Quiz 6 Flashcards
1
Q
what are the major components of innate immunity
A
complement protiens
neutrophils
macrophage
innate lymphoid cells
2
Q
what are the major mechanisms of the innate immune system
A
-invaders may be distroyed directly through reconition of foreign molecules of lack of self-MHCs
-the signaling action of cytokines ramps up the cellular response
-phagocytes recognize opsonizing “tags” and opsonized antibodies & destroy marked cells
3
Q
what are the 3 pathways to activate the complement cascade
A
classical
lectin
alternative
4
Q
what is the classical complement cascade?
A
recognition of antigens by antibodies produced by B-lymphocytes
5
Q
what is the lectin complement cascade
A
recognition of foreign sugars in cell membrane
6
Q
what is the alternative complement cascade?
A
automatic destruction of cells that can’t inactivate C3
7
Q
what is the life cycle of a neutrophil?
A
-born in marrow
-“marginal pool” stored in marrow, usually in adult form,
waiting to release
-released in circulation, usually in adult form, but possibly as band cell
-enters connective tissue via rolling adhesion and diapedesis
-“dies” upon use
8
Q
what do tertiary granules in neutrophils do
A
facilitate migration to
target; disolve tissue in it’s way
9
Q
what do specific granules of neutrophils do?
A
kill bacteria with enzymes and reactive oxygen compounds
10
Q
what do azurophilic granules in neutrophils do?
A
lysosomal enzymes digest bacteria
11
Q
pyrogen
A
a substance that causes a rise in temperature (fever reaction) in a human or animal through the activation of the innate immune system
12
Q
what is pus made out of
A
dead neutrophils
13
Q
what is the cell that turns into a macrophage
A
Formed in marrow as a monocyte
Migrates via diapedesis through endothelium to connective tissue & differentiates to become a macrophage
14
Q
what are the organ specific macrophages in the lungs
A
alverolar macrophages
15
Q
what are the liver specific macrophages
A
kupffer cell
16
Q
how do macrophages kills cells
A
1 - recognizing a foreign substance
2 - engulfing it in a phagosome
3 - killing it by attaching lysosomes
macrophages are also antigen presenting cells
17
Q
how do macrophages recruit other cells
A
via cytokine release
18
Q
describe the macrophages activated states
A
marcophages can acts differently depending on the envirnment
there are many ddifferent activated macrophage states
19
Q
what is the macrophage classical activation for
M1
A
phagocytosis
20
Q
what is the macrophages alternative activation for
M2
A
tissue remodeling and repair
21
Q
what do Lymphocytes, non-B, non-T, CLP-derived do
A
They promote inflammation and tissue repair
22
Q
what do group 1 Innate Lymphoid Cells (ILC) target?
A
intracellular pathogens
23
Q
what do group II Innate Lymphoid Cells (ILC) target?
A
parasites
24
Q
what so group III Innate Lymphoid Cells (ILC) target?
A
bacteria and fungi
25
what is the main role of the adaptive immune system
produce antibodies
26
what do B-cells do?
-extracellular pathogens
- when activated, become Ig-producing plasma cells
27
what do Tc-cells do
-MHC1 recognition
-direct killing of cells by lymphotoxins
-recognize intracellular pathogens
28
what surface receptor do Tc-cells have?
CD8
29
what do Th-cells do
-MHC2 recognition
- indirect killing of cells by lymphokine signaling
30
what suface receptor is with Th-cells
CD4+
31
what are the antigen presenting cells
B-cells for their specific antigens
macrophages
dendritic cells
32
what is the structrure of antibodies
heavy chain, light chain and constant regions
33
all antibodies are specific for how amny antigens
1
34
what are the two forms antibodies come in
membrane bound or free flotting
35
what does The Fc (constant) region of a n antibodies do
allows for easy recognition & binding by other proteins
| is the Ig class
36
which part of the antibodies gives antigen specificity
Fab
37
what antibodies do B -cells first secrete?
B-cells make IgM antibodies first, but in the presence of cytokines, B-cells can switch the class of antibodies that they make
38
IgG
-most common antibody in blood and CT
- good diffusibility
- only antibody that crosses placenta, provides “passive” immunity of fetus
39
IgD
- the mysterious one
- present on naive B-cells during development, together with IgM
- may regulate B-cell maturation
- does not bind complement
- present at very low levels in blood
& secretions
40
IgE
- mast cell IgE receptors trigger degranulation
- great for parasitic infections
- responsible for allergies and anaphylaxis
41
IgM
- pentamer (sometimes hexamer) of IgGs
- excellent at bringing together multiple C1 complement molecules that will then start the complement cascade
- excellent at early response to infection
- more sensitive to the amount of antigen present
42
IgA
-prodominant in the intestines
-protects mucosal sufaces
-secreted in breast milk
-“clip” region confers resistance to acids does not bind complement
-passive defender of the gut
43
describe the activation of B-cells
Critical density of antigen causes “activation”
44
what are memory B-cells
A small population differentiate to
memory B-cells, specific to the antigen that caused activation, and persist throughout life
45
what antibodies do naive B-cells express
IgD & IgM
46
what happens after a B-cell is activated?
