Term
| difference between T-cell receptors and antibodies |
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Definition
Antibodies recognize 3D shape of antigens
T-cell recepotrs recognize antigen+MHC |
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Term
| What are the four responses CD4 cells can have when activated, and primary features of each response? |
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Definition
Th1 - activation of macrophages and cytotoxic CD8 cells (TIMMI)
Th2 - promotes antibody production
Th17 - promotes chronic inflammation
Treg - modulates or supresses immune responses |
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Term
What is considered the pivotal point of the Th1 pathway?
What are it's fucntions? |
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Definition
- production of INF-γ
Functions:
1) activates macrophages
2) potent inducer of endothelial adhesion and homing receptors that attract additional effector cell trafic to the area
3) control display of MHCI and MHC II determinants on APC (exponential upregulation of antigen specific response)
4) Supression of the Th2 and Th17 responses |
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Term
| What transcription factor is characteristic of TIMMI/Th1? |
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Definition
| -T-bet "master regulator" |
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Term
First two steps in Th1 immunopathway
What is the result? |
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Definition
1) uptake of a complex antigen by dendritic cell
2) production of IL 12 and IL 18 by dendritic cell
- exposure to IL 12 commits a niave (Th0) cell to Th1 cell |
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Term
| Six things that happen to dendritic cell after uptake of complex pathogen |
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Definition
1) termination of phagocytosis
2) intracellular processing of the pathogen proteins to peptides
3) Upregulation of MHC II
4) Upregulation of costimulatory molecules on cell surface
5) Migration to lymphoid tissue
6) Upregulated synthesis of IL12 and IL18 |
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Term
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Definition
IL 2: stimulates proliferation of activated T cells
IL 21: very potent activator of CD8 cytotoxic cells |
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Term
After production of INF-γ, what is the next cytokine produced by Th1?
What is its function? |
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Definition
IL 2 and IL2 recepotrs are both upregulated?
- supports rapid proliferation of antigen stimulated T cells and enhances NK and B-cell responses |
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Term
| What is the prerequisite for stimulation by IL2? |
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Definition
| - Th1 activation/committment of IL12 |
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Term
| What is the end result of TIMMI? |
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Definition
| - recruitment of activated killer cells (macrophages and NK's) to an area of infection |
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Term
Which is the primary macrophage activating cytokine in Th1?
What 2 things does it cause killer cells to do? |
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Definition
INF-γ
- activate their oxidizing systems
- produce proinflammatory cytokines |
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Term
| Two big functions of pro-inflammatory cytokines? |
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Definition
1) activate immune effector cells
2) recruitment of final arbitrators of inflammation (neutrophils and monocytes) |
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Term
| Four proinflammatory cytokines |
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Definition
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Term
5 Functions of IL 1
What stops it? |
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Definition
- Raise body temp in conjunction with IL6 by affecting hypothalmus
- stimulation of marrow forming cells, increasing production of leukocytes
- mobilize neutrophil from bone marrow to
- facilitates Tcell responsivencess to IL2
- neuroendocrine effects to cause release of ACTH
-IL-1ra - receptor antagonist that competes for IL1 recepotr - stops unbridled IL1 response |
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Term
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Definition
- synergistic presence with IL1
- major requirement for Th17 as well
*big difference is that is has a growth and differentiation effect on B cells and bone calcium metabolism |
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Term
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Definition
- very borad proinflammatory effects: activates endothelium, promotes vasodilation and increases MHC expression
Under normal, non inflammatory conditions, it has a critical role in maintaining homeostasis by regulating apoptosis |
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Term
| Which proinflammatory cytokine works in concernt with IL-6 to produce morbidity that ranges from flu-like symptoms to septic shock, respiratory distress syndrome etc? |
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Definition
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Term
IL-8 functions
What is it produced by? |
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Definition
- stimulates proliferation
- MOST POTENT STIMULOUS for mobilization neutrophils to site of infection
- produced by macrophages, neutrophils and many other cell types |
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Term
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Definition
- highly specific and sensitive
- mononuclear cells (lymphocytes) from peripheral blood are incubated with highly specific TB antigens. If patient has or has had TB, INF-γ is released and can be detected |
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Term
NK cells do not express what?
What do they express and what can they provide?
