T cell Robinson Flashcards
Gamma Delta T cells
MHC type system that recognizes lipid rich antigens
- important for host/environment interfaces
- produce several early cytokines like 1, 6
Gamma Delta T cells
MHC type system that recognizes lipid rich antigens
-important for host/environment interfaces
What are T cells responses regulated by?
specific cytokines and Tregs
What type of antigen conformations do antibodies recognize?
3D
What type of antigen conformations do t-cells recognize?
peptides in the context of MHC
If an antigen is prestented by an MHC2 to a niave CD4 Tcell what 4 responses could occur?
Th1, Th2, Th17, Treg
If an antigen is presented by an MHC2 to a naive CD4 T Cell what 4 responses could occur?
Th1, Th2, Th17, Treg
-commitment to a subset depends on host genetics, type of infection, and which type of TLR and cytokine profile
Th1
enhances and amplifies cellular mediated immunity by activating macrophages/ and or promoting cytotoxic responses by CD8
Th2
promotes optimal antibody production
Th17
chronic inflammation
Treg
modulates or suppresses immune responses
T-FH
high affinity antibody production in the germinal center of a lymph node
What does commitment to a subset depend on?
which TLR system is activated and which cytokine profile becomes dominant at the time of presentation
Where do activation steps of the various cd4 cells occur?
following initiation-activation steps occur in the secondary lymphoid tissues
How many chain peptides are on a cytokine?
2 usually encoded by separate genes
What 2 things do all cytokines exhibit?
pleiotropism and redundancy
-at concentrations similar to hormones
What do lymphocytes and macrophages use cytokines for?
to regulate the intensity of an immune response
Do most cell/cytokine systems have agonist/antagonist dynamics?
yes
Can cytokines actions vary and depend on the state of the target cell?
yes
What provokes the classic Th1 response?
Infections by organisms that require phagocytosis and intracellular killing
What is the obligatory Th1 helper initiator cytokine?
12
What is the obligatory Th1 helper initiator cytokine?
12(also has a potent effect on NK cells)
What co-stimulatory molecules do Th1 cells upregulate when activated?
CD 28 and CD 154 (40L)
REQUIRED DETERMINANT
What cytokines does Th1 provide to propagate the TMMI response?
IL-2 and INF gamma
What 3 things is INF gamma produced by?
- Th1(CD4)
- NK
- activated CD8 cells
What 3 things does INF gamma do?
- activator of macrophages
- upregulated of MHC2 and endothelial receptors
- suppressor of Th2 and Th17
What does Il21 do and what produces it, what 2 circumstances does it exist?
Th1 cells produce IL 21-
potent promoter of CD8 killing acitivity
in absence of INF gamma it is a potent promoter of B cell growth and development
What is IL 2 produced by?
Th1 and CD8
What strongly depends on IL2?
Tregs
What does IL 2 do?
- critical growth cytokine
- acts in autocrine and paracrine needs
- IL2R expressed as a functional unit after antigen activation
- genetic defects in its assembly result in severe immune deficiency disease
What has Th1 helper activation developed to provide?
an antigen specific way to recruit highly activated macrophages
Can small numbers of Th1 recruit vast numbers of macrophages?
yes
The end result of TMMi is activated macrophage, what does the macrophage produce? What do these cytokines do?
-Tetrad
1, 6, 8, and TNF alpha
-wide range of autocrine and paracrine and systemic effects that promote inflammation
What does pro-inflammatory IL 1 respond to? What 4 functions does it have?
-responds to stress
- promotes neutrophil growth and emigration from the marrow
- Acts with IL 6 on CNS to cause fever, depression
- neuroendocrine effects on adrenal gland
* 4. Stimulates APCs to increase Ag presentation
-antagonist is IL-1Ra
What does pro-inflammatory IL 1 respond to? What 4 functions does it have?
-responds to stress
- promotes neutrophil growth and emigration from the marrow
- Acts with IL 6 on CNS to cause fever, depression
- neuroendocrine effects on adrenal gland
* **4. Stimulates APCs to increase Ag presentation
-antagonist is IL-1Ra
What does IL6 a pro-inflammatory cytokine do?
- many effects redundant with Il-1
1. primary cause of fever and other constitutional signs of infection
2. T-cell “vitamin” it promotes responsiveness to IL-2, accelerates antigen activation - **3. strong growth and differentiation effects on Bcells in the presence of other B cell cytokines and effects on bone mineral metabolism where it activates osteoclasts
- it is required for optimal Th17 development
- may be required for Th-FH development
WHat does TNF alpha a proinflammatory cytokine do?
- Plays a central role in the immune system
1. macrophage activator
2. activator of endothelial homing and adhesion molecules
3. upregulates MHC and other cytokines
4. potent inducer of apoptosis and angiogenesis - systemic effects that range from flu-like symptoms to death
- positive feedback
WHat does TNF alpha a proinflammatory cytokine do?
- **Plays a central role in the immune system
1. macrophage activator
2. activator of endothelial homing and adhesion molecules
3. upregulates MHC and other cytokines
4. potent inducer of apoptosis and angiogenesis - systemic effects that range from flu-like symptoms to death
- **positive feedback
What does IL 8 do? When is 8 produced?
- *1. NEUTROPHILS to the site of infection
- produced mainly by macs, neutrophils, and during intense inflammation by endothelial cells
- actually a chemokine
What does delayed hypersensitivity mean?
archaic term for TMMI
What is the bump from TB skin testing from?
macrophages recruited by CD4
What is the bump from TB skin testing from?
macrophages recruited by CD4
-less than 5% will be TB specific T cells
What is an example of non specific lymphocyte cytotoxicity?
