Midterm Flashcards
(364 cards)
1
Q
Why do warm-blooded, long-lived animals require complex immune systems?
A
Infectious agents such as bacteria can rapidly divide in warm-blooded creatures
2
Q
What are examples of some viruses?
A
polio, pox viruses, influenza, hepatitis B, HIV
3
Q
What are examples of protozoans?
A
trypanosomes, leishmania, malaria
4
Q
What are examples of some fungi?
A
candida, aspergillus
5
Q
What are examples of some worms?
A
tapeworms, filaria
6
Q
How many bacteria are there in the world?
A
~4-6 x 10^30 bacteria
7
Q
What is the term for the community of microorganisms that live in a particular habitat? What are examples of some of these habitats in the bod?
A
microflora
skin, oral, respiratory tract, GI tract, urogenital and eye microflora
8
Q
What percent of our intestinal contents are intestinal microflora?
A
20%
9
Q
What is one reason we really need microflora?
A
provides molecular signals for the development of the immune system
10
Q
What are three characteristics of germ-fee animals?
A
- mucosal immune system is undeveloped
- spleen and lymph nodes are undeveloped
- serum hypgammaglobinemia (low antibody levels)
11
Q
Can you reverse the undeveloped mucosal immune system, spleen, and lymph nodes in an adult germ-free animals?
A
not all abnormalities can be reversed
12
Q
Can all bacteria cause diseases in humans?
A
nope
13
Q
Who are the most prominent scientists in the history of the germ theory?
A
Joseph Lister
Robert Koch
Louis Pasteur
14
Q
Who established that a particular germ could cause a specific disease?
A
Koch
15
Q
What are the four Koch’s postulates?
A
- infected tissue must show the presence of a particular microorganism not found in healthy animals
- the microorganism must be isolated and grown in a pure culture
- when injected into a healthy animal, the microorganism must cause the disease associated with it
- this “second generation” microorganism should then be isolated and shown to be identical with the microorganism found in I
16
Q
What is the study of a cause of disease including its origin and what pathogens, if any, are involved?
A
etiology
17
Q
What do gram negative bacteria have that gram positive bacteria do not have?
What color do gram negative bacteria stain?
A
lipopolysaccharide outer leaflet of outer membrane
pink
18
Q
Which has a thicker peptidoglycan layer? What does peptidoglycan function as? What color do these bacteria stain?
A
gram positive
purple- violet binds to peptidoglycan
19
Q
What are ways that our body kill cytoplasmic pathogens? What pathogens would you find in the cytoplasm?
A
CTLs, NK cells, T cells, macrophages
bacteria, protozoa, viruses
20
Q
What is an example of a pathogen that is vesicular?
A
mycobacteria
21
Q
What are ways to kill extracellular pathogens? What are examples of extracellular pathogens?
A
antibodies, PMN (?), complement
bacteria, protozoa, viruses, fungi, worms/helminthes
22
Q
How are extracellular microbes able to survive?
A
they grow extracellular being simply immersed in nutrients
23
Q
How do intracellular microbes survive?
A
They invade and replicate intracellular within animal cells were they utilize host-cell energy sources
24
Q
What is the only way to eliminate intracellular bacteria? How is tissue damage caused?
A
cellular immune response- they’re shielded from antibodies
tissue damage is caused by the host response- inflammation rather than by bacterial factors
25
What does Mycobacterium tuberculosis cause? Is it intracellular or extracellular? What is the mechanism of pathogenicity?
(intracellular)
tuberculosis, leprosy
macrophage activation resulting in granulomatous inflammation and tissue destruction
26
What does Legionella pneumophila cause? Is it intracellular or extracellular? What's the mechanism of pathogenicity?
(intracellular)
Legionnaire's disease
cytotoxin lyses cells and causes lung injury and inflammation
27
What are the two principal pathogenic mechanisms extracellular bacteria cause disease?
- induces inflammation, which results in tissue destruction at site of infection
- bacteria produces toxins with pathologic effects
28
What are exotoxins? What are endotoxins?
exotoxins are actively secreted by the bacteria
| endotoxins are components of bacterial cell walls
29
What disease does Staph aureus cause? Is it intracellular or extracellular? What is the mechanism of pathogenicity?
extracellular
skin and soft tissue infections, lung abscess
systemic: TSS, food poisoning
enterotoxin-induced inflammation and cytokine release causing skin necrosis, shock diarrhea
30
What disease does Clostridium tetanus cause? Is it intracellular or extracellular? What is the mechanism of pathogenicity?
tetanus
extracellular
tetanus toxin causes irreversible muscle contraction
31
What disease doe Neisseria meningitidis cause? Is it intracellular or extracellular? What is the mechanism of pathogenicity
meningitis
extracellular
acute inflammation and systemic disease caused by potent endotoxin
32
What disease does Escherichia coli cause? Is it intracellular or extracellular? what is the mechanism of pathogenicity?
UTIs, gastroenteritis, septic shock
extracellular
toxins increased chloride and water secretion; endotoxin (LPS) stimulates cytokine secretion by macrophages
33
Is E coli gram positive or negative?
negative- LPS is its endotoxin
34
What are noninfectious foreign substances that can also elicit an immune response?
antigens (Ags)
35
What elicits autoimmune responses?
self Ags
36
What are the primary and secondary fixed elements of the immune system?
Primary: BM, thymus
Secondary: spleen and lymph nodes, mucosal immune tissues
37
What are examples of mobile elements of the immune system?
immune cells
| soluble (humoral components): antibodies, complement, acute phase proteins
38
What are the granulocytes?
neutrophils, eosinophils, basophils
39
What are the lymphocytes?
