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
Delayed-Type (Type IV) Hypersensitivity
Three Phases
1) ____ exposure to antigen: induction of the response; macrophage gobbles up the bacterial cell/protein > processes and presents protein in context of ____ (must be a professional APC); peptides presented to T cells, provides signal #1 and #2 for the ____; undergoes proliferation, some cells will diff into effector ____ cells, others will diff into ____ cells (secondary responses to the antigen)
2) re-exposure to antigen: generation of ____ cells; mature ____ cells
3) go to site where antigen has been deposited, activated by present of antigen and secrete ____ that accumulate inflammatory cells
takes ____ hours for 2) and 3) > called a delayed-type reaction (as opposed to immediate via IgE activation of mast cells)
primary self-class II CD4+ effector TH1 memory
effector T
CD4+ TH1
cytokines
24-48
Delayed-Type (Type IV)
Hypersensitivity
can also see them in context of ____
some people are allergic to haptens, posion ivy, nickel and chromate
allergic to latex; mediated by ____ (earlier), lesions on hands is manisfestations in response to proteins found on latex
allergies
type I hypersensitivity
Effector Functions of TH2 Cells
IL4 > ____ via plasma cells***
____ and ____ cells*** in relation to infection by helminths
production of IL5 > upregulation of production of ____ in bone marrow, and their activation, and collectively in context of this and IgE: helminthic functions are dealt with effectively
TH2 subset is important in activating ____ (differently than TH1 subset)
IgG IgE mast eosinophils macrophages
Roles of Th Subsets in Antimicrobial Immunity
KNOW THIS TABLE; do not need to know diseases, and only cytokines he mentioned
don’t forget about Treg subset
include: production of TGFbeta by Tfh
do not need to know the roles in diseases, or any cytokines he didn’t mention in lecture
YA
Transplant Rejection
Types of Transplants
between the same person = ____
between members of same species that aren’t genetically identical = ____
between species = ____
syngeneic
allogeneic
xenogeneic
Allografts in Dentistry
buy bone from cadavers = ____
allograft
Xenografts in Dentistry
dead cow/pig = ____
xenograft
Patterns of Graft Rejection
three patterns of graft rejection
(1 and 2 involved with ____ HC, 3 is ____ HC)
1) hyperacute: no longer a problem bc of all the cross-matching and blood matching they do in transplants; would have antibodies that would recognize antigens on the grafted tissues > activate ____ and ____ and destroy vasculature (antibody-medaited response)
2) acute: what happens in the skin graft experiments; T cells (____ and ____) recognize ____ molecules > once activated, cyto T cells kill the cells of the transplanted organ, and then helper induces ____ reaction; and then production of antibody and get involved (but mostly cell-mediated)
3) chronic: takes ____ days to manifest itself; involved with activation of ____ cell response; involved with ____ complex antigens
major
minor
complement
neutrophils
CD4+
CD8+
non-self MHC
inflammatory
60
helper T
minor histocompatability complex
