Lecture 8- Overview of Immune Response in vivo Flashcards
Name the cells of innate immunity and their basic function?
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
Describe the origin and function of NK cells?
- Lymphoid cells with innate function
- Early response to viral and intercelluar bacterial infection
Describe how the NK cells perform their function?
Upon activation:
1) Directly lyse the target cells by exocytosis of perforin and granzymes
2) secrete cytokines IFN-Y, TNF-alpha
Which two surface receptors NK cells act through?
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
Describe the process of the antibody dependent cellular toxicity?
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
Describe the mechanism of innate immunity?
First response:
- Antimicrobial peptides at epithelial surfaces
- Recognition&phagocytosis via macrophages and neutrophils
- Killing of virus infected cells by NK cells
- complement activation
- Inflammation
describe the mechanism of inflammation?
- 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
What is the driving force behind inflammation?
Cytokines and chemokines
What is inflammation mediated by?
TLR
Which cells express TLR?
-Macrophages
-DC
-B and specific T cells
-Fibroblasts
Epithelial cells
What happens when the specific cells recognise the TLR?
-Upon recognition of PAMP:
signalling events leading to transcriptional activation of pro-inflammatory cytokine and chemokines
Name the pro-inflammatory cytokine and chemokines?
-TNF, IL-1, IL-6, IL-8 and IL-12
Which TLR are located on the surface and which are located on the intracellular compartments?
Surface TLR- 1,2,4,5,6
Intracellular TLR- 3,7,8,9
Name the three complement pathways?
1) Classical
2) MB-lectin
3) Alternative
what are the three functions of complement?
1) Recruitment of inflammatory cells
2) Opsonization of pathogens (phagocytosis)
3) Killing of pathogens (membrane attack)
Where is the adaptive immunity initiated?
-Peripheral lymphoid tissue
Pathogens infecting at these site will initiate the adaptive immune response at? :
1) Mucosal surface- at peyer patch
2) Blood -SPleen
3) Other sites- lymph nodes downstream of the site of the infection
Describe the steps in the initiation of adaptive immunity?
- 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
Name the three APC?
Dendritic cell
Macrohpages
B cell
Describe the role each APC perform in adaptive immunity?
- 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
What are the three types of signals delivered to T cell from the APC?
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
What is the main cytokine to promote proliferation and differentiation of activated T Cells?
IL-2
What is the difference in structure in resting T cells and activated T cells?
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
What is the other role of IL-2?
proliferation of B and NK cells
What is the result of IL-2 binding to its receptor?
T cell proliferation
What is the IL-2 production dependent on and IL2 effects?
Ligation of CD28 with B7 ligand
- Effects:
1) stabilisation of IL-2 mRNA
2) activation of transcription factors
Name the CD4 T cells subsets and what factors influences this change?
Th1, Th2 and Th17
which cytokines Th1, Th2, Th17 and Tfh cells and where do these act on?
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
How are the B cells activated by the same T cell?
B cells are activated by T cells that recognise the same antigen
describe the process of activation of B cell by T cell?
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
What is humoural immune response?
-Mediated by antibody molecules secreted by plasma cell
Describe the mechanism for humoural immune response?
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
What is the CD8 T cell activated by?
- 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
what does the activation of the CD8 cell may also require and how?
- 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
explain T cell mediated cyto toxicity?
-Cytotoxic CD8 T cells induce target cell undergo programmed cell death
-principle mechanism is Ca2+ dependent- release of specialised lytic granules
-
Which are the lytic proteins that are found in cytotoxic granules and state function?
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
Which other cytokines does CD8 cytotoxic also release?
IFN-y and TNF alpha
what is the function of the cytokines released by CD8 cytotoxic cell?
- Inhibit viral replication
- Activation of macrophages
- Increase expression of MHC
what are the control of T cell responses?
Inhibitory receptors:
1) CTLA-4 (during activation)
2) PD-1 (during effector function) Ligand is PD-L1
3) FAS Ligand is FASL
