Chapter 4 Pt II T Cell Activation Flashcards
What are the two steps to naive T cell activation?
- Antigen binding
- Co-stimulation
Describe co-stimulation. What happens if there is no co-stimulation?
Happens to only inactivated/naive T cells. Two signals are given to T cell. First signal is antigen-MHC binding to TCR. Second signal is the B7 (expressed on DC and macrophages) proteins interacting with CD28 on T cell surface. If no co-stimulation, meaning only 1 signal is received, then anergy results, meaning lack of immunity.
Which cytokines trigger proliferation and differentiation of T cell?
IL-1 and IL-2 from APCs or other T cells
What happens when anergy occurs?
Lack of immunity:
-tolerance to antigen
-unable to divide
-no cytokine secretion
What do activated T cells do?
-Enlarge and proliferate in response to cytokines
-Differentiate and perform functions according to T cell class
Describe steps of clonal selection/activation of T cells
- DC or macrophage phagocytoses antigen and presents fragments to naive T cell
- T cell recognizes antigen-MHC complex and TCR/CD4 or 8 proteins bind antigen-MHC complex. Also, co-stimulators molecules bind
- Clone formation: activated T cells become memory and effector cells
Primary T cell response peaks within a _____.
Week
T cell apoptosis occurs between _____ and ____ days
7 and 30 days
Why do T cells apoptose after 1 week to 1 month?
Because activated T cells are hazardous if around too long. They produce a large amount of inflammatory cytokines, which leads to hyperplasia (too much proliferation) or cancer
Are B cells hazardous?
No, they stay in body for long amounts of time. So, they last longer than T cells
T cell effector activity wanes when?
Amount of antigen declines
What are the fates of effector and memory T cells as antigen wanes?
Effector activity declines and eventually T cells apoptose
Memory cells remain and mediate secondary response
Helper T cells activate which parts of adaptive immunity?
Both humoral and cellular arms
Without helper T cells _______
There is no immune response
What do helper T cells help to do?
-activate T and B cells
-Induce T and B cell proliferation
-secrete cytokines to recruit other immune cells
-amplify innate defenses (activate macrophages, mobilizes lymphocytes and macrophages, attract other types of WBCs)
Why is there no co-stimulators protein on Th cell activating B cell?
Because helper T cell is already activated. Co-stimulation only happens to naive/inactivated T cells
Do B cells necessarily need helper T cells to become activated?
No, they can be activated by binding T cell-independent antigens. Their response is weak and short-lived. However, most antigens need helper T cell co-stimulation to activated B cells
Describe B cell activation by helper T cell
- Helper T cell binds with antigen displayed on MHCII
- Helper T cell releases IL-4 and other cytokines as co-stimulators signals to complete activation
Cytotoxic T cells require which cell for activation? How does this cell help?
Helper T cells, which cause DCs to express co-stimulators molecules required for CD8 activation
Describe CD8 cell activation
- Helper T cell binds DC
- Helper T cell stimulates it to express co-stimulators molecules
- DC activates CD8 cell while helper T cell secretes IL-2 to further help activation
*Note that helper T cell binds MHCII on DC while CD8 binds MHCI on same APC
List and describe the subsets of helper T cells
-TH1: mediate most aspects of cellular immunity
-TH2: defend against parasitic worms and mobilize eosinophils, promote allergies
-TH17: link adaptive and innate immunity by release in IL-17, may play role in autoimmune disease
Where to activated cytotoxic T cells reside?
Circulate in blood, lymph, and lymphoid organs
Targets of cytotoxic T cells?
-virus-infected cells
-cells with intracellular bacteria/parasites
-cancer cells
-foreign cells from transfusions or transplants
Two methods of direct killing by cytotoxic T cells?
- Exocytose perforins to create pores, also exocytose granzymes to enter pores and stimulate apoptosis
- T cell binds receptor on target cell and stimulates apoptosis
how do granzymes trigger apoptosis?
By activating enzymes that trigger apoptosis
Describe T reg function
-reduce immune response by direct cell contact or releasing inhibitory cytokines (IL-10 and TGF-beta)
-prevents autoimmunity by suppressing lymphocytes in periphery. Can induce tolerance to transplanted tissue
Together, which two cell types launch direct attack on Ag?
Effector T cells and non-specific killers (macrophages and NK cells)
What does TGF-beta stand for?
Transforming growth factor beta
Define cross-reactivity
When two antigens appear similar to immune system such that same Ab bind to both
Why can tetanus toxoid be used to immunize?
Because it cross-reacts with its toxin
How much tetanus toxin kills a mouse? How much toxoid required for immunization?
10^-12 g to kill mouse
10^-6 for immunization
Human blood group A cross-reacts with antiserum against ____ or ____
Streptococcus capsule
Influenza virus
Human blood group B cross reacts to serum against _____
E.coli
What are adjuvants used for? Examples?
To enhance immune response to immunogen. Example is aluminum potassium sulfate (alum) in USA. Causes immunogen to precipitate resulting in slow time-release so that immune system can develop memory and phagocytose easier
Adjuvants used in USA? Europe? Animals?
USA = alum
Europe = BCG (bacille Calmette-Guerin) as TB vax. Contains attenuated M. Boris, Corynebacterium, and Bordetella pertussis. Good at activating macrophages to phagocytose and present to T cells
Animals = Freund’s complete adjuvant that has killed Mtb