Upon ‘activation’, divides and differentiates to a plasma cell which secretes antibodies
47
where does a B-cells become specfic for an antibody?
in the bone marrow
48
T-cell receptor
on T-cells which recognizes antigens bound to
MHC and tells other cells their Identity
49
MHC-1
-exists on almost all cells
-recognized by Tc (CD8+)
-displays a protein being produced so passing cells can see what the cell is making
50
what is one cell that does not have MHC-1
syntrophoblasts in the placenta
51
MHC-2
exists on APCs
only recognized by Th (CD4+)
displays an internalized protein
52
what does Th1 do
| t helper
-helps Tc response and recruits macrophages
-helps aganits intracellular viruses
53
what do Th2 cells do
-helps B-cell response
-recruits eosinophils and basophils
-active against worms and allergies
54
what does Th17 do
| T helper
recruits neutrophils
-attacks extracellular bacteria
55
what do Treg do
| T cells
dampen the immune response
56
Stages of an Adaptive Immune Response
1 - activation of naive cells
2 - effector cell differentiation, clonal expansion
3 - contraction of population & production of memory cells
57
Primary (generative) Immune Organs
bone marrow
thymus
58
Secondary (effector) Immune Organs
peripheral MALT (including tonsils)
lymph nodes
spleen
liver
59
Thymocytes
thymic lymphocytes
60
where is The thymic stroma is derived from
endoderm
61
involution
replacement of tissue by adipose tissue
62
when is the thymus most active?
The thymus is most active in childhood
63
ERC role
| The Epithelioreticular Cells
”nurse” (or maybe “teacher”) cells for the thymocytes
64
“positive” selection
happens in thymic cortex -
assurance that TCR is functional and can recognize antigen
-AKA T-cell have a functional receptor (CD3, CD4, CD8)
65
“negative” selection
-occurs in the thymic medulla
- assures the antigen is not a “self” antigen
- the cells that are self reactive are killed by thymic macrophages
66
myasthenia gravis
-autoimmune response to nAchR is the most common disorder associated with thymic neoplasias
67
where do Liver, gall bladder, bile duct and pancreas derive from
endoderm foregut
68
The liver receives a systemic circulation via the
hepatic artery
69
The liver receives the majority of its blood from the digestive tract through a
venous portal system
70
Blood is returned through the ___BLANK______ which drain to the__BLANK______
hepatic vein
inferior vena cava
71
portal hypertension
increased blood pressure
in the portal vein
72
gall bladder
stores and concentrates bile
73
74
what is the flow of Lymphatics of the Liver
1) lymph drains (through space of Mall) via portal triad lymphatics to hilar nodes & cisterna chyli
2) lymph follows space around central vein & exits with hepatic vein
3) lymph drains to pericapsular regions & exits through capsule adventitial to diaphragm
75
what is the apical surface of a hepatocyte
the bile canaliculus
76
what is the lateral surface of the hepatocyte
hepatocyte faces other hepatocytes, and is separated from the apical surface via tight junctions
77
what is the basal surface of the hepatocyte
faces the space of Disse and the sinus (sinusoidal) capillaries
78
where are the hepatocyte microville
extend from the basal surface into the space of Disse and from the apical surface into the bile canaliculus
79
zone 3 in hepatocytes
pericentral
80
zone 1 in hepatocytes
periportal
81
what varies between the hepatic zones
Oxygen tension & metabolite concentrations in the blood also change dramatically with these zones
82
what is this pointing to
Kupffer cells
83
what are kupffer cells
-resident macrophages in the liver
-phagocytose blood-borne pathogens
-break down RBCs
-hemoglobin into bile pigment
-sits in sinus
84
what cells are these
Hepatic Stellate Cells
85
what are the major functions of a hepatic stellate cell
Vitamin A storage and
fibrosis during injury
86
where does the hepatocyte stem cell reside
the canal of Hering, the connection of the bile ductules with the hepatocyte plates
87
Activation of hepatic stellate cells causes what
initiates inflammation and wound healing response
88
cirrhosis
chronic fibrosis that is not reversible
89
steatosis
fatty accumulation in hepatocytes
90
Factors that commonly lead to cirrhosis of the liver
Hepatitis C virus
Alcoholic liver disease
non-alcoholic steatohepatitis (NASH) metabolic disorders
drug toxicity
91
jaundice
yellow coloration caused by systemic bilirubin pigment, not broken down
92
ascites
abdominal distention due to peritoneal fluid accumulation because of portal hypertension
93
fetor hepaticus
“liver stink” portal hypertension causes systemic shunting to the lungs. Thiols, normally removed by the liver, can be detected in expelled air
94
what cell is appart of the largerst resident macrophagee population in the body
