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Y2 Immunological Disorders > Week 3 > Flashcards

Week 3 Flashcards

1
Q

What are the stages of complement action?

A

1) Pattern Recognition Trigger
2) Protease cascade amplification / C3 converts reaction
3) Inflammation
4) Phagocytosis
5) Membrane attack

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2
Q

What is complement?

A

Immune surveillance system with effects on host cells and foreign intruders.

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3
Q

What are the main functions of complement

A

Eliminate cellular debris
Eliminate infectious microbes
Orchestrates immune response
Contributes to homeostasis by sending danger signals.
Lysis of bacteria, cells and viruses.
Triggering of inflammation and sectarian of immunoregulatory molecules and clearance of immune complexes from circulation.

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4
Q

What sections of the immune system is complement part of?

A

Innate and adaptive

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5
Q

In what ways is complement activated in the innate immune system?

A

Alternative pathway

Mannose-binding lectin pathway

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6
Q

How is complement activated in the adaptive immune system?

A

Via the classical pathway with antigen-antibody complexes.

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7
Q

What are the different possible pathways of complement ?

A

Alternative
Classical
Lectin

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8
Q

What occurs in the C3 converts reaction?

A

C3 converts converts C3 to C3a and C3b.

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9
Q

What is the purpose of C3a?

A

It is inflammatory

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10
Q

What is the purpose of C3b?

A

It is deposited on the microorganism and facilitate opsonisation and phagocytosis.

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11
Q

What amplification cascade system is used by the classical pathway ?

A

The C5-C9 pathway

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12
Q

What is the purpose of C5a in complement?

A

It is inflammatory

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13
Q

What is the purpose of the C5 amplification step of complement via the classical pathway?

A

Allows for a cascade that creates a pore in the membrane that facilitates lysis.

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14
Q

What are the issues with activating the complement system?

A

IF any of the genes or proteins that are used in regulation are damaged or lost, loss of regulation of complement can occur. This can have serious clinical consequences such as hyper-activation and being immunocompromised resulting in infection and sepsis.

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15
Q

In the Lectin pathway of complement, briefly outline the initiation process.

A

Mannose-binding lectin recognises and binds carbohydrates on the pathogen surface.

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16
Q

In the Classical pathway of complement, briefly outline the initiation process.

A

C1q interacts with pathogen surface or with antibodies bound to the surface.

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17
Q

In the alternative pathway of complement, briefly outline the initiation process.

A

C3 undergoes spontaneous hydrolysis and initiates deposition of C3 converts on microbial surfaces.

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18
Q

At what stage do all 3 pathways of complement converge and what happens at this stage?

A

All generate a C3 converts which cleaves into C3a and C3b. C3b is bund to the microbial surface whilst C3a is released.

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19
Q

What happens after the C3 converts stage in the lectin pathway of complement?

A

C3a and C5a recruit phagocytic cells to the site of infection and promote infection.

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20
Q

What happens after the C3 converts stage in the classical pathway of complement?

A

Phagocytes with receptors for C3b engulf and destroy the pathogen.

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21
Q

What happens after the C3 converts stage in the alternative pathway of complement?

A

Completion of the complement cascade leads to formation of a membrane-attack complex which disrupts cell membrane and causes lysis.

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22
Q

Outline the process of inflammation from the C3a cleavage process.

A

Small complement-cleavage products act on blood vessels to increase vascular permeability and cell-adhesion molecules.

Increased permeability allows increased fluid leakage from blood vessels and extravasio of immunoglobulin and complement molecules.

Migration of inflammatory cells increases.

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23
Q

What are some of the physical causes of inflammation?

A

Trauma
Heat or cold
Radiation

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24
Q

What are some of the infectious causes of inflammation?

A

Bacteria, viruses, parasites

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25
Q

What are some of the chemical causes of inflammation?

A

Simple chemical poisons and organic poisons

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26
Q

What are some of the immunological causes of inflammation?

A

Hypersensitivity reactions such as antigen-antibody and cell mediated reactions.

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27
Q

What are the signs and symptoms of inflammation?

A

Heat
Pain
Redness
Swelling

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28
Q

What happens to cause vascular congestion during inflammation?

A

Blood accumulates in organs or tissues which decreases venous return.

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29
Q

What are some of the issues that can come from vascular congestion due to inflammation?

A

Often leads to haemorrhage into surrounding tissues.

Can lead to fibrosis

Can lead to organ dysfunction.

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30
Q

How does venous congestion lead to congestive heart failure ?

A

Increased pressure in central veins causes them to expand, which puts pressure on hepatocyte cells that surround the veins. This disrupts normal functioning of the hepatocyte cells and leads to cell death.

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31
Q

If repeated cycles of vascular congestion occur, what can happen?

A

Micro-haemorrhages and fibrosis around central veins which can lead to permanent dysfunction and increased central venous pressure as well as congestive heart failure.

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32
Q

What vascular changes occur due to congestion in the lungs?

A

Accumulation of macrophages in the alveoli leads to micro-haemorrhages.

Chronic inflammation and fibrosis in the interstitial lung tissue.

Scarring of lung tissue leading to decreased lung compliance and impaired gas exchanged.

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33
Q

What effects does scarring of the lungs have?

A

Leads to decreased lung compliance and impaired gas exchange.

34
Q

What are the microscope signs and symptoms of inflammation?

A

1) Hyperaemia
2) Exudation of fluid
3) Emigration of Leukocytes through small blood vessel walls.

35
Q

What is Hyperaemia?

A

Increase of blood flow to different tissues in the body.

36
Q

What is exudation of fluid?

A

Fluid leading out of blood vessels into nearby tissues.

