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Immunology > Lec 12: Primary and secondary lymphoid organs > Flashcards

Lec 12: Primary and secondary lymphoid organs Flashcards

1
Q

What is more important, B cell or T cells?

A

T cells

these drive and coordiante the immune response

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2
Q

can you survive without either B or T cells? What would be the consequeces?

A

nopeee youd be bubble boy

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3
Q

Primary lymphoid organs

A

Thymus= development
and the bone marrow

where the immune cells develop

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4
Q

secondary lymphoid organs

A

spleen

lymph nodes= activation
= tonsils, adenoids, etc…

wher the adaptive immune responses are initiated

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5
Q

Tertiary lymphoid tissue

A

site of active infection and or immune activity

de novo lymphoid organs at the site of infection

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6
Q

Immune cell trafficing

A

know where the cells develop, where they further develop and which organs they develop in

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7
Q

CLPs and the Bone Marrow

required for B cell development

A

seat of hematopiesis

HSCs =hematopoietic stem cells

stromal cells= support HSCs

Osteoblasts = bone formation and control HSCs

endotheliad cells = line the blood vessel and regulate HSC differentiation

Reticular cells = connect bone and vessels

sympathetic neuron = control the release of HSCs form the bone marrow (central nervous system cross talk)

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8
Q

What is one reason that hematopoeisis decreases with age

A

with age, fat cells replace 50% of the bone marrow

B lymphocytes develop in the bone marrow

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9
Q

Cytokines involved in B cell differentiation

A

chemokine CXCL12 is essential for the generation of pre-pro-b and pro-b cells

Il-7 is essential for the generation of pro-B and pre-b cell differentaion

CXCL12 is also involved in homing antibody producing plasma cells to the bone marrow
-> plasma cells take up long-term residence inteh bone marrow and produce ig from within the bone marrow

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10
Q

Development of B cells from the bone marrow to the periphery

A

HSCs begin their life in close contact with osteoblasts. Once they differentiate into pre-pro-B cells they get the CXCL12 signal from stromal cells as well as a the secretion of IL7 from another stromal cell subset.

rearrangement of the immunoglobulin locus results in pre-BcR receptor and finally a mature BcR

at immature stage, selceiton process to eliminate self ractive B cells

The B cells then mature into follicular B cells (aka marginal zone b cells) in lymph nodes and the spleen

activate antigen specific B cells develop into either plasma cells (anti-body secreting) or memory B cells

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11
Q

negative selection of B cells in movement fromt he bone marrow to the periphery

A

selection process are in place to kill self-reactive B cell (by apoptosis in the bone marrow)

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12
Q

Thymus

A

T cells develop initially in the bone marrow but then migrate to the thymus to achieve full maturity

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13
Q

T cell Trafficking in the thymus

A

circulating T cell progenitors enter vi athe vasculature in teh corticory-medullary junction

CD4-CD8 double negative (DN) thymocytes migrate inot the capsule due to CXCR4 and CCR7 mediated chemotaxis

migration into the subcapsular zone mediated by CCR9 signals (deeper and deeper into the tissue)

CD4+CD8+ double positive (DP) thymocytes interact with cortical thymic epithliad cells (cTEC) for positive and negative selection

Positively selected DP tymocytes differentiate inot CD4+ or CD8+ single positive cells (SP) increased CCR7+ allows for migration towrds the medulla expressing CCR7 ligands

Further selection of SP thymocytes includes the deltion of tissue specific antigen-reactive T cells and the generation of regulatory T cells

matrue SP T cells expression sphingosine-1-phosphate receptor 1 (S1P1) guiding them to the circulation

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14
Q

Purpose of cTEC

A

these are cortical thymic epithelial cells

they aid in positive and negative selection of T lymphocytes

the are APCs that present self-antigens and will kill T-cells if they react to those self-antigens

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15
Q

corticor-medullary junction

A

where the circulating T cell progenitors enter the thymus

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16
Q

What cytokine induces double-negative T cells to migrate in the capsule

A

CXCR4 and CCR7 mediated chemotaxis

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17
Q

what is a double negative T cell

A

Lacks CD4 and CD8

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18
Q

What cytokine triggers DN T cells to migrate into the subcapsular zone

A

CCR9

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19
Q

What happens to T cells immediately after interacting with cTEC cells

A

positively selected double-positive cells differentiate into CD4 or CD8 single-positive cells

then, increases CCR7+ allows for migration towards the medulla expressing CCR7 ligands`

20
Q

AIRE

A

autoimmune regulator (AIRE) is a key TF in the thymus

AIRE binds to non-methylated histone 3 lysine 4 (H3K4), which marks promoters in closed chromatin regions (Non-expressed genes)

21
Q

TRAs

A

Tissue-restricted antigens

expression of tissue-rejected antigens in medullary thymic epithelial cells `(mTECs)

Thymocytes that react strongly to TRAs are negatively selected to undergo apoptosis, or they are redirected to become Treg cells

however around 5% can still be autoreactive

22
Q

mTEC

A

medullary thymic epithelial cell\

single positive thymocytes circulate in the medulla for about 5 days and encounter several hundred mTECs expressing various TRAs

mTECs share their TRAs with other mTECs, as well as with DCs

23
Q

which receptor helps to guide mature SP T cells towards circulation

A

sphingosine-1-phosphate receptor 1

24
Q

What happens to thymocytes that survive positive and negative selection not he thymus

A

they leave the thymus as naive t cells

Treg also leave the thymus and are involved in maintaining tolerance

autoreactive Treg could however break tolerance and induce autoimmune disease

25
Q

if you cut your finger where do the foreign antigens go? How do they get to their final destination

A

???

26
Q

Purpose of secondary lymphoid organs

A

areas where lymphocytes encounter antigen, become activated, undergo clonal expansion, and differentiate into effector cells

these organs include:

  • lymph nodes
  • spleen
  • mucosa-associated lymphoid tissue (MALT)
  • other diffuse and loosely organized areas

they are connected to each other via the blood and lymphatic circulatory systems

27
Q

which chemokines are essential for homing T cell to the lymph nodes

A

CCR7

28
Q

Which chemokine recru9its T cells back to circulation

A

S1PR1

29
Q

HEV

A

high endothelial venule

30
Q

read pg 57-60

A

and fig 2-13

31
Q

Organization of Lymph nodes

A

T cell and B cell activity are separated into distinct microenvironment

The cells will actively migrate toward each other during activation events that require B cell - T cell interactions

Cortex: B cells, macrophages and follicular DCs arranged into follicles

Paracortex: T cells and DCs

Medula: egress for lymphocytes

32
Q

Antigens enter B cell zone via the afferent lymph

A

antigen is taken up by resident SCS (subcapsular sinus) macrophages and follicular DC’s

B cells can respond to free antigens or antigen complexes (intact antigen)

33
Q

Migrating DCs bring antigen to the T cell zone

A

Migrating DCs entering via the HEV…

DCs can present intact antigen to B cells

DCs can present processed antigen to T cells

Migrating DCs can pass antigen to resident DCs in the para cortex

B cell and T cells migrate in the paracortex via processes that arise from fibroblast reticular cells (FRCs)

34
Q

Germinal Center (GC)

A

Area within secondary lymphoid organs where mature B cells proliferate and differentiate and mutate their antibody genes => affinity maturation
(issa sub-sect of a B-cell follicle)

Dark zones: proliferating B cells undergoing somatic hypermutation
Light zones: B cells bidn antigen on FDCs and receive survival signals form Th cells

35
Q

SHM

A

somatic hypermutation

occurs when B cells mutate their antibody genes

this is essential for the production of high-affinity antibodies

36
Q

Follicular DCs in Germinal centers

will be on the final

A

FDCs = non-haematopoietic cells

are integrated into the continuous stromal network within lymphoid organs

acquire antigens, which are retained in their native form for long periods of time (non-degenerative endosomal vesicles periodically cycle antigen to the cell surface)

Retention of antigen by FDCs is important for an efficient germinal center reaction

37
Q

how does Th cell parring occur

A

during the formation of GCs, activated B cells engulf cognate antigen and present it to T cells in the paracortex

if successful Th cell parring occurs, prolonged interaction promotes B cell proliferation

38
Q

What does BCR somatic mutation allow

A

for affinity maturation to occur in the GC

Generates B cells with improved antibody specificity for antigen

affinity maturation is the process by which TFH cell-activated B cells produce antibodies with increased affinity for antigen during the course of an immune response. With repeated exposures to the same antigen, a host will produce antibodies of successively greater affinities

39
Q

What is the final outcome of B cell - T cell interaction in the GC

A

some B cells become memory cells

Plasma cells will travel to medulla or bone marrow to secrete antibodies

memory B cels can reside in the lymph node or recirculate

40
Q

How long can the establishment of the GC take

how long will they remain active for

A

4-7 days to establish

can remain active for 3+ weeks

41
Q

X-associated lymphoid tissue

A

lymphoid follicles can be found in mucosal membranes of digestive, respiratory and urogenital tracts (type I) and the skin (type II) epithelium

M (Microfold) cells are specialized to transport antigen across type I epithelium

Pocket of DCs, B cells and T cells resides below the M cells and sample incoming antigens

42
Q

BALT

A

bronchus associated lymphoid tissue

43
Q

MALT

A

Musoca associated lymphoid tissue

44
Q

iBALT

A

inducible bronchus associated lymphoid tissue

45
Q

NALT

A

nasal associated lymphoid tissue

46
Q

GALT

A

gut associated lymphoid tissue

47
Q

IEL

A

intraepithelial lymphocytes

Immunology (23 decks)

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