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Immunology
Test 1
157
Biology
Undergraduate 4
08/16/2013

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Term
Immune System:
Definition
Complex defense system that protects animals from pathogenic
microorganism and cancer. Does this by means of a large variety of cells and
molecules that are capable of specifically recognizing an eliminating an apparently
unlimited of foreign molecules.
to do this the immune system preforms two functions: Recognition and
Response.
Term
Recognition:
Definition
not only has the ability to distinguish foreign material from the
body's own cells and proteins, but also has the ability to recognize subtle
chemical difference between that foreign material or proteins/cells (albumen in a
mouse and albumen in a rat)
Term
Effector Response
Definition
once it has been recognized the immune system initiates a response, ____ ____
Later exposure to the same material will initiate a Memory Response (faster and
stronger...ex vaccine)
Term
observation
Definition
Study of immunology grew out of ____ (Once they got sick they didn't get
sick again).
Term
plague
Definition
Earliest account of this observation was in Athens in 430BC from a
___. Only those who had gotten the plague and recovered were allowed to
take care of the sick because they knew they would not contract it again. this
help the prevention from person to person.
Term
First prevention
Definition
Turks and Chinese 15th century, took dried crust from small pox
pustules and had their soldiers inhale the dust. Whoever recovered did not
receive it again
Term
Edward Jenner
Definition
1798- Small pox outbreak in London- ___ ___ noticed that milk maids
who previously had cow pox did not get small pox. He reasoned that somehow
the cow pox must somehow be a preventative of small pox. He took the fluid of
a cow pox lesion and injected it into a little boy, and a few days later he took the
fluid from a small pox lesion and the boy did not get sick. (small pox 30% fatality
rate) first disease that could be prevented for almost 100 yrs.
Term
Louis Pasteur
Definition
1800's- experimenting with a bacteria that caused fowl cholera
(fatal disease in chickens). infected the chickens with an old bacteria, he reasoned
that the old bacteria lost their ability to cause disease--attenuation. He prepared
a fresh culture and started infecting chickens and noticed that the chickens that
received the old culture of bacteria did not die, he reasoned that these
attenuated bacteria somehow gave the chickens resistance. called the attenuated
bacteria--vaccines.
he developed attenuated vaccines for anthrax...had never given any to people
yet.a boy was bitten by a dog with rabies. he had a attenuated vaccine with rabies.
he gave the vaccine to the boy and the boy survived a disease that was
virtually 100% fatal. first account of the use of attenuated vaccines on humans.
(did not know how the vaccines worked...although it did work)
Term
vonBenhring and Kitasato-
Definition
1890- ____ _ ____- took serum from from animals that were
immune to diphtheria and transferred to non immunized animals and those
animals became resistant to disease. over the next decade researchers discovered
that the components of the serum could neutralize toxins, ppt toxins, and
glutamate the bacteria...the component that was responsible was determined to
be gamma globulins (immunoglobulins). because its mediated by antibodies it is known as humoral immunity.
Term
Elie Metchnikoff
Definition
1893- ___ ____- noticed that cells contributed to immunity. he observed
that certain white blood cells (phagocytes) were able to ingest microorganisms
and other foreign materials. He also noticed that phagocytes were more active in
animals that had been immunized.
He reasoned that the WBC and not serum were the major factor of
immunity= cell mediated immunity
Term
Merril Chase
Definition
1940- __ __ transferred cells from a guenia pig that were immune to TB
into cells that were not immune to TB
Term
humoral and cell
mediated immunity.
