Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Host and Defense > Week 8 > Flashcards

Week 8 Flashcards

1
Q

What are the four major antibiotic resistance mechanisms? Describe them

A

Prevent access to target - drug can’t get in or drug gets in but cant get pumped back out before affecting target

Modify or protect antibiotic target - target is altered structurally OR target is overexpressed (so you need much more drug)

Modification/inactivation of antibiotics - drug is inactivated before affecting target.

Modify expression of Bactrian factors needed to activate the antibiotic (prodrug)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Name three antibiotic tolerance mechanisms

A

Biofilm formation

Spores

Persister cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are two ways bacteria may restrict access of antibiotic to target?

A

Alter envelope to inhibit uptake

Boost expression of efflux pumps (gene amplification)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

The ____ mutation in ____ rRNA protects against macrolides like erythromycin

A

A2580G

23S

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Tetracycline binds ____ rRNA in ____ subunit, and distorts the ___ site

A

16S

30S

A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Bacteria may grow resistant to tetracycline by protecting their ribosomes via ___ or via ___ of a ____ that pertubs the ____ in 16S rRNA that is involved in tetracycline binding

A

Mutation

HGT acquisition

GTPasse

Helix

*basically, an enzyme is activated to unwind an rRNA so that it is not recognized by tetracycline. Note that this make the ribosome less effective, but it is resistant to tetracycline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How does vancomycin kill bacteria?

A

Prevents normal cross-linking of peptidoglycan.

Vancomycin binds to D-Ala-D-Ala preventing cross linking

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe vancomycin resistance

A

Involves four enzymes that prevents vancomycin from preventing peptidoglycan cross-linking

The multiple enzymes that are required for resistance is what caused bacteria to take so long to grow resistant to vancomycin.

Enzymes are VanH, VanA, VanB, VanX

VanX will reform peptidoglycan cross-linkage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How do some bacteria grow resistant to penicillin by modifying the target?

A

Penicillin normally binds to transpeptidase to prevent cross-linking.

Point mutations in transpeptidase causes resistance. (Note, however that transpeptidase will be less effective with these point mutations)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are two ways in that bacteria can grow resistant to antibiotics by modifying or inactivating the antibiotic?

A

Inactivation by hydrolysis

Inactivation by steric hinderence.

B-lactamases do this

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How do B-lactamases work?

A

Break a bond in the B-lactam ring of penicillins to disable the molecule.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How do B-lactamase inhibitors work? (Like clavulanic acid)

A

Clavulanic acid is a suicide molecule. It interacts with B-lactamases to be cleaved but remains attacahed to B-lactamase to inactivate it.

**note that bacteria have also developed anti-B-lactamase inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are three ways in which antibiotics can e modified for deactivation? What enzymes accomplish this? How is it that these modifications are detrimental?

A

N acetylation

O phosphorylation

O adenylation

Aminoglycoside inactivating enzymes

Modifications disrupt hydrogen-bonding network used to bind 16S RNA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Some bacteria can gain resistance by modifying expression of bacterial factors needed to activate the antibiotic (prodrugs). Give two examples of prodrugs

A

Metronidazole is activated by the bacterial factor flavodoxin in H. Pylori and P. Gingivalis

Isoniazid is activated by the bacterial catalase/peroxidase enzyme KatG in. MTB. Isoniazid will then continue to inhibit the synthesis of mycolic acid required for MTB cell wall

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

In what two ways is resistance acquired?

A

Mutation

Horizontal gene transfer

Note that E. Coli has a one in a billion chance of becoming resistant to streptomycin. But because of fast growth rates and high numbers, this probability becomes meaningful

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What four things are contributing to the spread of resistant bacteria?

A

Overuse of antibiotics

Overpopulation

Poor hygiene

Travel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Name four pathogens that are becoming increasingly resistant

A

Extended-spectrum B-lactamase producing enterobactericae

Carbapenem-resistant enterobacteriacae

Clostridium difficile

Super neisseria gonorrhea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the three different priority pathogens in the list for R&D of new antibiotics?

