
T Lymphocytes (T Cells)
“Born” in bone marrow, then to thymus
where they become immunocompetent,
meaning they get receptors on their
surface for one antigen
Must pass a test to be sure they can
recognize foreign antigens, but not attack
self-antigens (only 2% pass)
Graduation = multiple & form clones of
identical T cells that recognize that one
specific antigen, then leave thymus as
naive T lymphocytes
B Lymphocytes (B Cells)
Born and become immunocompetent in
bone marrow (develop receptors on
surface for specific antigen)
Must pass same test to be sure they will
tolerate “self” cells and recognize foreign
or “nonself” cells
Then multiple & form clones of identical B
cells that recognize that one specific
antigen and leave marrow as naive B
lymphcytes
Major Histocompatiblity Complex
(MHC) Proteins
Complex = genes are on chromosome #6
Glycoproteins on surface of cells (except
RBC), about 200,000 per cell
Unique to each person
Shaped like hotdog bun, they pick up
antigens from inside the cell, migrate to
the surface & hold them in their central
groove
Class I on all cells (except RBC)
. Acting like an information relay, the MHC
Class I (MHC-I) molecules retrieve bits
and pieces of the proteins from inside the
cell and display them on the cell surface.
MHC complexes essentially give
a read out of what's inside the cell
Antigen-Presenting
Cells (APCs)
1. Phagocytosis of
antigen
2. Break down into
molecular fragments
3. Display (present) the
epitopes on its MHC
proteins
Class II MHC proteins
on APCs only
macrophages, B cells,
reticular & dendritic
cells
p 831
Cellular Immunity
Cytotoxic T (TC) cells = carry out direct
attack on enemy cells
Also known as T8, CD8, or CD8+ cells
because they have a surface glycoprotein
for binding to other cells called CD8
Helper T (TH) cells = promote actions of TC
cells and play a key role in humoral
immunity & nonspecific defenses
Also known as T4, CD4, or CD4+ cells due
to CD4 glycoprotein
Cellular Immunity
Memory T (TM) cells = descended from
cytotoxic T cells and provide memory of
initial exposure to an antigen, providing for
a very rapid response if exposed again
Immunity as a Three Act Play
Act One = Recognition
Act Two = Attack
Act Three = Memory
OR
“the three Rs of immunity”
Recognize
React
Remember
Recognition
Naive T cells inspect
cells MHC proteins &
antigens
Self antigens = okay
Viral proteins, abnormal
antigens made by
cancer cells = Respond
Like a sign that says,
“I’m infected” or
“I’m a cancer cell”
TC cells only MHC-I
TH cells only MHC-II
p 833
T Cell Activation
Receptor on T cell surface
must match foreign
antigen on MHC
= binds MHC
Second binding called
costimulation required
for activation
Triggers clonal
selection, repeated
mitosis which produces a
clone of T cells with
receptors for same
epitope
p 833
T Cell Attack
Helper T cells secrete
interleukins that;
1. Attract neutrophils &
natural killer cells
2. Atrract macrophages
& stimulate
phagocytosis
3. Stimulate T and B cell
mitosis & maturation
p 833
p 834
T Cell Attack
Cytotoxic T cells attack &
destroy cell with a
release of chemicals
For example, Perforin
creates pores in cell
membrane that kill it
Recall the Membrane
Attack Complex
p 833
p 834
Memory
Some TC and TH cells become memory cells
Memory T cells are long-lived & much more
numerous than naive T cells
They require fewer steps, so respond to
antigens much more rapidly
If the body is exposed to that antigen again,
the attack, called the T cell recall
response is so quick that there are no
symptoms
Humoral Immunity
Instead of directly attacking enemy cells, the
B lymphocytes produce antibodies that
bind to antigens and tag them for
destruction by other means.
Like cellular immunity, it also has 3 parts;
1. Recognition
2. Attack
3. Memory
Recognition
Immunocompetent B
lymphocytes act as
APCs
1. Receptor must bind to
its specific antigen
2. Endocytosis
3. Digestion of antigen
4. Presentation of
epitope in MHC-II on
cell surface
Now called sensitized B
lymphocyte
p 835
Recognition (cont’)
Sensitized B lymphocytes
then must bind with a
helper T cell, which
secretes interleukins
that complete
activation
Activation triggers clonal
selection – B cell
mitosis giving rise to a
battalion of identical B
cells with receptors for
the same antigen.
p 835
Recognition (cont’)
Most B cells become
plasma cells that
develop mainly in the
germinal centers of
the lymphatic nodules
of the lymph nodes.
Plasma cells produce
antibodies at a rate
of 2,000 per second
over 4 to 5 days until
they die.
p 835
p 836
Antibodies, also called immunoglobulins (Ig)
have a monomer made of four polypeptides
Note the;
Variable region with
a specific antigenbinding site
Constant region is
the same for each
class
5 classes include;
IgA, IgD, IgE, IgG,
and IgM
p 837
p 837
An individual probably makes about
2 million different antibodies.
The human immune system may be capable
of making at least 10 billion antibodies
and possibly 1 trillion antibodies.
How Antibodies Render Antigens Harmless
1) Neutralization Only the part of an antigen that
binds human cells is pathogenic, so antibodies
bind these active regions & neutralize them.
p 838
How Antibodies Render Antigens Harmless
2) Complement Fixation
Antibodies IgM and IgG
bind to foreign cells,
particularly bacteria and
mismatched RBCs, which
allows complement to
bind & trigger cytolysis.
p 837
How Antibodies Render Antigens Harmless
3) Agglutination An antibody may have up to
10 binding sites; thus, it can bind to antigens on
more than one cell at a time. This immobilizes
microbes and prevents them from spreading.
Effective in mismatched
RBCs and more
importantly against
bacteria.
p 838
How Antibodies Render Antigens Harmless
4) Precipitation Antibodies link antigen
molecules (not whole cells) together.
p 838
How Antibodies Render Antigens Harmless
This creates large Ag-Ab complexes that
come out of solution so they are available
for complement to bind them to RBCs or
be phagocytized by eosinophils .
As RBCs pass through the liver & spleen,
the macrophages remove and destroy the
Ag-Ab complexes.
This is the principle means of clearing
foreign antigens from the blood.
Memory
During clonal selection memory B cells are also
created in the germinal centers in lymph nodes.
They form plasma cells within hours and mount a
very quick secondary response, that prevents
any symptoms.
p 838