Definition
1950- discover of lymphocytes (WBC)- as the mediator of both __ __ __ __ ___
Term
Bruce Glick
Definition
__ __ - demonstrated that there were two types of lymphocytes-
T-lymphocyte- derived from the thymus- mediates cellular immunity
B-lymphocyte- derives from the Bursa of Fabrirusa (birds) and bone marrow
(mammals)- mediated humoral immunity
Term
Innate immunity
Definition
___ ___- nonspecific, represents the body's first line of defense (anything
foreign)
Term
Adaptive immunity
Definition
__ __- specific, body's response to a specific particle (specific
protein, germ). Two types: Cell Mediated and Humoral
Term
Humoral immunity-
Definition
antibody production
Term
Cell mediated immunity-
Definition
T-cells recruit other cells to clear or eliminate the
germ.
Term
Innate Immunity-body's first line of defense against foreign materials.
4 defense barriers
Definition
Anatomic, Physiologic, Phagocytic, and Inflammatory
Term
Anatomic-
Definition
skin (page 144-table), mucus membrane,
sweat has antibacterial proteins, skin secretes sebum (skin oil) which has
antibacterial properties, skin is relatively dry and most microorganisms
don't like dry environments, and we are constantly shedding dead skin which makes it hard for pathogens to get a good foothold.
mucus membranes line our respiratory, GI, and Genitourinary tracts.
Include tears, saliva, mucus secretion what they do is wash away
pathogens and release substances that would either inhibit or kill
microorganisms. Mucus is very vicious which traps the pathogen so that
they can be sent to the nearest body opening and eliminated.
In our Resp. tract we have cilia which "beat" to move particles up the
reparatory tract so they can be coughed out or swallowed.
Mucus membranes have Normal Flora, microorganisms that naturally live
in these body sites, and play a very imp. part in body defenses. they take
up all the tissue biding sites leaving none available for pathogens.
Term
Physiologic
Definition
includes body temp. and pH. Soluble factors. Cell-Associated
receptors
ex. some animals that are resistant to some human pathogens for the
simple reason that their body temp are much higher than ours and the
pathogen can't grow at that temp.
ex. can only study salmonella if you give it to a person or maybe a chimp,
you can't give it to a rat because their temp is too high
when you get a fever your body is trying to make the environment less
favorable to the bacteria.
pH ex. stomach acid: most organisms can't stand the acidity of our
stomach acid. if they are swallowed they have to deal with their stomach
acid.
Term
soluble factors
Definition
lysozyme: found in tears and mucus secretion, and other body
secretions. they degrade cell walls.
Interferon: antiviral activity. produced by viral infected cells. it protects
neighboring cells from being infected by the virus. it helps contain the
virus.
Complement: group of serum proteins that interact together to either
kill the pathogen or to facilitate its clearance.
Pattern Recognition (Pathogen-associated molecular patterns-PAMPs):
the ability to recognize a particular class of molecules that are not
part of the body. (soluble factors work based off of this)
Transferin- protein found in serum. this strongly binds iron. by binding
to iron it makes it unavailable for the bacteria which needs iron to
grow. (not pattern recognition)
Cell-associated receptors- PAMPs- ex. toll-like receptor (TLR) TLR-2
is a class of these receptors- recognizes lipopolysaccharide of gramneg
bacteria. in binding to this it stimulates the response of a variety
of molecules involving inflammation.
Table 5-3 (don't have to memorize)
Term
Phagocytic-
Definition
response is to ingest and kill microorganisms. preformed
primarily by monocytes, neutrophiles, macrophages.
Term
Inflammatory
Definition
tissue damage caused by injury or infection will induce a
series of events that we call an inflammatory response. Results in either
stimulation immune response or clearance of the microorganism by
components of innate immunity.
Term
3 major events that occur during inflammation
Definition
Vasodilation, Increased vascular permeability, and an Influx of phagocytes from the capillaries into the tissues
Term
vasodilation-
Definition
this is when the blood vessels increase in diameter
because of increased blood flow to that area. Results in tissue redness
and increase in body temperature (at least in that sight)
Term
Increased vascular permeability-
Definition
fluids and white blood cell passing
from the capillaries into the tissues. Fluid that accumulates in the tissues
is referred to as an exuade, causes swelling. swelling is called edema
Term
Influx of phagocytes from the capillaries into the tissues-
Definition
During this process the phagocytes attach to the walls of the capillaries, margination.