A

Priority 1: Critical

Priority 2: High

Priority 3: medium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the three bacteria that are classified under priority 1 (critical)?

A

Acinetobacter baumannii, carbapenem-resistant

Pseudomonas aeruginosa, carbapenem-resistant

Enterobacteriaceae, carbapenem-resistant, ESBL-producing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are 6 bacteria that are considered priority 2 (high)?

A

Enterococcus faecium, vancomycin-resistant

Staphylococcus aureus, methicillin-resistant, vancomycin intermediate and resistant

Helicobacter pylori, clarithromycin-resistant

Campylobacter spp. Fluoroquinolone-resistant

Salmonella, fluoroquinolone-resistant

Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone resistant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Name three bacteria that are considered under the priority 3 (Medium)?

A

Streptococcus pneumoniae, penicillin-non-susceptible

Haemophilus influenzae, ampicillin-resistant

Shigella spp. Fluoroquinolone-resistant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Antibiotic tolerance contributes to ___ and ____ infections. What are some methods bacteria use to tolerate antibiotics?

A

Chronic

Recurrent

Spores
Biofilms
Persister cell formation
Intracellular niches

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

> ___% of human infections may involve biofilms

A

65

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are six ways in which biofilm formation enhances the ability of bacteria to tolerate antibiotics?

A

Extracellular matrix

Altered protein expression

Decreased metabolism

Increased stress resistance

Increased gene exchange

Persister cell formation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are persister cells?

A

Dormant bacteria that are insensitive to many stresses and antibiotic treatment.

Persister cells can remain dormant during antibiotic treatment, but after become reactivated

Note that antibiotics may not kill all of the dormant bacteria, but they can lower total bacteria numbers to regain control (sometimes)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

B cells are not stockpiled, but constantly replaced. About how many B cells are replaced each day? What is the mature half-life?

A

30 billion per day

50-100 days

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Name the different stages of B cell development in the bone marrow, starting with stem cell

A

Stem cell

Early pro-B cell

Late pro-B cell

Large pre- B cell

Small pre- B cell

Immature B cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

At which stage of B cell development is the heavy chain rearranged?

A

Early pro-B cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

At which stage in B cell development do you have negative selection?

A

Immature B cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What is the function of immature B cells?

A

They move around the periphery from lymphoid organ to lymphoid organ, looking to be activated by an APC. Once activated, they will colonally expand into a large number of plasma cells and memory cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What are memory B cells

A

Respond to subsequent infection.

Also produce antibodies directly after expanding to prevent immediate reinfection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What is an early pro-B cell?

A

RAG proteins activated to Rearrangement of D-J heavy chain on BOTH chromosomes

No immunoglobulin production yet

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What is a late pro-B cell?

A

V-DJ rearrangement of heavy chain on first chromosome, then second. If neither work, the cell will die.

Note that about 50% will die

Still no immunoglobulin being produced

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

What is the first checkpoint in immature B cell development?

A

Between late pro-B cell and large pre-B cell

Checks to see if heavy chain is functional

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

What is a large pre-B cell?

A

VDJ is rearranged and heavy chain is being produced

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What is a small pre-B cell?

A

Heavy chain is still being produced

V-J rearranging of light chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is the second checkpoint in immature B cell development?

A

Between small pre-B cell and immature B cell

Checks to see if light chain is functional

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

How do stromal cells drive B cell development?

A

Signaling factors, adhesion molecules, and growth factors are physically attached to the surface of bone marrow stromal cells

As a developing B cell moves along the stromal cell, the signaling factors change, causing changes in the B cells’ RAG gene expression and other factors

Pro-B cells are programmed to die in the absence of survival signals from the stromal cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What is a way you can get dysfunctional rearrangement when producing the heavy chain?

