Lecture 8- T Cell Response to Antigen Flashcards
What do T helper (CD4) cells do?
- Monitor the body for extracellular microbial infections
- Activate/stimulate other immune cells to fight infection (especially B cells & macrophages)
What do Cytotoxic T-cells (CD8) do?
destroy host cells infected with intracellular microbes
- destroy tumor cells
What are the 2 types of Dendritic cells and what are their functions?
- Regular: present Ag to helper and cytotoxic T cells
- Follicular: Trap Ags for B cells
Naive T helper cells only respond to:
Antigens presented by dendritic cells in the primary immune response
Co-stimulation
Where are immature dendritic cells located and what do they do?
- in tissues (epithelial and mucosa)
- capture Ags, trap and internalize them
(they migrate to the lymph node, are drained by lymph secretion then are matured)
Where are mature dendritic cells located and what do they do?
- lymph nodes
- present Ags to T cells
What are Langerhans cells?
dendritic cells of the skin
Helper T cells typically begin as _____.
Th-0 (Th-O?)
differentiate depending on cytokines from APC and in the environment
What are the different type of T helper cell differentiations?
- Th1
- Th2
- Th17
- T regulatory cells (Treg)
- small number become memory cells
+ TFH (follicular helper)
[he doesn’t mention TFH in text but it’s in a photo]
Stimulated/primed Th cells first secrete ______.
IL-2
(T cells growth factor, exerts both an autocrine and paracrine effect)
[self activating]
What is the function of T γδ lymphocytes?
To respond to mucosal pathogens
Dendritic cells detect:
PRRs (pathogen recognition receptors) & cytokines secreted by other cells at infection site
What do T helper cells produce?
CD40 ligand & cytokines
What are the 4 steps in dendritic function?
1 - recognize antigen is present
2 - travel/migrate to lymph node
3 - activate naive T cell w/ aid from co-stimulatory molecules
4 - cytokines detected by DC → dictate what Th-cell should proliferate
Differentiation into Th1 is influenced by ____.
- IL-12 (secreted by APCs)
- IFN-γ (secreted by activated NK cells and Th cells themselves)
What does CD40 ligand do?
- binds to the CD40R on an APC
- Causes the APC to produce more MHC 2 and B7 (co-stimuilatory receptors for rhe T-cells)
- higher frequency of APC-induced T cell activation
Differentiation into Th2 cells is influenced by ____.
IL-4 (secreted by other Th2 cells and mast cells)
What 4 things does Th1 secrete?
- IL-2
- IL-12
- IFN-γ
- TNF
What is IFN-γ (interferon gamma) ?
potent macrophage activator
- stimulates activated B cells
- stimulates Th-cell differentiation
- stimulates CD8 into CTL
What does TNF (Tumor necrosis factor) do?
- activates vascular endothelium expression of adhesion molecules
- aids in WBC recruitment
What is the main function of Th1?
to aid macrophages in fighting intracellular infections [bacteria & protozoa]
What are the main effector cells of Th1 immunity?
- Macrophages → enhance phagocytic activity : mediated by IFN-γ
- PMNs
- CD8 → stimulated to differentiate into Cytotoxic lymphocytes [CTLs]
- NK cells
- IgG B cells → opsonizing & complement fixing
What 5 ILs does Th2 secrete?
- IL-4
- IL-5
- IL-9
- IL-10
- IL-13
What does IL-4 do?
- Stimulates proliferation of primed B cells
- High levels promote IgE class-switching → allergic reactions mediated by IgE
4 y/o is allergic to prime and bees. That’s all that is in his classroom, so he has to switch
What does IL-5 do?
- Stimulates B cell differentiation into plasma cells
- High levels activate eosinophils & mast cells → act against helminths
- facilitates class-switching to IgA → w/ aid from TGF-B & BAFF cytokines
What does IL-13 do?
Increases mucus production & peristalsis in intestine
What are the main effector cells of Th2?
- B cells
- Eosinophils
- Mast cells
- Basophils
What is Th2 responsible for?
Humoral immune system and allergic reactions
(because it hosts the immunity effectors against extracellular parasites)
What does Th17 secrete?