37
Q

What are the advantageous results of exudation?

A

Fluid increases the diction of toxins.

38
Q

What are the cells of the inflammatory response?

A 
Neutrophils
Eosinophils
Basophils and Mast cells
Monocytes and Macrophages
Lymphocytes and plasma cells
39
Q

What are the functions of neutrophils as part of the inflammatory response?

A

Degrade cell debris

Phagocytose microbes

40
Q

Where are neutrophils made ?

A

Bone marrow

41
Q

What cells are first to the site of an inflammatory response?

A

Neutrophils

42
Q

What are the functions of Eosinophils as part of the inflammatory response?

A

They reduce allergic hypersensitivity responses.

Degrade mast cell mediators.

43
Q

What happens to basophils and mast cells upon activation?

A

Degranulation

44
Q

What are macrophages derived from?

A

Monocytes

45
Q

How do monocytes and macrophages aid the inflammatory response?

A

They release chemotactic factors.

46
Q

What do chemotactic factors do?

A

Stimulate cellular migration and locomotion

47
Q

What are the largest Leukocytes?

A

Monocytes

48
Q

What do monocytes differentiate into?

A

Macrophages and Myeloid lineage dendritic cells

49
Q

What initiates the classical pathway of complement ?

A

IgG and IgM clusters - antibody dependent.

50
Q

What are the purposes of C3a and C5a?

A

They release and trigger pro inflammatory signalling via G-protein coupled receptors.

They chemoattrract Neutrophils, Monocytes and Macrophages to sites of complement activation. The promotes phagocytosis.

51
Q

How do C3a and C5a promote phagocytosis?

A

Via the interaction of opsonins with complement receptors.

52
Q

How do microbes evade complement?

A

Capturing complement initiation without activating them.

Depleting complement components.

53
Q

How do microbes inhibits convertase activity?

A

They recruit complement regulators to their surface or secrete regulator mimics. This leads to inhibition of converts activity or prevention of immune signalling.

54
Q

How is complement coordinated with innate immunity?

A

Using toll-like receptors.

55
Q

What different type of crosstalk can occur between complement and toll like receptors?

A

Synergistic

Antagonistic

56
Q

What is synergistic crosstalk?

A

Interaction of two or more agents to produce a combined effect greater than the sum of their separate effects.

57
Q

How is crosstalk helpful to innate defence ?

A

It validates the presence of genuine danger, justifying and necessitating the amplification of the hosts antimicrobial and anti-inflammatory response.

58
Q

What is the aim of complement-coagulation interplay?

A

To enhance local clotting and prevent microbial spread throughout the circulation

59
Q

What do each of complement and coagulation provide in their interplay?

A

Complement amplifies coagulation using C5a

Components of the coagulation cascade amplify complement activation.

60
Q

What can happen when coagulation-complement crosstalk is uncontrolled ?

A

It can lead to life threatening conditions such as disseminated intravascular coagulation.

61
Q

How does complement help humeral immunity?

A

It promotes the effector function of the antibody response.

62
Q

How can complement cause inflammatory diseases?

A

Accumulation and unsuccessful removal of cellular debris by complement may lead to autoimmune disorders and neurodegenerative diseases with a chronic inflammatory component.

63
Q

What can excessive complement activation cause?

A

Rare but severe kidney diseases that often lead to renal failure.
Alzheimers.

64
Q

How do acute-phase disorders affect complement reactions?

A

They trigger a more aggressive complement response that can lead t tissue damage.

65
Q

What is hyperaemia?

A

Excess blood - generally in the vessels in the tissue where the inflammation is occurring.

66
Q

What is exudation?

A

Movement of fluid and proteins into the extracellular space which causes the swelling during inflammation.

67
Q

What is opsonisation?

A

Deposition of C3b onto a microorganism. This acts a a marker for phagocytes and other cells which will the engulf this cell.

68
Q

Why do we have the complement system? -

A
  • Key components of the immune responses and homeostasis.
  • Immune surveillance of host cells
  • Removal of cell debris
  • Immune surveillance for microorganisms
  • Removal of infectious microorganisms
69
Q

What is the complement system?

A
  • Enzymes and proteins that complement clearance of microorganisms and damaged cells.
70
Q

What complement pathways are innate?

A

Alternative

Mannose-binding lectin

71
Q

What complement pathway is adaptive?

A

Classical

72
Q

What is the main purpose of C3a?

A

Inflammation

73
Q

What is the main purpose of C5a?

A

Inflammation

74
Q

What is the main purpose of C3b?

A

Opsonisation and phagocytosis

75
Q

What is the main purpose of C5b?

A

Helps form pore that leads to lysis of cells

76
Q

How is the complement system regulated?

A
  • Control proteins in the plasma are at higher concentration that in complement process.
  • Control proteins on the membrane of self-cells prevent complete lysis.
77
Q

What are the causes of inflammation?

A 
Physical
Infection
Chemical
Immunological
Damage to tissues
78
Q

What are the vascular changes that occur during inflammation and what effects do these changes have?

A
  • Blood accumulation
  • Decreased venous return caused by block of venous return.
  • Chronic congestion
  • Haemorrhage into tissues
  • Inflammation leads to fibrosis
  • Fibrosis causes organ dysfunction
79
Q

What are the signs of inflammation?

A
  • Hyperaemia
  • Exudation of fluid
  • Emigration of leukocytes through small blood vessels.
80
Q

How is exudation of fluid helpful in the inflammatory response?

A

It brings along mediators that can help the inflammatory response.

81
Q

What is the purpose of fibroblasts in the inflammatory response?

A

Aid tissue repair

Y2 Immunological Disorders (9 decks)

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