Lecture 8- Overview of Immune Response in vivo

Question 1

Name the cells of innate immunity and their basic function?

Answer 1

1) Macrophages-phagocytes found in tissues
2) Neutrophils- phagocytic cells found in bloodand migrate to tissue in response to IL-8
3) Mast cells-In tissues- affect permeability
4) Natural Killer cells-lymphocytes: clearance of virus and tumour (lacks antigen specificity)
5) Dendritic cells- phagocytic and macropinocytic: migrate to tissues and present antigens for adaptive immune response

Question 2

Describe the origin and function of NK cells?

Answer 2

• Lymphoid cells with innate function

- Early response to viral and intercelluar bacterial infection

Question 3

Describe how the NK cells perform their function?

Answer 3

Upon activation:

1) Directly lyse the target cells by exocytosis of perforin and granzymes
2) secrete cytokines IFN-Y, TNF-alpha

Question 4

Which two surface receptors NK cells act through?

Answer 4

1) Activating receptors- initiate killing
2) Inhibitory receptors- abort killing
NK cells distinguish healthy cells from infected or cancerous cells through a balance of activating and inhibitory receptor

Question 5

Describe the process of the antibody dependent cellular toxicity?

Answer 5

1) antibody binds antigen on the surface of target cells
2) Fc receptor on NK cells recognise bound antibody
3) Cross linking of Fc receptor signals the NK cell to the target cell
4) target cells DIES by apoptosis

Question 6

Describe the mechanism of innate immunity?

Answer 6

First response:

• Antimicrobial peptides at epithelial surfaces
• Recognition&phagocytosis via macrophages and neutrophils
• Killing of virus infected cells by NK cells
• complement activation
• Inflammation

Question 7

describe the mechanism of inflammation?

Answer 7

• Initiated by macrophages and dendritic cells
• call other cells (neurtophils monocytes and more macrophages ) for help and leukocytes
• prevent the spread of infection (coagulation of blood vessels)
• repair the wounded tissue

Question 8

What is the driving force behind inflammation?

Answer 8

Cytokines and chemokines

Question 9

What is inflammation mediated by?

Answer 9

TLR

Question 10

Which cells express TLR?

Answer 10

-Macrophages
-DC
-B and specific T cells
-Fibroblasts
Epithelial cells

Question 11

What happens when the specific cells recognise the TLR?

Answer 11

-Upon recognition of PAMP:

signalling events leading to transcriptional activation of pro-inflammatory cytokine and chemokines

Question 12

Name the pro-inflammatory cytokine and chemokines?

Answer 12

-TNF, IL-1, IL-6, IL-8 and IL-12

Question 13

Which TLR are located on the surface and which are located on the intracellular compartments?

Answer 13

Surface TLR- 1,2,4,5,6

Intracellular TLR- 3,7,8,9

Question 14

Name the three complement pathways?

Answer 14

1) Classical
2) MB-lectin
3) Alternative

Question 15

what are the three functions of complement?

Answer 15

1) Recruitment of inflammatory cells
2) Opsonization of pathogens (phagocytosis)
3) Killing of pathogens (membrane attack)

Question 16

Where is the adaptive immunity initiated?

Answer 16

-Peripheral lymphoid tissue

Question 17

Pathogens infecting at these site will initiate the adaptive immune response at? :

Answer 17

1) Mucosal surface- at peyer patch
2) Blood -SPleen
3) Other sites- lymph nodes downstream of the site of the infection

Question 18

Describe the steps in the initiation of adaptive immunity?

Answer 18

• DC in the peripheral cells ingest microbes and activated
• DC become APC
• Migrate to lymph nodes and present antigen to naiive lymphocyte
• Lymphocytes with the appropriate receptors undego clonal selection and expansion

Question 19

Name the three APC?

Answer 19

Dendritic cell
Macrohpages
B cell

Question 20

Describe the role each APC perform in adaptive immunity?

Answer 20

• Activation of macrophages and Dendritic cells:
  1) recognition of PAMPs by innate immune receptors
  2) production of cytokines
  3) Expression of co-stimulatory molecules (CD40/CD86)
• B cells present antigens to the T cell to receive help from T effector cells

Question 21

What are the three types of signals delivered to T cell from the APC?

