Cell-Mediated Immunity (Lecture 5) Flashcards
B Cell Differentiation
For most antigens, B cell activation necessitates binding of the ____ to the cell’s antigen receptor and interaction between the ____ cell and a ____ cell.
This requires ____ contact between the cells and expression of membrane and secreted molecules (____) by the T cell that bind to receptors on the B cell.
antigen B T physical cytokines
B Cell Differentiation
B cell activation is a ____-step process initiated by binding of antigen to the B cell antigen receptor (antibody)
B cell: expresses BOTH ____ and ____; ____ APC; can take up the antigen that it’s ____ for, internalize via RM endocytosis, and present the antigen as a ____ molecule; now a T cell can come along and provide step 2, must recognize the peptide in associated with class II, and the molecules (CD) reciprocally expressed, induces T cell to secrete ____ to bind the B cell which fully activates the B cell
B cells are unique > the only example where ____ in antigens that they’ll process and present; all other APC are nonspecific, anything they bind and get within cytoplasm (pro APC), or any cell that is made inside of it; no specificity whatsoever
common in ____ responses to antigens
remember, B cells also express ____, so cyto T cells can also attack infected B cells
two
MHC class I
II
professional
specific
class II
cytokines
specificity
memory
MHC class I
B Cell Differentiation
Binding of antigen to membrane ____ results in the delivery of biochemical signals that initiate the ____ process.
immunoglobulin
activation
B Cell Differentiation
there are antigen-dependent and indepedent stages of lymphocyte development
indepedent of presence of antigen > everything occurring in ____ > undergoing series of differentiation events [the ____ of segments of DNA that encode light/heavy chain proteins] so they can produce Ab molecules that can be express on cell surface; express ____ and ____ molecules before they leave BM; any B cell that has affinity for self receptor (autoreactive), it is induced to undergo ____ in bone marrow > only cells that get out should be capable of binding foreign antigens
when B cells leaves BM > everything else is dependent on presence of antigen; activation of B cell can require the presence of ____ or can be independent of ____ (activated directly)
independent: activation by ____ antigen > crosslink ____ receptors on same cell (mimics both signal one and two) > differentiates into ____ that secretes ____ (limited to illiciting production of IgM, not the greatest immune response) (this is typically the first thing to occur relative to the ____ response)
bone marrow random rearrangement IgM IgD apoptosis
T cell
T cell
polysaccharide multiple plasma cell IgM humoral
B Cell Differentiation
T dependent types of antigen: B cell interacts via ____ (desiginated here as TH2, TH1 can also do this) > B cell induced to undergo ____ > differentiate into ____, and a subpopulation into ____; the plasma cells can undergo ____ > stop producing IgM and class switch to unique isotypes of Ab (cytokines that mediate this are ____, ____ or ____; these cytokines secreted by T cells fine tune the humoral immune response, at mucosal > IgA, parasite > IgE , systemic EC > IgG)
Helper T proliferation plasma cell memory cell class switching Tfh Th1 Th2
Functions of TH1 and TH2 Cells
Induction of Class Switching in B cells
default pathway in absence of T cell help > ____; in presence of T cell > IgM, IgG, IgA, IgE
***____ (produced by Th1 subset of cytokine) will induce class switching to ____
***____ (Th2 derived cytokine); class switching to ____
gamma interferon
IgG
IL4
IgE
Function of Tfh Cells in Mucosal Immunity
secondary lymphoid is found underlying mucosal tissue; in gut > ____ patches
in peyer’s patches, are areas that are involved in T cell and B cell activation > large number of ____ helper T cells > secrete ____ > induces class switching of cells to produce ____
peyer’s
follicular
TGFbeat
IgA
Function of the TH17 Subset
Th17 secretes large number of cytokines, secretes ____ (pro-inflam molecule); ____ is an inducer of inflammation
associated with ____ of inflammatory reactions; can affect biology of endothelial, fibroblasts, epi cells and macrophages [these all express receptors]; these cells then secrete more ____ molecules (do not need to know all these other molecules) > which then results in recruitment of ____ recruitment > therefore, Th17 immunity against ____ infection (macrophages via phago and neutrophils via phago)
the downside of this mechanism? when proinflam molecules are unregulated > play important role in ____ responses; and they can also play a role in ____
IL17
TNF-alpha
upregulation
pro-inflam
granulocyte
extracellular bacterial
chronic inflammation
AIDs
Function of the Treg Subset
Generally act to ____ immune reactions.
