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Immunology lec 2 (TI) cells and organs of the immune system


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All blood cells arise from what?
Hematopoietic stem cells (HSCs)
Stem cells are capable of what?
Where are stem cells located?
in the bone marrow
Stem cells give rise to many components, so they could be referred to as what?
Erythrocytes (RBCs) comprise approx. what %age of blood cells?
about 50%
Name 6 components derived from stem cells?
1. erythrocytes

2. granulocytes

3. monocytes

4. mast cells

5. lymphocytes

6. platelets
Where does hematopoiesis begin relative to human development?
in embryonic yolk sac
What occurs during the 3rd month of gestation?
this is the 2nd trimester, and stem cells migrate from yolk sac to liver and spleen
What occurs after the 7th month of gestation?
this is the last trimester, the bone marrow takes over hematopoiesis
What occurs with hematopoiesis once adulthood is reached?
the long bone marrow is filled in with fat and hematopoiesis occurs in flat bones
Name 5 flat bones where you would see hematopoiesis in adults?
1. cranium

2. pelvis

3. sternum

4. ribs

5. vertebra
The 2 pathways under which hematopoiesis may occur?
1. myeloid progenitor

2. lymphoid progenitor
Which hematopoietic pathway gives rise to dendritic cells?
the myeloid progenitor
Which hema" pathway gives rise to NK cells?
lymphoid progenitor
The hematopoietic cell is self ??
At what point can a hematopoietic stem cell no longer change it's lineage?
once it becomes a lymphoid or myeloid progenitor
Where do almost all hematopoietic cells become commited to one of the pathways?
while in the bone marrow (in the fat = stroma = mesh-like)
What does H.I.M. stand for?
hematopoietic inducing microenvironment (seen in stroma)
What else is found in stroma?

(this is besides hematopoietic stem cells)
fibroblasts and endothelial cells
Regulation for hematopoiesis occurs at what level?
the gene level
How many blood cells will you make in a lifetime?
What are GATA-2 and Ikaros?
factors (genes)...transcription factors essential for hematopoietic lineages
If GATA-2 is disrupted during neogenesis what does it lead to?
Which 3 lineages are dependent upon GATA-2?
1. erythroid

2. myeloid

3. lymphoid
What is Ikaros involved with concerning mice?
inv. with KO mice...gene is Knocked out of mice...mouse will be born alive but will die early
Which lineage is dependent upon the ikaros factor?
How long is the life of a neutrophil?
about 1 day before apoptosis
What is apoptosis?
programmed cell death...relative to homeostatic control of hematopoiesis
What does apoptosis control relative to homeostatic control of hematopoiesis?
controls lifespan to maintain proper number of progenitor cells
Name some distinct morphologic changes related to apoptosis and homeostatic control of hematopoiesis?
includes a decrease in the volume of the cell...plasma membrane will look irregular...then blebbing occurs...DNA ladder breaks...cell breaks and is inflammation caused
How does apoptosis differ from necrosis?
in necrosis the plasma membrane weakens...this changes the tonicity...fluid rushes in and cell bursts causing a release of intracellular contents like hydrolytic enzymes...this does cause inflammation
B cells are not only produced in the ? but also do what there?
bone marrow, mature
Where were B cells first discovered?
in the bursa of fabricius in chickens
Where do T cell precursors mature?
they leave the bone marrow and mature in the thymus
Each B cell and T cell is specific for a particular what?
BCR stands for what?
B cell receptor
TCR stands for what?
T cell receptor
BCRs and TCRs are both ? ? proteins.
integral membrane (embedded in plasma membrane)
How are BCRs and TCRs present at the cell surface?
by thousands of identical copies
When are BCRs and TCRs made?
before a cell ever encounters an antigen
How are BCRs and TCRs encoded?
by genes assembled by the recombination of segments of DNA
BCRs and TCRs have a unique what?
binding site
The binding site of a BCR or a TCR binds to what?
a portion of the antigen called an antigenic determinant or epitope
The binding between a BCR or TCR and an antigen depend upon what? What is this similar to?
The binding depends upon complementarity of the surface of the receptor and the surface of the epitope...this is similar to the binding between an enzyme and a substrate
The binding between a BCR or TCR and an antigen occurs by ? forces. What is this similar to?
non-covalent forces...similar to the binding between an enzyme and a substrate
2 results of successful binding of an Ag receptor to the epitope?
1. stimulation of the cell to leave Go and enter the cell cycle

