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USMLE Pathology > Chronic Inflammation > Flashcards

Chronic Inflammation Flashcards

1
Q

What is chronic inflammation characterised by?

A

Lymphocytes and plasma cells in tissue

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2
Q

What stimuli may cause chronic inflammation?

A
  • Persistent infection (most common)
  • Infection with viruse, mycobacteria, parasites, fungi
  • Autoimmune diseases
  • Foreign material
  • Some cancers
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3
Q

What do TCR complexes recognise?

A

Antigens presented on MHC

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4
Q

What do the activation of T cells require?

A
  • Binding of antigen/ MHC complex

- Additional 2nd signal (B7 binding to CD28)

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5
Q

What provides the additional 2nd signal in CD4+ T-cell activation?

A

B7 on APC binds CD28 on CD4+ T cells providing 2nd activation signal

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6
Q

What do activated Th (CD4+ve) cells secrete?

A

Cytokines that help inflammation

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7
Q

What are the 2 subsets of Th cells?

What do these activate?

A

TH1 subset
- CD8+ve cells and macrophages

TH2
- B cells

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8
Q

What do TH1 cells secrete?

A
  • IL-2 (T-cell growth factor and CD8+ T cell activator)

- IFN-y (macrophage activator)

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9
Q

What do the TH2 subset cells secrete?

A
  • IL-4 (class switching to IgG and IgE)
  • IL-5 (eosinophil chemotaxis and activation, maturation of B cells to plasma cells and class switching to IgA)
  • IL-10 (inhibits TH1 phenotype)
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10
Q

What do CD8+ve cytotoxic T cells recognise?

What is the primary signal?

A

Intracellular antigens (presented on MHC I)

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11
Q

What interleukin is the CD8+ve cytotoxic T cell activated by?
What is this interleukin produced by?

A

IL-2 from CD4+ve TH1 cell

  • This acts as the secondary signal
  • Primary signal is from MHC I
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12
Q

What do cytotoxic T cells produce to kill the target cell?

A
  • Perforins - hole in target
  • Granzyme - apoptosis
  • FasL - binds to Fas on target cell - activating apoptosis
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13
Q

What does granzyme activate?

- This is the key enzyme in apoptosis

A

Caspase

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14
Q

What are the 3 ways to activate apoptosis / caspases?

A
  • Intrinsic mitochondrial pathway - cytochrome C leakage
  • Extrinsic receptor pathway - FasL activating Fas or TNF-a binding
  • CD8+ve T cell dumping granzyme
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15
Q

Immature B cells are produced in the bone marrow
They undergo Ig rearrangement to become naive B cells
What do naive B cells express?

A

IgM and IgD on its surface

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16
Q

How do B-cells become active? (2)

A
  • Antigen binds to surface IgM or IgD to become plasma cell which will secrete that immunoglobulin
  • B-cell antigen presentation to CD4+ helper T cells via MHC II (plus 2nd activation signal w. CD40L from Th2)
17
Q

What cluster of differentiation receptor binds to a Ligand on the hleper T cell which provides the 2nd activation signal?

A

CD40 receptor on B cell binds CD40L on Th cell providing 2nd activation signal

18
Q

What does secondary activation of the Th cell result in?

What do they then secrete?

A

IL-4 and IL-5

19
Q

The activation of Th2 cells results in the production of IL-4 and IL-5
What are the effects of these interleukins on the B cells?

A
  • Mediate B-cell isotype switching (to IgE, IgG, IgA, hypermutation and maturation to plasma cells)
20
Q

What are the 2 subtypes of chronic inflammation?

A

Granulomatous and non-granulomatous

21
Q

What are the characteristics of a granuloma (granulomatous inflammation)?

A
  • Epitheloid histiocytes (macrophages with abundant pink cytoplasm)
  • Surrounded by giant cells and rim of lymphocytes
22
Q

How can granulomas be subdivided?

A

Divided into noncaseating and caseating subtypes

23
Q

What is the key characterstic of a granuloma?

A

Epitheloid histiocytes (macrophages with abundant pink cytoplasm)

24
Q

What do noncaseating granulomas lack?

A

Central necrosis

25
Q

What are examples of conditions with noncaseating granulomas?

A
  • Sarcoidosis
  • Beryllium exposure
  • Crohn disease
  • Cat scratch disease
  • Reaction to foreign material (e.g breast implants in axillary lymph nodes)
26
Q

What disease has a characterstic stellate shaped granuloma?

A

Cat scratch disease

27
Q

What diseases have caseating granulomas?

A
  • TB

- Fungal infections

28
Q

What stain can be used to diagnose a fungal infection w. caseating granulomas?

A

GMS stain

- Silver stain

29
Q

Describe the steps involved in a granuloma formation?

A
  • Macrophages present antigen via MHC II to CD4+ helper T cells
  • Macrophages secrete IL-12 inducing CD4+ helper cells to differentiate into TH1 subtype
  • TH1 cells secrete IFN-y, which converts macrophages to epitheloid histiocytes and giant cells
30
Q

What do macrophages secrete to induce CD4+ helper cells to differentiate into TH1 subtype?

A

IL-12

31
Q

What do TH1 cells secrete which converts macrophages into epitheloid histiocytes and giant cells?

A

IFN-y

USMLE Pathology (15 decks)

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