B cells, T cells, NK cells
40
What are two types of cells found in the blood that can phagocytize?
neutrophil, monocyte
41
What are the primary lymphoid organs? What are their functions?
thymus and bone marrow
| produce the cellular components of the immune system
42
What are the secondary lymphoid organs? What are their functions?
adenoids, lymph nodes, spleen
| locations where the immune responses occur
43
Where can you find diffuse scattering of lymphoid cells?
deep to the epithelium in the connective tissue
| GI tract, GU tract, respiratory passages
44
Which is more common: primary or secondary nodules?
secondary nodulars
45
What do primary nodules consist of? When in our lifetime would you have them?
consist of only small lymphocytes, no germinal center
| prenatal
46
What type of nodule contains germinal centers? What do you find in the outer rings of these nodules?
secondary nodule
lymphoblasts
lymphocytes and memory cells collect in the outer ring
47
Tonsils are what type of tissue
partially encapsulated aggregates of lymphoid nodular tissue
48
What infiltrates the epithelium of the tonsils
lymphocytes
49
What two things would you see if you looked at pharyngeal tonsils under a microscope
pseudo stratified columnar ciliated epithelium
germinal center
no crypts
50
What would see if you looked at palatine tonsils under a microscope
stratified squamous epithelium
thick partial connective tissue capsule
germinal centers
10-15 invaginations called crypts
51
What would you see if you looked at lingual tonsil under a microscope
stratified squamous epithelium
no well defined capsule
germinal centers
one crypt per tonsil
52
How many palatine, pharyngeal, lingual tonsils does everyone have
2
1
1
53
Where do you find MALT?
GI tract, respiratory tract, urinary tract
54
What is the type of MALT that is found in Peyer's patches in the ileum
GALT
55
What would you see if you looked at GALT from Peyer's patches under a microscope
abundance of villi
single or clusters of lymphoid nodules
simple columnar epithelium with Goblet cells
56
What would you see if you looked at GALT from the appendix under a microscope
no villi
crypts
simple columnar epithelium with Goblet cells
57
What are types of apical specializations?
microvilli, stereo cilia, cilia, flagella
58
What are the functions of microvilli
to increase cell surface area
59
What are the majority of the immune cells produced from? CD?
CD34+ hemopoietic stem cell (HSC)
60
Where can you find hemopoietic stem cells?
fetal liver/spleen
| neonate and adult bone marrow
61
What do stromal cells do?
interact with HSC and produce
- stem cell factor (SCF)
- granulocyte-colony stimulating factor (G-CSF)
- monocyte colony-stimulating factor (M-CSF)
62
What are examples of stroll cells?
epithelial cells, fibroblasts, macrophages
63
What are stem cell factors needed for?
HSC self-renewal
64
What is G-CSF needed for?
the development of neutrophils
65
What is M-CSF needed for?
development of monocytes
66
What does CD stand for? What does it indicate?
cluster of differentiation
| indicates a defined subset of cellular surface receptors that identify cell type and stage of differentiation
67
What lab order would provide the complete hematologic picture of a case at least from the morphologic standpoint?
DIFF (differential leukocyte count) and CBC (complete blood count)
68
What is the stain that is usually used for blood smears? What is it a mixture of?
Gismo smear
| basic stain methylene blue and acidic stain eosin
69
What two white blood cells would dominate a blood smear compared to other WBCs?
neutrophils (40-60%)
| lymphocytes (20-40%)
70
What are the markers (CDs) for T cells?
CD3
CD4
CD8
71
What are the markers (CDs) for B cells?
CD19
| CD20
72
What are the markers (CDs) for NK cells?
CD56
73
What are the markers (CDs) for macrophage/monocytes?
CD14
74
What is another name for neutrophils? What do their nucleus look like? What do they mediate?
polymorphonuclear leukocytes
neutrophil is segmented into 3-5 connected lobules
mediate the earliest phases of inflammatory reactions
75
Where do we make neutrophils? What cytosine stimulates the production of neutrophils? How long can a neutrophil circulate in the blood? After entering tissue, how long can they function?
bone marrow
G-CSF
circulate for hours or few days
die within 1-2days of entering tissue
76
What do we call a WBC count that is above the normal range in the blood? What is it usually in response to?
leukocytosis
bone marrow's response to infection and inflammation caused by trauma, gout, rheumatoid arthritis, rheumatic fever, thyroiditis, acute stress or primary bone marrow disease (CML)
77
What allows for the rapid response to the demand for increased WBCs? How big of a response can we get and how quickly?
bone marrow stores a lot of maturing cells
| 2-3 fold increase (leukocytosis) possible in 4-5 hours
78
In response to infection/inflammation the bone marrow is release immature WBCs. What do we call this?
left shift
79
What do we call the reduction in the circulating WBC count to
leukopenia
| neutropenia
80
What is another name for neutropenia? If severe what can it cause? What often causes neutropenia? What would a patient present with that would make you suspect neutropenia?
agranulocytosis or granulocytopenia
life-threatening infection
chemotherapy or radiation therapy
frequent or unusual infections
81
What is the main function of neutrophils? What else can they do? What are in the granulocytes of neutrophils?
main function is phagocytosis
produce inflammatory mediators-cytokines, prostaglandins, leukotrienes
granules contain: peroxidase, lysozyme, degradative enzymes, defensins
82
What is protein contained within neutrophils that act against bacteria, fungi, and many enveloped/nonenveloped viruses?
defensins
83
What granulocytes are stained by:
1) neutral dyes
2) eosin
3) basic dyes
1) neutrophils
2) eosinophils
3) basophils
84
What do you use to stain lysosomes that contain enzymes and other microbicidal substances?
azure dye to give azurophilic granules
85
What are three ways neutrophils kill bacteria?
phagocytosis
degranulation
NETs
86
What are NETs? What is the main function of NETs? What do neutrophils do after producing NETs?
neutrophils release neutrophil extracellular traps (NETs) and continue directional chemotaxis (spread NETs) and phagocytosis
main function of NETs is preventing bacterial dissemination
87
What do cell of the macrophage lineage arise from? Where?
