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PA20351 > The innate immune system > Flashcards

The innate immune system Flashcards

1
Q

What are the ways in which the body can react to foreign (non-self) and self antigens?

A

Immune response (elimination of antigen) and immune deficiency to foreign antigens, and autoimmunity and tolerance to self antigens. Tolerance and immune response as the correctly functioning responses.

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2
Q

What is the innate immune system?

A

A common set of responses turned on by most microbial agents - it is non specific.

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3
Q

What is the adaptive immune system?

A

The individual response to being exposed to a specific antigen. This immune system is capable of change during the response - this is called adaptation.

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4
Q

When does the adaptive immune system start functioning?

A

At around 6 months old, but adaptive immunity can be acquired through the mothers blood.

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5
Q

What are the components of the innate immune system?

A

Physical barriers (epithelial surfaces), cellular components (phagocytes and NK cells), complement system and mediators of inflammation and cytokines.

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6
Q

What is acute inflammation?

A

The movement of white blood cells from the blood stream into the tissues - this is a good thing.

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7
Q

What cells produce cytokines?

A

White blood cells.

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8
Q

What are some of the physical barriers to invading pathogens?

A

Epithelial surfaces such as the skin, GI tract and respiratory tract.

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9
Q

What do epithelial surfaces secrete?

A

Anti-microbial substances known as defensins.

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10
Q

What increases the secretion of antimicrobial substances?

A

Cytokines - specifically IL-1 and TNFalpha.

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11
Q

What must pathogens do in order to infect the body?

A

They must pass through the tight junctions of the epithelia into the underlying smooth muscle and tissue. Epithelial often have cilia to try and prevent this entry.

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12
Q

What are antimicrobials?

A

Broad spectrum antibiotics that help to decrease the amount of pathogens that are sitting on the surface of the epithelial cells.

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13
Q

What do peritoneal lymphocytes secrete?

A

Antibodies against LPS (lipopolysaccharide - endotoxin)

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14
Q

What are the characteristic features of neutrophils?

A

They have a large, multi-lobed nucleus and have many intracellular organelles.

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15
Q

What are the characteristic features of macrophages?

A

They are large cells with a rounded nucleus and have many intracellular organelles.

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16
Q

What are the characteristic features of dendritic cells?

A

They are large cells with a smaller nucleus:cytoplasm ratio than other cells. They have membrane protrusions (“dendritic”).

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17
Q

What are the characteristic features of natural killer cells (NK)?

A

They are smaller than macrophages but with similar morphologies.

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18
Q

What are the most common type of white blood cells?

A

Neutrophils.

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19
Q

What is the difference between macrophages and monocytes?

A

They are known as monocytes when circulating in the blood and macrophages in the tissues.

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20
Q

What are the functions of neutrophils?

A

Phagocytosis. They release reactive oxygen and nitrogen species and antimicrobial peptides.

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21
Q

What are the functions of macrophages?

A

Phagocytosis, release of inflammatory mediators, antigen presentation, release of reactive oxygen and nitrogen species, release of cytokines and complement proteins.

22
Q

What are the functions of dendritic cells?

A

Antigen presentation,release of costimulatory signals, reactive oxygen species, interferons and cytokines.

23
Q

What are the functions of natural killer cells?

A

Lysis of viral-infected cells, interferon and macrophage activation.

24
Q

What is the cellular function of the innate immune system?

A

Recognise structures on microbes that are not present on mammalian cells using pattern recognition receptors.

25
Q

What are some pattern recognition receptors found on white blood cells?

A

Mannose receptors, receptors for opsonins, toll-like receptors and 7-transmembrane alpha helical receptors.

26
Q

What does binding of the pathogen to receptors on innate cells result in?

A

Phagocytosis of the pathogen by macrophages or neutrophils, killing of the infected cell by NK cells and presentation to T cells by APCs (dendritic cells).

27
Q

What are the cells involved in the immune system?

A

Neutrophils, macrophages, dendritic cells and natural killer cells.

28
Q

What are mannose receptors?

A

Carbohydrate quality receptors that are found on the surface of organisms. Binding causes phagocytosis and production of cytokines.

29
Q

What are toll-like receptors?

A

They are found on most cells of the innate immune system and respond to a variety of microbial markers, such as LPS, ds RNA and bac peptidoglycans.

30
Q

What does binding to toll-like receptors result in?

A

Upregulation of inflammatory gene expression, production of cytokine and reactive oxygen intermediates.

31
Q

What are some genes involved in the inflammatory gene expression?

A

TNFalpha, IL-1, IL-12, E-selectin and iNOS.

32
Q

What is iNOS?

A

Inducible nitric oxide synthases - these are involved in catalyzing the production of nitric oxide which is an important cellular signalling molecule.

33
Q

What is LPS?

A

Lipopolysaccharide, also known as endotoxin. It is a product of gram negative bacteria cell wall.

34
Q

How is LPS involved in the innate immune system?

A

It stimulates the innate immune system and is pathogenic - it induces local and systemic inflammation and is a potent activator of macrophages inducing cytokine release and reactive oxygen bursts.

35
Q

What is systemic inflammatory response syndrome?

A

It is a inflammatory state that affects the whole body and can be induced by LPS. It includes fever, neutrophilia and septic shock.

36
Q

How does phagocytosis occur?

A

The microbe binds to cell surface receptors and is endocytosed. The phagosome formed then fuses with lysosomes containing degrading enzymes.

37
Q

What degrading enzymes are found in lysosomes?

A

Lysozyme, collagenase, elastase and ROIs and NO.

38
Q

How are reactive oxygen species formed?

A

From arginine by iNOS.

39
Q

What are some reactive oxygen species?

A

Superoxide, hydrogen peroxide.

40
Q

What is the function of natural killer cells?

A

They recognise microbial markers on the surface of infected cells, and perforins make moles in the membrane that allow the entry of granzyme. The infected cells die by apoptosis.

41
Q

What activates natural killer cells?

A

IL-12 from macrophages, IFNgamma.

42
Q

What is the complement system?

A

A cascade of plasma proteins that is activated by microbes resulting in their destruction.

43
Q

What is a zymogen?

A

An inactive substance that is converted into an enzyme when activated by another enzyme.

44
Q

How are zymogens activated?

A

Cleavage.

45
Q

What are the pathways of the complement system?

A

The classical, alternative and lectin.

46
Q

What is the classical complement pathway?

A

C1 detects antibody bound to the microbe and cleaves C2/4.

47
Q

What is the alternate complement pathway?

A

A direct recognition of the microbe.

48
Q

What is the lectin complement pathway?

A

Mannose receptor binds lectin and cleaves C4.

49
Q

What happens in the subsequent steps of the complement pathway?

A

C3 is cleaved to C3a and C3b. C3a results in inflammation and C3b is deposited on the microbe (opsonization and phagocytosis). C5 is then cleaved to C5a and b that causes further inflammation, and then a membrane attack complex is formed due to this cascade that causes lysis of the microbe.

50
Q

What is the function of cytokines?

A

They mediate many of the effector functions of the innate system.

51
Q

What is TNF/IL-1?

A

The majority is produced by LPS challenged macrophages. They are pro-inflammatory cytokines and they stimulate neutrophil migration to the site of infection.

52
Q

What is IL-12?

A

They are produced by macrophages and dendritic cells and promote NK cytolysis. It stimulates IFNgamma production in T and natural killer cells, and IFNgamma stimulates macrophages to kill microbes.

PA20351 (11 decks)

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