Kupffer cells
95
what happens when liver transplants are coupled to skin or heart transplants in mice
Liver transplants in mice are protective to simultaneous skin or heart transplants
96
how is Hepatitis (B, C) linked to liver
hepatitis B and C take advantage of the liver’s unique immune system
97
fact about liver transplants
Liver transplants can thrive without immunosuppressant drugs
98
what is complement
proteins that can kill and tag (opsonization) the invader
99
how are antibodies to one specific antigen selected for each B-cell
chosen at random through the process of VDJ recombinatio
100
how do B-cells switch to produce another anitbody
-under the influence of cytokine signals
-has to have the same class specificity
101
sphincter of Oddi
controls bile and pancreatic secretions
102
what is the exocrine product of the liver
bile
103
cholangiocytes
-bile ductules are lined by these distinctive cuboidal cells
-sensing lumenal bile with a primary cilium, modifying bile composition via a variety of transporters, signalling the immune system, and occasionally contributing to liver pathologies
104
Glisson’s capsule
connective tissue that surrounds the liver
105
how does metistatic cancer affect Kupffer cells
In the setting of metastatic cancer, Kupffer cells have been shown to delete activated T-cells from circulation, facilitating metastases and causing immunotherapy to be ineffective
106
what is endomitosis and what cells does it
-chromosome duplication without cell division
-megakaryocyte
107
what cells is this
megakaryocyte
108
what disease is this?
Paget’s disease
too much bone reabsorbtion
109
what happens to the thalymus with age
it involutes
110
label a lobe, cortex, medulla, and capule
111
what is special about thymic capillaries
they are sheathed and surrounded by an ERC call and endothelial cell
112
what happens to lymphocytes in the thymic medulla
-negative Selection
-either CD8+ or CD4 + T-cell receptors pass test to not recognize self-antigens
-If don't pass test eaten by thymic macrophages
113
what happens to lymphocytes in the thymic cortex
-positive selection
-both CD8+ and CD4+ lose either CD8 or CD4
-T-cells pass test to recognize antigens
114
label
115
what are these and what are they made of
-Hassall’s corpuscles
-These are sheets of squamous ERCs, piled up like the layers of an onion
-cytokeratin that comprises them is characteristic of a specific subtype of medullary ERCs
116
red marrow
marrow containing predominately hematopoietic cells
117
where is red marrow most often found in adults
-long bones, in the vertebral column, and conveniently in the pelvis
-The crest of the ilium is the preferred biopsy site
118
what is this showing
an involuted thymus
119
what is this showing
cross-section of bone with yellow marrow
120
what is this diagram called
the classic liver lobule
121
what is this diagram called
portal lobule
122
what is this diagram called
liver acinus
123
label
124
what is the central structure called
central vein
125
what is this pointing to
bile duct/ canniliculi
126
liver sinusoidal endothelial cell
The endothelial cell of the liver is of a distinct lineage, differing in gene expression from other endothelia and producing proteins that are important to the immune system
127
what is this pointing to
gisson's capsule
128
what is this pointing to?
kupffer cell
129
what is going on with is liver
chronic alcoholism affects hepatocyte fat metabolism, so you are left with more adipocytes, which become stored in your liver
130
what is going on with this liver
cirrhosis
fibrosis caused by alcoholism is harder to reverse but still possible b/c liver can regerate
131
what is this pointing to
adventitia between the liver and gallbladder
132
what is the evolution of the sites of hematopoiesis
-Yolk Sac: hematopoietic islands form here in the 3rd-4th week of gestation, peaking in 2nd month
-Liver: hematopoiesis begins here in the 5th week, peaks at 5-6 months gestation
-Bone Marrow: hematopoiesis begins here in the
5th month of gestation, continues to adulthood
-Red Marrow: limited to specific locations after
puberty.
133
what is the most important site of heamatopoiesis in the fetus
liver
134
what is the most important site of heamatopoiesis in the fetus
liver
135
where are macrophages stored
spleen
136
where is the largest site for marginated neutrophils
postcepillary venules of the lug
137
Vasculogenesis
creation of new blood vessels in the mesoderm layer
138
where do early blood vessels originate from
extraembryonic (lateral sphlancnic) mesoderm
139
Angiogenesis
The sprouting of vessels from existing vessels
140
how does vasculature migrate
medially and dorsally - some of the first major vessels are the perineuronal vascular plexus surrounding the neural tube.