2. repeated mitosis leads to the dev. of a clone of cells bearing the same antigen receptor, that is, a clone of cells of the identical specificity
Where is the antigen receptor located?
on the Ab
Where is the epitope located?
on the Ag
3 ways that BCRs and TCRs differ?
1. their structure

2. The genes that encode them

3. the type of epitope to which they bind
What do BCRs bind?
soluble antigens
How is a bound Ag molecule engulfed into a B cell?
by receptor mediated endocytosis
Once an Ag is engulfed into a B cell what happens to it?
it is digested into fragments
After an Ag has been engulfed by a B cell and digested into fragments what happens?
The fragments are then displayed at the cell surface nestled inside a MHC II
Once a B cell displays fragmented Ag at its cell surface what binds to it?
TH cells specific for this structure (ie with complementary TCRs)
B-cells secrete lymphokines that do what two things?
1. stim. the B cell to enter the cell cycle and develop, by repeated mitosis, into a clone of cells with identical BCRs switch from synthesizing their BCRs as integral membrane proteins to a soluble version

2. differentiate into plasma cells that secrete these soluble BCRs, which we now call ANTIBODIES
What is a CD8+ T-cell?
-they secrete molecules that destroy the cell to which they have bound

-the best understood of these cells are the cytotoxic T lymphocytes (CTLs)
CD8+ T cells bind what?
epitopes that are part of MHC I
What do CD4+ T cells bind?
an epitope consisting of an Ag fragment lying in the groove of MHC II
CD4+ T cells are essential for what?
for both cell mediated and antibody mediated branches of the immune system
Describe cell mediated immunity as it relates to CD4+ T cells?
the CD4+ cells bind to Ag presented by Ag-presenting cells (APCs)...The T cells then release lymphokines that attract other cells to the area and results in inflammation
Name two APCs?
(Ag presenting cells)

1. phagocytic macrophages

2. dendritic cells
Define inflammation?
the accumulation of cells and molecules that attempt to wall off and destroy the antigenic material ANTIBODY MEDIATED IMMUNITY
CD4+ cells (TH) bind to what? What does this result in?
Ag presented by B cells...this results in the development of clones of plasma cells secreting Abs against the antigenic material
The CD4+ T cells releases cytokines that alert all cells of what?
alerts all cells (including B cells) to make Abs
NK cells comprise what %age of lymphocytes?
small fraction (about ~2-10%)
NK cells are highly specialize to do what?
kill certain types of target cells

1. host cells that have become infected with virus

2. host cells that have become cancerous
The killing accomplished by NK cells is done by what?
done by the exocytosis of granules containing perforin and granzymes...similar to cytotoxic T cells
What does perforin do?
released in NK cell granules...perforates cells allowing fluid in and eventually causing it to burst
NK cells are preprogrammed to recognize what? This causes them to have no need for what?
preprogrammed to recognize their no need to develop into a clone of identical cells like T and B cells other words there is no reason to clone out because they kill directly
Speed at whick NK cells respond? What does this provide?
respond rapidly, thus providing another arm of innate immunity
In addition to killing target cells what do NK cells secrete?
Cytokines such as

1. anti-viral cytokine IFN-gamma

2. inflammatory cytokine TNF-alpha
What is IFN-gamma?
"interferon gamma"...a cytokine that is released by NK cells...informs other cells of virus so they can protect themselves...was once a much hyped target for drug developers but ended up being a disappointment
NKT cells may be a link between what?
innate and adaptive immunity
NKT cells may be called an ? ? ? cell.
antibody production accesory
NKT cells are not the same as what?
NK cells
NKT cells are T cells with a what?
an alpha-beta TCR....however, they also express some of the cell surface molecules of NK cells (hence the name)
NKT cells are able to secrete what?
large amounts of either IFN-gamma, or IL-4 and IL-13 (cytokines) that enable the B-cells production of Abs
What cytokines released by NKT cells are very important in asthma?
IL-4 and IL-13
Why are NKT cells possibly a link bn innate and adaptive immunity?
because they may possibly function to provide quicker help than the several days needed by conventional TH cells
In addn to defending against some infectious agents, NKT cells have been implicated in protecting against these three things?
1. autoimmune diseases

2. graft rejection

3. tumors
NKT cells have recently been shown to be present in large numbers where?
in the lungs of patients with asthma and prob. play a major role in the lung inflammation characteritic of the disease
What distinguishes NKT cells from other cells?
Essentially what is a mononuclear cell?
a WBC with one nucleus...not a granulocyte
How long do mononuclear cells stay in circulation? What happens after circulation?
in circ. for 8 hours (so short lived), then migrate to tissues where they metamorphize into macrophages (big eaters)
Macrophages have more ? ? than monocytes?
hydrolytic enzymes...(this is how they combat Ag)
What do macrophages secrete?
soluble factors

