Lecture 4 - Overview of the Immune Response Flashcards Preview

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

Flashcards in Lecture 4 - Overview of the Immune Response Deck (77):
1

What is an immune response?

Reaction to:
- components of microbes
- other foreign molecules
- 'danger'

2

What are the four principles of the immune response?

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

3

What are the requirements of the immune response?

- no harm to host
- rapid
- present at birth
- appropriate for pathogen

4

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

Molecular differences

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

5

What is the difference between PAMPs and Antigens?

Which receptors detect each?

PAMPs: pathogen associated molecular patterns
- common to all pathogens
- PRRs

Antigen:
- unique to a particular organism
- Antibodies / Antigen receptors

6

Assess the innate immune system in the following criteria:
- specificity
- diversity
- memory
- response time
- magnitude of response
- cells
- chemical barriers
- soluble proteins

- specific to PAMPs
- limited diversity
- no memory
- rapid response
- no change in magnitude
- Macrophages, NK cells
- Antimicrobial molecules
- Cytokines, complement

7

Assess the adaptive immune system in the following criteria:
- specificity
- diversity
- memory
- response time
- magnitude of response
- cells
- chemical barriers
- soluble proteins

- specific to antigens
- huge amount of diversity
- memory
- slow response time
- magnitude increases with exposure
- Lymphocytes
- IgA (antibodies)
- cytokines

8

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

Myeloid progenitor:
• neutrophils
• eosinophils
• basophils
• macrophages

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

9

What factors determine the fate of the progenitor cells?

Bone marrow stromal cells

CSFs: colony stimulation factors

10

What are the different types of PRRs?

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

11

What are DAMPs?

Danger associated molecular patterns

12

What does TLR-2 bind?

Components of the bacterial cell wall:
- peptidoglycan

13

What does TLR-4 bind?

LPS

14

What does TLR-5 bind?

Flagellin

15

What does TLR-9 bind?

CpG-DNA

16

What do NLRs bind?

Peptidoglycan on G- cells
DAMPs

17

What are some examples of DAMPs?

Free fatty acids
Stress metabolites

18

What happens when TLRs and NODs are engaged?

Expression of different cell surface receptors
- Cytokine production
- Defensin production

19

What happens when Mannose receptors are engaged?

Phagocytosis

20

What is ligation of RIGs associated with?

Anti-viral immunity

21

What are the constitutive factors that mediate innate IS?

- Complement proteins
- C reactive protein
- Mannose binding lectin
- Lysozyme

22

What does lysozyme do?

Disrupts the cell wall (peptidoglycan)

23

What does C reactive protein do?

Binds to the capsule --> phagocytosis

24

What are defensins?

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

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