141
what do angiogenesis tip cells do?
direct the formation of stalk cells into vascular lumens
142
parenchyma
developing blood cells (hematopoietic islands)
143
what do bone marrow stromal cells do?
all marrow stromal cells
are active in regulating and supporting hematopoiesis
144
describe which can regerate between stem ells, progenitor cells, and percursor cells
stem cells are pluripontent, progenitor cells are more resitricted in lineage, precursor cells are totally restricted to lineage
145
CMP gives rise to
| common myeloid progenitor
eosinophils, basophils, neutriphils, monocytes, erythrocytes
146
what do CLP give rise to
| common lymphoid progenitor
lymphocytes
147
as we get further down in differentiation what happens to the likelyhood of trans differentiation
it goes down
148
can progenitors make more of themselves
Progenitors (the CFUs) can make more of
themselves; precursor cells cannot
149
which cells have a CD33 marker
granulocyte lineage
150
which cells have a CD45 marker
CMP progenitors
151
what cells have a CD14 marker
monocytes and mature neutrophils
152
what cells have a CD34 marker
CLP and CMP
153
what is the erthythrocyte lineage in order
blast, basophillic erythroblast, polychromatophillic erythroblast, orthrochromatophilic erythroblast ,reticulocyte
154
what is the neutrophil lineage in order
blast, promyelocyte,
early neutrophillic myelocyte, late neutrophilic myelocyte, neutrophilic metamyelocyte, band cell, mature neutrophil
155
what is the eosinophil lineage in order
blast, promyelocyte, early eosinophillic myelocyte, late eosinophilic myelocyte, eosinophilic metamyelocyte, mature eosinophil
156
how is EPO regulated?
-Oxygen levels
-Renin-Angiotensin system (sensing blood pressure)
-other hormones like insulin
157
BFU-E
erythrocyte progenitor cell
requires several cytokines for survival
high proliferative potential
14 days to RBCs in culture
motile – can be present in peripheral blood (!)
158
CFU-E
progenitor cell
highly dependent on EPO
7 days to RBCs in culture non-motile, found in marrow only
159
what cell is in the last stage for mitosis in the erythrocyte lineage?
Polychromatophilic erythroblast
160
what cell do erythrocyte precursers leave as
recticulocytes
161
what percent of circulating recticulocytes is normal
1%
162
what stain is used for reticulocyte count
methylene blue
163
what is the shape of a reticulocyte
Shape is intermediate between spheroid and biconcave
164
how do reticulocytes leave the marrow
-Reticulocytes leave the marrow by piercing through endothelial cells
-endothelium controls release by making holes
165
what stage do granulocytes leave the marrow
mature
166
what percent of granulocytes in normal in peripheral blood
3%
167
what do each neutrophil granule do
-primary (azurophilic): lysosomes
-secondary (specific) :kill bacteria with enzymes and reactive oxygen compounds
-tertiary: chemotactic
168
what granules do basophils have?
histamine (vasodilator)
heparin (anticoagulant)
169
what triggers fast degranulation in basophils
binding of IgE surface antibodies
triggers fast degranulation
170
compound exocytosis
stacking of granules at cell membrane for future relsease
171
what cell is this
band cell
C-shaped nucleus, without chromatin bridges
-normally present in peripheral blood in small quantities but over 2% can indicate pathology
172
what is the monocyte lineage
monoblast, promonocyte, circulating monocyte, in tissue can become, macrophages, dendritic cells,
osteoclasts
173
whatis the lymphocyte lineage
lymphoblast, prolymphocyte, circulating lymphocyte
174
how are platlets formed
Platelets from megokaryocytes next to megokaryocytes sit sinus and dangle tendrils out of sinus and platlets bud off
175
what is endomitotic division and what cell does it
megokaryocytes
copies chromosome a fails to devide
~128n cell
176
what is the megakaryocyte lineage
(Pro-) Megakaryoblast →
(Pro-) Megakaryocyte
177
what gives platelets their shape
microtubles
178
alpha granules in platelets
α granules contain fibrinogen and coagulation factors
179
δ granules in platelets
δ granules contain factors that promote the clotting cascade - they are also called “dense bodies” or “dense core granules”
180
λ granules in platlets
λ granules are lysosomes
181
where are platelets stored?
