Cellular Immune Response 1: Dendritic Cells, Macrophages And Lymphocytes Flashcards
What are cytokines
Small , soluble peptides used extensively by the immune system to communicate and influence cell growth, differentiation and function
Features of cytokines
Pleitropy, autocrine function, paracrine function, endocrine effects, synergism
Cytokines require specific cell surface ____ through which to mediate their range of actions on different cells
Receptors
Cytokines typically __ their cel receptor and own ___
Upregulate
Secretion
Class I cytokine receptors
Interferon
Class II cytokine receptors
I’ll-2, 3
TNF receptor family
For cheomkines
What are two methods of control cytokines
Receptors released as soluble forms and also cytokine binding proteins to neutralize the effects
Current definition of dendritic cells. What do they dooo and what to the poses
- Dendritic morphology
- Machinery for sensing pathogens
- Ability to process and present antigens to CD4 and CD8 T cells
- Can activate T cells from naive state
- Dictate T cell future function and action
Common subtypes of DC
MDC, PDC, specialized DC, like LANGERHANS
MDC
MYELIOID
PDC
Plasmacytoid
Langerhans-a specialized DC
In skin
What is a marker for mature myeloid DC
CD1c
CD80, 86
HLA class I
HLA class II
Marker for mature plasmacytoid DC
CD123 (il-3 receptor)
CD80, 86
Class I for antigen presentation to CD8
Class II for presentation to CD4
What is the first function of DC
Pathogen sensing
How do dc sense pathogens
Pattern recognition receptors , which bind to structures common to pathogens
What do PRR bind to
Common molecular patterns-PAMPS
What are the PRRs that have been conserved through evolution
TLR
In sensing can the DC tell the difference between staph and strep
No
Do MDC and PDC have the same PRR
No
MDC is more specialized for _ response and PDC is more specialized for _ response
Antibacterial
Antiviral
What TLR are on mDC
TLR2, 3, 4, 5
TLR2
Senses peptidoglycan on gram positive bacteria
TLR3
Senses ds RNA from viruses
TLR4
Senses lipopolysaccharide on gram negative bacteria
TLR5
Senses flagellin on bacteria
What TLR are on pDC
TLR7, 8
TLR 7
Senses single stranded RNA on viruses
TLR9
Senses double stranded DNA on viruses
What is the mDC response to TLR binding
Activation and production of it-12
What is the outcome of TLR2, 4, 5 and is-12
Strong inflammatory T cell response against bacteria
What are TLR2, 4, 5, . Where are they
Cell membrane
Where are tlr3, 7, and 9
Internal phagosome
What happens when virus stimulates pDC through pamps
TLR3, 7, 9
What does TLR4 cause
Activation of il12 and ifn-a
What do TLR7 and 9 do
Activation and production of IFN-1
Outcome of viral stimulation through pamps of TLR3, 7, 9
Strong inflammatory T cell response against viruses
What happens when immature mDC becomes mature
Pinocytotic->not pinocytotic
Low expression of molecules to T cell activation->upregulate CD80, 86, and HLA molecules
Low expression of machinery required to process and present antigen->begins to process microbial antigens in readiness to present them
Localized and sedentary->active migration to local lymph node
Minimal secretion of cytokines->active section of cytokines, especially il12
Changes in pDC when becomes active
Small and round->enlarge and become dendritic shape
Upregulate molecules for T cell activation and secrete interferon a which potent antiviral and pro inflammatory effects
Type I interferons
Antiviral
2 forms a and b
IFN-a
Made by lots of cells but especially pDCwhich
IFN-b
Mainly from stromal cells such as fibroblasts
Receptor for interferon 1 and 2
Both type I IFN receptor
IFN are ___
Paracrine
Interferons for virus or bacteria
Virus
What else do IFN do
NK
Potentiate mDC
Enhance MHCI expression
Increase MHCII too
Who would we treat with recombinant IFN
Chronic carriers of virus such as hepatitis
Net result of activating DC
Can activate naive T cell
Where does the DC activate the naive T cell
Lymph node
The mature DC has 3 signals. What is signal 1
Presentation fo peptide antigen from a pathogen bound to surface MHC
DC signal 2
Co stimulation, typically throughCD80 and 86
DC signal 3
Cytokines, mainly il12 from mDC
What APC is the strongest T cell activator
DC
Overall DC picture
Immature-waiting for activation
Pinocytosis/phagocytosis or viral infection-activated
Activated-migrate and change function to activate naive T cells in lymph nodes
Break down proteins into bite size peptides they can present
How do DC get to lymph nodes? What chemokine is important
Lymphatics
Lymph nodes upregulate CCR7, a homing chemokine
What is a mononuclear phagocyte
Monocytes and macrophages
What do MNP do
Phagocytes
Monocytes are in _ and macrophages are in _
Blood tissue
Monocytes spend onyl a matter of days int he circulation before seeding to tissues where they differentiate to form what
Macrophages and dendritic cells
*espciailly during inflammation
What is CFU-GM
Colony forming unit for granulocytes and monocytes
What do CFU-GM become in the bone marrow over 6 days
CFU-GM->monoblast->promonocyte
What does a promonocyte become and where is it found
Monocytes in the blood for 3 days
What do. Monocytes become in tissues and how long are they there
Macrophages months
Lung macrophag
Alveolar macrophage
Bone macrophage
Osteoblast
Brain macrophage
Microglia
Blood monocytes are divided into two categories: those expressing ____ (like TLR4) and those expressing _ and _(the FcyRIII)
Cd14
Cd14 and cd16
Alveolar macrophages are specialized for removing what.
Microorganisms and debris in the air
Macrophages in the gut lamina are specialized for what
Bacteria
What are osteoclasts
Multinucleated giant cells that resort bone
What are 3 important properties of MNP
Process and present antigens to T cells
Release soluble factors(cytokines)
Killing, especially engulfed organisms
What are the surface markers found on MNP
CD16, 14 Cd35 CD11b/CD18 Cd4 Cd64 MHCII
What is cd35
Complement receptor 1(CR-1) for C3b
CD11b/CD18
Leukocyte function associated antigen 1 (LFA-1)
Cd64
FcyRI
What do monocytes do when there is inflammation
Upregulate migration to tissue and differentiation to macrophages
Under inflammation (LPS) what do macrophages fo
Pro inflammatory and microbicidal phenotype
Upregulation of HLA and antigen presenting machinery
Secrete TNFa, IL-1 and IFN-y
Macrophages can ingest and kill ___ ___, such as ___ ___
Intracellular microorganisms, mycobacterium tuberculosis
Tissue macrophages involved in chronic inflammatory foci(Tb) may undergo terminal differentiation into ___ ___ ___
Multinucleated giant cells
Where are multinucleated giant cells typically found
Granulomata..characteristic of tb
Il-1 is a cytokine mainly produced by ____ and ______
Dendritic cells
Monocytes/macrophages
What is il-1 secretion a response to
Stimuli like bacterial lipopolysaccharide
What does it-1 do
Pro inflammatory effects
Promotes coagulation and increases endothelial expression of adhesion molecules
Promotes release of il6
Has endocrine effects, inducing fever and synthesis of acute phase proteins in the liver
When it TNF produced
Response to gram negative bacteria
What secretes TNG
Monocytes/macrophages, dendritic cells, and T cells
Tnfb
Lymphotoxin