1. inflammatory mediators

2. T-cell activators
What are macrophages activated by? (3)
1. IFN-gamma

2. inflammatory mediators

3. bacterial cell wall components
Monocytes are found in ? and macrophages are found in ?.
monocytes in plasma in circulation...macrophages in tissue
monocytes have fewer ? than macrophages.
monocytes nucleus is ? than when it becomes a macrophage.
What are pseudopodia?
structure on macrophage that helps it move to site of infection, also engulfs Ag
Tissue specific macrophages found in the gut?
intestinal macrophages
Tissue specific macrophages found in the lung?
alveolar macrophages
Tissue specific macrophages found in the liver?
kupfer cells
Tissue specific macrophages found in the connective tissue?
Tissue specific macrophages found in the kidney?
mesangial cells
Tissue specific macrophages found in the brain?
microglial cells
Tissue specific macrophages found in the bone?
The lungs are an important vehicle by which what enters the body?
Ag...the alveolar macrophages are deep in the lungs, they are 1 cell deep and are important for Ag that you do not cough up
Anything that you swallow has to go through here?
the liver (where there are kupfer cells to combat Ag)
The microglial cells of the brain are important for what?
they are tissue specific macrophages that are important if the BBB gets breached by Ag
What do the osteoclasts in the bone do?
they are a tissue specific macrophage that don't really go after Ag...they eat up broken down bone so it can be replaced
What is meant by the stmnt "complex Ags adhere well"?
complex Ags are whole bacterial cells or viral particles...they adhere well to macrophages thus making it easier to "eat" them
What adheres poorly and is thus tougher for a macrophage to "eat"?
isolated proteins and encapsulated bacteria
Abs function as opsonin. What does this mean?
opsinization is when an Ab sees something foreign and "climbs all over it", coats it
The digestion and presentation of an Ag by a macrophage forms what?
an MHC II complex
Steps of the digestion and presentation of an Ag.
1. Bacteria engulfed by pseudopedia of macrophage

2. phagosome forms, surrounding the bacteria inside the cell

3. phagosome with bacteria fuses to lysosome creating a phagolysosome

4. Class II MHC is formed inside the phagolysosome

5. the phagolysosome that releases the degraded material by exocytosis

6. The cell surface then has the class II MHC/ antigenic peptide
Exocytosis is a process that is dependent upon what?
What is the most abundant granulocyte?
How long do neutrophils live for?
few days (short lived)
Neutrophils are the first to arrive where?
at the site of inflammation
How do neutrophils move into tissue?
by extravasation initiated by chemotactic factors
What are the chemotactic factors that initiate that extravasation of neutrophils into tissue?
they are released by dmg tissues...some clotting factors...signal breach of skin when cut...TH cell included...many different kinds
What is leukocytosis?
an increased number of circulating neutrophils
How many granules do neutrophils have? Why is this important?
a lot...important for killing bacteria
How much glycogen do neutrophils have? Why?
they have a lot because they have an enormous energy reqt from movement (extravasation)
Eosinophils and Basophils are granulocytes or agranulocytes?
Eosinophils are what kind of phagocytes?
mobile phagocytes (like the neutrophils)
Eosinophils act in defense of what?
parasitic infections (and also allergies)
A raised count of eosinophils indicates what?
a parasitic infection
Basophils are not ?.
Basophils play an important role in what?
in some allergies...they secret a pro-inflammatory mediator
Which granulocytes play an important role in some allergies and which is more involved with parasitic infections?
allergies = basophils

parasitic inf. = eosinophils
How many mast cells do we have?
very few
Where are mast cells found?
in many tissues
Mast cells are ? containing ?.
histamine containing granulocytes
What does histamine cause?
swelling, itching, vasodilation
What is Cromolyn sodium?
a med. that prevent degranulation of mast cells so that they can't release histamine
Where are dendritic cells found?
everywhere, except brain
What is the most abundant kind of dendritic cell?
langerhans cells
Which was the first cell of the immune system to be discovered?
dendritic cells (langerhans cells) in 1868
Dendritic/langerhan cells resemble what?
dendrites of nerve cells...they have long dendritic nerve processes
Dendritic/langerhan cells are versatile in what? Why?
in their ability to capture Ag...because of their long processes
Are dendritic/langerhan cell's phagocytic or pinocytic?
Where are langerhan cells derived from?
bone marrow
What is a subfamily of dendritic cells? What is different about them?
"follicular dendritic cells"...they don't capture Ag...found in the lymph B-cells...where ever you find B-cells you will find these...they are accessory cells
The two general classes of immune system organs?
1. primary lymphoid tissues

