chapter 12 Flashcards
What are the 6 antibody-mediated effector functions?
- Neutralization
- Agglutination
- Opsonization
- Complement Activation
- Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)
- Antibody-Dependent Degranulation and Mediator Release
protects against viral or bacteria infection or the damaging effects of toxins
neutralization
enhances neutralization and more efficient clearance of pathogens form the body
agglutination
promotes and/or enhances the engulfment of antigens by phagocytes
opsonization
results in the generation of the membrane attack complex (MAC), creating pores in pathogen membranes and killing the microbe
complement activation
activates the killing activity of several types of cytotoxic cells, e.g., NK cells
antibody-dependent cell-mediated cytotoxicity (ADCC)
triggers mediator release from granulocytes
antibody-dependent degranulation and mediator release
Which immunoglobulin has the highest molecular weight?
IgM because it is a pentamer
Which antibody is the first produced in a primary response?
IgM
describe the effector functions of IgM:
-lower affinity
-pentavalent
-very good at complement fixation leading to MAC formation and target lysis
-efficient at forming dense Ab-pathogen complexes that are efficiently engulfed by macrophage
What are the subclasses of IgG and their distinct effector capability?
-Human IgG1/IgG3 effective at complement fixation
– Mouse IgG2a/human IgG1 good at mediating ADCC by NK cells
What is the major Ig isotype found in secretions like tears and mucus?
IgA
describe the effector functions of IgA:
-effective at neutralizing toxins and pathogens
-does not fix complement, so does not drive inflammation
-long half-life in secretions due to protease-resistant amino
acid sequence in Fc region
describe the effector functions of IgE:
-best known for role in allergy and asthma
-may also play a role in protection against parasitic helminths and protozoa
-degranulation of eosinophils/basophils
-release of molecules such as histamine to damage large pathogens
what are the 3 subsets of cytotoxic effector cells?
-cytotoxic T lymphocytes
-NK T cells
-NK cells
*these eliminate infected cells and abnormal tumor cells
CTLs recognize and kill infected/tumor cells via ___________________
TCR activation
CTL signal 1:
TCR binds peptide presented by APC on MHC class I
CTL signal 2:
-costimulatory signal transmitted by CD28-B7 (B7-1: CD80, B7-2: CD86) interaction between T cell and APC
– APCs get help from T cells to upregulate stimulation molecules
CTL signal 3:
provided by IL-2, inducing proliferation and differentiation into CTL form
-4 peptide-bound MHC I molecules bound together and conjugated to a fluorescence marker
MHC tetramers
Describe how CTLs can be tracked with tetramers:
-tetramer recognizes CTLs with a TCR capable of binding peptide/tetramer
-flow cytometry is used to detect fluorescent cells
-very sensitive
What are the two mechanisms for initiating CTL-mediated apoptotic death of target cells?
- Directional delivery of cytotoxic proteins (perforin and granzymes) that are released from CTLs and enter target cells.
- Interaction of the membrane-bound Fas ligand on CTLs with the Fas receptor on the surface of target cells.
What is Fas-FasL mediated cytolysis?
- FasL is found on CTLs
- Fas is found on target cell
- Fas bound by FasL initiates a death signal leading to apoptosis
Natural killer cells make up 5-10% of what population?
circulating lymphocyte population
-non-specific cytotoxicity
-the first line of defense against viral infection
-Kill virus and other intracellular pathogen-infected cells, and tumor
-Produce cytokines to regulate innate and adaptive immunity
natural killer cells
How are NK cells different from CTLs?
– No Ag Specific TCR
– No MHC restriction
– No memory, same intensity regardless of repeated
exposure
What are candidates for activating signals in the missing self model?
C-type lectins
Describe the inhibitory receptors of the missing self model:
– CD94/NKG2 recognize HLA-E
* If HLA-E is present - inhibitory signal, no killing
* No HLA-E (during viral infection) - no inhibitory signal, killing
– KIRs recognize specific MHC molecules - inhibitory signal, no
killing
Describe the entire process of the missing self model:
-Normal cells present a ligand for the activating (killing) receptor on NK cells AND an MHC class I ligand for the inhibitory receptor
-When viruses infect cells, some may inhibit MHC class I expression
to evade detection and elimination by CTLs
-The balance of inhibitory vs activating signals determines whether NK is
activated or not
How do NK cells induce apoptosis of their targets?
Once activating signal molecules are engaged, NK cells use mechanisms very similar to CTLs to induce target cell death
– Release of perforins/granzymes at junction of two cells
Describe the nature of NK cells:
-large granular lymphocytes
-lack T cell receptor, CD3 proteins, and surface IgM and IgD
-thymus not required for development
-normal numbers in SCID patients
What are the many functions of NK cells?
-kill virus infected cells and cancer cells (nonspecific)
-killing is not dependent on foreign antigen presentation by Class I or II MHC proteins
-killing is activated by failure of a cell to present self antigen in association with Class I MHC proteins or by a reduction in the number of Class 1 MHC proteins on the cell surface
-kill by producing perforins and granzymes, which causes apoptosis of target cell
NKT cells bridge ______________________immune systems.
innate/adaptive
What does the TCR of NKT cells recognize?
glycolipids presented by nonpolymorphic CD1d
Describe NKT cells:
Can act as helper cells (secreting cytokines) or killer cells
– Killing seems dependent on Fas-FasL interactions
* Include both CD4+ and CD4– cell types
* Don’t form memory cells
* Possess NK surface proteins rather than T-cell varieties
