10/26 Intro to Immunology Flashcards
what are the two different branches of the immune system?
innate and adaptive (aquired)
what is the chain of lymphocyte activation and function?
antigen receptors; clonal selection; effector cell activities; antigen presentation; activation control;
what are the lymphoid organs?
Thymus, lymph nodes; spleen.
what does the thymus do?
T cell development
what do the lymph nodes do?
filter lymph
what does the spleen do?
filter blood
what are the central lymphoid organs?
Thymus; bone marrow
what are the peripheral lymphoid organs
lymph nodes and spleen
basic process of immune response to a “problem”
- recongnize the problem through antigen receptors 2. Send singnals through cytokines. 3. respond to the problem: effector activities.
provides rapid, steriotyped responses to invading pathogens and damage
Innate immunity
specialized cells of the innate immunity:
granulocytes and macrophages, dedritic cells, natural killer cells.
Soluble factors of the innate immunity?
complement, C-reactive protein, mannose binding lectin
ancient and diverse innate immunity!!!!
defensisn, RNAi, just about every cell is involved.
slower but very flexible immunity
adaptive immunity
specialized cells of itne addaptive immunity
lymphocytes
special targets of the adaptive immunity
persistent infections, viral infections, cancer cells.
provide long term systemic protection
antibodies from the adaptive immunity
how are the innat and adaptive interconncted?
adaptive requires innate to get started. innate system responds to cues from adaptive.
how would a human without addaptive or innate immune differ in duration of infection?
no innate immunity, the infection explodes out of control right away; no addaptive and you get chronic low infection!
what types of receptors are found in the innate immune system
receptors that recongnize constant features of pathogens (PAMPs: pathogen associated molecular patterns). (like: LPS (lipopolly sacharides of bacteria), dsRNA, unmethylated CpG DNA, N-formyl methionine in proteins (bacteria). —- such as Toll-like receptors!!!
what would the 10 different toll receptors in humans probably lead to the production of?
antimicrobial peptide genes
innate receptor genes present in germ line DNA, from billions of years of development that recognize PAMPs !
Toll-like receptors (TLR)
what type of receptors do adaptive immune use?
they use receptors made by genetic rearrangements and mutation during organism’s life…not present in germ line DNA…and make receptors like sIG (surface immunoglbulin) or TCR (t-cell recpetors) that look like antibodies !
low MW glycoprotiens that are used to regulate immune responses of both innate and adaptive systems
cytokine signals
what cells can produce cytokines?
both the immune and non-immune cells
regulates inflammation, fever, etc. that represent host response to infectioin
cytokines
regulate hematopoiesis
cytokines
what if you mis-regulate the cytokines?
cytokine storm!!!! like the 1918 influenza or haunta virus
what if there is a bacterial infection that is recognized by the macrophages…how do we get PMN in to help out?!
macrophsges recognize, release CXCL8 signal (chemokine), activates integrins on PMNs, activated PMNs enter tissue and follow the CXC8 gradient.
how can PMNs recognize and take care of a bacteria?
they recongize receptors for bacterial products or for antibody molecules bound to bacteria and then phagocytose them.
how is PMN a good example of innate/adaptive immunity interactions
they can react to both bacterial products or to antibodies.
what are the products of macrophage cytokines?
PMN recruitment; vascular permeability, generate fever, stimulate cell proliferation and release from marrow.
what is the simple cell to cell signaling of interferons?
one cell infected by a virus and it will produce interferon gene products that produce interferon that is sent to neighbor cells that will cause neighbors to turn on genes for antiviral proteins that block viral reproduction.
what else do interferons do besides cell to cell protection
they are a part of innate and adaptive cells and anti-cancer activity
what is the path of T-cell development?
Pre T cells in thymus become naive T cells and then sent to peripheral lymphoid tissue and become activated T cells.
What is the path of B-cell development?
B-cells in bone marrow produced to naive B cells and then sent to peripheral lymlphoid to become activated B cells
what is a naive immune cell
one that is ready to go but hasn’t encountered antigens yet
what leads to activation of naive cells?
the incounter with antigen in peripheral lymphoid tissue.
what differentiates a T or B cell?
the type specific surface antigen receptor!
why is a T/B cell specific for an antigen
all of the antigen receptors are of one kind on a lymphocyte
what happens when naive cell binds antigen?
they either die (clonal elimination); becomes inert (clonal antigen); or clonal selection (it becomes a cell that divides to provide many with that receptor)
what is the product of clonal selection?
effector and memory cells
what is the differnce in memory and effector cells
effectors respond to the antigen, and memory cells don’t do anyghing, hang out in lymphnodes, and then provide pool of cells to provide secondary response very quickly
how is primary and secondary response differ for addaptive immunity
primary is slow secondary is quick and before symptoms usually
why is it good to generate a random limitless supply of antigen receptors in lymphocytes?
allows for at least billions of different antigen receptors and a vast capacity to recognize and respond to various antigens
why is it bad to generate a random limitless supply of antigen receptors in lymphocytes?
self - reactive receptors will be generated!!! (autoimune disease can occur!)
