Simms

Question 1

A patient is diagnosed with sarcoidosis. What would be strongly associated with this pathology?

Answer 1

TNF-alpha.

Sarcoidosis involves granuloma formation. When there is chronic inflammation, prolonged levels of TNF-alpha leads to granuloma formation.

Question 2

TNF-alpha can activate what 3 pathways?

Answer 2

• NF-kappaB
• MAPK/ERK
• caspase 8-apoptosis

Question 3

What secretes TNF-alpha?

Answer 3

Macrophages, lymphocytes, fibroblasts, etc.

Question 4

Is IL-10 anti or pro inflammatory?

Answer 4

anti-inflammatory

Question 5

Is IL-4 anti or pro inflammatory?

Answer 5

Both!

IL-4 is a regulatory anti-inflammatory cytokine that down-regulates acute inflammation and promotes eosinophil-based allergic inflammatory state.

Question 6

…………is an innate immune system pattern recognition receptor that binds to the phosphocholine expressed on the surface of dead or dying cells and some bacteria. Binding activates complement, promoting phagocytosis.

Answer 6

C-reactive protein (CRP)

Question 7

Is granulomatous inflammation synonymous with chronic inflammation?

Answer 7

No!

Granulomatous inflammation is a type of chronic inflammation and, if present, suggests certain disorders (Mycobacterial infection, fungal infection, sarcoidosis, etc.)

Question 8

A female has severe cramping due to excess prostaglandin production. Prostaglandins are synthasized by which pathway?

Answer 8

Arachadonic acid pathway.

Question 9

Is IL-1 pro or anti-inflammatory?

Answer 9

pro-inflammatory

But note that IL-1 –> increased ACTH –> increased cortisol (cortisol is anti-inflammatory)

Question 10

What produces IL-1?

Answer 10

Macrophages, endothelial cells, APC/dendritic cells, and B lymphocytes.

Question 11

What are the effects of IL-1?

Answer 11

• elevated core temp
• acute phase protein production
• chemotaxis of monocytes and neutrophils
• endothelial adhesion molecule production
• T cell activation, proliferation, IL-2 secretion
• B cell proliferation
• NK activation
• Vasodilation

Question 12

A 60 year old male is being treated for osteoarthritis with a selective COX-2 inhibitor. He reports acute onset of shortness of breath and chest pain that radiates into his jaw and left arm. What should he have initially been prescribed for his arthritis to avoid this, and why?

Answer 12

A non-selective COX inhibitor such as Asprin!

COX-1 is constitutive. If we block only COX-2 with a selective inhibitor, we still get TXA2 production via COX-1, which can lead to thrombus formation.

Aspirin blocks both COX 1 and 2, which suppresses (via irreversible inhibition) the production of prostaglandins and thromboxanes.

Question 13

A patients lung biopsy shows marginated neutrophils. Which substance is the most likely cause of the position of the neutrophils?

a. bradykinin
b. C5a
c. histamine
d. NO
e. prostaglandin E2

Answer 13

b. C5a

One of the effects of C5a is activation of immune adhesion molecules, which would allow the neutrophils to adhere and access the site of infection.

Question 14

What is the major proinflammatory pathway in the immune system?

Answer 14

NFkB pathway

(Nuclear factor kappa light chain enhancer of activated B cells)

Question 15

NFkB (a transcription factor) exists in the cytoplasm in its inactive form, complexed with………

Answer 15

IkB

* PAMPs or DAMPs bind PRRs, which causes IkB phosphorylation by IKK (a kinase). NFkB dimers can now translocate to the nucleus and bind to DNA.

Question 16

What are the main ILs produced when the NFkB pathway is activated?

Answer 16

IL-1 & IL-6

Question 17

NFkB is encoded by 5 different genes encoding 5 different monomers. Monomers combine to form different functional cytoplasmic dimers. NFkB has 2 seperate pathways! What are they?

Answer 17

Canonical pathway and non-canonical pathway.

Question 18

In the……………. NFkB pathway, there is rapid development with transient effects. This is good for immune activation, cytokine secretion, and pro-inflammatory effects.

Answer 18

Canonical

Question 19

The……………. NFkB pathway leads to slow development but long-lasting effects. This is used for normal lymphoid organ development, promotion of acute inflammation, B lymphocyte survival/maturation, and differentiation of osteoclasts.

Answer 19

non-canonical

Question 20

What mediates vascular dilation?

Answer 20

NO

Bradykinin

Prostagland E2

Note that increased vascular permeability is mediated by histamine, bradykinin, prostaglandin E2, C3a, C5a & leukotrienes.

Question 21

What does purulent mean?

Answer 21

Pus!

Question 22

Purulent inflammation is dominated by neutrophils. It is most common with what kind of infections?

Answer 22

Bacteria or fungi

Question 23

Allergic inflammation is a subtype of serous inflammation. It is acute inflammation dominated by…………

Answer 23

eosinophils.

ex: allergic conjunctivitis

Question 24

Acute inflammation inhibits the hepatic formation of albumin, transferrin, transthyretin and retinol binding protein. These are known as what?

Answer 24

Negative acute phase reactant proteins.

Question 25

To test for inflammation, we could measure..................... which should be produced by the liver.

Answer 25

acute phase proteins \*During acute inflammation these function to destroy bacteria and inhibit bacterial growth.

Question 26

Early response pattern of acute phase reactants shows elevation primarily in the.......... fraction of serum proteins with a small rise in alpha-1 fraction.

Answer 26

alpha-2

Question 27

Late/Chronic inflammation shows elevation in the alpha-2 fraction, alpha-1 fraction, beta fraction and gamma fraction. Here is the diagram:

Answer 27

Question 28

If there is an increase in immature neutrophils (aka band or stab cells) the peripheral blood is said to exhibit a.......... shift! This is leukocytosis.

Answer 28

Left

Question 29

............ infections cause a leukocytosis composed predominantly of lymphocytes rather than neutrophils.

Answer 29

Viral \* This is leukopenia. It is characteristic of viral or overwhelming bacterial infections.

Question 30

The presence of large azurophilic granules in the cytoplasm of segmented and band neutrophils can indicate what? \* Note that this is commonly seen with Dohle bodies and/or cytoplasmic vacuolization

Answer 30

severe infection active autoimmune diseases autophagocytosis

Question 31

...........are single or multiple blue cytoplasmic inclusions adjacent to the cell membrane. They are remnants of rough endoplasmic reticulum.

Answer 31

Dhole bodies \* Commonly seen in band cells in conjunction with toxic granulation. \* common causes: Severe infection with left shift, burns, trauma, malignancy, leukemoid rxn, Fanconi syndrome, May-hegglin anomaly, Chediak-steinbrinck-higashi syndrome.

Question 32

Leukocyte...................... is commonly seen during severe physiological stress, such as in sepsis, with thermal burns, chemoRx, etc.

Answer 32

vacuolization

Question 33

A...............rxn is when there is a WBC count \> 50,000. It will be composed of neutrophils (commonly with Dhole bodies or toxic granulation) & band cells.

Answer 33

Leukemoid \* It is important to rule out leukemia via microscopic, cytogenic, and immunophenotypic analysis.

Question 34

It is important to note that in a leukemoid rxn, ................ cells are NOT present in the peripheral blood. Anemia and thrombocytopenia is NOT present either. Flow cytometry will show NO evidence of clonal leukocyte proliferation.

Answer 34

blast