Then they squeeze through the walls into the tissues, diapedesis. Then
they migrate through the tissue into the sight of the wound/damage,
chemotaxis. The accumulation of white blood cells at the site is what we
call pus.
Term
when all of this come together. it is referred to as the 5 clinical signs of
inflammation.
Definition
Redness, Swelling, Heat, Pain, Loss of function (sometimes).
Term
Hematopoiesis-
Definition
formation of red and white blood cells
Term
all blood cells arise from a type of cell called
Definition
a hematopoietic stem cell. stem cells carry bone marrow
Term
stem cells differentiate into
Definition
lymphoid progenitor cell
Myeloid progenitor cell
These progenitor cells determine the type of immune response to
various growth factors and cytokines.
Term
lymphoid progenitor cell
Definition
produce T and B cells (lymphocytes) and Natural Killer cells
Term
Myeloid progenitor cell
Definition
produce most other RBC, WBC, and platelets
Term
Lymphocytes
Definition
make up 10 to 40 percent of bodies WBC and 99% of the cells found in the
lymph
continually circulate in the blood and are able to maculate into tissues and
form lymphoid organs
Term
three major types of Lymphocytes
Definition
T cells - cell mediated immunity
B cells - humoral immunity
Natural Killer cells (most impt.)-
lymphocytes that do not have the surface markers of B and T cells.
More involved in innate immunity.
do not need specific receptors.
Term
Resting B and T cells
Definition
are small nonphagocytic cells. ~6mm in size.
commonly referred to as naive B and T cells. When they interact with an
antigen in the presence of cytokines they enlarge into lymphoblast
(15mm across). these lymphoblast proliferate (undergo a series of
divisions) and differentiate into a series of effector cells. which function in
eliminating the antigen. some also differentiate into memory cells, cells
that are responsible for life-long immunity to that antigen (e.g. vaccine).
Term
effector B cells
Definition
plasma cells are ___ __ ___
produce and secrete antibodies
Term
Effector T cells (2 types)
Definition
T-helper cells (TH)
T-cytotoxic cells (TC)
Term
T-helper cells (TH)
Definition
secrete cytokines that stimulate and regulate immune response
Term
T-cytotoxic cells (TC)
Definition
cells that kill foreign cells of virus infected cells.
Term
B-lymphocytes (B-cells)
Definition
mature in bursa of fabricus in birds and in bone marrow of mammals.
can bind the free and soluble antigens
can be distinguished from other cells by certain surface markers (pg. 39
table).
CRI (CD35) & CR2 (CD21)-complement receptors.
CD32- receptor for fc region of IgG
CD40- interacts with surface of TH cells.
important in differentiation for memory and plasma cells.
Term
T-lymphocytes (T-cells)
Definition
derived from bone marrow then migrate to the thymus to mature.
recognize antigen only when its bound to a cell membrane protein called
MHC (major histocompatibility complex).
MHC is found on the surface of antigen-presenting cells, on virus infected
cells, cancer cells, or transplanted cells.
this is how our body distinguishes us from foreign things.
Term
2 main types of MHC
Definition
Class I MHC
Class II MHC
Term
Class I MHC
Definition
expressed on all nucleated cells in the body
Term
Class II MHC
Definition
only on antigen-presenting cells
Term
some have surface marker CD4--generally TH cells--
Definition
interact with antigen
bound to class II MHC
Term
others have surface marker CD8--
Definition
interact with class I MHC
Term
cytokines
Definition
When TH cells are activated by antigens bound to class II MHC they
secrete ___ that play an important role in activation of an immune
response.
these cytokines activate B cells, other T cells, and other WBC that are
involved in the immune response to that antigen.