M-CSF
| bone marrow
88
Would you see monocytes or macrophages in the circulating blood normally? What would you find in the tissue?
mature monocytes enter the blood circulation then migrate into tissues where they mature into macrophages
89
What is an increased number of monocytes called? What is it in response to usually?
monocytosis
chronic infections, autoimmune disorders, certain cancers, proliferation of macrophages can occur in tissues (sarcoidosis)
90
What is a low number of monocytes in the blood called? what can cause this?
monocytopenia
| can occur in response to endotoxemia or chemotherapy
91
What are macrophages in the connective tissue called?
histiocytes
92
what are macrophages in the liver called?
kupffer cells
93
What are macrophages in the lungs called?
alveolar macrophages
94
what are macrophages in the CNS called?
microglial cells
95
What are the functions of tissue macrophages?
phagocytic cells and antigen-presenting cells
96
What do macrophages release?
```
cytokines and chemokine
reactive oxygen intermediates (ROI)
nitric oxide (NO)
defense's
enzymes: lipases, galactosidases
```
97
What do tissue macrophages produce to drive Th1 cell responses?
TNF, IL-12, IL-23
98
What do Th1 cells produce that provide a positive amplification loop that increases microbicidal and tumoricidal activity of tissue macrophages?
interferon-y
99
What do tissue macrophages produce that makes them important drivers of chronic inflammatory and autoimmune diseases?
TNF and IL-1B
100
How do tissue macrophages help with wound repair?
secrete cytokines/chemokines, matrix metalloproteinases and their tissue inhibitors that regulate the recruitment of cells to and deposition of ECM components at site of tissue injury
101
How do macrophages activate T lymphocytes at the site of infection?
present Ags
102
What do the granules in eosinophils contain?
basic proteins, peroxides, antimicrobial substances
103
In what type of reactions do we see a lot of eosinophils?
allergic reactions and reactions to parasite infections
104
What do eosinophils produce?
granules for extracellular digestion of infectious pathogens
| inflammatory mediators- cytokines, prostaglandins, leukotrienes
105
What are the functions of mast cells and where do you find them? What do they express receptors for?
They serve functions that can amplify or suppress innate or acquired immune responses
They are tissue-fixed, at sites exposed to environment
express receptors for pathogen associated (PAMP) and damage-associated molecular patterns (DAMP)
106
What do mast cells release that attract neutrophils?
IL-8
107
Why would you want mast cells to be located close to blood vessels?
they can regulate vascular permeability and effector-cell recruitment
108
How do mast cells control the behavior of surrounding cells?
through the release of mediators
109
Do neutrophils and monocytes require activation to be recruited into tissue sites?
nope
110
How do neutrophils and monocytes enter the tissue?
| What does this migration cause?
through post-capillary venues except parenchymal tissues (liver, lungs, kidney) where all blood cells enter through capillaries
inflammation
111
For neutrophil recruitment cascade, what is rolling dependent on? What about adhesion, crawling, and transmigration?
selectin-dependent
| integrin-dependent
112
What lines the luminal part of the endothelium to induce conformation changes in neutrophil integrins? What do these interactions result in?
IL-8 (neutrophils have IL-8 receptor)
| result in arrest, adhesion, crawling, and transmigration of neutrophils
113
What guides neutrophils to the preferential site for transmigration?
chemokine gradient
114
What is produced by tissue macrophages that induce rapid induction of pre-formed p-selectin on the surface of endothelial cells?
TNF and IL-1
115
What selection initiates rolling on the endothelium? What selection stabilizes the rolling?
P-selectin initiates
| L-selectin stabilizes
116
What controls transmigration of monocytes?
CCL2 and MCP-1
117
What shape do cells adopt following diapedesis?
amoeboid shape
118
What do leukocytes migrate on once under the basement membrane to get to the site of infection?
migrate along collagen fibrils
119
Where on a leukocyte would you expect to find chemotactic receptors?
located on the leading edge
120
What are the cytotoxic mechanisms of NK cells? DO they have Ag receptors? Do they belong to innate or adaptive immunity?
secretion of perforin
no
innate
121
What are targets of NK cells?
virus-infected cells, cancer cells, transplant cells
122
Do NK cells arise from precursors in the same lineage of B or T cells?
nope it's unique!
123
Do we see NK cells in adults only? How can we increase their numbers/activity?
we see them in the body at birth
| IL-15 and IL-2 increase number/activity but do NOT activate them. they're always active.
124
What is the difference between stereo cilia and regular cilia?
stereocilia are non-motile whereas cilia are
125
What are the functions of stereocilia? Cilia?
stereocilia work in absorption and secretion
| cilia generate currents for movement of fluids and particulate matter
126
What is the function of tight junctions?
prevent movement of membrane proteins between apical and lateral domains
prevent water-soluble materials from passing through
127
Whats another name for zonula adherens? What are their functions?
anchoring junctions
| fasten cells to each other or to extracellular material
128
What types of plaques do zonula adherens use?
myosin, tropomyosin, vinculin
129
What's another name for macula adherens? What is their function?
desmosomes
| provide firm cell-to-cell adhesion
130
What make up gap junctions? What's the function?
connexions
| mediate intercellular communication by allowing rapid spread of information
131
What do hemidesmosomes bind to in the basal lamina?
fibronectin in lamina lucida
132
What makes up the basement membrane?
basal lamina and reticular lamina
133
What in the thick skin gives it fingerprints?
epidermal ridges and furrows that correspond to the dermal papillae
134
What type of glands do we find in thin skin?
sweat and sebaceous glands
135
What layer of skin is only found in thick skin?
stratum lucidum
136
What are the five layers of epidermis from deep to superficial? What can you find in the epidermis?
