Transcript T CELLS - TeacherWeb

NOTES:
CH 43, part 1
The Immune
System Nonspecific &
Specific
Defenses
The lymphatic system is closely associated
with the cardiovascular system.
LYMPHATIC PATHWAYS
Lymphatic capillaries
● microscopic, closed-end
tubes that extend
into intercellular spaces
● receive LYMPH through
their thin walls
(LYMPH = the fluid of the lymphatic
system)
● lymphatic capillary networks parallel blood
capillary networks
Functions of lymph:
1) returns to the bloodstream small proteins
that leaked out of blood capillaries
2) transports foreign particles, such as
bacteria or viruses, to lymph nodes
**if lymph movement is impaired, it may
accumulate within the intercellular
spaces and produce EDEMA, or
swelling
(example: after surgery, the lymphatic
vessels and lymph nodes around the
wound may be damaged, causing fluid to
accumulate around the surgery site and
lead to swelling)
Lymph Nodes:
Structure of a Lymph Node:
● lymph nodes are subdivided into nodules
● nodules contain
masses of
lymphocytes
and macrophages
Locations of Lymph Nodes:
● lymph nodes aggregate in groups or
chains along the paths of larger lymphatic
vessels
Functions of Lymph Nodes:
● filter potentially harmful foreign particles from
lymph
● are centers for the production of lymphocytes
(attack invading viruses, bacteria, parasites,
etc.)
● contain phagocytic cells
(engulf and destroy foreign
substances, damaged
cells, cellular debris)
THYMUS AND SPLEEN
Thymus:
● shrinks slowly after puberty
● contains large numbers of
LYMPHOCYTES which
mature into T CELLS (T
lymphocytes) – important in
providing immunity (more on
these later…)
Spleen:
● largest lymphatic organ
● resembles a large lymph node (divided
into lobules)
Spleen:
● spaces within splenic
lobules are filled with blood
● contains many macrophages,
which destroy/remove foreign
particles and damaged RBCs
from the blood
**the spleen filters blood as
the lymph nodes filter
lymph!**
So, how does the body
defend itself???
The body has nonspecific and
specific defenses against
infection / pathogens.
Why don’t
YOU have
mold on your
skin???
● PATHOGEN: a disease-causing agent;
causes infection
-pathogens include:
viruses
fungi
bacteria
protozoans
Nonspecific Defenses:
● general defense
● provide protection against
many different pathogens
● involve physical and
chemical barriers, fever,
inflammation, phagocytosis
Specific Defenses:
● very precise
● target certain pathogens
● also known as IMMUNITY
● involve specialized
lymphocytes (T cells and B
cells) that recognize and
respond to specific
pathogens
**nonspecific defenses are
quick to respond; specific
defenses are slower-torespond
NONSPECIFIC DEFENSES
1) Species Resistance
● each species is resistant to certain
diseases that may affect other species
● examples: measles, mumps,
gonorrhea, and syphilis infect
humans but not other animal species
● one species may be resistant to a disease that
affects another species because its tissues
somehow fail to provide a suitable environment for
the pathogen (temperature, chemical environment,
receptors, etc.)
2) Mechanical Barriers = FIRST
LINE OF DEFENSE
● mechanical barriers / physical barriers
include:
-skin (and associated hairs)
-mucous membranes
-fluid (sweat and mucus)
● as long as they remain intact, they can
keep out many pathogens
SKIN
MUCUS
SALIVA
**all other
“nonspecific
defenses” are
considered the
SECOND LINE
OF DEFENSE
3) Chemical Barriers
● gastric juice: contains
hydrochloric acid and
enzymes (e.g. pepsin) that are
lethal to pathogens
● tears: contain the enzyme
LYSOZYME
(which has antibacterial action)
● the salt in perspiration
accumulates on the skin and
kills bacteria on the skin
3) Chemical Barriers (cont.)
INTERFERONS:
chemicals released by
virus-infected cells;
they stimulate other
immune cells to:
-synthesize antiviral
proteins that stimulate
phagocytosis, block
virus replication
Interferons:
● most effective against cold and flu virus
● now mass-produced by recombinant DNA
technology to be potentially used as
treatment for viral infections and cancer!
3) Chemical Barriers (cont.)
COMPLEMENT
SYSTEM:
● group of 20 proteins;
● catalyze a series of
steps resulting in lysis
of invading microbes
and/or inflammatory
response
4) Fever
● higher body temperature increases the
rate of phagocytic cells
● also lowers iron levels in the blood
(bacteria and fungi require iron, so this
slows their growth)
5) Inflammation
● produces: localized
redness, swelling, heat
and pain
● HISTAMINE and
prostaglandins released
by damaged tissues
attract WBCs to the site
 the mass of WBCs,
bacterial cells, and
damaged tissue forms a
thick fluid called PUS
6) Phagocytosis – removes foreign
particles from the lymph and blood
● the most active
phagocytes in blood are
NEUTROPHILS and
MONOCYTES
● Monocytes give rise to
MACROPHAGES
● MACROPHAGES are found in the
linings of blood vessels in the:
-bone marrow
-liver
-spleen
-lungs
-lymph nodes
EOSINOPHILS:
● kill antibody-coated parasites
Specific Defenses / Immunity
Immune System…
● the body’s “third line of
defense”
● characterized by:
 specificity
 diversity
 self / non-self
recognition
 memory
ANTIGENS…
● ANTIGENS: specific foreign molecules
that trigger an immune response; usually
located on a cell’s surface
-antigens include:
proteins
glycoproteins
polysaccharides
glycolipids
ANTIGENS…
● before birth, body cells sort “self” proteins
and other large molecules
● lymphocytes develop receptors that allow
them to differentiate between nonself
(foreign) and self antigens
● nonself antigens combine with T cell and
B cell surface receptors and stimulate
these cells to cause an immune reaction
LYMPHOCYTES (T and B Cells)
● originate in the red bone
marrow
● some reach the THYMUS,
where they mature into
T CELLS
● others, the B CELLS, mature in
the RED BONE MARROW
● both T cells and B cells reside
in lymphatic tissues and organs
(lymph nodes, spleen, etc.)