“stored” in circulation
182
what activated platelets
clotting factors
183
how long do platelets last
10 days
184
what does G-CSF cytokine recruit
neutrophils
185
what does the GM-CSF cytokine recruit
leukocytes
186
what does the EPO cytokine recruit
erythrocytes
187
what does the IL-2 cytokine recruit
T-cells
188
what is anemia
Reduction in the oxygen carrying capacity of the blood
189
what are common causes of anemia
-Blood loss via trauma or genetic defects
– Kidney disease (kidney and liver make erythropoietin) – Bone marrow cancer
190
polycythemia
Too many RBCs
↓ ability of tissues to get O2 blood is very viscus and can't flow properly
191
Leukemia
disorders of white blood cells
192
what is the leukemia basic classification
* First letter:
– A for Acute – few mature circulating WBCs
– C for Chronic – abnormal function in circulating WBCs
* Second letter:
– M for Myelogenous = affecting myeloid cells
– L for Lymphocytic = affecting lymphatic cells
* Third letter:
– L for Leukemia = abnormal proliferation of leukocytes, sometimes called ‘cancer of the blood’
193
Acute Leukemias characteristics
* Very few mature leukocytes (WBC’s) in blood. Blood may contain cells normally found in marrow.
* Marrow is full of rapidly dividing immature cells that do not differentiate.
* Anemia and bleeding are common as normal cells in marrow are affected by crowding.
194
treatment for Acute Leukemias
drugs, radiation, bone marrow transplants and autologous stem cell transplants
195
purpose of a bone marrow biopsy
used to evaluate the overall composition of the marrow, including bone and stroma
196
autologous bone marrow trasnplant
-stem cells are harvested prior to irradiation, will not stimulate immune system
-risk of the same disease recurring
197
allogenic stem cell transplants
*cells from an HLA-matched donor are used
*risk of graft-vs-host disease
-effective a transplantation o f an
Immune system
198
Activating pain neurons has what effect
shown in mice to mobilize HSCs into circulation
199
which cells have white nucleolus
blasts and promyleocytes
200
big cell in middle
blast
201
blast
202
promylocyte
203
promylocyte
204
what cell is this?
large cells with echromatic nuclei
and visible nucleoli
no azurophilic granules
blast
205
what cell is this?
-large cell w/ nucleoli and azurophilic granules
promylocyte
206
early neutrophilic myelocyte
207
late neutrophilic myelocyte
208
neutrophilic metamyelocyte
209
band cell
210
cell in middle
early eosinophilic myelocyte
211
late eosinophilic myelocyte
212
eosinophilic metamyelocyte
213
basaphilic erythroblast
214
polycromatophilic erythroblast
215
orthochromatophic erythroblast
216
megakaryocyte
217
what is wrong with this blood smear
acute monocytic mleukemia
too many nucleated cells to be in normal blood
218
what are the main secondary lymphatic cells and patches
1)MALT, GALT, BALT, peyer's patches
2)tonsils
219
what are the main secondary lymphatic organs
lymph nodes
spleen
220
lymph consists of
* extracellular interstitial fluid from connective
tissue
* immune cells, chiefly lymphocytes, also DCs
* bound Ig molecules Cantibodies
* lipids (e.g. central lacteals)
* macromolecules & particulates
221
what is the path of lymphatic vessels
lymphatic vessels originate in the periphery, and carry lymph from connective tissue all over the body,
through a system of lymph nodes, back to the venous circulation near the heart
222
what are the main 3 functions of the lymphatic system
1) clearance of extracellular proteins & return
of fluid to circulation
2) transport antigens or experienced
immune response lymph node to mount an immune response
3) absorb fats (chylomicra) from the gut
223
where do lymphatics sprout from
veins
224
Reticulated Epithelium
-Immune tissue envades epithelia
-leaky basement membrane
-reduced # of desmosomes
225
where is cancer most likly to metasticize
at the 1st lymph node
226
Superficial
cervical
nodes drain what
| lymph notes
head and neck
227
Axillary nodes drain what
| lymph nodes
* lateral (drains arm)
* apical (drains upper quadrant of breast)
* anterior (drains some chest)
* central (secondary)
228
Epitrochlear nodes drain what
| lymph nodes
distal arm
229
Inguinal nodes drain what
proximal leg
230
Popliteal nodes drain what
| lymph nodes
distal leg
231
Hilar nodes drain what
lungs
232
Mediastinal nodes drain what
heart, esophagus, diaphragm
233
lymph nodes are what kinds of structures
advential
234
most common site of leukocyte extravasation to CT
postcapillary venues
235
whaat is special about High Endothelial Venues
-highly active endothelial cells undergo reversible metaplastic transition to cuboidal shape & euchromatic nucleus
-add lymphocytes to CT
236
Lymph node - the antibody response
-Processing of antigen
- APC cells present to Th
-Selection - of appropriate B cells for that antigen
-Proliferation (clonal expansion) of selected cells; dependent on Th co-activation need T-helper cells to proliferate B -Cells
-Differentiation - to antibody-producing plasma cells
237
how are the spleen and the lymph nodes similar
where blood cells can leave the vasculature
238
Flow cytometry
can be used to measure cell morphology, useful for blood and marrow, or to separate cells based on immunological markers
239
immunohistochemistry
can be used in situ to demonstrate the location of marked proteins. Tagging a fluorescent molecule to the antibody is a common technique
240
ELISA
uses antibodies to measure the presence of proteins in multiple samples – commonly used clinically
usefull for solubilized things
241
PCR
is a technique to amplify DNA so that it can be readily detected. Cycle threshold (CT) is important. For example, COVID is typically detected with between 14-45 cycles, but there’s no universal standard
242
how does a flow cytometry work?
