Inflammation

Question 1

78 – Prostacyclin (PGI\b2)
1: is synthesised by mast cells
2: mediates vascular spasm
3: is an antagonist of platelet aggregation
4: production is inhibited by aspirin

Answer 1

FFTT
Robbins 6th ed. Page: 70-71
1: produced by endothelial cells
2: potent vasodilation

Question 2

23699 – Ferritin
1: is located in lysosomes
2: is visible by light microscopy in routine paraffin sections
3: is stored in mononuclear phagocytic cells
4: levels in serum reflect iron stores except in inflammation

Answer 2

TFTT
Robbins 5th ed. PAGE: 28-29; 610

Question 3

14798 – Cytokines
1: act locally on immediately adjacent cells
2: have individual actions in modulating cell function which are specific for each cytokine
3: bind to non-specific receptors on target cells
4: are involved in stimulating cell growth but not cell differentiation

Answer 3

TFFF
Refer to Robbins, 6th Ed, Ch 7, page 191-192

Question 4

15841 – Actions of the cytokines interleukin-1 (IL-1) and tumour necrosis factors (TNF alpha and beta) in defence reactions in the body, include
1: when released systemically, protecting against shock
2: enhancing leukocyte-endothelial adhesion in acute inflammation
3: activating fibroblast migration and collagen synthesis
4: influence on the hypothalamus resulting in fever

Answer 4

FTTT
IL-1/TNF is all pro-inflammation, pro-healing (including healing by fibroplasia). Hence, responses 2, 3 and 4 are all True (fibroplasia and collagen synthesis are stimulated). However, the vasoactive and prothrombocoagulant effects can be devastating when there is avid systemic release/activation of IL- 1/TNF systemically (as, for example in severe bacteraemia [septicaemia in non-Robbins terms]), when widespread vasodilatation and increased vascular permeability contribute to the syndrome of irreversible shock (and to DIC also).

Question 5

23779 – Interleukin-1 (IL-1), secreted by cells of the mononuclearphagocyte system (MPS), has been demonstrated to have an important direct role in
1: inhibiting proliferation of T helper cells
2: endothelial cell activation
3: hypothalamus-mediated fever induction
4: enhancement of monocyte/macrophage bactericidal capacity

Answer 5

FTTF
Robbins 5th ed. Chapter: 3 Pages: 71, 174

Question 6

15528 – Complement
1: may be activated in the absence of immune complexes
2: is important in the formation of granulomas
3: binds to the mast cell membrane and inhibits degranulation
4: kills target cells by triggering apoptosis

Answer 6

TFFF
Refer to Roitt, 9th Ed, page 11-14

Question 7

8621 – Complement may play an important part in each of the following activities EXCEPT
A. increasing vascular permeability
B. phagocytosis of bacteria
C. release of histamine from mast cells
D. activation of fibrinolysis
E. destruction (killing) of bacteria

Answer 7

D
Robbins, 6th ed, Ch 3 and 5

Question 8

15928 – S: Complement activation through the ‘bypass’ mechanism is of critical importance in early defence against infection by virulent pyogenic bacteria not previously encountered because R: some subgroups of immunoglobulin G (IgG) do not activate complement by the ‘classical’ pathway following reaction with specific (bacterial) antigen.

Answer 8

S is true, R is true but not a valid explanation of S
Complement activation is critical to a successful acute inflammatory reaction and to opsonisation of bacteria in the early phases of acute inflammation in immunologically ‘unprimed’ individuals. This must protect the person until infection is controlled by innate mechanisms or until an immune response is generated. Subgroup 4 of IgG does not (after reacting with specific Ag) activate complement; IgG2 is a poor complement activator. However, the phenomenon under discussion has nothing to do with subgroup IgG activation of complement - this important ‘bypass activation’ of complement takes place far earlier than the immunologic production of Ig capable of dealing with this ‘new’ bacterium and is the ‘stopgap’ protection, pending Ig release.