LYMPHOCYTE FUNCTIONS
**a lymphocyte must be ACTIVATED
before it can respond to an antigen**
*CLONAL SELECTION:
 antigen-specific selection of a lymphocyte;
 activates lymphocytes to divide and
differentiate to produce CLONES of
effector cells (& memory cells) designed to
eliminate the antigen that provoked the
initial response
SPECIFICITY & MEMORY!
T CELLS and the CELLULAR IMMUNE RESPONSE
* T cells are activated when an antigenpresenting cell displays a foreign
antigen
antigen
Antigen
Presenting
Cell
(APC)
T cell!
Antigen Presentation:
● Carried out by a group of approx. 20
glycoproteins that make up the
MAJOR
HISTOCOMPATIBILITY
COMPLEX (MHC)
Two main classes of MHC molecules:
● Class I MHC: located on all nucleated body cells
*cytotoxic T cells (TC) bind to fragments of
antigens displayed by class I MHC
● Class II MHC: found only on specialized cells
(macrophages, B cells, activated T cells)
*helper T cells (TH) bind to fragments of
antigens displayed by class II MHC
Antigen-Presenting Cells (APCs):
-cells that take up antigens (B cells,
macrophages);
-engulfed foreign matter binds to a class II
MHC molecule and is conveyed to the outside
of the APC;
-foreign antigen is recognized by a helper T
cells (TH);
-this interaction is enhanced by CD4, a
membrane protein on TH cells.
CD4
T CELLS and the CELLULAR IMMUNE RESPONSE
Example:
1) a macrophage engulfs and digests a
pathogen
2) the macrophage displays the antigens on its
cell membrane using
class II MHC.
3) the macrophage
encounters a HELPER
T CELL with the
appropriate antigen
receptor  activates T
cell
4) activated helper T cell
stimulates B cell to
produce antibodies
specific for the
displayed antigen
**Activated TH cells secrete CYTOKINES:
-CYTOKINES = factors that stimulate other
lymphocytes;
-Interleukin-2 (IL-2): stimulates B cells to
differentiate into antibody-secreting plasma
cells and induces cytotoxic T cells to become
active killers.
-Interleukin-1 (IL-1): secreted from APCs;
promotes activation of helper T cells.
**Other T cells: CYTOTOXIC T CELLS:
 recognize nonself antigens on cancer cells or
virus-infected cells;
 antigen-activated TC cells kill body cells that are
infected by pathogens (or are cancerous).
TC cells recognize and bind to antigen-class I MHC
markers (host cells display antigens with class I
MHC molecules);
(TC cells have special plasma membrane
proteins called CD8, which have an affinity for
class I MHC molecules…remember that class I
MHC is found in all nucleated body cells)
Cytotoxic T Cell Response:
-cytotoxic T cells then bind to the surfaces of
the antigen-bearing cells, and release a
protein (PERFORIN)
that cuts openings in
these cells, causing
them to burst (LYSE)
Before…..…..After
A fully intact cancer cell
surrounded by the immune
systems killer t-cells. The
cancer cell is surrounded and
attacked by the killer T-Cells
of the immune system.
Scanning electron microscope
pictures shows killer t-cells
attacking the cancer cell.
Notice the tentacles of the
cancer cell.
Notice how the cancer is completely flattened
and totally destroyed. During the killing
process, granules in a T-Cell fuse with the cell
membrane and release units of the protein
PERFORIN. These combine to form pores in
the target cell membrane. Thereafter fluid and
salts enter so that the target cell eventually
bursts.
T cells…
*Some T cells do not respond to the antigen on
the first exposure…they remain as MEMORY
T CELLS; upon a second exposure to the
same antigen, they respond quickly
B CELLS and the HUMORAL IMMUNE RESPONSE
* B cells are
activated when
they encounter an
antigen that fits
its antigen
receptors
B CELLS and the HUMORAL IMMUNE RESPONSE
Example:
1) a B cell encounters an antigen that fits its
antigen receptors
2) the activated B cell divides, enlarging its
clone (especially when stimulated by a
helper T cell!)
3) some activated B cells specialize into PLASMA
CELLS (antibody-producing cells)
*(antibodies react against the antigen that
stimulated their production!)…more on this later
4) some activated
B cells differentiate
into MEMORY B
CELLS (respond
to subsequent
exposures)
TYPES OF ANTIBODIES
● antibodies are soluble proteins called
IMMUNOGLOBULINS (Ig)
● 5 major types of antibodies: IgG, IgA,
IgM, IgD, and IgE.
Antibody Structure and Function:
● epitope: a localized region on an antigen’s
surface that is recognized by antibodies
● structure:
ANTIBODY ACTIONS
● antibodies work by:
1) attacking the antigens directly
(attaching to antigen)
-cause them to clump together
(AGGLUTINATION) or form insoluble
masses (PRECIPITATION)
-makes it easier for phagocytes to engulf
the antigens / antigen-bearing agents &
eliminate them
AGGLUTINATION!
ANTIBODY ACTIONS
2) activating COMPLEMENT
-a group of proteins that work together to
produce a variety of effects:
● attract phagocytes
● rupture foreign cell membranes
● coating the cells, making them more
susceptible to phagocytosis
Complement
System
ANTIBODY ACTIONS
3) stimulate changes in local areas that
help prevent the spread of the antigens
(i.e. promote inflammation)