A

Most problems occur with junctional diversity. A stop codon could be added in

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What is a pre -BCR (pre-B cell receptor)? What is expressed along with it?

A

The heavy chain used as a receptor. Expressed in the ER

A surrogate light chain is expressed with it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What is a surrogate light chain?

A

Essentially a placeholder protein

Binds to heavy chain to ensure a light chain can bind to the heavy chain

Allows heavy chain to bind two other proteins, Igbeta and Igalpha

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Since antibodies really have no ____, they cant signal. Thus they bind to ___ and ___ to send all of the signals from the pre-BCR. This is how it functions as a first checkpoint. When the heavy chain interactis with Igbeta, will cause a signal to pass the first checkpoint because it produced a functional heavy chain. This will turn off the ____ expression, initiates ____, and leads to ____

A

Cytoplasmic tail

Igalpha, igbeta

RAG

Cell division

Allelic exclusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What are the four functions of igbeta signaling?

A

Checkpoint clearance

Turns off RAG proteins

Initiates cell division

Allelic exclusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What is allelic exclusion? Why is this important?

A

Allows a functional heavy chain to produced by only one chromosome

This is important because it will the antibody specific for only one epitope

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Why is it that large pre-B cells go to small pre-B cells?

A

Large pre-B cells go through a bunch of division (leading to smaller cells) (about 100 small pre-B cells per one large pre-B cell)

They replicate because you want to invest in a promising B cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What three things occur in the transition from large pre-B cell to small pre-B cell?

A

Cell division (100 smalls produced)

RAG genes reactivated (for rearranging the light chain). **note that now they all share the same heavy chain, but they can each produce different light chains

Unique recombination per cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What is different between heavy chain rearrangement and light chain rearrangement?

A

Light chain rearrangement can have a few attempts whereas heavy chain only has one chance to produce a functional chain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

You have two chromosomes that can code for light chain: the ___ and ___. Usually the ___ rearranges first

A

Kappa

Lambda

Kappa

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

How many light chain recombination attempts possible per chromosome?

A

4-5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

If pre-B cells cannot produce functional light chain, they will die. But approximately ___% of small pre-B cells survive

A

85

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Describe the second checkpoint in B cell development

A

Functional antibody on cell surface (including light chain). Utilizes Igbeta signaling to promote the survival of these cells (absense of this signalling will lead to apoptosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What stage of B cell development does negative selection occur?

A

Immature B cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What is negative selection?

A

Kills B cells that recognize self antigen

If immature B cells bind to self antigen in bone marrow they will be retained in bone marrow

If immature B cells do not bind to bone marrow, they will move to the blood and express IgD and IgM. Here they will be exposed to more self antigens. If they recognize self antigen in the periphery, they will become anergic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Exposure to self antigen ensures tolerance (meaning the inability to bind to self antigen). What are the two types of tolerance?

A

Central tolerance - tolerance gained in the bone marrow

Peripheral tolerance - tolerance gained in the circulation and secondary lymphoid tissues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What happens if an immature B cell recognizes self antigen in the bone marrow?

A

It is retained in the bone marrow and goes back into a small pre-B cell state to rearrange its light chain, so long there is genome left. If none left, it will die. Once it finally produces a good light chain, it will be released into periphary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Immature B cells migrate to lymph nodes via ___

A

HEV (high endothelial venules)

57
Q

Chemokines attract B cells to ___ into the ____, then into the ____. Here, interactions with ____ and ___ drive the maturation of B cells

A

HEV

Lymph node

Primary follicle

Dendritic cells

Cytokines

58
Q

Describe the process of B cell maturation (positive selection). B cells release ____ to stimulate the ____ to release ____ . Once B cells are matured, they produce more ___ than ____

A

In the primary follicle, immature B cells interact with follicular dendritic cells.

