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

Lecture 4 - Overview of the Immune Response Flashcards

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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
What is mannose binding lectin?
It is a protein on the cell that binds to mannose on the invader, triggering the complement cascade
26
How may the complement cascade be activated?
Classical pathway: antibody binds to invader Mannose binding lectin pathway: MBL binds to mannose on microbe Alternate pathway: binding directly to the pathogen
27
What are the effector responses of the complement cascade?
Opsonisation: coating, ready for phagocytosis MAC: pore-formation in the cell wall of the bacterium Chemotaxis: recruitment of inflammatory cells
28
What are the induced soluble factors that mediate immunity?
Cytokines | Chemokines
29
What are cytokines?
Secreted proteins that warn neighbouring cells that there is an invader present
30
What are chemokines?
Secreted protein that attract cells to the site of infection
31
What is the receptor of a B cell?
Antibody
32
What is the receptor of a T cell?
T cell receptor
33
What is the structure of antibody?
Fab: variable region Fc: constant region Two light chains Two heavy chains
34
What is the structure of a T cell receptor?
Constant and variable region | Alpha and beta chain
35
What can antibodies bind?
Molecules associated with extracellular pathogens
36
What can T cell receptors bind?
Peptides associated with intracellular antigens
37
Describe the location of innate leucocytes of the innate immune system
Blood --> infected tissue
38
Describe how neutrophils migrate from blood to tissues
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
Describe the locations of the elements of the adaptive immune system
Circulate in blood Secondary lymphoid tissue (interact here with APCs) Migrate to infected tissue
40
How is it possible that pathogens present at peripheral sites can interact with circulating lymphoctes?
The lymphatic system APCs are the relay mechanism
41
Describe the generalised flow of lymph
- Infected tissue - Afferent lymphatic vessel - Lymph node - Efferent lymphatic vessel - Thoracic duct - Venous system - Back to infected tissue
42
Where do naive lymphocytes come into contact with pathogens?
In secondary lymphoid organs
43
What are some secondary lymphoid organs?
Spleen Lymph nodes Peyer's patches Adenoids
44
What are some primary lymphoid tissues?
Bone marrow | Thymus
45
Describe blood flow through lymph nodes
Artery in through hilum 2. Lymphocytes move through HEV into Paracortex and cortex 3a. B cells: B cell zone, follicle 3b. T cells: Paracortex 4. Encounter lymph that has come in through the afferent lymphatic 5. Activated lyphocytes exit via vein 6. Vein leaves via hilum
46
Describe how lymphoctes move from circulation into the lymph node Where does this occur?
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
What is different about migration of neutrophils into infected tissue, and migration of lymphocytes into the lymph node
Same process, different selective molecules
48
Where do T cells hang out in the lymph node?
Paracortex
49
Where do B cells hang out in the lymph node?
B cell zone, follicle
50
What determines where the lymphocytes will migrate to, once in the lymph node?
Chemokines
51
How are T cells activated?
(Adhesion) 1. Antigen presented to their TCR on MHC of APC 2. Costimulation 3. Cytokines
52
Which MHC molecules interact with which T cell?
CD4+ cells: MHC II | CD8+ cells: MHC I
53
How does peptide come to be on MHC I?
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
How does peptide come to be on MHC II?
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
Describe costimulation of APCs and CD4+ cells
CD80, CD86 interact with CD28
56
Describe Signal 3 of CD4+ cell activation
Specific cytokines (depending on the PAMP-PRR interaction), controlling the differentiation of CD4+ cells.
57
TGF-B skews Th cells towards...
Treg
58
IL-6 skews Th cells towards...
Th17 | Tfh
59
IL-12 skews Th cells towards...
Th1
60
IL-4, IL-33 skews Th cells towards...
Th2
61
What is the role of Treg?
Downregulates immune function
62
What is the role of Th17?
Neutrophil recruitment
63
What is the role of Th1?
Inflammation
64
What is the role of Th2?
Parasite immunity | Allergy
65
What is the role of Tfh?
B cell proliferation and differentiation
66
What is the result of PRR-PAMP binding?
``` Signal transduction Gene transcription: • chemokines and cytokines • defensins • cell surface receptor expression ```
67
Compare the lifespan of macrophages and neutrophils
Macrobphages: long lived Neutrophils: short lived
68
Where are macrophages found? Compare this with neutrophils
``` In places where infection is likely: • respiratory tract • digestive tract • connective tissues • liver • spleen ``` Neutrophils: in the blood
69
Describe what happens when Macrophages and Neutrophils phagocytose pathogens?
Upregulation of killing mechanisms Release of cytokines and chemokines
70
How do neutrophils and phagocytes recognise pathogens? | What happens next?
* PRR * FcR * C3bR After binding, there is rearrangement of the actin cytoskeleton, extension of pseudopods --> phagocytosis
71
How do phagocytes kill pathogens once they have engulfed them?
``` Granules fuse with the phagosome: • ROS • hydrolases • defensins • lysozyme ```
72
Describe how larger invaders such as nematodes are killed
Too big to engulf --> extracellular killing * Macrophages + Neutrophils + Eosinophils gather * Exocytosis of granules * Extracellular killing of the pathogen
73
Describe the response to virus infection
1. Invasion 2. PRR - PAMP (weird genome elements) 3. IFN-a and IFN-B production 4. Induction of NKs
74
Describe the mechanism of action of NKs
1. Stimulated by IFN 2. Recognise virally infected cells, because there is reduced MHC I expression 3.
75
How do NKs recognise virally infected cells?
Viruses in cells downregulate the expression of MHC I so that they can avoid detection by CTLs. NKs recognise the fewer MHC I
76
What is really important about DCs?
They link the innate and the adaptive immune responses
77
Describe the mechanism of action of DCs
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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