Term
TH I response-
Definition
supports inflammation, activates macrophages, other T cells
Term
TH2 response-
Definition
activates mainly B cells and stimulates antibody production
Term
TC cells-
Definition
when they are stimulated (by antigens from Class I) they give rise to
cytotoxic T lymphocytes (CTLs).
produce very few cytokines, instead acquire the ability to stimulate cancer
cells, virus infected cells
Term
CD8
Definition
Tc cells
Term
CD4
Definition
TH cells
Term
Types of CD4+ T cells
Definition
TH 1-Intracellular pathogens
TH2- extracellular pathogens
TH17-secrete the cytokine IL-17 (Interleukin 17)
TFH (follicular TH)- involved in B cell activation
Treg (T- regulatory)- turn off, or inhibit, the immune response
Term
TH 1
Definition
Intracellular pathogens
T cells involved in response against intracellular pathogens
organisms that grow inside of cells
Term
Treg (T- regulatory)
Definition
turn off, or inhibit, the immune response.
play an important role in preventing autoimmunity.
not only have CD4, they have CD25 cell marker.
Term
Natural Killer Cells (NK cells)
Definition
do not have the surface markers of B and T
cells. do not recognize specific antigens like B and T cells. involved in killing
virus infected cells and tumor cells.
surface marker that makes them unique- CD16
also function in antibody-dependent cell-mediated cytotoxicity (ADCC)--
means that they kill cells that are coded with antibodies
Term
Other types of Leukocytes:
Definition
Granulocyte
Monocytess
Term
Granulocytes
Definition
visible granules in cytoplasm
Term
Granulocytes
Definition
Neutrophils
Eosinophils
Basophils
Mast Cells
Dendritic cells
Term
Neutrophils
Definition
• phagocytic
• most abundant WBC
• they have a multi-lobed nucleus (have everything that Monocytes have
except antigen presentation)
• usually the first to arrive at the site of injury. besides phagocytosis they
have multiple ways of killing microorganisms. same as macrophages
except antigen presentation
Term
Eosinophils
Definition
• phagocytic
• don't play as important a role as neutrophils
• major role is against parasitic worm infection, but can play a role
against inflammation
Term
Basophils
Definition
• non-phagocytic
• play a role in allergic response
body wide (anaphylaxis)-bee sting, peanuts
Term
Mast Cells
Definition
• non-phagocytic
• found in tissues, not circulating in the blood like others
• involved in inflammation and allergic reactions
more localized not body wide
Term
Dendritic cells
Definition
• have long membrane extensions that resemble that resemble
dendrites of nerve tissue.
• what we call antigen-presenting cells. *important*
Term
Monocytes
Definition
do not have granules
large phagocytic WBC
Term
Monocytes
Definition
Macrophages
Term
Macrophages
Definition
• monocytes that reside in tissues
Term
Organs of Immune System
Definition
Primary lymphoid organs
Secondary lymphoid organs
Term
primary lymphoid organs
Definition
site of lymphocyte maturation
• humans: thymus and bone marrow
Term
secondary lymphoid organs
Definition
organs that trap the antigen and provide a side where the lymphocytes
interact with the antigen.
bone marrow, spleen
Term
Mucosal-associated lymphoid tissue (
MALT)
Definition
• tonsils
• appendix
Term
Gut-associated ‣ lymphoid tissue (GALT)
Definition
lymph nodes
GALT is a part of MALT
Term
Primary lymphoid tissue
Definition
thymus
Term
thymus
Definition
site of T cell maturation
‣ flat bilobed organ found above the heart
Term
each lobe is surrounded by a capsule and each lobe is divided into lobules
and each lobule has 2 compartments
Definition
• outer compartment is called the cortex (has immature T cells--
thymocytes)
• Inner compartment is called the medulla (contains few thymocytes)
Term
Function of the thymus
Definition
is to generate and select populations of T cells that will protect
the body from infection
Term
as thymocytes develop a very large diversity of T cell receptors are
generated by gene rearrangement. This process produces some T cells
with receptors that will recognize
Definition
antigen MHC complex. most of the T cells that are produced do not recognize the antigen MHC
complex, or will react with self antigen complex with MHC.