1) put a sample down a tube and flash a light at it
2) a computer measures the forward and side scatter
3) forward scatter relates to cell size and side scatter relate to granularity
243
If there is a pathogen in your environment, what are the three options for dealing with it
Avoidance
Resistance
Tolerance
244
what are examples of avoidance
skin
mucosal surfaces
245
what is the tolerance antigen
igA
246
autoimmune disease results from a lack of
-an appropriate tolerance response
-specifically, B- and T- lymphocytes must tolerate proteins that belong
247
what is going on here
celiac disease
only crypts no villi
248
gluten is digested to what
gliadin
249
what immune reponse happens in celiac disease
Production of IgG against gliadins leads to inflammation & eventual tissue destruction in the presence of gluten
250
M-cells
-M-cells and thinner and are
specialized for the transport of lymphocytes
-some organisms take advantage of M-cells to gain entry in the cell
251
HIV
-“hides” in Th cells
-evades the “sterilization” that is the usual endpoint of adaptive immunity
-leaves the individual “immunocompromised”
-has a slow rate of replication
-decreases T-helper cells until the person dies from a infection or autoimmune disease
252
what is the theory about how to prevent allergies
early exposure to antigens lowers rates of allergies
-allergies are more prevalent in western societies
253
ppl with allergies produce what antibody
IgE
254
Antigen binding to IgE causes what
mast cells to degranulate
255
B-cells produce what antibody
IgE
256
Th cells regulate what
allergic reponse
257
M2 macrophages promote what
tissue homeostasis
258
what is the morphology of the ddisease asthma
-acute changes driven by Th2 cytokines, IgE
-also causes chronic tissue remodeling( local cells producing cytokines and unregulation)
259
what is the difference between alveolar and intersitial macrophage immune responses
-alveolar macrophages patrol the lumen and they usually dont have a huge reaction when they see something forgein becasue they see that shit all the time
-interstitial macrophages if it sees promotes inflammation because this means that something has crossed the barrier
260
what is the arrow pointing to?
hyaline membrane
261
function of tonsils
Tonsils are merely folds in the epithelium, creating tonsilar crypts, which trap food and extrinsic substances together with saliva or other secretions for a length of time sufficient to permit immune surveillance
262
Typically 80-95% of cells in lymph are what
B- and T- lymphocytes
263
where to lymph vessels mainly drain
thoracic duct and right lymphatic duct(upper right quadrant of the body)
264
Effete RBCs
those which can no longer deform themselves adequately to fit through small capillaries. Splenic macrophages may also recognize and remove senescent cells through investigation of their various surface markers
265
wat are the connective tissue structures that divide the spleen
trabeculae
266
what is the series of vasculature of the speen in order of entry
splenic artery, and courses in succession through trabecular arteries, central arteries, radial arteries, penicillar arteries, sheathed capillaries, splenic sinuses, trabecular veins and the splenic vein
267
where is the rgion of the lowest flow rate in the spleen
white pulp
268
splenic nodules
lymphoid follicles of the spleen
269
what is the role of reticular fibers in the spleen
form a circle around splenic sinus and mechanically prevent defective erythrocytes from entering the splenic sinuses
270
how do Mycobacterium tuberculosis evade termination
the TB bacteria is able to modify the phagosome membrane to make it incapable of binding to the lysosome
271
what cells are targeted in diabetes mellitus type 1
pancreatic islet β-cells
272
what cells are attacked in myasthenia gravis
Ach receptors
273
what cells are attacked in pemphigus vulgaris
desmogleins of desmosomes
274
what cells are attacked in rheumatoid arthritis
citrullinated proteins of cartilage - fibrinogen, vimentin, collagen type II, α-enolase
275
what cells are attched in multiple sclerosis
myelin basic protein of myelin sheath
276
what is the traditional method for generating antibodies for staining for IHC
raise an animal (typically mouse or rabbit) in a pathogen-free environment, expose it to the antigen of interest (possibly bound to a carrier protein), harvest plasma and harvest the resulting antibodies from plasma. Antibodies thus produced are often tagged with their species of origin
277
what is the function of the tonsils
allow the various lymphocytes access to potential ingested foreign substance
278
what is this showing
reticular epithelium
279
what is this showing
intraepithelial lymphocyte: a lymphocyte within an epithelial layer
280
what cells are in each area
281
what structure is this
lymph node
282
283
in the lymph node what is this pointing to
macrophoges
284
what are these collectively called and where were they seen
mitotic figures
in the center of a lymphatic follice
285
where is practically the only place in the body where erythrocytes are “allowed” to exist outside of an endothelium-lined space
spleen
286
marginal zone
-at the interface of the red and white pulp
-where blood leaves the systemic circullation
287
what is this
marginal zone
288
trabecular artery
as the name suggests, this is an artery that runs within the trabeculae. You can recognize one because it is surrounded by dense connective tissue
289
central artery
unlike trabecular arteries, the central arteries are surrounded by white pulp
290
splenic sinus
These are the venules into which blood must return if it is to exit the spleen. Blood cells, both white and red, must traverse first the rings of reticular fibers then the epithelium in the basal to apical direction.