Lymphotoxin

Follicular dendritic cells

BAFF (B cell activating factor)

Now B cells are mature. They then produce more IgD than IgM

59
Q

What happens to an immature B cell if it doesn’t undergo positive selection within a few days?

A

It will become anergic

60
Q

What happens B cells once they are considered mature?

A

They remain in the lymph node for a few days, then circulate in the body, going from lymph node to lymph node

61
Q

What are the four steps of mature naive B cell activation in lymph nodes?

A

Antigen exposure in cortex

Interaction with T cells in T cell area

Migration, secondary lymphoid follicle formation, and colonial expansion in germinal centers

Plasma cell production and antibody secretion

62
Q

Why is it that dysfunctional B cell development can result in cancers?

A

Due to mutations that lead to unregulated replication or excessive proliferation of precursor B cells

63
Q

What are CD8 cytotoxic T cells?

A

Kill virus-infected cells and some intracellular bacteria

64
Q

What are CD4 Th1 cells?

A

Activated infected macrophages. Provide help to B cells for antibody production

Targets extracellular bacteria

65
Q

What are CD4 Th2 cells?

A

Provide help for B cells for antibody production, especially switching it IgE*

Targets helminths/parasites

66
Q

What are CD4 Th17 cells?

A

Enhance neutrophil response

**promote barrier integrity (prominent in mucosal surfaces)

67
Q

True or false… TCRs may be secreted

A

False… they are only expressed on the cell surface

68
Q

TCRs primarily bind to ___

A

Polypeptides. Not so much polysaccharides or lipids like antibodies can

69
Q

CD8 cells interact with MHC ___ whereas CD4 cells interact with MHC ___

A

1

2

70
Q

What is the function of MHC1 and where is it found?

A

MHC1 is found on most cells in the body. They are used to present self antigen. This will tell the T cells if they are healthy or diseased

71
Q

What are the two different classes of TCRs? Which is most common?

A

Alphabeta (most common)

Delta gamma

72
Q

What are some differences between alpha-beta T cells and delta gamma T cells?

A

Alpha beta: adaptive immunity, common in circulation (not tissues), developed and matures in thymus, positive and negative selection

Delta gamma: not involved in classic adaptive immunity, monitors tissue health (so its common in tissues not circulation), develops but does not mature in the thymus, limited positive and negative selection

73
Q

True or false.. T cells may express both alpha-beta and delta-gamma TCRs

A

False… only one type

74
Q

Delta chain genes are embedded within the ___ chain gene

A

Alpha

75
Q

The alpha chain is similar to the ___ chain in antibodies in that it has the same ____ segments whereas the B chain is similar to the ___ chain in antibodies in that it has ____ segments

A

Light

V, J, C

Heavy

V, J, D, C

76
Q

True or false.. TCR genes undergo genetic rearrangement and junctional diversity similar to B cells

A

True

77
Q

Which has more diversity, TCRs or immunoglobulins? Why?

A

TCRs

Because they have a longer genome

Also note that TCRs have a LOT more joining segments

78
Q

True or false.. TCRs can bind directly to soluble antigen

A

False… they can only bind antigen if it is presented b MHC

79
Q

TCRs are not really able to signal on their own. They require ____ for signaling

A

CD3

80
Q

What cells express MHC2?

A

APCs (macrophages, dendritic cells, B cells)

81
Q

MHC1 will present ___ antigen whereas MHC2 will present ____ antigen. MHC1 is expressed on cell membrane by ___ antigen loading whereas MHC2 is expressed on cell membrane by ____ antigen loading

A

Intracellular

Internalized

ER antigen loading

Vesicular ER loading

82
Q

What is the difference between MHC1 and MHC2 structure?