‣ the thymus induces the death of complexes that can't react with antigen
MHC complex or will react too strong to with our own bodies. (90%)
• only 5% go on to mature into T cells.
Term
the role of the thymus has been studied in
Definition
mice (removed in early
childhood) there is a drastic reduction of the number of circulation T
cells and an absence of cell-mediated immunity.
• nude mice-don't have hair- they also don't have a thymus- there is a
human equivalent to this called DiGeorge's syndrome- thymus fails to
develop because of that there is an absence of T cells and cellmediated
immunity. they also have a much greater risk of infection
Term
Thymus function decreases with
Definition
age. they thymus reaches it's max size at
puberty then begins to get smaller. the loss of thymus mass is
accompianies by loss of T cells.
• at age 35, generates is only 25% of newborns. at 65, only 2% of
newborns.
Term
Lymphatic System
Definition
system that brings antigens to organs
Term
as blood circulates throughout the body, ‣ plasma seeps through capillary
walls into tissue.
Definition
• when a plasma enters into tissue it is referred to as interstitial fluid
• fluid permeates all tissues and invades all cells in the body
Term
under normal circumstances, most fluid will return back to the
circulatory system through venuels
Definition
the remainder of the fluid with enter a network of thin walled tubes
called the primary lymphatic capillaries.
Term
the largest vessel is the thoracic duct
Definition
duct•
it empties out into the left subclavian vein, this vein collects
lymph from every part of the body except the right side of
the head.
• lymph from these two parts is collected in the right subclavian
vein.
Term
when a foreign antigen enters tissue it is picked up by the lymphatic
system and carried to various secondary lymphoid tissues, such as
Definition
lymph nodes, which trap the antigen.in addition as lymph passes from tissues to lymphatic vessels, it
becomes enriched with lymphocytes
• the lymphatic system carries both antigens and lymphocytes
from the tissue to lymphoid organs where the lymphocyte can
interact with that trapped antigen to become activated and
create an immune response.
Term
secondary lymphoid organs.
Definition
located along the vessels of the lymphatic system.
Term
Vary in their composition
Definition
others are organized intro structures called lymphoid follicles.
• consist of aggregate of cells surrounded by draining lymphatic vessels
and capillaries.
Term
in its resting state they are called
Definition
primary follicles.
Term
after interaction with an antigen. the primary follicle enlarges to
become a
Definition
secondary follicle--consist of a ring of packed B cells
surrounding a germinal center.
Term
germinal center contains
Definition
proliferating
Term
the lymph node and the spleen are the most organized
Definition
both in addition to lymphoid follicles, they have distinct regions of B
and T cell activity
Term
the mucosa associated with lymphoid tissue are less organized and are
found in various sites of the body
Definition
Term
Lymph Nodes:
Definition
sites where an immune response is mounted to antigens in the lymph.
Term
antigens that are carried into the lymph node are trapped by a network
of
Definition
dendritic cells and phagocytic cells
Term
the lymph node can be divided into 3 concentric regions:
Definition
Cortex
Paracortex
Medulla
Term
Cortex
Definition
outer most layer
Term
Paracortex
Definition
the layer beneath the cortex
Term
the initial activation of B cells occurs in the
Definition
TH enriched paracortex. once actived TH and B cells will form small foci of proliferating B
cells at the edges of the paracortex
Term
the foci they will reach their
Definition
at that time, few B cells and TH cells migrate to the primary
follicles in the cortex where interactions between follicular
dendritic cells.