291
what are the smallest vessels of the arterial vascularization of the spleen
penicillar arteries
292
what is the arrow pointing at
splenic sinus
293
what are these showing
These are regions within the red pulp where reticular fibers encircle the splenic sinuses. Specifically, they are attached to the basement membrane of the sinus endothelium. Thus, blood must squeeze first through the reticular fibers, and second through the endothelial cells, in order to re- enter the sinus
| topology is often described as “staves and hoops of a barrel”.
294
what cells can caner occur in
Can occur in any nucleated Cells AKA not RBC's
295
what type of cancers are more common
cancers from epithelial cells
296
Hodgkin lymphoma
Cancer of blood cells in lymph that move of lymph
297
what is this pointing to?
Reed-Sternberg cells (defective plasma cells) are the hallmark of a Hodgkin’s Lymphoma diagnosis
298
what are the key behavior characteristics of solid tissue tumors
-Commitment to division
mitosis - metaplasia
loss of original cell functions
loss of MHC-1
no time to carry out the role always dividing
-Migration
EMT:epithelial morphologymesenchymal
loss of attachment proteins (cadherin proteins)
-Nutrition seeking behavior
entosis
recruitment of vasculature
299
what are driver mutations
-promote mutations
-directly drive cancer initiation and progression
300
what are passenger mutations
-accumulate over the lifetime, may change phenotype or drug response
-may stear mutaion toward a cancer state
301
p53
Proteins exist (for example, ATM, ATR, p53) that detect DNA damage and arrest the
cell cycle, giving cellular machinery time to repair the damage
*If damage is irreparable, apoptosis (programmed cell death) is an option
*If checkpoint mechanisms are damaged, cancer may result
302
what signals can p53 respond to
-lack of nucleotides
-UV radiation
-ionizing radiation
-oncogene signaling
-hypoxia
-blockage of transcription
303
what responses can p53 initate
-cell cycle arrest
-DNA repair
-block angiogenesis
-apoptosis
304
examples of EMT
neural crest
305
examples of MET
blood vessel formation coelomic epithelium mesonephric duct
306
which cancer is predisposed to go through EMT
meanoma because melanocytes are motile
307
what are the tumor types where EMT has a key role
breast, skin, pancreatic, lung, colorectal, hepatocellular, blader
308
when a cell becomes a cell of the CT what happens
there is much more M2 (antinflammatory) and tolorgenic responses
309
Cannibalism
he engulfment of live or dead cells or debris by cancer cells - a marker of malignancy
310
Entosis
the uptake of live cells into other cells through an invasive mechanism, typically involving cell-cell adhesion proteins and actin-myosin mediated contraction
311
Emperitosis
NK cells
entotically invading cancer
cells and dying intracellularly
312
VEGF
-a potent angiogenic factor
-Many types of cancers synthesize VEGF
313
how does EMT affect tumor vascularization
EMT allows for better tumor vascularization
314
metastasize
-take advantage of the lymphatic and ultimately systemic circulation to travel to sites distant from the site of origin
-may take up residence elsewhere in the body
315
what is this showing
metastasis of
primary pancreatic cancer
316
how do you stage Epithelial Cancers
317
what is the seed and soil theory of metastases
metastases occur when the local conditions match the growing preferences of tumor cells
318
what are the main sites of metastases
brain bone lung liver
319
whta is the gold standard of cancer imaging
PET scan
uses radioactive glucose to visualize the cancer
320
which cancer responds well to treatment
bladder cancer
321
what cancer respond poorly to treatment
pancreatic (exocrine) cancer
322
what are some cancer treatmentscancer treatments
-radiation
-surgery
endocrine therapy
-gene therapy
-marrow transplantation
-chemotherapy
-targeted therapy
-combination therapy
323
how does radition work
kills dividing cells
324
how does chemotherapy work?