A

MHC1: alpha chain and B2 microglobulin

MHC2: alpha and beta chains

83
Q

True or false… erythrocytes do not express MHC1 or MHC2

A

True

84
Q

Describe the difference between MHC1 and MHC2 loading on the cell membrane

A

MHC1: intracellular antigen is broken down by proteasome. Antigen is put into ER where MHC1 exists. MHC1 is then loaded onto cell membrane

MHC2: after pathogen is phagocytosed and broken down in vesicle, another vesicle containing MHC2 fuses with it. Then MHC2 is loaded onto the cell membrane

85
Q

in MHC1 antigen loading, the heavy chain of MHC1 is stabilized by ____ until ____ binds. Then ____ is released to form another complex, the peptide loading complex. A peptide delivered by ____ binds to the heavy chain, forming the mature MHC1. Then the MHC1 dissociates from the peptide loading complex and exported from the ___ to the ____

A

Calnexin

beta2-microglobulin

Clanexin

TAP

ER

Cell membrane

86
Q

Intracellular peptides of ____ residues are expressed by MHC1. Peptides are trimmed before expression by a ____

A

8-10

Proteosome

87
Q

How can crosspresentation of endocytosed antigen on an APC occur? Why is this bad?

A

The antigen can get into the ER where MHC1 is located

Most antigen is presented via MHC2

The presentation of antigen on MHC1 targets the APC for death

88
Q

Describe MHC2 antigen loading

A

Internalized antigen in vesicles is fused with another vesicle containing MHC2. This is then sent to the cell membrane

89
Q

How do APCs present the presentation of self antigen on MHC2?

A

Invariant chains block the binding of peptides to MHC2 in the ER. Then, in the vesicles, the invariant chain is cleaved, leaving behind CLIP* in the active site of MHC2. CLIP prevents the binding of peptides to MHC2 in vesicles. Then, once fused with a vesicle full of pathogen antigen, HLA-DM facilitates the release of CLIP to allow the binding of antigen in MHC2

90
Q

What is CLIP?

A

Class 2 associated invariant chain peptide.

It prevents the binding of self antigen in MHC2

91
Q

What are some things that T helper cells can do?

A

Stimulate macrophages to lyse the phagocytosed stuff

Stimulate B cells to isotype switch or produce antibodies

92
Q

In the development of T cells, only about ___% will survive

A

2

93
Q

T cells are developed in the ____. TCR development occurs within the ___. Selection occurs as thymocytes move from ___ to ___

A

Thymus

Cortex

Cortex to medulla

94
Q

Why is it that even though the thymus degenerates with age (thus reduced T cell production) the T cell response doesn’t really diminish?

A

T cells have long half lives. CD4: 4.2 years. CD8: 6.5 years

When they are activated, however, they may last for decades

95
Q

True or false… T Cell progenitors dont commit until they reach the thymus. How do T cells tell if they are in the thymus?

A

True

They can tell if they are in the thymus by notch1 (T cell transcription factor complex) signaling and pax-5 signaling (B cell transcription factor)

96
Q

What are the two main phases of T Cell development?

A

Double negative and double positive

97
Q

What is the first thing that is rearranged in a developing T cell in a double negative stage?

A

Beta chain or delta gamma chains.

If delta gamma chains rearrange before the Beta chain rearranges, it will become a delta gamma T cell, if the Beta chain rearranges first it will become an alpha beta T cell (alpha beta is more common)

Beta chain will form a pre-TCR

98
Q

What is the first checkpoint in T Cell development?

A

The formation of a pre-TCR from a beta chain

99
Q

What happens once the T cell passes the first checkpoint by producing a functional ___?

A

Pre-TCR

It will go through a series of replication to have a bunch of cells with the same beta chains

100
Q

After T cells have proliferated after producing functional pre-TCR (beta chain), what happens?

A

It enters the double positive stage by expressing both CD4 and CD8, while rearranging alpha chain (or delta gamma)

101
Q

What happens if delta-gamma rearranges before the alpha chain rearranges?

A

The T cell will become a delta gamma T cell.

Note that the T cell has two chances to become delta gamma… before arrangement of beta chain and before arrangement of alpha chain

102
Q

After rearrangement of the alpha chain, what happens?

