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PRIN 13 Inflammation Flashcards

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1
Q

What does the Lymphatic System include?

A 
Lymph nodes
Lymphatic Vessels
Tonsils
Thymus
Spleen
Peyer's Patches
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2
Q

What IS Lymph?

A

An ultra filtrate of blood

contains tissue fluid, WBC, fats & chyle) from GI

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3
Q

What makes lymph flow through vessels?

A

Contraction of skeletal muscle

One-way valves

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4
Q

Superficial & Deep Drainages … what do they follow?

A

Superficial drainage follows the veins

Deep drainage follows the arteries

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5
Q

What are the 2 major deep lymph drainage pathways?

A

Right Lymphatic Duct

  • drains R side of head R side of thorax
  • drains into R subclavian vein

Thoracic Duct

  • drains all the rest of the body
  • drains into L subclavian vein
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6
Q

When are lymph nodes palpable?

A

Superficial Nodes are palpable when inflamed
(eg):
Cervical nodes > 1cm
Inguinal nodes > 1.5cm

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7
Q

Which are the palpable lymph nodes?

A

EPIC-Ap

Cervical
Axillary
Epi-trochlear
Inguinal (superfic)
Popliteal
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8
Q

Which are the NON-palpable lymph nodes?

A

Parasternal
Aortic
Iliac
Inguinal (deep)

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9
Q

Inflammation which lymph nodes is suggestive of cancer?

A

Supra-clavicular Nodes & Virchow’s/Sentinal Nodes

from abdomen & thorax

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10
Q

Pathway of lymph drainage in breasts

A

Lateral & Inferior regions … axillary nodes

Medial regions … Parasternal Nodes … Subclavian Nodes … Subclavian Veins

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11
Q

Pathway of lymph drainage in testes

A

Lumbar & aortic nodes

not palpable

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12
Q

Pathway of lymph drainage in scrotum

A

Superficial inguinal nodes

palpable

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13
Q

What are central/primary lymphoid organs?

A

Sites of generation & early maturation of WBC

Bone Marrow
Thymus

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14
Q

What are Secondary Lymphoid Organs?

A

Lymph nodes
Spleen
Tonsils
Mucosal Tissue …

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15
Q

What arises from Hematopoietic Stem Cells?

A

Lymphoid Progenitors
(B&T cells)
&
Myeloid Progenitors

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16
Q

What arises from Myeloid Progenitors?

A

Granulocyte / Macrophage Progenitor
*BEN, Monocytes (Macro & DCs)

Megakaryo & Erythrocyte Progenitor
*Platelets & RBC

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17
Q

What is pus?

A

Accumulation of dying neutrophils responding to the site of infection

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18
Q

What is left shift?

A

Sign of Early neutrophil release from BM

L Shift Products look more like monocytes and have not developed the normal multi-lobed nucleus

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19
Q

What are the 3 APCs?

A

“Big-MD”

Macrophages
DCs
B-cells

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20
Q

What is the function of the spleen?

A

Capture Ags from blood

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21
Q

What are germinal centers?

A

LOCATED IN LYMPH NODES
Region where lymphocytes have been stimulated by Ag

Result: Clonal expansion of activated B-cells

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22
Q

What is the Paracortical area of the lymph nodes?

A

Site where T-cells are interacting with APC & B-cells

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23
Q

Within the spleen, what is Red Pulp & White Pulp

A

RED: where aged RBCs are destroyed

WHITE: lymphoid areas

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24
Q

Which cells serves as the bridge between Innate and Adaptive Immune Systems?

A

Dendritic Cells

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25
What do neutrophils respond to?
Chemotactic factors | Neutrophils migrate toward higher concentration of chemotactic factors
26
Which cells are phagocytic?
Nasty-MD neutrophils monocyte/macrophage DCs
27
Within the complement system, what are the 3 pathways?
Classical Lectin Alternative
28
Within the complement system, when do all 3 pathways unite?
Cleavage of C3: C3a - anaphylatoxin C3b - cleaves C5
29
What do T cells do?
Circulate through system checking out antigens presented on the MHC of APCs
30
What do Abs do?
Bind to Ag of microbes & serve as a flag. Microbe cell becomes coated in Abs (ADCC) (antibody coated cell) Signals for destruction via phagocytosis by NK & Macrophages NOTE: Abs kill INDIRECTLY by simply acting as an opsonin
31
What system kills via MAC?
Complement System kills via Membrane Attack Complex (lyses cells)
32
Which complement pathway is initiated by Ab-Ag complex?
Classical Pathway
33
What is the clinical result of not having a functional Complement System?
Infection | Autoimmunity
34
What do NK cells do?
Attack cells with intracellular disturbances that do not look normal (eg) tumor cell, virus infected cell
35
What do Neutrophils do?
Devour extracellular pathogen. In the process of neutrophills sacrifice themselves
36
What is pus?
Dying / Dead neutrophils
37
What are PMNs?
aka Neutrophils Polymorphic Nuclei
38
Why do cancer patients receiving treatment have poor immune response?
Cancer treatment targets quickly dividing cells. Neutrophil development is inhibited
39
What is ROS?
Reactive Oxygen Species molecules produced in "oxidative bursts" that function in lysosomes (eg) H2O2, radicals, HOCl
40
Which cells kill pathogens by production of ROS?
MEN Neutrophils Macrophages Eosinophils
41
What is CGD?
Chronic Granulomatous Disease Impaired innate immune system due to lack of oxidative bursts (ROS) Results in recurrent bacterial infections
42
What is the primary, most IMPORTANT role of DCs?
Antigen Presentation
43
PAMP vs PRR | Which cell has what?
MICROBE-PAMP (pathogen associated molecular pattern) PHAGOCYTE-PRR (pattern recognition receptor) Note: each PRR only recognizes one PAMP
44
How is Homeostasis maintained in the Innate System?
EARLY: Neutrophils & Macrohages act as the alarm signal & trigger inflammation LATER: DCs down-regulate inflammation & promote healing
45
What happens within a few minutes following tissue injury?
``` Vasodilation Increased Blood Flow Increased Permeability Resident Macrophages defend Extravasation ```
46
What happens within a few hours following tissue damage?
Neutrophil infiltration into tissues
47
The first immune cells to attack pathogen is what? | How does it do it?
Resident Macrophages have PRR that recognize PAMP on pathogen. * **Phagocytosis ... * **Call the alarm: Release Cytokines: IL1, IL6, TNFa
48
What are the LOCAL effects of the released cytokines?
IL1, TNFa: up-regulate adhesion molecule NO, IL1, IL6, TNFa: Vasodilate Increase Vasc. Perm. TNFa: Promote chemotaxis & activation of neutrophils
49
What releases NO?
Local endothelial cells
50
What explains pain during acute inflammation?
Kinin Cascade activated by contact with collagen & BM FUNCTION: cleaves HMWK into Bradykinin
51
What is Bradykinin ? | What does it do?
9aa peptide Promotes vasodilation Increase Vasc. Perm. Stimulates pain nerve fibres
52
What activates Mast Cells?
C3a C5a TLR
53
What do Mast Cells Release?
Histamine IL6 TNFa (cytokines are released contributing to redundancy)
54
What is Histamine? | What does it do?
Small amine molecule that binds to receptors on endothelial cells & smooth muscle cells Causes: Promotes vasodilation Increase Vasc. Perm.
55
By 6 hours following injury, what immune cells predominate?
Neutrophils (PMNs)
56
Steps in Neutrophil Extravasation
(1) Rolling adhesion (2) Tight Binding (3) Diapedesis
57
What mediates neutrophil tight binding?
LFA-1 on Neutrophil ICAM-1 on endothelial cell
58
Besides neurophils, what other immune cells respond to the cry for help?
Monocytes | Recruitment is more gradual than PMN recruitment
59
What are the SYSTEMIC effects of cytokines?
IL-1, IL-6, TNFa: To Brain ... released prostaglandins ... fever To Liver ... Secrete APRP (CRP) etc.. IL-6, TNFa: To Bone Marrow ... Leukocytosis ... neutrophilia
60
Exogenous
Bacterial Infection MHC2 CD4+ T_helper
61
Endogenous
Viral MHC1 CD8+ CTL
62
What are the 3 signals that activate T Cells?
(1) MHC-Ag to TCR (2) Costimulation (3) Cytokines help differentiation of T Cells
63
What do CTLs do?
Cytoxic T Lymphocytes (when activated) kill by inducing the infected cell to undergo apoptosis
64
Which cells can present via MHC1?
All cells in the body ... any cell can become virally infected
65
Which cells can present via MHC2?
APCs: "Big MD" Macrophages B-cells DCs
66
Which are the BEST APCs? | Why? 2 reasons
(1) have the most PRRs | (2) provide the best costimulation of Naive T cells
67
What is an example of a co-stimulatory signal as presented by a DC?
B7 on DC interacts with CD28 on T-Helper
68
What is an example of cytokine release finishing the activation of a T-helper cell?
IL-2 via autocrine by T-helper "self kick in the pants"
69
What type of cytokines does the DC release?
IL-12, TNFa
70
How do Abs kill a microbe?
INDIRECTLY: | *bind Ag of pathogen and act as flag calling NK cells to come and kill
71
What do NK cells do?
Wander the system and hunt down cells that don't look quite right .... (eg) tumor cells, cells covered in Abs, infected cells
72
Besides its role in complement activation, what does C3b do?
Acts as Opsonin C3b binds to pathogen and enhances the ability of a macrophage to engulf it
73
What does TH1 do?
secretes INFy which activates macrophage to up-regulate lysosome mechanisms
74
Acute vs Chronic Inflammation What are the predominant cells involved?
ACUTE: Neutrophils CHRONIC: T Cells, Macrophages
75
Acute vs Chronic Inflammation What is a bacterial example of cause?
ACUTE: S aureus CHRONIC: M. Tuberculosis
76
HOW does M Tuberculosis cause chronic inflammation
Bacteria survive in lysosomes of macrophages Macrophages accumulate and started going "crazy" whereby they spew out their proteolytic enzymes
77
What is a Tuberculous granuloma?
Attempt to section off damaged area in lungs caused by exploded macrophages .... leads to loss of lung tissue function
78
Which cell is involved in the clean up after infection and inflammation is resolved?
Macrophages
79
What is Meningitis?
Inflammation of the meninges. | caused by N. meningitidis
80
Why did the Meningitis patient get a rash that eventually led to necrosis? MOA?
Bacteria had entered the blood stream (bacteremia) and circulated the system getting stuck in the smallest capillaries. The rash was caused by the body mounting an inflammatory response. Bacteria damaged endothelial cells. Inflammatory response resulted in the vessels becoming extremely leaky.
81
Why was Rifampin given to Anna's roommates?
Rifampin = RNA polymerase inhibitor Given as a chemo-prophylactic measure
82
What is DIC?
Dessiminated Intravascular Coagulation blood clots form throughout the body's small blood vessels. These blood clots can reduce or block blood flow through the blood vessels, which can damage the body's organs. Platelets get used up and internal bleeding occurs
83
Anna’s acute phase response resulted in ...
Fever neutrophilia high CRP
84
What is vasculitis?
Inflammation of SMALL blood vessels in response to encounter with pathogen stuck in capillaries
85
Which cell type infiltrates in large numbers into the rash sites:
Neutrophils
86
Why is Neissaria Meningitis so dangerous?
gram - bacteria releases LPS toxin as it dies
87
Signs of Sepsis
Bacteria present in blood stream accompanied by inflammatory response result in: * *Fever * *Elevated HR & RR
88
What marks the entrance into Septic Shock?
BP drops even though we are administering fluids
89
Disseminated Intravascular coagulation What tests are done?
d-dimer platelet count prothrombin time We must monitor our Meningitis patient for this!
90
What are the three amigos?
IL-1 IL-6 TNFa
91
Which cells present MHC-1? Which cells present MHC-2?
MHC-1: All nucleated cells MHC-2: APC's only (B cells, DCs, Macrophages)
92
What is the role of MHC I?
recognizing altered self and presents Ag to CTLs | i.e.: samples the intracellular milieu and presents intracellular antigens on the surface of cells
93
What is SIRS?
systemic inflammatory response syndrome
94
How do we diagnose Disseminated intravascular coagulation?
fall in blood platelet levels
95
What induces immediate endothelial cell retraction?
NO | histamine
96
What is the predominant immune cell type in granulomas
Macrophages
97
Which one of the following phases of drug development is most likely to include healthy human subjects?
Phase 1
98
Where does peptide loading of MHC Class I molecules with endogenous antigens occur?
ER
99
What are the phagocytes?
neutrophils, macrophages/monocytes DCs
100
Which cells are involved with resolving inflammation?
Macrophages
101
Which complement protein also acts as an opsonin?
C3b
102
Which complement proteins trigger mast cell degranaulation?
C3a, C5a
103
Which cell types can produce reactive oxygen species via a respiratory burst?
MEN Neutrophils Eosinophils Macrophages
104
Which cell type takes up microbes via antigen-specific receptors, then processes and presents microbial antigens?
B-cells note ... Ag specific!!!
105
Which cell type releases nitric oxide, a potent vasodilator?
Macrophages
106
Are neutrophils phagocytic and Ag presenting?
Phagocytic only They simply follow the trail of chemo tactic factors, gobble up cells and then die
106
How do CTL kill?
Once in direct contact with affected cell, CTL releases Perforin & Granyme B into it ... triggers Caspases ... apoptosis
107
In the case of persistent and localized antigenic stimulation (i.e.: mycobacterium, sutures, parasitic eggs etc) the immune system responds by walling off the antigen. What type of process is this?
Chronic Inflammation
108
Which cells are involved in resolving inflammation.
Macrophages
109
Which cell type presents antigen and activates naïve TH?
DCs
110
Which cell type takes up microbes via antigen-specific receptors, then processes and presents microbial antigens?
B cell
111
Which cell type releases nitric oxide, a potent vasodilator?
Macrophage, Endothelial Cells

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