what do b cells give rise to?
plasma cells which make antibodies
what is the effector activity of B-cells?
plasma cells secrete immunoglobulin molecules
coded for by the same gene that codes for surface receptor of B-cells
Igs – RNA splicing is secreted or membrane anchored.
how to secrete or membrane bind a Ig?
by replacing the membrane anchor and the protein is secreted
the antibody immunity is known as?
humoral immunity
tag cells for attack by Igs?
opsonize targets
what if a virus is bound by lots of AB?
they are nutrilized
what are two things that antibodies do?
they opsonize bacteria and nutrilize virus
what is a T cells
thymus dependent cells
what % is T cells
65-75%
life of T cells
years
TCR how different from B-cells
T cell antigen receptor, can only see antigen presented on another cell’s major histocompatibility complex (MHC) molecule
what is MHC in addaptive immunity?
major histocompatibiliity complex are cell surface, integral membrane proteins.
the effector activities of T cells:
Th = helper T cell, CD4 cells. they secrete cytokines, coordinate immune activity. Tc = cytotoxic T cell (killer T cell), CD8 Cells, kill cells. Treg - regulatroy T cells a type of CD4 that involve in suppressing immune activities.
what is one of the main activites of T helper cells?
they provide cytokines to promote the division of B cells to get active plasma cells.
what does AIDs target?
it targets Th cells
what about Tc killing how does that work?
provide cellular immunity by seeing an antigen with the CD8 complex and then release cytokines or enzymes that will kill or lead to the death of a cell.
act to suppress effector cell activation (especially self reactive)
Treg cells
why are Treg cells targets of intense clinical interest?
could turn on for transplants or off for cancer!
how are antigens usually presented to lymphocytes?
by specialized antigen presenting cells (APCs)
where are the APCs?
they are in the periphery (langerhans cells in skin) and they become activated and move to lymph nodes where they are called dendritic cells.
Present antigens to B cells in Lymph nodes
Follicular dedndritic cells
Professional APCs
they present antigens to T cells, and they are B cells, macrophages, and dendritic cells that are specific in lymph nodes.
the cells in lymph nodes that trap and present antigens to B cells
follicular dendritic cells (FDC)
How does antigen get presented to B cells
the FDC take antigens and trap them on the surface of themselves, and then it will signal B cells with cytokinses. There is very little processing of the antigen but not extensive. and then the FDC just shows it to the B cells.
How would an antigen be presented to a T cell?
Most T-cell antigens are proteins; inside a cell the proteins are cut into small peptides and are bout to an MHC molecule and the MHC-peptide complex is pt on the cell surface. The T-cell then uses the TCR to “see” the peptide.
What is required to activate and later for the activity of T-cells?
the TCR must recognize both an antigen and an MHC molecule.
What class of MHC is for the CD4 T cells?
MHC class II cells present peptides to CD4 cells
what class of MHC is for CD8 T cells
MHC class I are for CD8 T cells.
What type of cells could present antigen to most Th cells?
most Th cells are restricted to MHC class II and only professional APCs express MHC class II!
What type of cells could present antigen to most Tc cells?
most Tc cells are restricted to MHC class I and all cells except RBCs express MHC class I cells.
May be called HLA in humans or H-2 in mouse
MHC
How is the presentation to CD4 cells by MHC class II and to CD8 cells by MHC class I different in as far as the way that the antigens are processed.
Class II will take peptide form extracellular by endocytosis and then break and combine with MHC class II and present on surface. The Class I also endocytosis of extracellular peptides but may then spill into the cytoplasm of the cell and then be processed by proteasome and then sent to the ER and golgi where then combined with the class I MHC and presented on the surface. (the release of the antigen into the cytoplasm is the big difference!)
Professional cells can present what type of MHC?
class I and class II
What is required after a T-cell receptor binds to an MHC to fully activate the naive T-cell? (this makes the professional presenting cells special in the ability to activate T-cells)
the CD28 on the T-cells must also bind to a B7 on the APC for a “second handshake” which causes the T cell to release IL-2 and to express IL-2 receptor to bind the IL-2 and then the cell divides and begins clonal expansion
why can only professional antigen presenting cells activate a niave T-cell?
they are the only ones to express B-7
if a cell is not a Pro antigen presenting cell, how does it activate a T cell
It can’t activate a naive T-cell but it can signal an active Tcs (cytotoxic T cell). by expressing MHC class I receptors.
how does a virally infected cell signal a Tcs?
proteins from the cell and any invading pathogens cut by proteasome, and transported to rough endoplasmic reticulum by transporter of antigen peptides (TAP) peptides then mind to MHC class I and displayed and then activated CD8 T cell (Tc or CTL) see the peptide and release the cytotoxic factors which kill the cell.
when would a pro antigen receptor express B7 in order to activate naive T-cells?
when there is infection, as sensed through toll-like receptors!
How can we eliminate self-reactive T-cells?
lack of proper secondary interactions (B7 etc.) lead to clonal elimination or anergy of antigen stimulated cells.
what is expressed most of the time on MHC class one?
just self proteins!