```
basale
spinosum
granulosum
lucid
corner
```
free nerve endings (unencapsulated)
137
What layer of the epidermis is bound to the basal lamina by hemidesmosomes? What is it bound to keratinocytes by? Is it mitotically active
stratum basale
desmosomes
it's mitotically active
138
What gives the stratum spinosum cells a prickly appearance? Are they mitotically active? What does it produce when it thickens with pressure?
tonofilaments
yes
corns and calluses
139
What is the function of the stratum granulosum?
uses granules to be a barrier to foreign material and protect body from dehydration
140
What makes the stratum lucid translucent?
no organelles or nuclei
| has lots of keratin
141
What cells are continuously exfoliated? What are they filled with?
stratum corner
| mature keratin
142
Of the keratinocytes, melanocytes, langerhans, and merkel cells, which is most abundant in the epidermis? What does it make? What is it the final location of?
keratinocytes
makes keratin and lamellar granules
final location of melanin
143
What layer do you find melanocytes? What do they do?
```
stratum basale (No desmosome)
make melanin then transfer it to keratinocytes
```
144
What is the function of melanin?
protects cell nuclei from UV radiation
tyrosinase enzyme is UZ sensitive
cytocrine secretion
145
What are dendritic cells in the epidermis? What layer do you find them?
langerhans cells
| stratum spinosum
146
What are langerhans cells involved in? What are they easily damaged by?
immunologic skin reactions
| UV radiation
147
What do Langerhans cells look like under a microscope?
pale cytoplasm with long processes
| contain Birbeck's granules
148
What cells do you expect to respond to an infection in the first few hours?
innate immunity- phagocytes, complement pathway, NK cells
149
What cells do you expect to finish off an infection but won't show up for at least a day after the beginning of the infection?
B lymphocytes -> antibodies
| T lymphocytes -> effector T cells
150
What makes B and T cells highly selective?
the antigen receptors they have on their surfaces
151
When do we stop developing B lymphocytes? What about T lymphocytes?
B lymphocytes develop throughout lifetime
| T lymphocytes are generated in the thymus during fetal stage
152
What type of antigens can B cells recognize?
proteins, carbohydrates, lipids, nucleic acids
153
Does an individual B cell express a bunch of different B cell receptors? What are the functions of BCRs?
no they express identical receptors
| recognition of antigens
154
What are the functions of antibodies?
neutralize and eliminate extracellular microbes and microbial toxins
prevent dissemination of microbes
155
What kind of antigens can TCRs recognize? What do they require to "see" antigens?
peptides only
| antigen-presenting cells
156
What do cytolytic T lymphocytes (CTLs) kill?
infected host cells (intracellular microbes)
157
What are the three types of professional APCs? What are their functions?
dendritic cells, macrophages, and B cells
| when activated, they activate T helper lymphocytes
158
What are non-professional APCs? What do they activate?
any infected nucleated cell in the body
| activate cytolytic T lymphocytes
159
What reside in the epithelium to capture microbes?
dendritic cells
160
After they capture microbes, where do dendritic cells go and what do they do?
transport the Ags to the lymph nodes where protein Ags are displayed for recognition by T lymphocytes
161
Where are blood borne Ags presented by APCs?
spleen
162
PALS + lymphoid follicles =
white pulp
163
White pulp is surrounded by ____ which is rich in ____ ?
red pulp
| vascular sinusoids
164
What surrounds splenic arterioles? What does this thing contain?
periarteriolar lymphoid sheath (PALS)
| T and B cell zones
165
Which MHC class do non-professional APCs express?
class I MHC only
166
Which MHC class do professional APCs express?
classes I and II MHC
167
What do T helper cells recognize? What do they express?
```
Ads presented by class II MHC
they express CD4+
```
168
What do cytolytic T cells recognize? What do they express?
express CD8+ that directs them to Ags presented by class I MHC
169
How do cytolytic T lymphocytes know to kill infected cells?
infected cells will display the peptide Ags in the class I MHC (all nucleated cells have class I MHC so they can all present to CTLs)
170
What are the phases of adaptive responses
- recognition of Ag by specific lymphocytes
- activation of lymphocytes (clonal expansion and differentiation)
- effector phase (elimination of Ag)
171
What causes immune response to decline? What happens to antigen-stimulated lymphocytes?
declines as antigens are eliminated
| some die by apoptosis and some survive as memory cells
172
What part of the antibody determines the effector property of the antibody?
the constant region (Fc)
173
What does the hinge domain of the antibody provide?
flexibility to allow optimal Ag binding
174
What does it mean when an antibody neutralizes a virus or toxin?
blocks its interaction with cell surface receptors
175
What antibody can activate the complement cascade?
IgM
176
What does opsonization by antibodies mean?
Abs bind to Fc receptors on tissue macrophages and neutrophils that enhances phagocytosis
177
How does antibody-dependent cell-mediated cytotoxicity work?