‣ interaction of B cells and TH cells will occur
‣ this interaction (of dendritic, B, TH) causes formation of
secondary lymphoid follicles (each central germinal center)
Term
Medulla
Definition
some of the plasma that you generate in the germinal center will
migrate to the medulla...many migrate to the bone marrow
‣ the lymph leaving these activated lymph nodes will be enriched
with antibodies produced by the plasma cells in the medulla and
will have 50x more lymphocytes that will enter the lymph nodes
you start producing antibodies
Term
Spleen
Definition
located high in the left abdominal cavity
‣ plays major role in mounting a immune response to antigens in the blood
‣ specializes in filtering blood and trapping blood born antigens
Term
2 major compartments of the spleen
Definition
red pulp
white pulp
Term
red pulp
Definition
network of sinusoids that contain macrophages, RBC, a few
lymphocytes.
‣ where old and defective RBC are removed from circulation
Term
white pulp
Definition
surrounds branches of the spleenic artery forming a
periarteriolar lymphoid sheath - populated mainly by T cells and
primary lymphoid follicles are attached to the sheath.
• rich in B cells and they have a germinal center
Term
blood born antigens and lymphocytes enter the spleen into a
Definition
marginal
zone--populated by lymphocytes and macrophages
Term
Mucosa-Associated Lymphoid Tissue (MALT)
Definition
Mucosa membrane lines respiratory, gastrointestinal, and unirarygenito tract.
Term
Mucosal epithelia layer contains intraepithelial lymphocytes
Definition
Many are T cells
‣ Lamina propia lies beneath epithelial layer
• There are lotts of B cells, activated T cells, plasma cells, and
macrophages all in loose clusters
• They play an important role in delivering samples of foreign antigen to
underlying MALT
Term
This antigen transport is carried out by specialized cells called
Definition
M cells
Term
When it reaches mucosa associated lymphoid tissues the mucosa
activates B cells that differentiate into plasma cells that secrete
Definition
IgA, the major class of antibody in mucosa secretion
Term
Cutaneous-Associated Lymphoid Tissue
Definition
Epidermal layer of the skin (outer) is composed largely of specialized
epithelial cells called keratinocytes.
‣ secrete cytokines that induce local inflammation
Term
Also present in the epithelial layer are
Definition
langerhans cells
‣ a type of dendritic cell that internalizes antigens by phagocytosis
Term
then the langerhan cells undergo maturation and
Definition
migrate to the regional lymph nodes
where they present that antigen to T cells
Term
The epidermis also contain intra-epithelial lypmphocytes
Definition
mostly T cells and they play an important role in eliminating antigens that
enter through the skin
Term
Dermis
Definition
skin layer beneath the epidermis
they have scattered T calls and macrophages
‣ T cells appear to be previously activated T cells or memory cells
Term
Leukocytes Activation and Migration
Definition
Cell adhesion molecules (CAMs)
chemokines
Term
Cell adhesion molecules (CAMs)
Definition
hold ourcells together used by leukocytes to interact with cells
in order for leukocytes to enter inflammed or infected tissue they
must adhere to and pass between endothelial cells of blood vessels.
