INF Year 2 TB1 > Week 3 > Flashcards

Week 3 Flashcards

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1
Q

Lymphcytes and lymph return to blood via which duct?

A

thoracic

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2
Q

List the main sections of a lymoh node

A

Afferent and efferent lymphatic vessels
Germinal centres
Paracortical area
medullary cords
Medullary sinus

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3
Q

What do naive lymphocytes do?

A

Recirculate in the blood and lymph nodes

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4
Q

what receptor do naive lymphocytes express?

A

CCR7

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5
Q

WHere are the chomkindes CCL21 and CCL19 made?

A

Secondary lyphoid tissues

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6
Q

What do the chemokines CCL21 and CCL19 do?

A

attract the lymhocytest to teh lymph nodes

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7
Q

Which chemokine do B cells make that ninds CXCL13?

A

CXCR5

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8
Q

What are the 4 stages of a lymphocyte entering a lymph node?

A

Rolling
activation
madhesion
diapedesis

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9
Q

What are the chemokines involved with each of the 4 stages of a lymphocyte entering a lymph node?

A

Rolling= [L selectin bonds to glycam1]
activation= CCL21-CCR7
adhesion= [LFA-1and ICAM1]
diapedesis= CCL21, CXL12

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10
Q

What specific wall does a lymphocyte need to cross to enter a lymoh node?

A

High endothelial venules

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11
Q

What happens to a naive T cell if it is activated in teh lymph node?

A

Retained for several days and proliferate

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12
Q

WHat does S1P stand for?

A

Sphingosine 1 phosphate

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13
Q

What does S1P do?

A

Egress of T cells from lymph nodes is mediated by increasing S1p gradient

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14
Q

Describe the generaation of an antibody respinse in the lymph node

A
  1. naive t cells are primed by dendritic
    2.become t effector cells
  2. T cells interact with B cell specific for the same antigen in the lymph node
  3. T cells activate naive B cells
  4. B cells proliferate
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15
Q

How does a germinal center in a lymph node form?

A

Activated B cells migrate into a nearby follicle
Forms a germinal centre
rapid proliferation and somatic mutation occur

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16
Q

How do antigens enter the spleen?Q

A

Via the blood (unlinke LN there is no direct connection witht he lymphatic system

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17
Q

WHat kind of infections does the spleen deal with?

A

Blood bourne

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18
Q

Whats the difference between the white and red pulp in teh spleen?

A

White= Secondary lymphoid tissue that collects antignes form blood
Red= site of red blood cell destruction

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19
Q

What route does blood take in the white pulp of the spleen?

A

From the trabecular artery into the central arteriole
Then thru the periarteriolar lymphoid sheath and into the marginal simus and drains nto the trabecular vein

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20
Q

Where in the spleen are T cells activated?

A

PALS (periarteriolar lymphoid sheath )

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21
Q

Define asplenia

A

Having no spleen

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22
Q

What is the effect of asplenia?

A

increased risk of sepsis form polysaccharide encapsulated bacteria.
treatment= vaccination and prophylactic antibiotics

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23
Q

What are the three main immune responses to extracellular pathogens?

A
  1. response to lymph/ blood borne pathogens
  2. response at mucosal surfaces
  3. IgA class switch, secretion and fucntion
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24
Q

What does GALT stand for?