What prevents them from over activity and destructiveness? |
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Definition
- NO CD3 complex, alpha, beta, gamma or delta cahins
- have no antigen specific receptors and are not MHC restricted
- express INF-γ and can provide immediate response (bridging between innate and adaptive immune responses
- killer inhibitory receptors: supress cytotoxicity. These recognize normal MHC class I markes. These will be turned off only if there is an absence of self-MHC and NK activating receptor |
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Term
| Two ways NK cells can kill |
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Definition
1) cytotoxic mechanisms similar to CD8
2) antibody dependent cell mediated cytotoxicity via Fc receptors |
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Term
Three cytokines that activate CD8 cytoxicity and what cells secrete them?
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Definition
IL2, IL21, INF-γ
-produced by NK cells and CD4 helper cells in Th1. |
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Term
| What is the effect of IL21 on CD8 cytotoxic cells? |
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Definition
- acts as a potent proliferative stimulus to antigen activated CD8 cells.
- enhances CD8 killing mechansims |
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Term
| Cross presenting by APC's |
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Definition
1) Presentation of MHC II to CD4 helper cell allows it to express IL2, IL21 and INF-γ, which will enhance killing by CD8
2) Simultaneous presentation of MHC I to CD8, maximizing CD8 activation |
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Term
| 5 Steps for CD8 cytoxicity |
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Definition
1) Recognition step: MHC + Class I molecule with specific antigen peptide
2) Rapid adhesion
3) Killing mechanims: perforins (osmolality disruption) and injection of granzymes
4) Disengagment and refreshing of killing capacity
5) Turning off of cytotoxicity: in absence of antigen, T cell loses its CD8 expression, switching on apoptosis via Fas/FasL |
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Term
| What happens to CD8 cells that do not apoptose after cytotoxicity is stopped? |
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Definition
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Term
What transcription factor is present in a Th2 cell?
What is the dominant cytokine from dendritic cells? |
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Definition
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Term
| What is likely to trigger a Th2 response |
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Definition
| soluble antigens circulating in the blood and extracellular pathogens |
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Term
| What types of cells drive Th0 to be a Th2 cell? |
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Definition
1) dendritic cells producing IL4
2) other committed Th2 cells producing IL4
3) B cell presentation of antigen promotes IL-4
4) Mast cells/basophils produce IL4 |
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Term
What is the major source of IL-4 in the Th2?
What other cytokines are involved after the activation of Th2 cells? |
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Definition
- the Th2 cell itself
-IL21, Il5, IL6, IL10 |
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Term
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Definition
- In presence of INF-γ, IL21 activates CD8 cells
- in absence of INF-γ, IL21 promotes B-cell proliferation, differentiation and survival |
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Term
| What is required for IgE response to parasites and other allergic responses? |
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Definition
| IL 4 and IL-13 in conjucntion with allergy prone genes |
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Term
| What effect do IL4 and IL13 have on cytotoxic response? |
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Definition
| decrease cytotoxic and inflammatory functions of monocytes and macrophages |
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Term
What is the most important supressor of the Th1 response?
What does this do? |
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Definition
IL-10
- stimulates proliferation, differentation and isotype switching of B cells |
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Term
| Four things antibodies are used for by the immune system |
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Definition
1) make pathogens including viruses, more attractive to NK cells, macrophages and neutrophils
2) Recoginze and mount effective immune responses to antigens that are not efficiently taken up by phagocytic cells
3) Bind toxins for efficient elimination
4) Target mutant and infected cells for killing |
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Term
| What dictates type of T cell response? |
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Definition
1) type of antigen
2) TLR activated
3) Dominant cytokine |
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Term
What is the signature cytokine for a Th17 response (and two others that make up the trio required for it)?
What is the main trascription factor associated with it?
What type of pathogen usually evokes this? |
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Definition
- IL23 (IL 6, TNF-β)
- ROR
- bacteria and fungi |
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Term
After activation by Il-23, TNF-β and IL-6, T cells commited to Th 17 express what cytokine?
What does it do? |
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Definition
IL-17
- recruits neutrophils, especially skin and mucosal surfaces |
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Term
Two places where Tregs are generated
What cytoines are responsible? What cytokine must be absent?
What else do they require? |
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Definition
- thymus
- peripheral lymphoid tissue
- TGF-β, IL10
- IL6 must be absent
-IL2 is required for proliferation |
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Term
| Four ways to get cytotoxicity with cross presentation |
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Definition
1) NK cell interacts with antigen on infected cell, produces INF-γ, which activates CD8
2) CD8 recognizes antigen in MHC class I on infected cell
3) CD4 recognizes antigen+MHCII on dendritic cell and secretes INF-γ, IL2, IL21, activating CD8 cytotoxicity
4) CD8 recognizes antigen+MHC class I on dendritic cell |
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