A

It enters the second check point: forming a functional TCR

If it passes, it will form single positive T cells, which will then undergo positive and negative selection

103
Q

Thymic location influences T cell development. They go from immature to mature as they progress from __ to ___ of the thymus

A

Cortex to medulla

104
Q

What happens if at any point, the delta gamma chains rearrange first?

A

The T cell leaves the thymus with little selection

105
Q

Once a T cell enters the double positive stage, what drives the cell to express both CD4 and CD8?

A

B chain

106
Q

In regards to Beta chain rearrangement, each T cell gets ___ attempts at producing a functional beta chain because they get ___ attempts per locus and there are ___ genres

A

4

2

2

107
Q

True or false… the Beta chain locus is organized the same way that immunoglobulin loci are organized

A

False… they are organized differently

108
Q

Once beta chain is formed it binds o a surrogate alpha chain analogue to make the pre-TCR. Here, it may or may not bind to ____ to allow signaling. It will signal for ____ and ____. This is the first checkpoint. If no signaling occurs, it will ___

A

CD3

RAG function halts
Proliferation

Die

109
Q

How do pre-TCRs recruit CD3?

A

They form a hero diner or super dimer to form a pre-TCR complex

110
Q

When RAG is turned back on to rearrange the alpha chain in T cells, it also induces the expression of ___ and ___

A

CD4 and CD8

111
Q

Why is it that a T cell can still become a delta gamma cell after it has already produced functional pre-TCR and is in the process of rearranging alpha chain?

A

The delta chain sits right in the middle of the alpha chain locus

112
Q

What is the difference between positive and negative selection in the development of a T cell?

A

Positive selection : functional TCR

Negative selection: no self-antigen binding

113
Q

Describe the process of positive selection in T cells

A

Epithelial cells in the thymus posses both MHC1 and MHC2. T cells have a few days to successfully bind to either of these MHC receptors. If they bind moderately or strongly, they live. If they dont bind, or bind weakly, they die.

Note that if they dont bind well, tehy can still go back and rearrange their alpha chain to bind better. But they only have a few days to do this.

This is the second checkpoint, to make sure they can bind to MHC

114
Q

How does positive selection determine if it will be CD4 or CD8?

A

When T cell binds to the epithelial cell in the thymus, whichever it binds to first (MHC1 or MHC2) the strongest, it will become CD8 or CD4 accordingly

If it is destined to become CD8, it will shut down the expression of CD4 coreceptors

115
Q

Describe negative selection in T cells

A

APCs present self antigen to T cells. If they bind strongly, the T cell will die.

Central tolerance occurs in the thymus and peripheral tolerance occurs in the periphery

Then mature naive T cells enter the blood stream going from lymph node to lymph node

116
Q

Metronidazole is a prodrug that is activated by ____ found in ___ and ____

A

Flavodoxin

H. Pylori

P. Gingivalis

117
Q

What are the different levels of sepsis? (6) briefly describe them.

A

Infection - inflammatory response to microbes. Invasion of normally sterile tissues

SIRS - systemic response to a variety of processes

Sepsis = infection + SIRS criteria (2 or more)

Severe sepsis - sepsis + organ dysfunction

Septic shock - sepsis + hypotension despite fluid resuscitation

Multiple organ dysfunction syndrome - organ dysfunction that results in… Homeostasis cannot be maintained without intervention

118
Q

What is SIRS? What are its four criteria?

A

Systemic inflammatory response syndrome

Abnormal temperature (>38 or <36)

Fast heart rate (>90 BMP)

Fast respiratory rate (> 20 rpm)

Abnormal WBC levels (>12,000 K/ul or <4000)

119
Q

Define bacteremia

A

Presence of viable bacteria in the blood stream

120
Q

Define septic shock

A

Sepsis-induced hypotension despite adequate fluid resuscitation along with the presence of perfusion abnormalities that may include but are not limited to…

Lactic acidosis
Oliguria
Acute alteration in mental status

121
Q

What things may cause SIRS without infection?