2. secondary lymphoid tissue
What occurs in primary lymphoid tissues?
this is where maturation/immunocompetence of immune cells occur
Name two primary lymphoid tissues?
1. thymus (T cells)

2. bone marrow (b cells)
What occurs in secondary lymphoid tissues?
provide sites for mature immune cells to interact with Ag
Name 6 secondary lymphoid tissues?
1. lymph nodes

2. spleen


4. Other components of MALT

5. adenoids

6. tonsils
What does MALT stand for?
Mucosa membrane-associated lymphoid tissue
How much lymph fluid do we generate from plasma in 24 hours?
about 2.9 Liters
Where is the thymus located?
behind and above the heart
Describe the general structure of the thymus?
flat...composed of two parts
1. cortex (outer histiological layer)

2. medulla
What does the thymus do as we get older?
the medulla atrophies
What does the appendix have to do with immunity?
it doesn't really affect immunity anymore (kind of just handed down from our ancestors)
The thoracic duct is associated with what?
the left subclavian vein
Where does all returning lymph fluid go? What is the exception?
from the thoracic duct to the left subclavian vein where it goes on to become part of our interstitial fluid...the exception is the right side of the heart and the right arm, this lymph goes to the right lymphatic duct
What is the cortex of the thymus packed with?
immature T-cells (thymocytes)
What happens to thymocytes in the thymus?
these immature T-cells undergo gene rearrangement so that they can distinguish self from nonself
By the age of ?, the thymus' medulla T-cell production decreases by 80%, by the age ? is decreases by 98%.
How much does the thymus weigh in an infant vs an adult?
30g in infant, 3g in adult (it is the result of the thymus' medulla shrinking with age)
The thymus functions to develop what?
thymocytes with an enormous diversity of TCRs
More than what %age of thymocytes do what before they reach maturity?
more than 95% die by apoptosis
2 examples of failures of thymus development?
1. DiGeorge's syndrome (very sick children)

2. nude mice
In adults, what fills 50% of bone marrow space in long bones? So what happens? hematopoiesis goes and takes place in flat bones
The bone marrow is the site of what?
B-cell maturation and proliferation
The B-cell maturation and proliferation in the bone marrow are stimulated by what?
by the secretion of cytokines by stromal cells
B-cells are the source of 90% of what? (2)
1. IgG

2. IgA
What are lymph nodes?
sites where immune responses occur
Lymph node structure?
Bean-shaped, clustered at junctions of lymphatic vessels

-after stim. and dev. in primary and 2ndary follicles, germinal ctrs form
3 parts of lymph nodes?
1. cortex

2. paracortex

3. medulla
Describe the cortex of the Lymph nodes?
mostly B-cells, macrophages, dendritic cells
Describe the paracortex of the lymph nodes?
mostly T-cells, dendritic cells with high levels of MHC II (necessary for presenting Ag to TH)
Describe the medulla of the lymph nodes?
sparsely populated with Ab secreting plasma cells
What does a proliferation lead to in the lymph nodes?
swelling and discomfort
Is the spleen more important to kids or adults?
2 parts of the spleen?
1. red pulp

2. white pulp
The red pulp of the spleen is the site of what?
of destruction of old/defective ertythrocytes (RBCs)
The white pulp of the spleen is populated by what?
lymphocytes and macrophages
Which area of the spleen really plays a role in immunity?
the white pulp
Can you live w/out a spleen?
yes, but in childhood you will be very prone to bacterial sepsis
How do adults fair w/out a spleen?
better than kids, but susceptible to bacteremia (but not that big of deal)
What is PALS?
periarteriolar lymphoid SHEATH...takes up most of the white pulp of the spleen...surrounds arteriole flow...where you find many cells
Swollen lymph nodes that don't hurt may indicate what?
a serious disease...such as lymphoma
What transports Ag into/out of the lymph nodes?
the lymphatic arteries and veins
What is a bobo?
a painful swollen lymph nodes
MALT is located where?
diffusely located
MALT is populated by what?
T-cells, some B-cells, plasma cells, and macrophages
6 components of MALT?
1. GALT (gut-"")+peyer's patches

2. BALT (bronchial-"")

3. NALT (nose-"")

4. SALT (skin-"")

5. VALT (vascular-"")

6. CALT (cutaneous-"")

"" = "associated lymphoid tissue"

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