target DNA REPLECATION
325
what is the most effective cancer treatment
combination therapy
326
Cancers curable with chemotherapy alone
choriocarcinoma
childhood ALL (Dr. Sidney Farber, 1947)
Burkitt lymphoma
Hodgkin disease
acute promyelocytic leukemia
large follicular center cell lymphoma embryonal carcinoma of testis
hairy cell leukemia
327
how does age affect cancer risk
cancer risk goes up with age
328
what cancer is second most frequent cause of cancer deaths in US
breast cancer
329
how does age affect breast cancer
breast cancer has a huge age dependence
330
what genes are involved in familial breast and ovarian cancers
BRCA1 & BRCA2 tumor suppressor genes
331
what percent of brest cancers are ductal and lobular
Ductal (80%)
Lobular (10%)
332
what is this showing
lactiferous duct biopsy- breast cancer
333
what stains can you use on breast tissue
estrogen and progesterone
334
HER2 receptor
The HER2 receptor is one of a class of surface receptors that respond to growth factors. These signaling pathways are potentially relevant in many different cancers
335
what is one way you can tailor cancer treatment
Classification by receptor status lets us choose a treatment that is most effective
336
ER+ breast cancer
estrogen receptor
– tamoxifen (anti-estrogen) is a drug of choice
337
HER2/neu breast cancer treatment
can sometimes be treated with monoclonal antibodies
-herceptin/trastuzumab
338
Triple negative breast cancer
hardest to treat, no cell surface receptors, hard to make drugs against
339
what are the ABCD's of melanoma
A for asymmetry
B for border irregularity
C for color
D for diameter
E for evolving
340
what is the most important ABCDE of melanomas
E for evolving
341
what are the Categories of Biomarkers
diagnostic
prognostic
predictive
342
Melanoma S100 antibody
-diagnostic marker
-labels neuroectoderm and melanocytes are the only cells from the neural creast
343
Melan A antibody
diagnostic and predictive marker good for prognosis
344
which cells mediate tumor cell death
Tc and NK cells
345
FASL and TRAIL
cell death ligands
kill cell via apoptosis
346
PD-1
-PD-1 is the repector for PDL-1 (programmed death ligand)
-Activation of PD-1 on a T-cell may trigger T-cell apoptosis. This is a mechanism of immune regulation.
-Tumor cells upregulate PDL-1 in an attempt to evade immune detection
347
oncolytic virus
| targeted immunotherapies
a virus that selectively invades tumor cells and causes their destruction by normal immune mechanisms
348
anti-CTLA4
| targeted immunotherapies
CTLA4 is a surface receptor on Tregs responsible for inhibiting their function
349
anti-PD1
| targeted immunotherapies
Programmed Death Receptor & Ligand - PD1 is a surface receptor on Th that negatively regulates them. Blocking it keeps Th alive.
350
CAR-T
| targeted immunotherapies
Chimeric Antigen Receptor - select (or design) a population of T-cells that fight the tumor and expand them ex vivo
351
pembrolizumab
-blocks programmed cell death (PD-1) receptor
encourages Immune system to stay active
-treats melanoma
352
Adoptive T-cell therapy
We harvest tumor T-cells
to encourage immune System
353
ADC - Antibody-Drug Conjugate molecules
-We can find a drug that kills the tumor and use antibodies to bring the drug right to the tumor
-help us use very toxic drugs
354
Targeted therapies for melanoma
IFN-α
CTLA-4 MEK/MAPK KIT
355
what color are the azurophilic granules
blue
in the promyleocyte
356
what color are the secondary granules
eosinophilic and basophilic
in the myelocyte
357
Asthma is driven by what antibody
IgE
358
allergies are driven by what antibody
IgE
359
what antibody is involved in celiac disease
IgG
360
what is the tolerace antigen
IgA
361
in the lung the principle sites of metastasis are
brain, bone, adrenal gland, and liver
362
in the breast the principle sites of metastasis are
bone, lung, liver, and brain
363
in the prostate the principle sites of metastasis are
bone
364
in the colon the principle sites of metastasis are
liver and lung
365
in the pancreas the principle sites of metastasis are
liver and lung
366
in the skin the principle sites of metastasis are
Lung, brain, and liver
367
in the sarcoma the principle sites of metastasis are
lung
368
in the uveal the principle sites of metastasis are
liver
369
Keratomas
from keratinocytes