Ab tags tumor cells and virus-infected host cells
| NK cells bind Fc receptors on Ab and kills the infected/tumor cell
178
How does an antibody assist with degranulation?
mast cells, basophils, and eosinophils have Fc receptors that are bound by IgE which makes them degranulate
179
What about epithelial cells forms as a mechanical barrier?
the tight junctions that connect them
180
In what three ways does the innate immune system provide natural immunity against microorganisms?
phagocytes and intracellular killing
recruitment of other inflammatory cells
presentation of antigens
181
What two general types of cells are the first line of immune defense? What are examples of each type?
leukocytes; neutrophils, monocytes, tissue macrophages, eosinophils
lymphocytes: NK cells
182
What does activation of neutrophils lead to?
respiratory bursts and release of granules to control bacterial growth
183
What are the first cells to arrive on scene?
neutrophils
184
What three things will macrophages do for the innate immune system?
engulf organisms
release inflammatory mediators
act as professional APCs to link innate and adaptive immunity
185
What do NK cells kill and how?
kill infected host cells by a cytolytic mediator perforin
186
What is the term for transmigration through endothelium?
diapedesis
187
What activates the integrins on blood leukocytes? What state are they normally in? What does this state look like?
the binding of chemokines to the chemokine receptors on the leukocyte
normally in a low-affinity state
low-affinity is bent
high-affinity is extended
188
Which molecules regulate chemotaxis?
chemokine, C3a, C5a, leukotrienes
189
Which cells express E-selectin?
endothelial cells
190
Which cells express integrins?
leukocytes
191
How do defensins work? What are they effective against? Where do you find it?
they are a cationic (rich in Arg) antibiotic peptide
they insert into microbial membranes and destabilize ion channels
effective against ALL bacteria, fungi, and enveloped viruses
found in neutrophil granules
192
What does bactericidal permeability increase protein (BPI) do and where do you find it?
increases permeability of bacterial membrane
| in granules of neutrophils
193
Where do you find lysozyme and lactoferrin and what do they do?
in neutrophil granules
| bactericidal and bacteriostatic proteins
194
What does cathepsin G do and where do you find it?
a serine protease that digests collagen and proteoglycans
| in granules of neutrophils
195
How do monocytes transmigrate?
same as neutrophils! except their chemoattractants are different
196
What are the chemoattractants for monocytes?
macrophage inflammatory protein-1a (MIP-1a) and MIP-1B
197
What induces classical macrophage activation? By what cytokine?
induced by TLRs and by cytokine IFN-y
198
What is another name for classically activated macrophages? What are their functions?
M1
| involved in destroying microbes and inflammation
199
What induces alternative macrophage activation?
IL-4 and IL-13
200
What is another name for alternative macrophages? What are their functions?
M2
| tissue repair and control of inflammation
201
What signaling molecule is very important in wound healing? what is it a chemoattractant for?
TGF-B
| fibroblasts
202
What is in prokaryotes but not eukaryotes that phagocytes use to help distinguish self from non-self?
N-formylmethionyl peptide (fMet)
203
What are the NK cells direct involvement in immune response
NK cells recognize infected or stressed cells
| release granules and kill dysfunctional cells
204
What are the NK cells indirect involvement in immune response?
NK cells are activated by IL-12 produced by macrophages
| they secrete IFN-y that activates phagocytosis and killing of pathogens by macrophages
205
What activates NK cells and what produces it?
IL-12 produced by macrophages
206
How are NK cells activated by a virus-infected cell?
virus inhibits class I MHC expression on infected cell so the inhibitory receptor on NK cell is not engaged and allows the activating receptor to dominate activating NK cells to destroy the target cell
207
Are the activating receptor and inhibitory receptor of NK cells always on?
```
The activating receptor is on
Inhibitory receptor is on as long as it's engaged by normal class I MHC expression by target cells
```
208
What enzyme is associated with the activating receptor of NK cells?
protein tyrosine kinase is activated by the activating receptors
209
What inhibits the PTK of NK cells?
PTK is inhibited by inhibitory receptors that recognize class I MHC molecules and active protein tyrosine phosphatase (PTP)
210
What is the goal of the complement system?
to form the membrane attack complex (MAC) which creates holes in plasma membranes and kill pathogens
211
What initiates classical activation of the complement system?
binding of C1 protein complex to IgM or IgG which are deposited on the bacteria
212
What happens to the products of C3 being cleaved?
C3a plays a role in chemotaxis and inflammation
| C3b is deposited on the surface of the bacteria and serves as an opsonin and can form a complex to make C5 convertase
213
What does C3b acting as an opsonin do?
increases phagocytosis by phagocytic cells
214
What makes up C5 convertase
C4b2a3b
215
What happens to the products of C5 being cleaved?
C5b is responsible for initiating the self-assembly of the MAC
C5a anaphylatoxin is a potent mediator of inflammatory responses
216
What all is the MAC composed of?
C5b, C6, C7, C8, and numbers C9
217
What is 3d's involvement with B cells?
It binds CR2 and lowers the threshold for activity on B cells
this links innate to adaptive immunity
218
What does C3b bind to on macrophages to increase phagocytosis?
CR1
219
What is the result of solubilization and clearance of immunocomplexes? What complement proteins do this?
prevention of aggregation and spreads inflammation
| C3a and C3b
220
What is production of acute phase proteins regulated by? What are APPs produced by? What do they accompany?
IL-6
hepatocytes
inflammation for SYSTEMIC acute-phase response
221
What causes activation and maturation of antigen-presenting cell?
pathogen recognition through PRRs
222
What TLR recognizes gram-positive bacteria?
1, 2, 6
223
What TLR recognizes dsRNA?
3
224
What TLR recognizes gram-negative bacteria?
TLR4
225
What TLR recognizes flagellin?
TLR5
226
What TLR recognizes unmethylated CpG DNA?
TLR9
227
What receptors recognize microbial Ags?
BCRs and TCRs
228
In BCR, the NH-terminus of what are highly variable?
H and L chains (Vh and VL)
| antigen binding site
229
In TCR, the NH-terminus of what are highly variable?
Va and VB
230
Is the constant (c) region very variable?
noooooope!
231
What is another name for a BCR?
Ig molecule
232
Even though individuals codominantly express maternal and paternal sets of alleles for L and H chains, only one of the VLCL and VHCH alleles (either maternal or paternal) is expressed in a single B cell. Why?
allelic exclusion
233
What does allelic exclusion refer to?
individual B cells express only on of the VLCL or VHCH alleles (either maternal or paternal) even though individuals codominantly express maternal and paternal alleles for L and H chains
234
What things is allelic exclusion applied to?