Question 9

25324 – Effects of complement activation may include
1: opsonisation
2: lysis of bacteria
3: chemotaxis of neutrophils
4: haemolysis

Answer 9

TTTT
Roitt 9th Edition PAGE: 12-16 Robbins 5th ed. PAGE: 182-183

Question 10

25978 – Activators which induce platelet aggregation include
1: thromboxane A2 (TxA2)
2: nitric oxide
3: thrombin
4: adenosine triphosphate ATP

Answer 10

TFTF
Robbins 6th Edition Page: 120-122

Question 11

15923 – The following mediators are synthesised ‘on the spot’ and immediately released by injured/ stimulated cells
1: tissue thromboplastin
2: leukotriene B4 (LTB4)
3: Interleukin-2 (IL-2)
4: C3b opsinic factor

Answer 11

TTTF
Platelets (activated) and endothelial cells (injured), in particular, manufacture tissue thromboplastin. LTB4 is a product of the lipoxygenase pathway metabolism of arachidonic acid (from cell membrane phospholipid). IL-2 production is particularly the province of CD4+, TH2 cells in B cell ‘help’. Complement is, of course, a plasma protein system.

Question 12

15918 – Chemicals activated during/following tissue injury which normally circulate as inactive plasma precursors include
1: platelet activating factor
2: major basic protein
3: C3b opsinic factor
4: plasmin

Answer 12

FFTT
Platelet activating factor is stored in granules within some cells and manufactured ‘on the spot, on demand’ by others. Major basic protein is a product of eosinophil leukocytes - very effective in destroying multicellular parasites (and also bystander host cells). Complement components are, of course, plasma components (though some components are present in some cells also). Plasmin is another ‘cascade’ enzyme systems - contact activated.

Question 13

15994 – Fibroblasts proliferate and migrate during the healing process in response to the direct action of
1: cytokines
2: expression of adhesion molecules on endothelial cells
3: leukotrienes
4: platelet activating factor (PAF)

Answer 13

TFFF
Fibroblast proliferation and differentiation appears to be largely under the control of growth-promoting and growth-controlling cytokines. The influence of other factors such as extracellular matrix products (particularly fibronectin, laminin, etc and fibrino-peptides), although persuasive, is still equivocal. The endothelial adhesion molecules include members of the immunoglobulin family of proteins - they have no known influence on fibroblast ( or other ECM cell ) activity and the same goes for the two cell membrane phospholipid derivatives LT and PAF.

Question 14

15886 – Chemical mediators which increase permeability of venules during the acute inflammatory reaction include
1: platelet activating factor (PAF)
2: gamma interferon
3: bradykinin
4: histamine

Answer 14

TFTT
Platelet activating factor is derived from cell membrane phospholipid by phospholipase (PLA2) action, but not via pathways of prostaglandin or HETE/leukotriene metabolism. In low concentrations, it is an extremely potent inducer of vasodilator and permeability, as well as other aspects of the inflammatory process. Bradykinin and histamine are also both ‘classic’ permeability factors. Gamma-interferon has no effect on endothelial cells (other cytokines may act indirectly through endothelium-activation in pavementing, thus aiding ‘leukocyte-mediated’ permeability - but not directly).

Question 14

25980 – Increase in vascular permeability may account for the oedema in
1: acute anaphylaxis
2: adult respiratory distress syndrome
3: serum sickness
4: lymphoedema

Answer 14

TTTF
Robbins 5th Edition Page: 55&68 vs 180, 184&(677)

Question 15

15881 – Arteriolar dilatation occurring in the early stages of acute inflammation, is mediated by
1: prostacyclin (PGI2)
2: nitric oxide (NO)
3: leukotriene B4 (LTB4)
4: neutrophil lysosomal enzymes

Answer 15

TTFF
Prostacyclin and nitric oxide are both powerful vasodilating agents, both produced by intact endothelium. Leukotriene B4 is produced from arachidonic acid through the lipoxygenase pathway; it has powerful chemotactic effects, but does not directly influence either vascular flow or permeability. Neutrophil lysosomal enzymes appear to have no effect on vasodilatation and, in any case, are not active in the zone until acute inflammation is well established.

Question 16

15966 – S: Lysozyme (n-acetyl muramidase) is an effective antibacterial because R: lysozyme enzymatically destroys specific components of bacterial cell walls.

Answer 16

S is true, R is true and a valid explanation of S
Muramic acid-N acetyl glucosamine bond is found in the cell wall of all bacteria. Lysozyme specifically hydrolyses the bond, thus damaging the bacterial cell wall.