• cells of blood vessels
endothelial
Term
most CAMs belong to 4 families of proteins:
Definition
selectins
mucin-like proteins
integrins
Ig superfamily
Term
selectins
Definition
interact with glyco protiens that have sialic acid
are responsible from the initial binding of WBC to the
vasclar endothelial
Term
3 types of selectins
Definition
L-
E-
P-
Term
L- selectin
Definition
is found on most circulating WBC
Term
E- and P- selectin
Definition
is expressed on vascular endothelial cells during
inflamation
Term
Mucin-like proteins
Definition
glycoproteins that have sialic acid
these provide binding sites for the selectins
Term
integrins
Definition
a heterodimer protein - a protien that consists of 2 different
polypeptides
normally bind extracellular matrix proteins and provide
extracellular matrix interactions throuought the body
Term
leukocytes have a specific subset of integrins called beta-2 integrins
Definition
these bind members of the lg superfamily and proteins
associated with inflammation
Term
combination of integrins expressed on a cell will allow the cell to
bind
Definition
different CAMs on the endothelium
Term
Ig (immunoglobulin) superfamily
Definition
called this because these proteins have immunoglobulin like
domains
they are expressed on the vascular endothelium
they bind to integrins
Term
Chemokines
Definition
small polypeptides that control adhesion, chemotaxins, and activation
of different types of leukocytes
• some of these are primarily involved in inflammatory reactions
• others are involved in inflammation homeostatic/developmental roles
housekeeping chemokines-direct normal trafficking of leukocytes
‣ suck as directing newly formed leukocytes to their proper
destination
e.g. B cell direct • to thymus for activation
Term
inflammatory chemokines generally induce response to infection/injury
Definition
contact with a pathogen or the action of pro-inflammatory
cytokines, such as TNF-alfa, that will upregulate expression of proinflammatory
cytokines, including chemokines
Term
chemokines cause leukocytes to migrate to the affected sites by
inducing appearance of WBC to vascular endothelium
Definition
after squeezing through the vessel wall to tissue, leukocytes migrate
along an increased site of leukoctye or on to infection.
this chemokine action is mediated by receptors
most receptors will bind more than one chemokine
many chemokine will bind more than one receptor
‣ the binding of the chemokine to the receptor will trigger a
number of signal transduction pathways
Term
effects of chemokine attachment to receptor
Definition
1) abrupt and extensive change in cell shape
2) activation of leukocyte integrins
3) generation of O2 radicals
4) Degranulation
Term
activation of leukocyte integrins
Definition
will promote greater adhesiveness to the endothelium
Term
Degranulation
Definition
refers to the process of the releasing of granule contents into the
environments
• different WBC have different contents in their granules
neutrophils and macrophages - antimicrobial proteins
basophils - histamine
eosinophils- cytotoxic proteins
Term
Leukocyte Extravasation
Definition
during an inflammatory response various cytokines and other inflammatory
mediators will act on local blood vessels increasing expression of
endothelial CAMs
when this occurs the vascular endothelial mediator is now activated or
inflammed
leukocytes then entravasate the tissue and migrate to the site of injury or
infection
Term
leukocyte extravasation 4 steps
Definition
rolling
activation
arrest and adhesion
transepithelial migration
Term
rolling
Definition
mediated by selecting
• refers to a weak interaction that is easily broken
• interaction slows the cell down long enough to allow interactions
between chemokines presented on the surface on the endothelium
and the receptors on the leukocyte
the type of chemokine that is expressed • plays a role in determining
what type of WBC will be attracted to the injury or infection.
Term
activation
Definition
the binding of chemokines to receptors on leukocytes will induce
signal transduciton pathways
effects: activation and clustering of ... to promote stronger adhesion
to endothelium
Term
arrest and adhestion
Definition
mediated by integrin binding to Ig superfamily on the endothelium
Term
transepithelial migration
Definition
involves the WBC squeezing between two endothelial cells without
disrupting the integrity of the vessel wall
• this is mediated by platelet-endothelial cell adhesion molecule-1
(PECAM-1)
expressed on both the leukocyte and the endothelium
once through the integrins of the leukocyte binds the matrix proteins
within the matrix membrans, this allows leukocytes to follow the gradient
of chemokines to site of infection
Term
inflammation
Definition
a physiological response to a variety of stimuli.
‣ infection
‣ injury
Term
acute inflammation
Definition
has a rapid onset and lasts only a short while.
‣ generally this is accompanied by a systemic reaction that's referred to as
an acute phase response.
• characterized by a rapid change in the levels of certain serum (plasma)
proteins.
Term
chronic
inflammation.
Definition
some diseases will have a persistent immune activation that leads to __ __.
often with pathologic results or effects
Term
in the early stages of inflammation, the neutrophil is the major cell type that
will migrate to the site.