TCRs and BCRs
235
What determines the variable regions of the chains in TCRs and BCRs?
rearrangement of the DNA
236
What is the major mechanism of epitope-specific diversity of BCR and TCR?
DNA chromosomal rearrangement
237
What initiates rearrangement of BCR or TCR?
somatic recombination
238
What are RAG1 and RAG2? What cells is the expression of RAG1 and RAG2 restricted to and during what stage?
recombination-activating genes 1 and 2 encode enzymes performing recombination of BCR and TCR during the process of VDJ recombination
B and T lymphocytes during developmental stages
239
How many separate gene segments are in a chromosome 14 on a heavy chain? What are they?
4
| V, D, J, C (constant)
240
What's the difference between an immature B cell DNA segment for heavy chain and a mature B cell?
all copies but one are randomly deleted giving a single B cell a unique combination of V-D-J
241
What is the test for productive rearrangement? What is the chance of producing a productive rearrangement?
transcription and translation
| 10%
242
Why can B cells recognize any Ag possible?
the number of combinations possible is very big for the V, D, J genes
243
Where is junctional diversity generated?
at the points between the joining genes
244
What does junctional diversity result from?
loss of nucleotides by exonuclease
| addition of N and P nucleotides
245
What are P nucleotides derived from?
asymmetric opinion of hairpin loops
246
What does the opening of the hairpin loops produce for junctional diversity?
single stranded extensions that can be added into junctions or alternatively removed by exonuclease activity
247
What aids the addition of N nucleotides?
terminal deoxynucleotidyl transferase (TdT)
248
Does junctional diversity work for BCR or TCR
both
249
What is the cause of Omenn syndrome?
missense mutation -> only partial rag1/rag2 activity
250
What are symptoms of Omenn syndrome?
lack of B cells
decrease in T cell counts
severe immune deficiency with failure to thrive, diarrhea, red rush
251
What defect causes severe combined immune deficiency?
null mutation in rag1 and rag2 genes
NO enzymatic activities
(deficiency in adenosine deaminase)
252
What are symptoms of SCID?
total lack of B and T cells
| defect in both humoral and cell-mediated immunity
253
What do CD4+ T cells require?
APC and co-stimulation
254
Resting APCs express low levels of what?
co-stimulatory molecules
255
Activated APCs express high levels of what?
```
class II MHC
co-stimulatory molecules called B7-1 and B7-2 (CD80 and CD86)
```
256
Costimulation involves a protein ___ on APC and a protein ___ on T cells
B7 on APC
| CD28 on T cells
257
What is the immunological synapse?
close contact between T cell and APC
258
What three molecular pairs participate in the immunological synapse?
TCR/MHC-peptide pair
Co-stimulatory pair CD28(T cell)/B7(APC)
Adhesion pair LFA-1(T cell)/ICAM-1(APC)
259
What does the immunological synapse ensure?
effector molecules (cytokines) released by the cells are not affecting bystander cells
260
What is an analog for CD28 that can be found on T cells?
| What is its function?
```
CTLA-4
signal transduction (negative regulation)
```
261
Where are plasma cells mostly found?
lymphoid organs NOT in the plasma
262
What is one of the main functions of B cells? What can they do once activated and after performing this function?
professional APC to T cells
| can develop into memory B cells
263
What is the specific marker for B cells? What else does it do other than serving as a marker?
CD19
| coreceptor for BCR
264
What else do B cells need to be activated by protein Ags? What do we call protein Ags?
assistance of T helper cells
| thymus dependent or TD Ags
265
What do we call antigens of lipid, carbohydrate, or polynucleotide nature? Why?
thymus-indepdnet or TI Ags
| activate B cells without help of T cells
266
What generates a signal for B cell activation by TI Ags?
cross-linking
267
What is cross-linking when it comes to B cell activation by TI Ags?
multiple BCRs bind to a repetitive epitope on bacterium
268
What transduces the signal generated by cross-linking in B cell activation by TI Ags? What
Iga and IgB
269
Enzymes attached to the cytoplasmic portion of Iga and IgB catalyze what?
phosphorylation of signaling molecules
270
What is the co-stimulatory signal from T helper cells for B cell activation by TD Ags?
Th2 cell delivers second signal via CD40L (B cell has CD40)
271
What if a T cell receives a specific signal but never receives a co-stimulatory signal?
T cell becomes anergia (does not react)
272
What if a T cell receives a co-stimulatory signal but no specific signal?
there's no effect on T cell
273
In antibody-dependent cell-mediated cytotoxicity, what part of the antibody binds to what cell that will kill the target?
Fc region of bound Ig binds CD16 of NK cell
274
What are some examples of autocoids?
nitric oxide, eicosanoids, histamine, serotonin
275
What are the sequential enzymatic reactions that generate eicosanoids referred to as?
arachidonic acid cascade
276
What are eicosanoids?
a family of antacid lipid mediators derived from oxidative metabolism of a polyunsaturated fatty acid substrate with 20 carbons (arachidonic acid)
277
How do we get prostaglandin (PG)H2 endoperoxide?
cell membrane phospholipids---> arachidonic acid (via phospholipase A2)
arachidonic acid ---> prostaglandin (PG)H2 endoperoxide (via COX cyclooxygenase)
278
What type of enzymes give us prostacyclin or thromboxane from the same substrate? What is the substrate?
tissue isomerases
| prostaglandin (PG)H2 endoperoxide
279
What enzyme inactivates prostaglandins?