Natural Killer Cells
- *no Ag receptors
- older than T cells
- are not MHC restricted
What do Natural killer cells produce?
INF gamma
How do natural killer cells kill?
- **killing mechanism suppressed by normal MHC-1
- ->activated by altered MHC-1 in combination with activating ligand on the target cell - when pathogen complexed with antibody, natural killer cells through their Fc receptors recognize target cell with antibodies and kill it
What is an example of antigen specific cytotoxicity?
CD8
- recognize and kill foreign, mutated and viral infected cells
- recognition is via display of endogenously produced antigen in MHC-1 determinant
What do Natural killer cells produce?
INF gamma, IL21, IL2
When is there optimal activation of CD8?
- NK cells
- CD4 helper cells
- memory cells
What do Natural killer cells produce?
INF gamma, IL21, IL2 (antigen activated CD4 continues to produce these)
What 2 things does CD8 need to be activated?
- correct MH1 with specific antigen
2. INF gamma (produced by NK and CD4)
Do CD8 cells require co-stimulatory signal?
No, can kill repeatedly
What turns CD8 cytotxicity off?
dependent on viral display on targets, in the absence of specific targets they activate their own death by gnes Fas/FasL
-10% become memory cells
What turns CD8 cytotoxicity off?
dependent on viral display on targets, in the absence of specific targets they activate their own death by genes Fas/FasL
-10% become memory cells
What does the a dominant IL-4 cytokine cause?
Th2
Do Th1 and Th2 occur at the same time?
NO
What do B-cells recognize?
extracellular or soluble antigens
What are the cells that drive T0-T2?
- committed Th2 cells
- B cell presentation of antigen
- Mast Cells
- DC and TLR under specific gene influences
What is required for Th2 and what is that requirements major source?
Il4
major source Th2
What 3 cytokines are the major drivers of B cell differentiation and isotype switch?
IL 5,6, 10
-major source of these is TH2 cell
What 3 cytokines are the major supressors of a Th1 reaction?
Il 4, 10, 13
13 is a critical player in IgE
What 3 cytokines are the major suppressors of a Th1 reaction?
Il 4, 10, 13
13 is a critical player in IgE
What are the functions of Th2 response?
-Enhance b cell function and ultimately antibody produciton
- makes pathogens more attractive to macs and polys
- bind toxins
- target mutant/viral infected cells for killing
What is the costimulatory signal for the Th2 B cell response?
CD 40/ 40L
What is the dominant T helper response dictated by?
the type of infection, the type of TLR activated and the dominant cytokines present
What type of things invaders a Th 17 response?
Bacteria and Fungi that live outside of host cell
What do bacteria and fungi trigger?
DCs to produce TGF beta, IL6, and IL 17
What does Th17 produce?
IL 17
What does IL 17 do?
recruits neutrophils
Which ILs have to do with neutrophils?
8 ,7
Which ILs have to do with neutrophils?
8, 17
What does IL 17 do?
recruits neutrophils
-an inflammatory cytokine
Does Th17 have a central role in autoimmune disease?
yes
What are the cell surface markers on CD4 Th1 Regs?
3, 4, 25+ and Fox P3+
What are CD4 Th1 Regs influenced by and what do they depend on?
TGF beta
-depend on IL2 for survival
T follicular helper cells do?
- restricted to B-cell follicles in lymphoid tissue
- promotes high affinity antigen specific B cell response
- CD278, IL6, IL21
How does B-cell capture an antigen in the extracellular environment?
by displaying its specific angtigen receptor on its cell surface
What is Th17 suppressed by?
Th1 and Th2 and T regulator cells
When are iTregs induced?
during a normal immune response as a break mechanism on proliferation
What happens to stimulated T cells that do not receive co-stimulatory signals CD80 (b-7)
inactivation
convert to tregs
or commit suicide
That is the transcriptional factor of Tregs?
Fox P2
CD3, 4, 25+
That are key features of Tregs?
Fox P2
CD3, 4, 25+
and express CTLA4
What does CTLA4 do?
supresses T-call activation by competing with CD28 and down regulating CD80(B7) on DC
What is CTLA4 expression controlled by?
FoxP3
What is CTLA4 expression controlled by?
FoxP3
-someone gets sick and someone doesnt its cause CTLA-4 is highly polymorphic
Where can Tregs arise?
thymus
regional lymph nodes
peripheral sites (especially the gut)
What are converted to T-regs at peripheral sites during ongoing immune reactions when local cytokine concentrations begin trending to TGF-B and LESS IL6?
Tho–>Tregs
What happens as TGF-B becomes dominant?
- FoxP3 upregulated CTLA-4
- shuts down APC
Can Tregs make IL2?
NO but are dependent on it for IL2 survival and function
WHat strategies does the immune system ivoke to combat viral infections?
ALL STRATEGIES
Why is a b-cell response necessary in a viral infection?
Because the infection can leave the infected cell and that when B cells get it
What are CD8 memory cells called?
CD8-RM(resident memory)
How do CD8RM cells work?
Restrict their traffic patterns to areas of past infections and this enables them to rapidly respond to repeat infection
What happens to CD4-RMs when an antigen is not present?
they disappear
-when antigen is present they form clusters with macrophages
What do memory cells produce?
Il2, Il 21, and INF gamma that concomitantly activate an innate antiviral response
What is a side benefit to Memory cells/?
they prime the area of residence to be hyperreactive to viruses and presumable bacterial that were not the initial pathogens
-probably by training the macrophages by epigenetic mechanisms