- IL-17
- IL-21
- IL-22
- IL-23
What does IL-17 do?
recruits neutrophils to infection sight
What does IL-21 do?
stimulates B cells to produce IgG & IgA → guard mucosa
What does IL-22 do?
stimulates epithelial cells to produce antimicrobial peptides → resist microbial invasion
What does IL-23 do?
growth factor for other Th-cell to differentiate into Th17
What is the main function of Th17?
aid immune response to fungi & extracellular bacteria
Differentiation into Th17 cells is influenced by:
- APCs secrete IL-6
- Cytokines from Dendritic cells balance Treg & Th-17 differentiation
TGF-B, IL-6, IL-23
Differentiation into Treg or Reg-Th cells is influenced by:
- Cytokines from Dendritic cells balance Treg & Th-17 differentiation
- Once pathogen is eradicated
What does Treg secrete?
- IL-10
- TGF-B
What does IL-10 do?
suppresses macrophage function & reduces APC-B7 expression
CTLA-4 (Cytotoxic T-Lymphocyte-Associated Protein 4) binds to remaining B7 on APC = further lower TCR-APC stimulation
What does TGF-B do?
induces generation of more Treg & reduces CTL attack
What is the main function of Treg/ Reg Th?
Suppress immune response & prevents autoimmunity
What is PD-1?
Programmed deadth-1
- Appears on the surfaces of cells under attack
What does PD-1 bind to?
Effector T cells that are working AFTER infection is over
- Those effector cells become lethargic & non-functioning → stopped by PD-1 binding
What does IL-1 do?
- Increases vascular permeability which is how cells move through the endothelium to where they are needed in the tissues
- Stimulates the production of IL-6
What does IL-2 do?
Proliferation and differentiation of T-cells into effector cells
What does IL-6 do?
- Acts on the liver to produce acute phase proteins leading to inflammation
What does IL-8 do?
- Attracts and activates neutrophils
- also helps to increase vascular permeability
What does IL-12 do?
- Activates Natural Killer (NK) cells
- Induces lymphocyte differentiation
IFN-γ is secreted by _______.
NK cells and T-helper cells
- important in inhibiting viral replication
What is BAFF?
B-cell activating factor
What is TNF?
tumor necrosis factor
What is PMNs?
polymorphonuclear lymphocytes → neutrophils
What is LFA-1?
leukocyte function-associated antigen-1
- integrin/adhesion molecule that helps dock the T cell to the APC
What do CD8/ Tc cells recognize?
antigens displayed by MCH-1 on host cells and cross-presented on dendritic cells
- Intracellular antigens
- Tumor antigens
Tc cells may require ____ from activated T helper cells
co-stimulation via cytokines
Stimulated Tc cells proliferate and differentiate into ____.
Cytotoxic T-lymphatic cells (CTLs)
What occurs after signal transduction of Tc cells?
(secreting proteins & create pores in the membranes of the infected cells)
- The release of CTL granules at point of contact w/ the targeted host cells
- Granzymes & perforin (Receptor-mediated endocytosis)
What is the Fas-ligand?
death-inducing receptor
- engagement activates caspases (induce apoptosis)
What are the effector functions of CTLs?
- granzymes
- perforin
- Fas-ligand
What does perforin do?
- Inserts into endosomal membranes
- Facilitates movement of granzymes into cytoplasm
What do Granzymes do?
(Enzyme)
Activate caspase present in target cell → systems within the cell that control cell death & inflammation
When do memory T cells exist?
after the infection is eradicated
What are 5 features of memory T cells?
- Long-lived
- Present in lymphoid organs, mucosal tissues & circulation
- Functionally inactive
- Require IL-7 to remain alive
- Rapidly respond to repeat exposure to same pathogen
What is the first signal for naive T-cell activation?
- CR binds to specific antigen displayed by MHC 2
- CD4 co-receptor binds to MHC 2
What are the second signals for a naive T-cell to be activated? (co-stimulation)
- CD28 binds to B7 [on APC]
- Absence of co-stimulation → T cell remain in state of anergy [unresponsiveness] & undergoes apoptosis
CD28 binds to ____.
B7 on APC
What is the third event for naive T-cell activation?
clustering of TCR & co-receptors
- Formation of an immunologic synapse
- CD3 complexes → transduce signals to interior of Th-cell
LFA-1 [CD11] binds to _____ [on APC]
ICAM
(Leukocyte function-associated antigen-1)
CD40L [CD154] binds to _____[on APC]
CD40
- Activates APC to express more B7 molecules
- Activates secretion of IL-12 by APC
Gamma-delta T-cells are important in _______.
mucosal surfaces
Gamma-delta T-cells respond to:
- Cell surface antigen w/o processing & presentation on MHC → NO MHC restriction
- Stress proteins expressed on atypical class Ib MHC molecules, may be CD8
What are responses of Gamma-delta T-cells?
Secrete cytokines
Simulates Cytotoxic