15-OH PG dehydrogenase
280
When are PG or Tx made?
only upon stimulation which activates phospholipase A2 to liberate AA from cellular phospholipids
281
Are Pgs or Tx stored in cells?
noooooooope
282
What does autocoid inactivation involve?
rapid metabolic degradation of PGs or spontaneous hydrolysis of Tx and PGI2
283
How can different cells make different eicosanoids?
expression of isomerases and synthase enzymes vary among cells
284
What G protein is associated with thromboxane? What are some downstream effects?
Gq ---> PLC ---> DAG and IP3 ---> ^Ca
| smooth muscle contracts
285
What G protein is associated with prostaglandin? What are some downstream effects?
Gs ---> AC ---> cAMP
| smooth muscle relaxes
286
Why can most cell types make eicosanoids?
most cell types express COX
287
What cells in cardiovascular physiology produce thromboxane? what enzyme do they express?
platelets in the blood
| express Tx synthase
288
What cells in cardiovascular physiology produce prostacyclin? What enzyme do they express?
vascular endothelium
| express PGI2 synthase
289
What cells in cardiovascular physiology express thromboxane receptors?
platelets and vascular smooth muscle
290
What cells in cardiovascular physiology express prostacyclin receptors?
platelets and vascular smooth muscle
291
If someone's heart had an excess of TxA2 and a deficit of PGI2 what condition would they have?
coronary spasm such as angina pectoris
292
What receptors when occupied by their cognate ligands typically relax smooth muscles and cause vasodilation?
EP2, EP4, IP
293
What receptors when occupied by their ligands contract smooth muscles and cause vasoconstriction?
FP and TP
294
How can EP sub-types vary in dilation or constriction?
vary in G protein coupling
295
What is the eicosanoid for vasculature and what is its action?
PGE2
| permeability
296
What is the eicosanoid for the gut and what is its action?
PGE2
| mucosal cytoprotection, muscle tone, motility
297
What are the eicosanoids for the kidney and what are their actions?
PGI2, PGE2
| Na+, H2O excretion
298
What are the eicosanoids for the uterus and what are their actions?
PGF2a, PGE2
| uterine contraction
299
What is the eicosanoid of the CNS and what is its action?
PGE2
| temperature
300
What is the eicosanoid of the PNS and what is its action?
PGE2
| pain sensitization
301
What inhibits platelet aggregation?
PGI2
302
Platelets being exposed to what stimulates TxA2 formation?
collagen in the connective tissue
303
How does thromboxane take care of bleeds?
- amplifies platelet aggregation
- constricts blood vessel
- slows bleeding
304
What stops the thromboxane process from spreading throughout the blood stream? What keeps it local?
stimulus (collagen) is local
| PGI2 made by downstream endothelial cells opposes the action of TxA2 on blood vessels and platelet
305
When is COX-1 expressed?
constitutive-all the time
306
What does COX-1 synthesize in the gut? What is the stimulus? what is the role of this prostaglandin?
PGE2
gastric acid
mucosal cytoprotection, gut motility
307
IF you have a deficit of PGE2 in the gut what happens? What if you have an excess of PGE2?
deficit: ulcers
excess: diarrhea, cramps
308
What does COX-1 synthesize in the uterus? What is the stimulus? What is the role of this prostaglandin?
endocrine hormones and mechanical stretch
PGE2 and PGF2
dilate the cervix, contract the uterus ---> delivery
309
If you have a deficit of PGE2 or PGF2a in the uterus what will happen? What if you have an excess of PGE2 and PGF2a?
pre-mature labor
| birth
310
What does fetal lung maturation cause?
withdrawal of PGE2 ---> ductus arterioles closes
311
What does a deficit of PGE2 in the kidneys cause? what special enzyme can produce PGE2 in the kidneys?
leads to Na+ and H2O retention (edema), mild hypertension
| COX-2
312
Where does COX-2 complement the role of COX-1?
kidney and brain
313
When is COX-2 expression induced?
prominent role responding to pathological stimuli (cancer, inflammation)
314
Where can you find 15-OH-PGDH? What does it do?
lungs
| limits the systemic administration of PGs
315
Are autocoids hormones?
NO
316
How does inflammation stimulate production of PGs?
stimulates AA release
317
What would be the advantage of a selective COX2 inhibitor?
it would inhibit COX2 in the knee but leave COX1 in the tummy alone
318
What do SH2 domains bind?
phosphotyrosine-containing polypeptides
319
What do SH3 domains recognize?
proline-rich stretches in polypeptides
320
What do PH domains recognize?
PIP3 or other phosphatidylinositol-derived lipids
321
What domains are present on Syk and ZAP-70 tyrosine kinases? What motifs do they bind to in the Ag receptor complex?
SH2 domains bind phosphotyrosine motifs in the Ag receptor complex
322
What tyrosine kinase family recognizes PIP3 on the inner leaflet of the plasma membrane?
TEC family tyrosine kinase Btk
323
What are the adaptor proteins for B cells? What about T cells?
BLNK (B cell linker)
| LAT (linker for the activation of T cells)
324
What can adaptor proteins contain?
SH2 or SH3 domains
or proline-rich stretches
or tyrosine residues that can be phosphorylated by tyrosine kinases
325
Explain the process of attaching adaptor proteins in T cell activation starting with LAT
LAT is phosphorylated and recruits PLC (Ca signaling) and GADS adaptor
SLP-76 (proline-rich stretch) binds GADS's SH3 domain and recruits VAV after being tyrosine phosphorylated -> actin-cytoskeletal rearrangment
326
What are on the cytosolic side of activating/inhibiting immune receptors?
ITAMs
| ITIMs
327
What inhibitory receptor is found on B cells and myeloid cells?
FcyRIIB
328
How can a coreceptor increase cellular activation?
coreceptor with its signaling enzymes can increase ITAM phosphorylation and activation of the antigen receptor
329
What are the coreceptors for T helper and cytotoxic T cells?