Definition
neutrophil infiltration into the tissue will peak within hours of the
inflammatory response
‣ vascular endothelial cells will increase expression of E and P selectin
• Thrombin and Histamine will increase P selectin
Interleukin-1 (IL-1) will increase • and tumor necrosis factor alpha
(TNF-alpha) will increase E selectin.
‣ Neutrophils have mucin-like proteins that bind E and P selectin that
mediate attachment of neutrophils to the vascular endothelium
Term
Interleukin 8 and other chemokines act on the neutrophil
Definition
cause a change in the conformation of the integrin molecule on
neutrophil surface
• results in enhanced adherence and subsequent migration through the
vessel walls.
Term
once in the tissue the activated neutrophils will express increased or higher
levels of chemokine receptors, and will migrate up the gradient of
chemokines to the site of injury or infection
Definition
the neutrophils follow chemoattractants: create a gradient that attracts
neutrophils to site of injury
• chemokine
• complement products
Term
these activated neutrophils will secrete
Definition
reactive nitrogen and oxygen
products
‣ superoxide
Term
the accumulation of all dead cells, microorganisms, proteins, etc
Definition
is what we call pus
Term
the clinical hallmark signs of localized inflammation
Definition
swelling
redness
heat
pain
loss of function (sometimes)
Term
within minuets after an injury there is an increase in the diameter of nearby
blood vessels
Definition
vasodilatation
results in increase blood flow to the area
causes the • heat and redness to the area
Term
increased vascular permeability
Definition
due to leakage of fluid from the blood vessels into the tissue resulting in
swelling that we call edema
• caused by inflammatory mediators
bradykinins
histamine
prostaglandins
Term
within hours after the vascular changes, neutrophils attach to the vascular
endothelium and migrate through the tissue where they
Definition
phagocyte
‣ release oxygen radicles
‣ release antibacterial proteins
‣ secrete other inflammatory mediators
• MIP-1alpha (macrophage inflammatory protein)
• MIP-1beta (macrophage inflammatory protein)
attract macrophages to the site of injury
Term
macrophages arrive ~5-6 hours after onset of inflammation
Definition
they play an important role in the phagocytosis of pathogens and
they release more mediators that contribute to inflammation
• IL-1 (interleukin)
• IL-6
• TNF-alfa (tumor necrosis factor)
among other things, ALL of these attract more leukocytes
attract more leukocytes, eosinophils , basophils, and mast
cells
‣ ALL of these cells participate in clearing the antigen
Term
local inflammation is accompanied by acute phase (systemic) response
Definition
characterized by fever
‣ synthesis of hormones
• hydrocortisone
• ACTH
‣ Increased production of WBC
‣ increased production of large numbers of acute phase proteins in the
liver
• C-reactive protien
binds to variety of microorganisms and activates complement
Term
a lot of the acute phase effects are due to the combined actions of
Definition
L-1, IL-6,and TNF-alpha.
each one of these can act on the hypothalamus ‣ to induce fever.
‣ within 12-24 hours of the onset of acute phase inflammation increased
levels of these guys and other guys will induce production of acute phase
proteins in the liver
Term
TNF-alpha
Definition
also acts on vascular endothelium and macrophages to induce secretion
of CSF (colony stimulatory factor)
• stimulates hematopoiesis which results in the production of more
WBC
Term
some microorganisms are able to survive localized and acute phase
inflammation and they often induce
Definition
chronic inflammation that can result in
significant tissue damage.
‣ TB
‣ also occurs in several autoimmune diseases in which self antigens are
continually activating T cells.
Term
chronic inflammation also contributes to
Definition
the tissue damage and wasting associated with several cancers
also get accumulation and activation of macrophages
cytokines produced by chronically activated microphages can stimulate
fibroblast proliferation and collagen production
• resulting in fibrosis --development of scar tissue
Term
Chronic inflammation can also lead to
Definition
the formation of granuloma
• tumor like mass will a central area of activated macrophages
surrounded by activated lymphocytes
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