Treg responsible for turning the helminthic response ____; block ____, block production of ____ by B cells, inhibit ____ responses, block production of secretion of mucus; too much immune response > tissue destruction
***Q: ____is produced by regulatory T cells; importance of IL10 it inhibits the activation of ____ responses
(TH2 also inhibits the activation of the TH1 subset)
down modulate off vasodilation IgE TH2
IL10
TH1
Effector Functions of TH1 Cells
main functions associated with TH1: fine tuning the response to best address the infection
1) activate macrophages (via ____)
2) ***secrete ____ > class switching to ____ > IgG induce activation of ____ cascade, act as ____ (induce activity of phagocytic cells)
3) enhance killing of IC bacteria by neutrophils via secretion of ____ and ____ (do not memorize #3)
gamma interferon gamma interferon IgG opsonins lymphotoxin TNF
Immunity Against Intracellular Bacterial Infections
Acquired immune responses to microbes that reside within the phagosomes of phagocytes are mediated by ____ specific for microbial antigens. Cytokines produced by ____ are of particular importance.
Examples include:
• Mycobacteia
• Salmonella typhimurium
• Listeria spp.
bacteria living in phagosomes have figured out ways to survive: inhibit ____ of phagosomes w/ lysosomes, or if fusion occurs, they inhibit ____ responsible for killing (the others besides listeria)
some bacteria will try to escape the phagosome and enter the cytoplasm; difficult types of infection to eliminate (____ is an example)
T cells Th1 helper T cells fusion mechanism listeria
Immunity Against Intracellular Bacterial Infections
the cell processes and present some of bacterial antigen on cell surface that can now be recognized by CD4+ T cells (the Th1 subset is involved in the activation of the cell)
once the cell is activated; TH1 cells secretes ____, and the cell becomes activated > fusion of phagosomes with lysosomes > phagolysosomes, the ingested bacteria are degraded and killed
the red dots are mycobacterial cells in the micrograph; once activated, there are few red dots left
experiment:
infected diff types of cells with listeria (which enters the cytoplasm); incubate the cells for different periods of time in conjunction with T cells and even the media produced by T cells
mixing T cells with macrophages resulting in activated ____, the level of bacterial killing is very efficient > almost ____ of the bacteria are killed over the course of this experiment; in order for a macrophage to kill an IC bacterium > requires interaction with ____
gamma interferon
macrophages
100%
T cells
Effector Functions of TH1 Cells
____ serves as APC, processes bacterial antigens in class II molecules > presents to ____ cell, secretes gamma interferon, binds to surface of macrophage, and induces activation of the ____, results in fusion of phagosomes and lysosomes > enhanced killing of bacterial cells
what also occurs: genes encoding \_\_\_\_ molecules are upregulated, express more class II moelcules on surface, more effectively process and present bacterial antigens to \_\_\_\_ > exactly what you want happening because the macrophages need help in removing IC bacteria
will also upregulate ____ molecules (____) > recruit additional inflam cells to site where it is activated (acts as an ____ of inflammatory response) (will want it to be turned off by Treg eventually)
macrophage
CD4+
macrophage
class II T cells
pro-inflam
TNFalpha
amplifier
Immunity Against Intracellular Microbial Infections
bacteria contained within phagosomes are eliminated when phagosomes fuse with lysosomes; but the bacteria in the ____ are unaffected > their antigens can now be processed and presented via MHC ____ and then targeted by ____ cells
cytoplasm
class I
class I
cytotoxic CD8+ T
Immunity Against Intracellular Bacterial Infections
mycobacterium tuberculosis > inhibits ____ formation
microbes taken up into phagosomes, but m. tuberculosis has figured out a way to prevent fusion with lysosome
TH1 tries to activate the macrophage, but cannot be effective bc the ____ is inhibited; overtime: continually inhibited by T helper cells > formation of multinucleated giant cells (____) > overtime they get bigger and bigger > in the center: multi-nucleated giant cells, all have mycobacterium inside of them; on periphery is a layer of ____ cells, and on the outside are ____ cells (trying to stimulate macrophage to kill the bacterium within)
T cells contain infection within granuloma, but there are always viable organisms within; if the person becomes immune and T cells become ____, bacteria is released into tissue and infection > formation of ____ in this case
no symptoms other than a ____ test and a ____ when they undergo the test; but they have the potential of reactivating the ____
phagolysosome phagolysosome granuloma epitheloid helper T cells
immune
tuberculosis
+ TB test
+ chest x-ray
disease
