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Other Inflammations And Mediators Flashcards

1
Q

Examples of primary or preformed cell derived mediators of inflammation

A

Histamine
Serotonin
Lysosomal enzymes

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2
Q

Examples of newly synthesised cell derived mediators of inflammation

A 
PAF
NO
Prostaglandin
Leukotrienes
Cytokine
Chemokines
Free radicals
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3
Q

Plasma derived mediators of inflammation are

A

Complement
Coagulation
Kinin

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4
Q

Stain for mast cell

A

Toluidine blue

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5
Q

Histamine

A 
Richest source: mast cell
Earliest to be released
Causes:
1. Vasodilation
2. Vasoconstriction (larger vessels)
3. Increased vascular permeability
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6
Q

Triggers of histamine

A

C3a,C5a
IL-1, IL-8
Physical agents like heat, trauma,…

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7
Q

Serotonin

A

Sources: platelets (major), enterochromaffin cells of GIT
Functions: same as histamine

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8
Q

Lysosomal enzymes that take part in inflammation are located in

A 
Granules of neutrophils
Of two types:
1. Primary/azurophillic
Large, coarse
2. Secondary
Small , fine
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9
Q

Primary granules of neutrophils contain

A 
MPO (myeloperoxidase)
BPI (Bacterial Permeability Increasing protein)
Lysozyme 
Neutral proteases
Neutrophil elastase
Defensins
Phospholipase A2
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10
Q

Secondary granules of neutrophils contain

A 
Lysozyme
Lactoferrin
Type 4 collagenase
Phospholipase A2
Gelatinase 
Alkaline phosphatase
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11
Q

ANCA

A

Anti Neutrophilic Cytoplasmic Antibody

Two types:
1. C ANCA
Anti proteinase 3
2. P ANCA
Anti MPO ANCA
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12
Q

PAF

Sources, functions

A 
All leukocytes, mast cells and platelets
Most potent inflammatory mediator 
Function:
1. Increased platelet aggregation
2. Vasodilation
3. Increased permeability
4. Bronchospasm
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13
Q

The major arachidonic acid producing step

Clinical significance

A

Phospholipids of the cell membrane are acted by phospholipase to produce arachidonic acid
Steroids generally inhibit this step as a result steps are generally anti inflammatory (broad spectrum anti inflammatory)

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14
Q

Products produced by the cyclooxygenase pathway of arachidonic acid

A
  1. PGI2 prostacyclin
  2. TXA2 thromboxane A2
  3. PGD2, PGE2, PGP-2alpha : prostaglandins
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15
Q

Products of lipoxygenase pathway of arachidonic acid

A
  1. Leukotrienes

2. Lipoxins

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16
Q

Cycloxygenase pathway

A 
Arachidonic acid ➡️ PGG2➡️ PGH2➡️:
1. PGI2
2. PGD2, PGE2, PGF2 alpha
3. TXA2
There are two cycloxygenase enzymes: COX-1 and COX-2 (inducible)
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17
Q

PGI2 and TXA2

A

Prostacyclin
Vasodilation
Decrease platelet aggregation
Role in inflammation

Thromboxane A2
Vasoconstriction
Increases platelet aggregation
Role in hemostasis

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18
Q

General functions of PHD2, PHE2 and PGF2 alpha

A

Causes vasodilation
Bronchospasm
Increased vascular permeability

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19
Q

Specific functions of prostaglandins

A

PGE2 - causes fever and pain
PGD2 and PGF2 alpha - role in neutrophil chemotaxis and
PGF2 alpha - uterine and bronchial smooth muscle contraction

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20
Q

Lipoxygenase pathway of arachidonic acid

A

Arachidonic acid ➡️ 5-HPETE➡️ LTA4 ➡️:

  1. LTB4 (chemotactic)
  2. LTC4 ➡️ LTD4➡️ LTE4 (these cause increased vascular permeability and bronchospasm)
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21
Q

Lipoxin functions

A

Anti inflammatory:

  1. Inhibits neutrophil chemotaxis
  2. Inhibits NK cell activity
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22
Q

Leukotrienes antagonists

A

Montelukast, zafurlukast
Bronchodilators
Treatment of bronchial asthma

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23
Q

Aspirin and other NSAIDs

A

Inhibits COX-1 and COX-2

Inhibits cycloxygenase pathway

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24
Q

Different types of chemokines

A
  1. C-X-C chemokines: neutrophil
  2. C-C chemokines: all except neutrophils
  3. C chemokines: lymphocytes
  4. CX3C chemokines: monocytes
    a,b,g,d
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25
C-X-C chemokines
Alpha chemokine Chemokine specific for neutrophil Example: IL-8
26
C-C chemokines
Beta chemokine Specific for all leucocytes except neutrophils Eg., 1. eotaxin -eosinophils 2. MCP-1 : monocytes 3. MIP-1 alpha: both monocytes and macrophages
27
C chemokine
Gamma chemokine Specific for lymphocytes Example: lymphotaxin
28
CX3C chemokine
Delta chemokine Specific for monocytes One example: fractalkine
29
Important application of chemokine receptor
Chemokine receptors like CXCR4 and CCT5 act as co-receptors for HIV
30
Characteristics of chronic inflammation
1. Infiltration of tissues by mononuclear cells 2. Tissue destruction 3. Attempts at healing by angiogenesis and fibrosis
31
Macrophages of the body
1. Liver: kupffer cells 2. Brain: microglial cells 3. Spleen and lymph nodes: sinus histiocytes 4. Kidney: mesangial cells 5. Placenta: Haufbauer cells 6. Lungs: pulmonary alveolar macrophages or dust cells
32
Classical activation of macrophage steps
1. Induced by interferon-gamma and endotoxin 2. Produced IL-1, 6, 12 3. M1 macrophage produced
33
Mechanism of action of classically activated M1 macrophage
1. ROS 2. NO 3. Lysosomal enzymes Kills the bacteria Causes tissue destruction
34
Activation of macrophages via the alternate pathway
1. Induced by IL-4 and IL-13 2. Produces IL-10 and THF-beta 3. M2 macrophage
35
Action of alternatively activated M2 macrophages
1. Anti inflammatory | 2. Fibrosis (TGF-beta)
36
Granuloma
Collection of modified or activated macrophages called epitheloid cells surrounded by collar of lymphocytes and sometimes giant cells
37
Giant cell is formed by
Fusion of epitheloid cells
38
Types of giant cells
1. Foreign body giant cell 2. Langhan’s giant cells 3. Touton giant cell 4. Tumour giant cell 5. Reed-Sternberg cells 6. Osteoclastic tumour giant cell 7. Warthin Fikendy giant cell
39
Foreign body giant cells
Haphazard nuclei like tumour giant cells
40
Langhan’s giant cells
Nuclei arranged as horse shoe | Characteristic of TB
41
Touton giant cell
Nuclei surrounded by fat droplets | Characteristic of xanthoma
42
Warthin Fikendy giant cell is seen
Measles
43
Mechanism of granuloma formation
It is a type 4 hypersensitivity reaction 1. Antigen reacts with CD4 TH1 cells 2. Interferon-gamma is produced 3. Activates macrophage 4. Granuloma formation
44
List of granulomatous diseases
1. TB 2. Sarcoidosis 3. Leprosy 4. Syphillis 5. Chronic granulomatous disease 6. Cat scratch disease 7. Crohn’s disease 8. Wegner’s granulomatosis 9. Berylliosis 10. Churg Strauss syndrome
45
Granuloma classification
1. Immune granuloma 2. Foreign body granuloma: Haphazard nuclei
46
Caseating granuloma is seen in
1. TB 2. Histoplasmosis 3. Coccidiomycosis 4. Syphillis
47
Non caseating granuloma
1. TB 2. Sarcoidosis 3. Crohn’s disease 4. Hodgkins lymphoma
48
Naked granuloma
Absences of lymphocytic collar | Seen in sarcoidosis
49
Stellate granuloma
Cat scratch disease
50
Durks granuloma
Seen in P. falciparum malaria
51
Doughnut granuloma/ fibrin granuloma
Seen in Q fever
52
Eosinophilic granuloma
Seen in Churg Strauss syndrome
53
Necrotising granuloma
Wegner’s granulomatosis
54
NO formation
Also know as endothelium derived relaxation factor (EDRF) | Produced from arginine by NO synthetase via cGMP pathway
55
NO synthetase
3 forms 1. eNOS- endothelial 2. nNOS-neuronal 3. iNOS- inducible
56
Function of NO
1. Vasodilator 2. Smooth muscle relaxation 3. Decreases platelet aggregation 4. Microbicidal via PAN
57
Cytokines of acute inflammation
1. IL-1: fever 2. IL-6 3. TNF-alpha: Most important in systemic inflammatory response syndrome, cancer cachexia
58
Functions of cytokines of acute inflammation
1. Produce systemic effects of inflammation: fever, increased sleep, increased ESR, decreased appetite 2. Endothelial activation 3. Chemotaxis: IL-8
59
Cytokines of chronic inflammation
1. IL-12 2. IL-17 3. IFN-gamma (interferon): Important for granuloma formation
60
Most fibrogenic cytokine
TGF-beta | Transforming growth factor-beta
61
Anti inflammatory cytokines
IL-4,6: both pro and anti inflammatory IL-10,13 TGF-beta (fibrogenic)
62
Complement system
``` Series of 20 proteins activated by three pathways: 1. Classical: starts with activation of C1 2. Alternate: “” C3 3. Lectin/mannose binding pathway: “” C1 ```
63
The various pathways of complement activation are activated by
``` 1. Classical: Ag-Ab complexes 2. Alternate: LPS, cobra venom, endotoxins 3. Lectin/mannose binding pathway: by lectin or mannose ```
64
Most critical step in complement cascade
Formation of C3
65
Final step of complement cascade
C5b-9 membrane attack complex
66
Different types of chemokines
1. C-X-C chemokines: neutrophil 2. C-C chemokines: all except neutrophils 3. C chemokines: lymphocytes 4. CX3C chemokines: monocytes a,b,g,d
67
Functions of complement proteins
``` 1. Act as anaphylactic toxins: C3a, C5a 2. Opsonins: C3b 3. Killing of microbes: C5b-9 (membrane attack complex) 4. Chemotactic agents: C5a ```
68
Diseases caused by complement protein deficiencies
1. Hereditary angioneurotic edema 2. Risk of SLE 3. Risk of pyogenic infection 4. Paraoxysmal nocturnal haemoglobinuria
69
Hereditary angioneurotic edema
Deficiency of the complement protein C1 inhibitor (C1 INH)
70
Deficiency of C2 or early components of complement leads to
Risk of SLE systemic lupus erythematosis
71
Deficiency of C3 or late components of complement proteins
Risk of pyogenic infection
72
Kinin cascade
Produces bradykinin 1. Pre Kallikrein➡️ kallekrein by factor 12 Hageman factor 2. High molecular weight kininogen is produced 3. Bradykinin is produced
73
Bradykinin function
1. Increased vascular permeability 2. Pain 3. Vasodilation 4. Bronchospasm
74
Coagulation cascade factors
1. Fibrinogen: can act as opsonin 2. Thrombin: link between coagulation and inflammatory pathway Redistribution of E selectin 3. Fibrinopeptides: Chemotaxis
75
Deficiency regulators of complements like CD55, CD59
Paraoxysmal nocturnal haemoglobinuria | PNH
76
Alpha 1 anti trypsin deficiency is seen in
Panacinar emphysema | Liver disease
77
Microscopy of alpha 1 anti trypsin
PAS positive | Globules in hepatocytes

Pathology MBBS (17 decks)

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