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MIIM20002 - Microbes, Infections, Responses > Lecture 4 - Overview of the Immune Response > Flashcards

Lecture 4 - Overview of the Immune Response Flashcards

1
Q

What is an immune response?

A

Reaction to:

  • components of microbes
  • other foreign molecules
  • ‘danger’
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2
Q

What are the four principles of the immune response?

A

1/ Recognition
2/ Effector response
3/ Regulation
4/ Memory

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3
Q

What are the requirements of the immune response?

A
  • no harm to host
  • rapid
  • present at birth
  • appropriate for pathogen
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4
Q

In general, how does the immune system recognise ‘self’ from ‘non-self’?

A

Molecular differences

‘Non-self’ will have molecules on the surface that distinguish it from ‘self’

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5
Q

What is the difference between PAMPs and Antigens?

Which receptors detect each?

A

PAMPs: pathogen associated molecular patterns

  • common to all pathogens
  • PRRs

Antigen:

  • unique to a particular organism
  • Antibodies / Antigen receptors
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6
Q

Assess the innate immune system in the following criteria:

  • specificity
  • diversity
  • memory
  • response time
  • magnitude of response
  • cells
  • chemical barriers
  • soluble proteins
A
  • specific to PAMPs
  • limited diversity
  • no memory
  • rapid response
  • no change in magnitude
  • Macrophages, NK cells
  • Antimicrobial molecules
  • Cytokines, complement
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7
Q

Assess the adaptive immune system in the following criteria:

  • specificity
  • diversity
  • memory
  • response time
  • magnitude of response
  • cells
  • chemical barriers
  • soluble proteins
A
  • specific to antigens
  • huge amount of diversity
  • memory
  • slow response time
  • magnitude increases with exposure
  • Lymphocytes
  • IgA (antibodies)
  • cytokines
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8
Q

What are the two pathways of development for the cells on the immune system?

A 
Myeloid progenitor:
• neutrophils
• eosinophils
• basophils
• macrophages

Lymphoid progenitor:
• T lymphocytes
• B lymphocytes
• NK cells

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9
Q

What factors determine the fate of the progenitor cells?

A

Bone marrow stromal cells

CSFs: colony stimulation factors

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10
Q

What are the different types of PRRs?

A

TLR: toll-like receptors
NOD: nucleotide binding oligomerisataion domain
RIG: Retinoic acid inducible gene
Collectins: proteins that bind CHOs

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11
Q

What are DAMPs?

A

Danger associated molecular patterns

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12
Q

What does TLR-2 bind?

A

Components of the bacterial cell wall:

- peptidoglycan

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13
Q

What does TLR-4 bind?

A

LPS

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14
Q

What does TLR-5 bind?

A

Flagellin

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15
Q

What does TLR-9 bind?

A

CpG-DNA

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16
Q

What do NLRs bind?

A

Peptidoglycan on G- cells

DAMPs

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17
Q

What are some examples of DAMPs?

A

Free fatty acids

Stress metabolites

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18
Q

What happens when TLRs and NODs are engaged?

A

Expression of different cell surface receptors

  • Cytokine production
  • Defensin production
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19
Q

What happens when Mannose receptors are engaged?

A

Phagocytosis

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20
Q

What is ligation of RIGs associated with?

A

Anti-viral immunity

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21
Q

What are the constitutive factors that mediate innate IS?

A
  • Complement proteins
  • C reactive protein
  • Mannose binding lectin
  • Lysozyme
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22
Q

What does lysozyme do?

A

Disrupts the cell wall (peptidoglycan)

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23
Q

What does C reactive protein do?

A

Binds to the capsule –> phagocytosis

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24
Q

What are defensins?

A

Proteins that kill phagocytosed bacteria by putting holes in the cell wall

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25
Q

What is mannose binding lectin?

A

It is a protein on the cell that binds to mannose on the invader, triggering the complement cascade

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26
Q

How may the complement cascade be activated?

A

Classical pathway: antibody binds to invader

Mannose binding lectin pathway: MBL binds to mannose on microbe

Alternate pathway: binding directly to the pathogen

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27
Q

What are the effector responses of the complement cascade?

A

Opsonisation: coating, ready for phagocytosis

MAC: pore-formation in the cell wall of the bacterium

Chemotaxis: recruitment of inflammatory cells

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28
Q

What are the induced soluble factors that mediate immunity?

A

Cytokines

Chemokines

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29
Q

What are cytokines?

A

Secreted proteins that warn neighbouring cells that there is an invader present

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30
Q

What are chemokines?

A

Secreted protein that attract cells to the site of infection

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31
Q

What is the receptor of a B cell?

A

Antibody

32
Q

What is the receptor of a T cell?

A

T cell receptor

33
Q

What is the structure of antibody?

A

Fab: variable region
Fc: constant region

Two light chains
Two heavy chains

34
Q

What is the structure of a T cell receptor?

A

Constant and variable region

Alpha and beta chain

35
Q

What can antibodies bind?

A

Molecules associated with extracellular pathogens

36
Q

What can T cell receptors bind?

A

Peptides associated with intracellular antigens

37
Q

Describe the location of innate leucocytes of the innate immune system

A

Blood –> infected tissue

38
Q

Describe how neutrophils migrate from blood to tissues

A
  1. Chemotactic gradient, cytokines making endothelium leaky
  2. Congestion, margination, rolling, adhesion of neutrophils in the endothelium
  3. Diapedesis
  4. Neutrophils follow the chemokine gradient to the invader
39
Q

Describe the locations of the elements of the adaptive immune system

A

Circulate in blood
Secondary lymphoid tissue (interact here with APCs)
Migrate to infected tissue

40
Q

How is it possible that pathogens present at peripheral sites can interact with circulating lymphoctes?