Question 17

23274 – The monocyte/macrophage system of cells subserves
1: processing and presentation of antigens
2: control of fibroblast proliferation
3: induction of neutrophil adhesion molecules on endothelial cells
4: secretion of endogenous pyrogen, IL-1

Answer 17

TTTT
Robbins 5th ed. CHAPTER: 2 PAGES: 701; 76

Question 18

23974 – The mononuclear cells in an acute inflammatory exudate
1: morphologically resemble lymphocytes
2: are derived from stem cells in the germinal centres of lymph nodes
3: undergo chemotaxis in response to IgE antibody
4: are mainly transformed blood monocytes

Answer 18

FFFT
Robbins 5th ed. Chapter: 5 Pages: 59; 74; 76

Question 19

15856 – Monocyte (macrophage) chemotaxis into inflammatory foci is stimulated by
1: histamine
2: cytokines
3: activated complement products
4: activated T helper lymphocyte (TH1) secretions

Answer 19

FTTT
The amines which are important in acute inflammation are vasoactive, but not chemotactic. Cytokines (IL-8 family) and complement products (C5a) are chemotactic for PMN and monocytes. TH1 secretions include the ‘lymphokines’ of which MCF is a prominent member!

Question 20

15795 – Intact endothelium secretes
1: thrombomodulin
2: adenosine diphosphate (ADP)
3: an inhibitor of plasminogen activation (tPA inhibitor)
4: prostacyclin (PGI2)

Answer 20

TFFT
It is useful to assume that all of the actions of the intact endothelium are anticoagulant and antiplatelet (the endothelium also secretes a plasminogen activator (tPA), inducing fibrinolysis, nitric oxide, a powerful vasodilator, as well as heparin-like glycosaminoglycans etc) Materials secreted by the injured endothelium are procoagulant (eg vWF secretion) and proplatelet (eg ‘switch-off’ of PGI2 and tPA secretion), as well as ‘thromboplastic’ material.

Question 21

15897 – The most potent chemotactic agent for granulocytes is
A. complement activation product (C5a)
B. thromboxane A2 (Tx-A2)
C. high molecular weight kininogen (HMWK)
D. leukotriene (LTB4)
E. fibronectin

Answer 21

D
The two chemoattractants for granulocytes shown are C5a and LTB4. Of the two, LTB4 is generally stated to be the most powerful naturally occurring in inflammation. HMWK is an intermediate metabolite for the various ‘cascade’ enzyme systems active in inflammation and coagulation systems. Fibronectin is certainly chemotactic for fibroblasts (and perhaps also endothelial cells) in healing and possibly also has a role in chemotaxis for some cancers during the invasive process.

Question 22

15851 – Neutrophil chemotaxis is induced by
1: prostacyclin (PGI2)
2: bradykinin
3: activated complement products
4: oxygen-derived free radicals

Answer 22

FFTF
Prostacyclin and other cyclo-oxygenase pathway arachidonic acid derivatives are vasoactive, but not chemotactic. The same goes for bradykinin and the free radicals (NO as a vasodilator - probably the oxygen-derived free radicals only influence vascular actions through direct endothelial cell damage). C5a, on the other hand, is strongly chemotactic.

Question 23

15871 – Chemicals which have a direct chemotactic effect on neutrophil leukocytes include
1: leukotriene (LTB4)
2: bradykinin
3: prostacyclin (PGI2)
4: nitric oxide (NO)

Answer 23

TFFF
Leukotriene is the most potent chemotactic agent known. Others include C5a, bacterial products and cytokines ( IL-8 ‘family’). Products of the cyclo-oxygenase arm of arachidonic acid metabolism have no chemotactic action. Bradykinin causes increased vascular permeability, while NO mediates vasodilatation and tissue damage.

Question 24

23279 – Mechanisms of adhesions between leucocytes and endothelium include
1: increased binding activity of integrins
2: P-selectin/ICAM-1 (intercellular adhesion molecule-1)interaction in low-flow conditions
3: induction of endothelial adhesion molecules
4: redistribution of P-selectin by histamine stimulation

Answer 24

TFTT
Robbins 6th ed. Chapter: 3 Page: 57-59

Question 25

15876 – Leukocyte pavementing in acute inflammation is the result of the direct action of
1: bradykinin
2: ligand action of thromboxane-A2 (Tx-A2)
3: adhesion molecules expressed on endothelial cells
4: adhesion molecules expressed on leukocytes

Answer 25

FFTT
Direct causes of the phenomena of leukocyte adhesion to endothelium in zones of acute inflammation are the interactive adhesion molecules expressed on the surfaces of leukocytes and endothelial cells. These include redistribution of P-selectin and increased activity of integrins in leukocytes, together with cytokine-induced induction of endothelial adhesion molecules (these are of the immunoglobulin family). Expression of these interactive adhesion molecules is stimulated variously by histamine, thrombin, IL-1 and chemotactic agents. Bradykinin and Tx-A>Sub>2 have no influence, either direct
or indirect.