A

Pancreatitis
Trauma
Burns
Other

122
Q

What is it called when SIRS is a result of infection?

A

Sepsis

123
Q

Describe the progression of sepsis

A

Infection leads to SIRS leads to sepsis leads to severe sepsis

Severe sepsis includes sepsis + at least one sign of organ failure and Shock!

124
Q

Who gets sepsis?

A

Anyone can present with sepsis or severe sepsis

More likely in individuals with pre-existing diseases (immunocompromised)

125
Q

What types of bacteria are most associated with sepsis?

A

Gram negative bacteira

126
Q

Define the specifics behind hypotension

A

lower blood pressure than normal

<90 mmHG systolic (Reduction of SBP of 40mmHg from baseline)
Evidence of hypo-perfusion (lactic acidosis, low urine output, or change in mental state)

MAP=average pressure in a patients arteries during one cardiac cycle

127
Q

What is the equation for MAP?

A

MAP = average blood pressure in one cardiac cycle

MAP = SBP - 2 (DBP)/3

128
Q

What are the differentials diagnosis of shock/hypotension?

A

ENDSHOCK

Endocrine
Neurogenic (anaphylactic) 
Drugs (distributive)
Septic
Hypovolemia
Overdose (obstruction) 
Cardiogenic 
Kills
129
Q

Define septic shock

A

Sepsis is the clinical syndrome that results from a dysregulated inflammatory response to infection

Patient with a continued hypotension after a fluid bolus

130
Q

True or false… hypotension is often associated with organ damage/dysfunction

A

True

131
Q

What is the difference between primary and secondary multiple organ dysfunction?

A

Primary - result of well-defined insult (renal failure from muscle breakdown of products (rhabdomyolysis))

Secondary - dot due to infection itself, but due to host’s response to the infection (possibly a dysregulation of the innate immune system)

132
Q

Once the patient is known to have sepsis, you should see if they have severe sepsis (organ dysfunction ) by looking at signs and symptoms. What are the indications of organ dysfunction?

A

CNS - altered consciousness, confusion, phycosis, delirium

Respiratory system - tachypenea, hypoxemia, oxygen saturation, decreased ratio of arterial oxygen vs inspired oxygen

Liver - jaundice, increased liver enzymes, hypoalbuminemia, increased prothrombin time

Cardiovascular - tachycardia, hypotension, increased venous pressure, increased pulmonary artery occlusive pressure

Kidney - oliguria, anuria, increased creatinine

Hematological - thrombocytopenia, abnormal coagulation tests, decreased levels of protein C, increased D dimers

133
Q

What are the three mechanisms of tissue injury? Describe them

A

Ischemia - insufficient O2 (often an uptake problem, not always a delivery problem)

Cytopathic injury - inflammatory mediators cause damage

Increased apoptosis - programmed cell death

134
Q

What does PIRO stand for?

A

Predisposition
Insult - species infecting organism with special weapons
Response - activation of immune system
Organ dysfunction - collateral damage

135
Q

True or false… the balance of pro-inflammatory and anti-inflammatory mediators is key for survival

A

True

136
Q

How can you monitor tissue perfusion?

A

Clinical assessment of skin, urine output, MSE by using pH and lactate mechanisms (measuring rate of lactate clearance) - historical survival is <10% if lactate is > 10

137
Q

What is the treatment for someone with sepsis?

A

Fluids** (not a slow steady flow, but a lot in a short period of time)
Pressure
Monitor tissue perfusion
Monitor physiology and fluid responsiveness

Note that animal model treatments worked, but then didn’t work in humans

138
Q

As we age, the thymic tissue is displaced with what type of tissue?

A

Adipose tissue

Host and Defense (17 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions