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MI Immuno/Heme > Induced innate immune response and lymphoid tissue > Flashcards

Induced innate immune response and lymphoid tissue Flashcards

1
Q

Increase in vascular permeability has what affect on BP?

A

Decrease BP - in severe cases (coupled with vasodilation) can cause ischemic tissue injury

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2
Q

TLR3, TLR4, and NOD activavtion

Diagram

A
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3
Q

Signaling PRRs

A

Can be external (to detect extracellular PAMPs) or internal (to detect intracellular PAMPs)

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4
Q

TLR4

A

The prototype extracellular TLR that detects bacterial LPS

LPS binding protein (LBP) in serum facilitates TLR4 activation by binding to and transporting LPS to the TLR4 receptor complex

LPS/TLR4 binding activates the transcription factor NF-κβ

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5
Q

TLR3

A

Intracellular TLR and binds to dsRNA (viral PAMP) and utilizes a signalling pathway leading to production of type I interferons (IFN-α or IFN-β)

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6
Q

PAMP induction of inflammation

A
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7
Q

NOD-like receptors

A

NODR or nucleotide oligomerization domain-like receptors

Family of intracellular signaling PRRs that detect PPG subunits inside of cell

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8
Q

NF-κβ

A

Upregulates many host cell genes (like pro-inflammatory cytokines) that ultimately activate induced innate and adaptive immune functions

Including NADPH oxidase and iNOS

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9
Q

Activation of inflammatory cytokines

A
  1. Signaling PRRs activate NF-κβ which increases cytokine gene transcription
  2. Inflammasome activation - contains proteases that cleave cytokine pro-forms (like pro-IL1β) into mature active cytokines (like IL-1β)

Inflammasome activation also induces cell death by pyroptosis which is very pro-inflammatory due to DAMP release

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10
Q

Tumor necrosis
factor alpha
(TNF-α) and
Interleukin-1β
(IL-1β):

A

Increase vasodilation, vascular permability, and vascular endothelial adhesion molecule expression (E-selectin and VCAM-1)

Bind receptors on the endothelium and vascular smooth muscle - particularly TNF-alpha

Increase body temperature (these cytokine are endogenous pyrogens that act directly on the hypothalamus) - particularly IL-1beta

Increase tissue factor (TF) release from macrophages and endothelial cells this promotes local clotting by the extrinsic clotting pathway - or if systemic promotes disseminated intravascular coagulation (DIC) - particaularly IL-1beta

Both act on mucosal goblet cells and increase mucus secretion

TNF-alpha is the major mediator of vascular effects in SIRs and sepsis

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11
Q

IL-6

A

Increases liver release of actue phase proteins (like CRP, MBL, and fibrinogen)

Because IL-6 increases clotting factor production, it also involved in pathophysiology of DIC

Increases body temp (major endogenous pyrogen acting directly on hypothalamus)

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12
Q

IL-12

A

Activates NK cells to better kill target cell and produce the cytokine IFN-gamma

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13
Q

IL-8

A

Chemokine that increases recruitment of neutrophils to the site of infection or injury - bacterial PAMPs and DAMPs are strong inducers of IL-8 production and induce a strong neutrophil response

Binding of IL-8 to neutrophil receptors activates “inside out” signaling that increases the affinity of neutrophil LFA-1 for ICAM-1 on the endothelium

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14
Q

iNOS

A

Inducible nitric oxide synthase enzyme

Potent vasodilator

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15
Q

Pro-inflammatory cytokines

A

Tumor necrosis factor alpha (TNF-α) and Interleukin-1β (IL-1β) and IL-6

Produced in infected/damgaged peripheral tissues can enter circulation, CNS, and act on specific regions of the brain

Allows peripheral inflammatory responses to evoke sickness behaviors - appetite loss, fatigue, and sleepiness, increased pain sensitivity, social withdrawal, and anhedonia

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16
Q

TLR3

A

Binds viral dsRNA initiates IFN-α or IFN-β secretion

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17
Q

Type I IFN binding to IFN receptors on uninfected host cells

A

Activates transcription of genes that encode the enzymes ribonuclease L (RNase L) and protein kinase R (PKR)

These enyzmes are inactive unless host cell is subsequently virus infected

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18
Q

RNase L

A

Degrades viral and cellular mRNA - inhibiting translation of viral and host proteins

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19
Q

PKR

A

Inactivates a host ribosomal sub-unit (protein synthesis initiation factor elF-2) -turning off host cell ribosomes and preventing translation of viral and host mRNAs

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20
Q

IFN-α/β Therapy

A

Increases NK cell killing activity

Antiviral effects of type I IFNs are short lived and reversible:

Used in HPV and Hep C infections

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21
Q

What happens when an iDC binds a PAMP to its PRR?

A

This stimulates the iDC carrying pathogen antigen to migrate to nearby secondary lymphoid tissues and mature

Increase expression of B7 co-stimulatory molecule

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22
Q

Local vs. systemic inflammatory responses

A
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23
Q

Molecular basis of sepsis-induced organ failure

A
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24
Q

Compensatory anti-inflammatory response syndrome

A

Neuroinflammatory signals inhibit pro-inflammtory cytokine production, immune cells undergo apoptosis, anti-inflammatory immune cell populations (reg T cells and myeloid suppressor cells) expand and anti-inflammatory cytokines are produced

Can lead to lasting immunosuppression

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25
Q

SIRS

A
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26
Q

Sepsis

A

The presence of SIRS in response to a suspected or culture confirmed infection

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27
Q

Two most common types of infection associated w/ sepsis

A

Pneumonia and UTIs

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28
Q

Septic shock

A

BP<90 mmHG or a reduction >40 mmHg from baseline in the absence of other causes for hypotension

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29
Q

MODS

A

Multiple organ dysfunction syndrome

i.e. adult respiratory distress syndrome (ARDS), central nervous system dysfunction, CV, renal, and liver failure

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30
Q
A

Electron micrograph of plasma cells

“clock face” nucleus and golgi halo (asterisk)

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31
Q

IgA secretion in the mammory gland

A
  1. Plasma cells produce IgA dimers
  2. Membrane-bound Fc receptors on the basal surface of mammary epithelial cells recognize these IgA dimers
  3. IgA is internalized via receptor-mediated endocytosis
  4. IgA is transported in membrane-bound vesicles to the apical epithelial surface
  5. IgA is released into the mammary secretions
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32
Q

Areas of the body that lack lymphatics

A

CNS - immunoligically priviledged site

Cartilage (lymph and blood vessels)

Bone/teeth despite high metabolic activity

Placenta

Thymic parenchyma (functional tissue of thymus)

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33
Q

Lymphatic capillaries

A

Originate as blind-ended vessels

Single layer of endothelial cells - are not associated with pericytes (pericytes provied structural support and regulate endothelial permeability in blood capillaries)

Not fenestrated - lack small pores

No tight junctions between cells

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34
Q

Lacteals

A

Lymphatic capillaries that transport chylomicrons (lipids) to the liver

Chylomicrons are synthesized by intestinal epithelial cells and are exocytosed into lacteals

Smaller image - plica circularis

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35
Q

Lymphoreticular organs

A
  1. Thymus
  2. Lymph nodes
  3. Spleen

Characterized by internal structure consisting of network of reticular or stromal cells that surround and support parenchymal cells

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36
Q

Lymphoepithelial organs

A
  1. GALT (Gut)
  2. BALT (Bronchiolar)
  3. MALT (Mucosal)
37
Q

What embryological structures does the thymus originate from?

A

The third (and sometimes fourth) oropharyngeal pouch

Thymus is the first organ to acquire lymphoid functions - seeded by stem cells from yolk sac, then the liver and finally from the bone marrow

38
Q

Cortex of the thymus

A

Composed principally of T lymphocytes at various stages of development

Largest immature lymphocytes are towards periphery, mitotic figures often visible

Most T cells at center of cortex and in medulla are degenerating (clonal deletion)

Macrophages and APCs also in cortex

39
Q

Tonofibrils

A

Exhibited by thymic stromal cells - keratin cytoskeletal elements

40
Q

What keeps developing T lymphocytes in the thymus from being exposed to circulating antigens prematurely?

A

The stromal cells that form a blood-thymus barrier

41
Q

What cells seed the thymus?

A

Common lymphoid progenitor cells from the bone marrow

42
Q

What developing T lymphocytes first undergo positive selection in the thymus?

A

Developing T lymphocytes that can recognize foreign and self-antigen

After passing this positive selection - migrate to the medulla where negative selection occurs such that self-recognition T cells are eliminated

43
Q

Individuals with what syndrome lack a thymus?

A

DiGeorge syndrome - T-cell immunodeficiency

44
Q

What thymic stromal cells form boundaries within the thymus?

A

Types III and IV

45
Q

Hassal’s corpuscles

A

Fx not known

Dx feature of the thymus:

Concentric rings of reticular cells (type VI) seem to possess keratohyalin granules that calcify and die

46
Q

What thymic stromal reticular cells are critical for T selection?

A

Types II (+ selection) and V (- selection)

47
Q

Why does the thymus’ medulla stain lighter than the cortex?

A

There are fewer synthetically active lymphocytes in the medulla

Lymphocytes w/ abudant rER to synthesize surface proteins are involved in negative/positive selection and are located in the thymic cortex

48
Q

Characteristic features of all lymph nodes

A

A subscapsular sinus, trabecular or intermediate sinus and medullary sinus

49
Q

Reticular cells of the lymph nodes

A

Fibroblast-like cells - synthesize and secrete collagen III and ground substance that forms the surrounding stroma

Also express suface molecules and produces chemokines that attract lymphocytes and DCs

50
Q

What MHC do dendritic cells express?

A

MHC I and MHC II

51
Q

Follicular DCs

A

Have thin branching processes that interdigitate between B-lymphocytes in germinal centers; antigen-Ab complexes adhere to these processes and can be held for very long periods (sometimes years)

52
Q

High endothelial cells

A

Allow naive lymphocytes to home-in to the lymph node cortex

Naive lymphocytes express L-selectins and integrins - endothelial cells express E and P selectins and chemokines that attract lymphocytes

53
Q
A
54
Q

How do lymphocytes enter lymph nodes?

A
  1. Afferent lymphatic vessels, for primarily B-lymphocytes w/i lymph fluid
  2. Post capillary venules for immunologic surveillance by T-lymphocytes in the blood
55
Q

70-80% of circulating lymphocytes in the blood are ______ ?

A

T-lymphocytes

56
Q

What cells compose the capsule of the spleen?

A

Myoepithelial cells - form dense CT capsule of spleen and sends trabecula inward to incompletely divide the organ into compartments

57
Q

White pulp of the spleen

A

Splenic nodules (aka Majphigian bodies)

Equivalent to lymphatic tissue

Cyclidrical masses of lymphocytes arranged around a central artery that constitutes the periarterial sheath (PALS)

58
Q

Red pulp of the spleen

A

aka the splenic cords (aka cords of Billroth) - lie between the splenic sinusoids

Contains reticular fibers, RBCs, WBCs, macrophages, and lymphocytes

59
Q

Open circulation of the spleen

A

Endothelial cells that line the splenic sinuses are extremely long and arranged in a parallel fashion to the direction of the vessel

Unlike typical endothelial cells, there are few contact points between these endothelial cells, thus there are prominent intercellular spaces - allows blood cells to readily pass out of the sinuses

60
Q

Circulation in the spleen

A

Since open circulation predominate - erythrocytes in the red pulp cords must “reverse diapedesis” into sinusoids - serious complication in severe trauma or sickle cell disease

Open circulation is highly efficient as a blood filtering mechanism - blood is exposed to macrophages in the pulp cords

Open circulation also provides a mechanism for serveillance T and B cells to monitor foreign antigens in the blood

NO HEV in spleen (entry is unregulation)

61
Q

GALT and BALT

A

Are nodular lymphatic tissue

Peyer’s patches in the ileu - example of lymphatic nodules not surrounded by CT capsules (similar nodules are abundant in the appendix) - otherwise are simialr to nodules w/i the cortex of lyph nodes

Nodules consist primarily of B-lymphocytes and plasma cells

Specialized M cells (or microfold cells) are APCs in the epithelium above Peyer’s patches

62
Q

Tonsils

A
  1. Palantine tonsils
  2. Pharyngeal tonsil
  3. Lingual tonsils
63
Q

ID

A

Palatine tonsil

-Stratified squamous epithelium on oral surface
-numerous lymphatic nodules (L) and diffuse lymphoid tissue
-tonsillar crypts are common (TC)
-mucus-secreting glands (MG) are near base of crypts

64
Q

ID

A

Pharyngeal Tonsil (adenoid)

Single organ in the roof of nasal pharynx

-ciliated, pseudostratified columnar epithelium
-deep aspects w/ thin CT capsule

65
Q

ID

A

Lingual Tonsil

There are many lingual tonsils on the dorsal surface of the tongue

-stratified squamous epithelium
-deep aspects with flimsy CT capsule

66
Q

ID

A

Lymphatic nodules of ileum

67
Q

ID

A

Lymphatic nodules of bronchus

68
Q

ID

A

Lymphatic nodules of appendix

69
Q

ID

A

Lymphatic nodules of colon

70
Q
A
71
Q
A
72
Q
A
73
Q
A
74
Q
A
75
Q
A
76
Q
A
77
Q
A
78
Q
A
79
Q
A
80
Q

Septic shock

A

Evidence of SIRS (≥2 criteria), hypotension that is unresponsive to fluid resuscitation and organ dysfunction in response to an infection

81
Q

This effector protein promotes MAC-mediated lysis of bacteria and is produced by the liver in response to IL-6 stimulation

A

Mannose-binding lectin

82
Q

Which is produced by the NADPH oxidase enzyme?

A

Superoxide

83
Q

Which IL is specifically required for the tight binding of circulating neutrophils to the endothelium at sites of tissue inflammation?

A

IL-8

IL-8 and receptor

FLA-1 on neutrophil and ICAM-1 on endothelium

84
Q

Which inflammatory mediator increases E-selectin expression, promotes clotting, and contributes to the fever, appetite loss, and fatigue that accompany many infections?

A

IL-1𝝱

85
Q
A

Lymph node

86
Q
A

Thymus tissue

87
Q
A

Palantine tonsil

88
Q
A

A. Deep cortex

MI Immuno/Heme (35 decks)

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