Pathology Sub Committee comments: This question relates to molecules having a direct influence on leukocyte pavementing. 1. It is resonable to assess mediators directly causing pavementing (ie. leukocyte - endothelial adhesion) as the interactive adhesion molecules (selectins, integrins, ICAM-1, VCAM-1) on endothelial cells and leukocytes; 2. Mediators indirectly influencing pavementing are those which induce expression of those adhesion molecules on the surfaces of endothelial cells (IL-1, TNF) and of leukocytes (C5a at least); 3. Anything even more remote from direct influence (including bradykinin) is surely highly speculative as having any effect. Bradykinin certainly has no direct effect (ie. as an adhesion molecule per se) or even at the next level (ie influencing the expression of those adhesion molecules).

Question 26

15908 – Leukocyte pavementing in acute inflammation occurs because of the direct effect of
1: ligand action of LTB4
2: complement activation by-product (C5a)
3: adhesion molecules on endothelial cells
4: adhesion molecules of neutrophil leukocytes

Answer 26

FFTT
A number of chemical mediators of the acute inflammatory reaction influence the expression of adhesion molecules on both endothelial cells (these adhesion molecules are generally members of the immunoglobulin superfamily) and granulocytes (these are generally integrins). However they may be influenced to be expressed, it is the adhesion molecules themselves which are responsible for the adhesion (and therefore, for the pavementing).

Question 27

15866 – Phagocytic activity of neutrophil leukocytes is stimulated when the bacteria are opsonised by
1: alpha-interferon
2: IL-8
3: immunoglobulin
4: C3b and fibronectin

Answer 27

FFTT
The two major opsonins are the Fc fragment of immunoglobulin G and C3b, the so-called ‘opsonic fragment of C3’. The corresponding phagocyte receptors are FcgR which recognises the Fc fragment of IgG, and complement receptors CR 1, 2 and 3, which interact with C3b and C3bi. CR 3 also binds laminin and fibronectin; it is responsible for non-opsonic binding of some bacteria. The cytokines have no opsonic activity, although some may ‘activate’ phagocytes. IL-8 (‘family’) is chemotactic

Question 28

25339 – Mechanisms commonly used by phagocytic cells (neutrophils and macrophages) to kill micro-organisms include
1: formation of nitric oxide
2: production of superoxide radicals
3: production of the complement C1q
4: production of hydroxyl radicals

Answer 28

TTFT
Essential Immunology 9th ed. Pages: 8-10

Question 29

15903 – Opsonin-induced phagocytosis of bacteria is stimulated by
1: simultaneous binding of C3b and fibronectin to leukocyte receptor
2: interleukin (IL-6) receptor binding
3: gamma-interferon
4: receptor binding to IgFc

Answer 29

TFFT
C3b requires simultaneous binding with fibronectin for effective opsonin action. Fc receptors are present on granulocytes and macrophages - this ligand action of the Fc fragment of Ig is, of course, activated by the binding of the Fab fragment with antigen. Phagocytosis is most avid when both C3b and Fc ligands bind simultaneously to their respective receptors on the phagocyte; clearing of bacteria is enormously enhanced by the presence of both.