Answer 21

1) Activation - via TCR and MHC CII
2) Survival- Via CD28 and B7
3) Differentiation- APC release cytokines- IL-4, IL-6, IL-12 and IL-23

Question 22

What is the main cytokine to promote proliferation and differentiation of activated T Cells?

Answer 22

IL-2

Question 23

What is the difference in structure in resting T cells and activated T cells?

Answer 23

Resting- express only Beta and Y chains- allow binding of IL-2 with low affinity
Activated- added alpha chain and secrete further IL-2 and higher affinity for IL-2

Question 24

What is the other role of IL-2?

Answer 24

proliferation of B and NK cells

Question 25

What is the result of IL-2 binding to its receptor?

Answer 25

T cell proliferation

Question 26

What is the IL-2 production dependent on and IL2 effects?

Answer 26

Ligation of CD28 with B7 ligand

• Effects:
  1) stabilisation of IL-2 mRNA
  2) activation of transcription factors

Question 27

Name the CD4 T cells subsets and what factors influences this change?

Answer 27

Th1, Th2 and Th17

Question 28

which cytokines Th1, Th2, Th17 and Tfh cells and where do these act on?

Answer 28

1) Th1 releases- IFN-y acts onmacrohpages
2) Th2 releases IL-4,5 and 13 and acts on goblet cells and bone marrow
3) Th17- IL-17 and IL22 acts on stromal cells (GCSF and chemokines) and epithelial cell (antimicrobial peptides)
4) TfH - produces IL-21 and acts on B cell

Question 29

How are the B cells activated by the same T cell?

Answer 29

B cells are activated by T cells that recognise the same antigen

Question 30

describe the process of activation of B cell by T cell?

Answer 30

1) antigen recognition by Tfh cell induces signals that activate B cell
2) B cell proliferates and generates plasmablasts that form the primary focus
3) further differentiation can produce: germinal centre B cell
Plasma B cell (secrete antibody)
Memory B cell

Question 31

What is humoural immune response?

Answer 31

-Mediated by antibody molecules secreted by plasma cell

Question 32

Describe the mechanism for humoural immune response?

Answer 32

1) B cell activation by antigen and helper T cell
2) antibody secretion by plasma cells causes:
- Neutralisation- antibody prevents bacterial adherence
- Opsonisation-antibody promotes phagocytosis
- Complement activation: enhance opsonisation and lyses some bacteria

Question 33

What is the CD8 T cell activated by?

Answer 33

• Specific antigen and co-stimulation via CD80/CD86 molecules
• activation drives the production of IL-2 which drives proliferation
• Armed effector cells can now recognise and kill infected cells upon antigen recognition

Question 34

what does the activation of the CD8 cell may also require and how?

Answer 34

• CD4 T cell
• APC stimulates effector CD4 T cell to induce the expression of CD40L and IL-2
• stimulation of APC through CD40 increases B7 and 4-1BBL which both co-stimulate naive CD8 cell

Question 35

explain T cell mediated cyto toxicity?

Answer 35

-Cytotoxic CD8 T cells induce target cell undergo programmed cell death
-principle mechanism is Ca2+ dependent- release of specialised lytic granules
-

Question 36

Which are the lytic proteins that are found in cytotoxic granules and state function?

Answer 36

Perforin- polymerises to form a pore in the target membrane
Granzymes-serine proteases, which activate apoptosis once in the cytoplasm of the target cell
Granulysin- induces apoptosis

Question 37

Which other cytokines does CD8 cytotoxic also release?

Answer 37

IFN-y and TNF alpha

Question 38

what is the function of the cytokines released by CD8 cytotoxic cell?

Answer 38

• Inhibit viral replication
• Activation of macrophages
• Increase expression of MHC

Question 39

what are the control of T cell responses?

Answer 39

Inhibitory receptors:

1) CTLA-4 (during activation)
2) PD-1 (during effector function) Ligand is PD-L1
3) FAS Ligand is FASL