A

Gut associated lymphoid tissue

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25
What are the three parts that make up the GALT?
Peyers patches Intestinal lyphocytes appendix
26
What are peyer's patches?
Peyer's patches are organized lymphoid follicles in the lining of the small intestine, primarily the ileum, that are crucial for the immune system. Their main function is immune surveillance of the gut microbiome, which involves monitoring intestinal bacteria and initiating immune responses against potential pathogens while tolerating beneficial microbes. Specialized cells in the patch transport and present antigens to immune cells, triggering the production of antibodies, such as IgA, to fight infection
27
Where do M cells lie and what do they do?
Overlie peyers pathces Take up antigens from the lumen by endocytosis
28
Describe the priming and homing of T lymphocytes in the gut
1. T cells enter Peyers patches due to CCR7 and L selectin 2. T encounters antigens let in by M cells, becomes activated by dendritic 3. drain to lymph nodes 4. T cells stop expressinf CCR7/ L selectin, and start CCR9 and alpha4beta7 5. t cells go back to lamina propria and intestinal epithelium
29
What do alpha4beta7 integrin on T cells bind to on lamina propria?
MAdCAM1
30
What would T cells primed in the small intestine be expressing and what are their ligands?
CCR9, alpha e beta7 CCL25 and e-cadherin
31
What would T cells primed in the large intestine be expressing and what are their ligands?
CCR10, alpha e beta7 CCL28 and e-cadherin
32
How much IgA is secreted by musocal tissue per day?
about 5g
33
How do T cells in teh Peyer's patches and mesenteric lymph nodes promote IgA isotype switching?
via production of TGF beta
34
Why is the role of AID critical for homeostasis of the intestinal microbiota?
Isotype switching invloves Activation-induced cytidine deaminase AID deficiency cuases lack of of IgA and affinity matured IgM Mice lacking AID have 100fold more bacteria in upper small intestine
35
WHere will IgA bearing B cells home to?
lamina propria
36
What form of IgA can be transported across the intestinal epithelium by a poly g receptor?
DImeric IgA
37
What does Poly g receptor stand for?
Polymeric Immunoglobulin receptor
38
Where in the intestine do IgA dimers reside?
Mucus layer over epithelium (IgA neutralizes pathogens and their toxins)
39
What are the three main ways the immune system responds to intracellular pathogens?
1. NK killing of virally infected cells 2. CD8 respinds to intracytoplasmic viruses 3. Macrophage responds to intravesicualr bacteria
40
What kind of infection would a patient lacking NK cells be susceptible to?
viral infections
41
What does IFN gamma do and what secretes it?
activates macrophages and T cells
42
Nk cells cna recognise a virally infected cell because it lacks what expression?
MHC class 1
43
What does NK cell activation rely on?
A balannce of activating and inhibitory signals and ligands on the target cell. It relies on the qualitative difference in signalling
44
whats the difference between CD56 dim and CD56 bright?
CD56 dim and CD56 bright are two main types of Natural Killer (NK) cells, differing in maturity, location, and function: CD56 dim cells (90%) are mature, cytotoxic (kill targets), high in CD16, and live in blood, while CD56 bright cells (10%) are immature, cytokine-producing (immune regulators), low in CD16, and reside in tissues like lymph nodes, acting as immune communicators. Think of CD56 bright as the "managers" (cytokines) and CD56 dim as the "soldiers" (killers
45
How does the HCMV virus evade the NK response?
by encoding for proteins that bind and retain NKG2D (eg UL16 and UL142
46
How does the SARS COV2 virus evade the NK response?
By downregulating activating ligands (MICA and ULBP2)
47
How does the CMV and HSV virus evade the CD8 response?
Inhibit activity of TAP peptide transporters
48
How does the herpes virus evade the CD8 response?
decrease their MHC class 1 expression
49
describe the early host response to viral infection
Type 1 IFN (alpha and beta) TNF alpha IL-12 NK cells *Then later virus clearnace relies on virus specific CD8 T cells*
50
How does a host cell display peptides on it's surface so that CD8 can identify it?
1. viral proteins synthesized in the cytoplasm 2. viral proteins degraded by proteasomes 3. peptides go to ER via TAPs (trasporters of antigen processing) 4. peptides associate with MHC class 1 heavy chain and beta 2 microglobulin
51
What are the three signals that APCs deliver to naive T cells?
1. activation 2. survival 3. differentiation
52
What cells are the most effective at activating naive T cells?
Virus infected dendritic cells (hi B7)
53
What does an activated CD8 T cell make that drives its own proliferation and differentiation?
IL-2
54
Name the three ctyotoxic CD8 T cell effector proteins
Perforin Granzymes Granulysin
55
What does Perforin do?
aids delivery of granule contents into target cell cytoplasm
56
What does Granzymes do?
Serine proteases activate apoptosis of target cell via BID and procaspase 3 BID causes cytochrome C to be released from mitochondria causing apoptosis CAD induces DNA fragmentation
57
What does Granulysin do?
antimicrobial actions / induce apoptosis
58
What does Serglycin do?
this proteoglycan acts as a scaffold forming a complex with perforin and granzyme
59
How does pro caspase 9 induce programmed cell death?
caspase 9 cleaves procaspase 3 caspasde 3 cleaves teh inhibitor of caspase activated DNAse (ICAD)
60
How does cytochrome c trigger the formation of teh apopstosome?
Cytochrome C binds to Apaf 1 this self assembles into an apoptosome actiavting procaspase 9, whcih activates CAD to cleave DNA
61
How do CD8 T cells trigger extrinsic pathway of apoptosis?
Fas ligand on CD8 binds to Fas on virally infected cell
62
How does FasL binding to Fas trigger apoptosis?
1. conformational change to Fas 2. Fas then binds death domain containing adaptor protiens 3. caspase 8 is recruited and cleaves caspase 3 4. ICAd is cleaved, releasing CAD
63
What signals to macrophages that a cell is undergoing apoptoioisis?
Phosphatidylserine moves to outer leaflet and is replaced by phosphatidylcholine
64
What cells activate macrophages to become highly microbicidal?
CD4 T helper
65
Describe what happens in an activated macrophage
Phagosomes fuse wiht lysosomes, make ROS secretion of TNF alpha and IL12 Increased MHC II, B7, CD40, TNFR
66
WHat forms when intravesicular pathogens cannot be elminiated?
Granulomas (TB)
67
What cells are mainly responsible for helminth elimination?
Th2 cells makes IL13 to induce cell repair and sooth muscle contraction M2 macrophages are recruited eosinophils then mast cells are recruited IgE arms mast cells agains helminths
68
What factors influence Th1 vs Th2 responses?
-cytokines -TLRs -Adjuvants -dendritic cell type -conc and affintity of antigen -co stimulation -route
69
Where does IL12 come from and what does it do?
activates NK celss to secrete IFN gamma IL12 and IFN gamma promote naive T cell differnetiation inot Th1 cells
70
INF Year 2 TB1
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