A

The lymphatic system

APCs are the relay mechanism

41
Q

Describe the generalised flow of lymph

A
  • Infected tissue
  • Afferent lymphatic vessel
  • Lymph node
  • Efferent lymphatic vessel
  • Thoracic duct
  • Venous system
  • Back to infected tissue
42
Q

Where do naive lymphocytes come into contact with pathogens?

A

In secondary lymphoid organs

43
Q

What are some secondary lymphoid organs?

A

Spleen
Lymph nodes
Peyer’s patches
Adenoids

44
Q

What are some primary lymphoid tissues?

A

Bone marrow

Thymus

45
Q

Describe blood flow through lymph nodes

A

Artery in through hilum

  1. Lymphocytes move through HEV into Paracortex and cortex
    3a. B cells: B cell zone, follicle
    3b. T cells: Paracortex
  2. Encounter lymph that has come in through the afferent lymphatic
  3. Activated lyphocytes exit via vein
  4. Vein leaves via hilum
46
Q

Describe how lymphoctes move from circulation into the lymph node

Where does this occur?

A

This occurs at the HEV: (high endothelial vessels)

  1. Rolling and weak adhesion to endothelium
  2. Strong adhesion to endothelium
  3. Emigration into lymph node
47
Q

What is different about migration of neutrophils into infected tissue, and migration of lymphocytes into the lymph node

A

Same process, different selective molecules

48
Q

Where do T cells hang out in the lymph node?

A

Paracortex

49
Q

Where do B cells hang out in the lymph node?

A

B cell zone, follicle

50
Q

What determines where the lymphocytes will migrate to, once in the lymph node?

A

Chemokines

51
Q

How are T cells activated?

A

(Adhesion)

  1. Antigen presented to their TCR on MHC of APC
  2. Costimulation
  3. Cytokines
52
Q

Which MHC molecules interact with which T cell?

A

CD4+ cells: MHC II

CD8+ cells: MHC I

53
Q

How does peptide come to be on MHC I?

A
  1. Peptide produced within a cell
  2. Peptide broken down by proteasome
  3. Peptide delivered into ER through TAP complexes
  4. Peptide loaded onto MHC I
  5. MHC I transported to the cell surface
54
Q

How does peptide come to be on MHC II?

A
  1. Bacterium taken into the cell by endocytosis, broken down
  2. MHC II with invariant chain gets delivered to phagolysosome
  3. Peptide displaces invariant chain
  4. MHC II + peptide delivered to the cell surface
55
Q

Describe costimulation of APCs and CD4+ cells

A

CD80, CD86 interact with CD28

56
Q

Describe Signal 3 of CD4+ cell activation

A

Specific cytokines (depending on the PAMP-PRR interaction), controlling the differentiation of CD4+ cells.

57
Q

TGF-B skews Th cells towards…

A

Treg

58
Q

IL-6 skews Th cells towards…

A

Th17

Tfh

59
Q

IL-12 skews Th cells towards…

A

Th1

60
Q

IL-4, IL-33 skews Th cells towards…

A

Th2

61
Q

What is the role of Treg?

A

Downregulates immune function

62
Q

What is the role of Th17?

A

Neutrophil recruitment

63
Q

What is the role of Th1?

A

Inflammation

64
Q

What is the role of Th2?

A

Parasite immunity

Allergy

65
Q

What is the role of Tfh?

A

B cell proliferation and differentiation

66
Q

What is the result of PRR-PAMP binding?

A 
Signal transduction
Gene transcription:
• chemokines and cytokines
• defensins
• cell surface receptor expression
67
Q

Compare the lifespan of macrophages and neutrophils

A

Macrobphages: long lived
Neutrophils: short lived

68
Q

Where are macrophages found?

Compare this with neutrophils

A 
In places where infection is likely:
• respiratory tract
• digestive tract
• connective tissues
• liver
• spleen

Neutrophils: in the blood

69
Q

Describe what happens when Macrophages and Neutrophils phagocytose pathogens?

A

Upregulation of killing mechanisms

Release of cytokines and chemokines

70
Q

How do neutrophils and phagocytes recognise pathogens?

What happens next?

A
  • PRR
  • FcR
  • C3bR

After binding, there is rearrangement of the actin cytoskeleton, extension of pseudopods –> phagocytosis

71
Q

How do phagocytes kill pathogens once they have engulfed them?

A 
Granules fuse with the phagosome:
• ROS
• hydrolases
• defensins
• lysozyme
72
Q

Describe how larger invaders such as nematodes are killed

A

Too big to engulf –> extracellular killing

  • Macrophages + Neutrophils + Eosinophils gather
  • Exocytosis of granules
  • Extracellular killing of the pathogen
73
Q

Describe the response to virus infection

A
  1. Invasion
  2. PRR - PAMP (weird genome elements)
  3. IFN-a and IFN-B production
  4. Induction of NKs
74
Q

Describe the mechanism of action of NKs

A
  1. Stimulated by IFN
  2. Recognise virally infected cells, because there is reduced MHC I expression
    3.
75
Q

How do NKs recognise virally infected cells?

A

Viruses in cells downregulate the expression of MHC I so that they can avoid detection by CTLs.

NKs recognise the fewer MHC I

76
Q

What is really important about DCs?

A

They link the innate and the adaptive immune responses

77
Q

Describe the mechanism of action of DCs

A
  1. PAMP-PRR
  2. Pathogen antigen presented on MHC
  3. Expression of costimulatory molecules
  4. Migration to lymph node
  5. Activation of T and B lymphocytes

MIIM20002 - Microbes, Infections, Responses (32 decks)

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