CD4 and CD8
330
What is the coreceptor on B cells?
complement receptor type 2 (CR2/CD21)
331
What is an inhibitor of T cell receptors?
CTLA-4 (analog CD28)
332
What are inhibitory receptors in B cells?
CD22 and FcyRIIB
333
What is another name for CD80/CD86?
| What does it bind on T cells?
B7
| CD28
334
Why do the aB chains of a TCR need CD3 and the squiggle proteins?
TCR a and B chains have cytoplasmic tails that are too small to transduce signals so CD3 and squiggle proteins serve as signal-transducing subunits of TCR complex
335
How many polypeptides chains make up CD3 and what are they? On what cells do we find CD3?
three: y, d, E
| CD4 and CD8 T cells
336
What protein is in charge of adhesion on T cells? What does it bind to on an APC?
LFA-1
| binds ICAM-1 on APC
337
What is the negative regulation accessory molecule on TCR that is bound by ligands on tumor cells, tissue cells, and APCs?
program death-1
| PD-1
338
What does the CD4 coreceptor look like?
four extracellular Ig-like domains, hydrophobic transmembrane region, highly basic cytoplasmic tail (38 AAs long)
339
What does the CD8 co receptor look like?
composed of two related chains called CD8a and CD8B
they have a single extracellular Ig domain
highly basic cytoplasmic tail that is 25 AAs long
340
Describe early events in T cell activation starting with Ag recgonition
- recognize Ag, TCR complexes cluster with CD4 or CD8
- CD4-associated Lck becomes active and phosphorylates ITAMs of CD3 and squiggle chains
- ZAp-70 binds phophotyrosines of squiggle chains and is phosphorylated/activated
- ZAP-70 activates various adaptors such as LAT
- adaptors become docking sites for PLCy1 and exchange factors that activate Ras and MAP kinases
341
What is the function of activated Akt kinase?
contributes to T cell survival by inactivating pro-apoptotic proteins
342
How do we activate Akt kinase in T cells?
activated PI3-kinase is recruited to TCR complex and generates PIP3 from PIP2
PDK1 is PIP3-dependent which phosphorylates/activates Akt kinase
343
What protein is associated with LFA-1? So in what cell do you find it?
talin
| T cell
344
How does Lck activate MAP kinase? What transcription factor is synthesized and activated by the MAP kinase cascade?
Lack activates ZAP-70 upon Ag recognition
ZAP-70 phosphorylates LAT (adaptor protein)
LAT binds Grb-2 adaptor
Grb-2 docks the GTP/GDP exchange factor SOS
SOS converts Ras-GDP to Ras-GTP
Ras-GTP activates MAP kinase and ERK
cascade activates AP-1
345
How does a T cell use PLCy1 to induce numerous cellular responses? How do we activate PLCy1?
activated LAT binds PLCy1 and it is activated by ZAP-70
PLCy1 hydrolyzes PIP2 to generate IP3 and DAG
IP3 stimulates increase in cytosolic Ca
DAG activates PKC
PKC and Ca ions induce numerous cellular responses
346
What are two ways to generate AP-1?
calcium-calmodulin activates Nuclear factor of activated T-cells (NFAT)
Ras and Rac pathways
347
What kinase is important in activating NF-kB
PKC
348
What inactivates NF-kB?
IkB
349
How does PKC activate NF-kB?
PKC phosphorylates IkB and activated NF-kB can go to the nucleus
350
What transcription factors regulate gene expression in T cells?
AP-1 and NF-kB
351
Why does TCR engagement alone cause anergy?
calcium-mediated signals induce the activation of NFAT only
NFAT alone elicits the expression of a distinct set of anergy-inducing genes which inhibit T-cell function at different levels and induce a status of T-cell unresponsiveness
352
Iga and IgB on B cell surfaces are associated with what? How are Iga and IgB linked? What do they contain?
Membrane IgM and IgD
disulfide linked
contain ITAMs in their cytoplasmic tails
353
What complex has Src-Syk activation? What does Src-Syk activation lad to?
BCRs!
| activation of PLCy and Ras and Rac small GTPase which will be followed by activation of transcription factors
354
The activation of what three transcription factors follow Src-Syk activation? What do these transcription factors promote?
NFAT, Nf-kB, AP-1
| cell growth, differentiation, survival
355
what are examples of some Src kinases in BCR signaling?
Lyn, Fyn, Blk
356
What activates Src kinases? What do these activated Src kinases do? Where do you find them?
cross-linking by multivalent Ags brings together and activates Src kinases
which phosphorylate the ITAMs of Iga and IgB
BCR signaling
357
What's the point of phosphorylating the ITAMs of Iga and IgB? Where do you find them?
they provide a docking site for the tandem SH2 domains of the Syk tyrosine kinase
(remember Src kinases phosphorylate the ITAMs)
BCR signaling
358
Who activate the Syk kinase? What are they?
Lyn, Fyn, Blk kinases activate Syk kinase-associated with ITAMs
these three things are Src kinases
359
What enzymes are in charge of inhibitory signaling in lymphocytes?
E3 ubiquitin ligases
360
What do inhibitory receptors do?
recruit and activate phosphates that counter signaling events induced by Ag receptors
361
Ligand binding to an inhibitory receptor results in what?
phosphorylation of the ITIM tyrosine by a Src family kinase
362
What do the phosphorylated ITIMs recruit?
SH2 domain containing tyrosine phosphatase that can attenuate immune receptor signaling
363
TLRs, BCR, and TCR are all a part of the canonical or non canonical NF-kB signaling pathways?
canonical
364
What are features of the canonical NF-kB signaling pathways?
- rapid and transient
- independent of protein synthesis
- respond to numerous stimuli
- diverse functions