Question 30

24219 – Opsonins which directly enhance phagocytic engulfment of bacteria include
1: immunoglobulin G subtypes
2: collectins
3: a derivative of complement component C3
4: intercellular adhesion molecule (ICAM)

Answer 30

TTTF
Robbins 6th ed. Chapter: 3 Page: 59; 62

Question 31

15558 – During healing of acute inflammation by resolution, the exudate is
1: removed via lymphatics
2: replaced by reticulin
3: phagocytosed by macrophages
4: replaced by granulation tissue

Answer 31

TFTF
Refer to Robbins, 6th Ed, Ch 3, page 78

Question 32

15836 – Resolution of inflammation, with regeneration, leads to restoration of normal structure and function following
1: pneumococcal pneumonia
2: uncomplicated healing of a sutured surgical incision
3: pulmonary infarct
4: paracetamol-induced hepatic necrosis

Answer 32

TFFT
In both pneumococcal pneumonia and paracetamol poisoning, although there may be cell injury and necrosis (of pneumocytes and hepatocytes respectively), the basement membrane is not damaged and remains as a framework along which regenerating cells can migrate. Despite careful suturing of a skin incision, there is always some scarring and dermal appendages do not regenerate. Basement membrane does not survive pulmonary infarction - scarring results (although, interestingly, elastic
tissue survives).

Question 33

16010 – Resolution of inflammation and regeneration lead to complete restoration of normal structure and function following healing of
1: renal papillary necrosis
2: acute viral hepatitis
3: hypovolaemic acute renal tubular necrosis
4: liver abscess

Answer 33

FTTF
Renal papillary necrosis and liver abscess both result in total destruction of the ‘framework’ of the tissue involved - healing by scarring is the best possible outcome here. In acute viral hepatitis
(apoptotic cell death, not necrosis), cells regenerate along the intact basement membrane framework as they also do following acute renal tubular necrosis. Although oliguric renal failure caused by hypovolaemic shock is a hazardous disorder, when recovery occurs without complications (eg infection etc), eventual complete restoration of ‘pre-injury’ renal structure and function occurs.

Question 34

15983 – Granulomatous inflammation may be composed of
1: a compact mass of immature granulation tissue
2: a compact mass of lymphocytes and plasma cells
3: a mass of macrophages and giant cells
4: a mass of epithelioid cells and giant cells

Answer 34

FFTT
The clear distinction between epithelioid cells and macrophages and the clear implications of their different morphologies and functions is poorly dealt with in Robbins. Nevertheless, at least the book makes it clear that there are both innate (non-immune - characterised by macrophages, ie. phagocytic) and immune (characterised by epithelioid cells - which are not phagocytic, but are
synthetic and secretory and probably also fulfil a ‘barrier’ function before fibrosis). Granulomas are not composed of granulation tissue, not primarily made up of immunocytes (lymphocytes and plasma cells), though both may be present.

Question 35

9066 – Focal granulomatous lesions resembling those of sarcoidosis are characteristic of
1: primary syphilis
2: berylliosis
3: Echinococcus granulosus infestation
4: the reaction to yersiniae

Answer 35

FTFF
Robbins, 6th ed, Ch 3; Ch 9 and Ch 16

Question 36

15167 – Granuloma formation is characteristic of
1: Crohn’s disease
2: primary biliary cirrhosis
3: sarcoidosis
4: cat scratch lymphadenitis

Answer 36

TTTT
Refer to Robbins, 6th Ed, page 83, 878, 817

Question 37

21783 – Classical immune (epitheloid) granulomas are characteristically seen in
1: lepromatous leprosy
2: mycobacterial infections in AIDS patients
3: Cryptococcus neoformans infections
4: sarcoidosis

Answer 37

FFFT
Robbins 6th ed. Chapter: 3; 7; 9 Page: 83-84; 248; 351; 386.

Question 38

15999 – Myofibroblasts in granulation tissue
1: cause wound contraction
2: contain contractile cytoplasmic filaments
3: secrete collagen
4: develop from fibroblast progenitor cells

Answer 38

TTTT
Myofibroblasts are important cells in wound healing and variants of this (chronic inflammation, tumour fibroplasia etc). In all of these, ‘wound contraction’ leads to a scar which, in uncomplicated healing, is smaller than the original tissue it replaces; in other circumstances, this leads to such problems as bowel obstruction in cancer, Crohn disease etc. All of the suggested functions and the cell origin are true. ‘Wound contraction’ is common and important - that message does not come through clearly in Robbins, but the gist of the phenomenon and its importance is clear - where there is granulation tissue, there is wound contraction, occurring early in connective tissue healing.

Question 39

23049 – Keloid formation
1: contains abundant amounts of dense collagen
2: is commoner in males than in females
3: is commoner in Negroes than in white races
4: usually shows premalignant changes

Answer 39

TFTF
Robbins 5th ed. Page: 90