Inflammation Flashcards

1
Q

What is inflammation?

A

State where the body is trying to home the immune response to a certain area

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2
Q

What are the functions of receptors?

A

Provide information to tell the cells where they are and what is around them

Allows cells to sense the environment

Transmit signals from the cell surface to the nucleus to change gene expression and function

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3
Q

What are cytokines?

A

Soluble messengers between cells

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4
Q

What are the different families of cytokines?

A

Interleukins

Interferons

Tumour Necrosis Factor

Colony-stimulating factors

Chemokines

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5
Q

Features of cytokines

A

Work through synergistic or antagonistic ways

Can de redundant

Can be pleiotropic

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6
Q

Which cells produce cytokines?

A

Activated immune cells

Epithelial cells

Stromal cells

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7
Q

What types of cytokines are released in the induction phase of inflammation?

A

Pro-inflammatory cytokines

Interferons

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8
Q

Examples of pro-inflammatory cytokines

A

TNF-a

IL-6

IL-1b

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9
Q

Examples of interferons

A

IFNa

IFNb

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10
Q

What are the effects of pro-inflammatory cytokines?

A

Local effects

Long range effects through travelling in the blood including liver, acute phase protein release and fever induction

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11
Q

What induces the release of interferons?

A

Viral infection

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12
Q

What are the effects of interferons?

A

Prevent viral replication

Activate dendritic cellls, macrophages and NK cells

Induce chemokines

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13
Q

What is released during the resolution phase?

A

Anti-inflammatory cytokines

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14
Q

Examples of anti-inflammatory cytokines

A

TGFb

IL-10

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15
Q

What is the main role of chemokines?

A

Attract other cells

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16
Q

Features of chemokines

A

Lots of redundancy in chemokine function

Several chemokines display similar activity and show shared receptor usage

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17
Q

Relevance behind naming system for chemokines

A

In the beginning, chemokines had more functionally descriptive names like Monocyte Chemotactic Protein-1

Now they have complex names denoted by L for ligand and a number linked to the receptor number

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18
Q

When are chemokines released?

A

During inflammation

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19
Q

Which molecules work in close association with chemokines?

A

Cell adhesion molecules

Work to get immune cells from the blood into the tissue

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20
Q

What dictates the type of leukocytes recruited into tissues?

A

Cellular distribution of receptors and cellular adhesion molecules

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21
Q

What is inflammation?

A

Process that rapidly recruits cells of the immune system to the sites of injury or infection

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22
Q

What are the signs of inflammation?

A

Swelling

Elevated temperature

Pain

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23
Q

What causes the signs of inflammation?

A

Increased blood flow

Entry of leukocytes into the tissue

24
Q

What are examples of pattern recognition receptors?

A

TLR

Scavenger receptors

Lectin

NOD like receptors

Complement prteins

Ficolins

Collections

25
Q

What are examples of surface PRRs?

A

TLR

Scavenger receptors

Lectin

26
Q

What are examples of solubles PRRs?

A

NOD like receptors

Ficolins

Lipopolysaccharide-binding proteins

27
Q

What is the complement system?

A

Key component of inflammation

30 or more proteins which act in an enzymatic amplification cascade to generate active complement components in several aspects of the immune response

28
Q

In which processes is complement important?

A

Opsonization

Inflammation

29
Q

What are the 3 ways to activate complement?

A

Classical

Lectin

Alternative

30
Q

What triggers the classical pathway?

A

Antibody antigen complexes

31
Q

What triggers the lectin pathway?

A

Mannose binding lectin

32
Q

What triggers the alternative pathway?

A

Bacterial wall components

33
Q

What is a key event in complement activation?

A

Splitting of C3

34
Q

Describe the splitting of C3

A

C3a and C3b are formed by cleavage by C3 convertase

35
Q

How do complement make MAC

A
  1. Complex of four (C5b. C6, C7, C8) complement proteins bind to the outer surface of the plasma membrane
  2. This complex binds many copues of C9 that hook up to one another, forming a ring in the membrane
  3. The ring structure is a pore in the membrane that allows free diffusion of molecules in and out of the cell
  4. If enough pores form, the cell is no longer able to survive
36
Q

What are the 3 phases of acute inflammation?

A

Vascular

Cellular

Removal of infectious agent

37
Q

Describe the vascular phase

A

Increased blood flow to infected tissues

Localised increased permeability

Endothelium becomes adhesive to allow chemotaxis into the tissues

38
Q

Describe the cellular phase

A

Leukocytes accumulate in local vasculature

Leukocyte migration into infected tissue

39
Q

Which two cells are important in acute inflammation?

A

Mast cells

Macrophages

40
Q

How are mast cells involved in acute inflammation?

A

Become activated by antigen receptors and complement

Contain granules with pre-formed histamine

Histamine causes blood cells to become more permeable

Mast cells become lipid mediators which break down arachidonic acid into leukotrienes and prostaglandins, which recruit more neutrophils

41
Q

How are macrophages involved in acute inflammation?

A

Release lipid-derived inflammatory mediators

Cytokines

Chemokines

Present antigens to T cells

42
Q

What is the acute phase response?

A

Once the local response has happened, the blood mediators travel to the periphery

Cytokines act on the liver to increase the secretion of APPs

This increases the release of complement, C-reactive proteins and coagulation factors

43
Q

What other organs do cytokines affect?

A

Brain

Causes fatigue and lack of appetite

44
Q

What is a key feature of inflammation?

A

Neutrophils enter the tissue

45
Q

Describe the process by which neutrophils enter the tissue

A
  1. Neutrophils are normally swimming in the blood
  2. When they approach inflamed area, the endothelium increases expression of P-selectin, causing the neutrophils to travel more slowly
  3. If endothelium is activated, TNF and other inflammatory mediators cause it to express VCAM
  4. Neutrophils have core receptors for these proteins, causing the neutrophils to bind firmly to the endothelium wall
  5. The neutrophil then crawls between gaps in the endothelium during diapedesis following a chemotactic gradient
46
Q

What is the resolution phase?

A

End point of acute inflammation

Aims to stop cells from entering the tissues once the inflammatory response has been effective

47
Q

Which cells are involved in the resolution phase?

A

Neutrophils mop up extra soluble mediators

Monocytes differentiate into macrophages and then into resolution macrophages

Neutrophils then undergo apoptosis, and are ingested by macrophages which leads to the macrophages switching off

48
Q

What are causes of chronic infection?

A

Persistent injury or infection - ulcer, TB

Prolonged exposure to a toxic agent

Autoimmune diseases

49
Q

What happens when individuals age?

A

There is a low-grade inflammation which leads to many conditions and prevents the immune system from working properly

50
Q

Which conditions have been linked to chronic infection?

A

Diabetes

Cancer

Neurological diseases

Autoimmune diseases

Pulmonary diseases

Arthritis

51
Q

Complement involved with clearance of immune complexes

A

C3b

52
Q

Complement involved with B-cell activation

A

C3d

53
Q

Complement involved with mast cell degranulation

A

C3a, C4a and C5a

54
Q

Complement involved with chemotaxis

A

C5a

55
Q

Complement involved with opsonization

A

C3b, C4b

56
Q

Complement involved with cell lysis

A

C5b-C9