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Inflammatory arthritis week > Chronic inflammation and wound healing - Pathology > Flashcards

Chronic inflammation and wound healing - Pathology Flashcards

1
Q

What are the 3 factors in chronic inflammation

A

Prolonged inflammation from persistence of injury causing agent,

Presence of lymphocytes and plasma cells in tissue

Delayed specific (adaptive) response

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2
Q

What are the 4 things that can cause chronic inflammation

A

Persistent infection of difficult onganisms (viruses, mycobacteria, parasites and fungi)

Autoimmune disease

FOreign material

Carcinoma

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3
Q

What role do macrophages play in chronic inflammation

A

Dominant role, become so within 48 hours of onset

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4
Q

How are macrophages activated via the classical pathway

A

Bacterial products engage TLRs, or by interferon gamma. M1 macrophages produce NO, ROS and upregulate lysosomal enzymes killinf ingested organisms.

Cytokines secreted, inflammation stimulated

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5
Q

Describe how macrophages are stimulated via the alternative pathway

A

Induced by cytokines other than interferon gamma. M2 macrophages secrete growth factors promoting angiogenesis, fibroblast activation and collagen synthesis. These focus on tissue repair

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6
Q

What is angiogenesis

A

The process where new blood vessels form from existing ones

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7
Q

Where are T-lymphocytes produced and where do they develop

A

Produced as progenitor cells in bone marrow, develop further in the thymus.

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8
Q

What two types of cell can progenitor T cells develop into

A

CD4+ T helper cells, or CD8+ cytotoxic T-cells

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9
Q

What do T-cells use for antigen surveillance?

A

TCR complex (TCR and CD3). THis recognises antigens on MHC molecules. T cells activated with a second signal

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10
Q

What is the second ligand that activated T helper cells apart from MHC II

A

B7 on antigen binding to CD28 on the T helper cell provides the necessary second activation signal

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11
Q

WHAT do T h 1 cells do

A 
Secrete interferon Gamma,
Promotes B-cells to class switch from IgM to IgG, 
Activates macrophages by classical path
Promotes Th1 cells and inhibits Th2 cells.

Involved against viruses and bacteria

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12
Q

What do Th2 cells do?

A 
Secrete IL4, 5, and 13. 
IL4 stimulates B cells to class switch to IgE, IL5 stimulates eosinophil (so does IL13) chemotaxis/activatin, and class switching to IgA

Involved against parasites or allergic reactions

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13
Q

How are cytotoxic t cells activated?

A

MHC I molecules present intracellular antigens, meet with TCR and CD8 co-receptor on cytotoxic t cell.

IL-2 from a CD4 T helper cell provides a second activation signal

Another cytotoxic t cell binds to oringinal cell via FAS ligand, activating apoptosis

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14
Q

What do naive B cells express to meet with antigens before maturation to plasma cells

A

IgM or IgD.

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15
Q

What happens once an antigen binds to a B cell

A

The antigen complex is preented to CD4+ helper T cells, along with MHC II. CD40 is a coreceptor, T helper cell secretes IL4 and IL5 to cause B cell to mature to plasma cell

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16
Q

What are the two types of granuloma

A

immune granuloma or foreign body granuloma

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17
Q

When do foreign body granulomas form?

A

Forms when the inciting agent cannot be readily eliminated,

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18
Q

When do foreign body granulomas form

A

In response to relatively inert foreign bodies in the absence of T-cell mediated immune responses

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19
Q

How do granulomas form

A

Macrophages present ingected antigen to CD4+ th cells. Macrophages release Il12 to form TH1 cells which secrete interferon gamma, converting macrophages into epithelioid histiocytes and giant cells

20
Q

What are the two basic principles of wound healing

A

regeneration and repair

21
Q

What is a labile tissue

A

One that possesses stem cells that continuously cycle to regenerate tissue

22
Q

What is a stable tissue

A

Cells that can re-enter the cell cycle to regenerate tissue when necessary

23
Q

What is a permanent tissue?

A

There is no significant regenerative potential

24
Q

What is replacement in a healing sense

A

Replacement of a damaged tissue with natice tissue

25
Q

What is repair in a healing sense

A

Replacement of damaged tissue with a fibrous scar

26
Q

when does the repair stage occur

A

When regenrative stem cells are lost or tissue lacks regenerative capacity

27
Q

What is the initial phase of repair?

A

Granulation tissue

28
Q

What makes up granulation tissue

A

Proliferated capillaries (nutrients), fibroblasts (III collagen) and myofibroblasts (wound closure)

29
Q

How does collagen change in scar formation

A

From type III (pliable) to type I (high tensile strength

30
Q

How are tissue regeneration and repair mediated?

A

Paracrine signalling as macrophages secrete growth factors targeting fibroblasts.

these result in gene expression and cellular growth

31
Q

What does transforming growth factor (TGF) alpha do

A

Promotes epithelial and fibroblast growth

32
Q

What does TGF beta do

A

Promotes fibroblast growth anf inhibition of inflammation

33
Q

What does Platelet derived growth factor (PDGF) do?

A

Encourages growth of endothelium, smooth muscle and fibroblasts

34
Q

What does fibroblast growth factor do

A

Promotes angiogenesis and skeletal development

35
Q

What does vascular endothelial growth factor do?

A

Promotes angiogenesis

36
Q

What are the four stages of wound healing

A

Coagulation

Inflammatory

Proliferative/granulation

Remodelling

37
Q

What is healing by primary intention?

A

Wound edges brought together (suturing) leading to minimal scarring

38
Q

What is healing by secondary intention

A

Edges not brought together, granulation tissue fills the gap, myofibroblasts contract the wound. Scar forms

39
Q

What is a hypertrophic scar

A

Excess production of scar tissue, localised around the wound

40
Q

What is a keloid scar

A

Exuberant production of scar tissue disporportionate of wound size.

41
Q

How does vitamin C deficiency play a role in delayed healing?

A

Disrupted collagen cross-linking

42
Q

How does copper deficiency play a role in delayed healing?

A

Disrupted collagen cross-linking

43
Q

How does zinc deficiency play a role in delayed healing?

A

Replaces type III with type I

44
Q

What is autoimmunity

A

Failure of self tolerance

45
Q

What is hypersensitivity

A

Excess immune reaction

46
Q

What are the four types of hypersensitivity reaction

A

Tyoe I (anaphylaxis, allergy, asthma)

Type II (Antibody mediated, haemolytic anaemia)

Type III (Immune complex related, SLE, glomerulonephritis)

Type IV (T-cell mediated, RA, Psoriasis)

47
Q

How do regulatory T-cells suppress autoimmunity?

A

Blocking T-cell activation and producing anti-inflammatory cytokines

Inflammatory arthritis week (2 decks)

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