Immune Response Flashcards
what is the classical pathway of the complement cascade?
antigen: antibody complexes
what is the MB-Lectin pathway of the complement cascade?
lectin binding to the pathogen surfaces
what is the alternative pathway of the complement cascade?
pathogen surfaces
define complement
the natural component of blood serum
compliment activation results in..
- recruitment of inflammatory cells
- opsonization of pathogens
- killing of pathogens
opsonization = kill it tag
recruitment of inflammatory cells results in the recruitment of
macrophages and neutrophiles
killing pathogens occurs by
rupturing the cell wall
what 2 types of attacks are launched against infectious agents by the adaptive immune system?
- humoral
- cellular
define humoral attack
soluble or fluid mediated by antibodies
define cellular attack
mediated by Tc cells, NK, & macrophages
macrophages and NK cells have an innate recognition for
- foreign invaders
- cells that must be destroyed
examples of foreign invaders include
- bacteria
- viruses
examples of cells that must be destroyed include
- necrotic
- marked for death
- displaying abnormal proteins
T lymphocytes display
T cell receptors to recognize antigens
list 3 examples of T lymphocytes
- Tc cells
- Th
3.Treg
helper T cells (Th) aid B cells to…. and CTLs to…
- produce antibody
- kill cells that need to be destroyed
regulatory T cells (Treg) suppress
CTLs and Th
normal body cells use what molecule to present fragments of their proteins on the surface
MHC class I molecules
explain how the body normally presents protein fragments on its cell surface
- proteins from cytosol are diverted into proteasomes
- proteasomes are broken down into oligopeptides
- oligopeptides are introduced into lumen of ER via TAP channel where they encounter MHC class I molecule
- complex is displayed at the cells surface
how is a cell able to display various olgiopeptides?
by displaying various forms of MHC class I molecules w/ different binding domains
antigen presenting cells are aka
dendritic cells (DC) and macrophages
describe steps that APS take to generate antibodies
APS= antigen presenting cells
- APS phagocytize antigenic particles
- particles become oligopeptides by proteolysis
- MHC class II molecules bind to oligopeptides & migrate to cell surface
- complex are presented to T cell in lymph nodes
where do the MHC class II molecules migrate from
the ER via the golgi apparatus
dendritic cells and macrophages phagocytize
ALL types of molecules
B cells phagocytize
molecules recognized by antigen specific cell surface antibodies
MHC class II and class I occur in what cell types?
class I occurs in all cell types
class II ONLY occurs in dendritic and macrophages
define langerhan cells
specialized phagocytic cells that reside in the skin
how are mature dendritic cells formed?
through APCs that take up antigen and migrate to the lymph nodes
explain the steps in maturation of dendritic cells
- langerhan cells take up antigen by phagocytosis and migrate to the lymph nodes where they mature into DC cells
- in the lymph nodes DC cells confront & present antigens to the T cells
- results in activation of T cells that initiate an immune response against antigens
antibodies function
- recognize antigens on cell surfaces
- direct killing of foreign cells
antibody kills foreign cells by
preventing
- viral absorption into host cells
- bacterial adherence to host cells
list the 5 mechanisms of killing
- antibody coating
- ADCC
- CTLs
- extrinsic apoptotic pathway
- natural killer cells
ADCC= antibody dependent cell mediated cytotoxicity
explain the antibody coating mechanism of action
-bacterium provokes macrophage to use Fc receptors to recognize/ bind to antibody molecule
-bacterium is phagocytized
- destruction by lysosomes within the cytoplasm of macrophage
explain the ADCC mechanism of action
-targeted mammalian cell becomes coated w/ antigens that recognize and bind antibodies
- NK cells use Fc receptors to bind antibody molecule
- binding activates NK cells introducing cytotoxic granules
- lysis of cell
explain the CTLs mechanism of action
- granules within the CTL are introduced to the target cell
- target cell goes into apoptosis & disintegrates
each CTL expressed a
specific antigen-recognizing T-cell receptor on its surface
Diversity of T-cell receptors leads to
antibody diversity
CTL release granules w/
perforin
perforin forms
cylindrical channels in plasma membrane
after cylindrica channels have been made..
granzymes go into cytoplasm of target cell
initiates apoptotic cascade (cleaving procaspases)
when there is the absence of a cellular target a…
synapse w/ the targeted cell forms
explain the extrinsic apoptotic pathway mechanism of action
- Fas ligand engages Fas receptor on targeted cell triggering receptor trimerization
- activates extrinsic caspase cascade
- cell dies
what is known as an alternative kill method
the extrinsic apoptotic pathway
explain the NK cells mechanism of action
by spreading its cytoplasm on the surface of the tumor
NK cells are programmed to target any cells
displaying abnormal levels of MHC I molecules on the surface
what greatly increases the risk for developing certain cancer
immunosuppression
if an antigen is being presented from a cancer cells then…
activated T lymphocytes will attack cancer cells with that antigen
explain how mice where immunized w/ the exposure to killed cancer cells
- mice were injected with killed original tumor cells
- when injected w/ live original tumor cells there was no tumor growth
- when injected w/ live tumor cells from another tumor there was tumor growth
immune signaling occurs via
chemokines
cytokines
define chemokines
a family of chemical messengers that attract leukocytes via chemotaxis
define cytokines
regulators of immune response (interferons and interleukins) that signal between cells
name the macrophage activators that are anti-tumor
LPS
IFN-y
list some ways that macrophages become anti-tumor
- cytokines
- chemokines
- tumor cell lysis
- reactive O and N species
- metalloproteinases
name the macrophage activator that is pro-tumor
hypoxia
list some ways that macrophages become pro-tumor
- pro-angiogenic cytokines/ enzymes
- reactive O and N species
- cytokines
- tissue factor
- metalloproteinases
- chemokines
macrophage mobilization includes
- macrophage phagocytizing apoptotic bodies
- macrophage phagocytizing tumor cell
list some immunoevasive strategies of cancer cells
- repress MHC-I proteins
- repress NK ligands
- destroy immunocyte receptors
- induce Treg formation
- release FasL and cytokines
- avoid FasL apoptosis
- upregulate CD47 expression
CD47= dont eat me signals
repressing MHC-I proteins hides the cancer cells from
Tc lymphocytes
repressing the NK ligands hides the cancer cells from
NK cells
destroying immunocyte receptors inactivates
NK and Tc cells
inducing Treg formation suppressed
Tc cells
releasing FasL and cytokines induces
apoptosis in immune cells
avoiding FasL apoptosis and increasing IAPs inhibits
IAPs = inhibitors of apoptosis proteins
caspases
up regulating CD47 expression leads cancer cells to
avoid phagocytosis
MHC class I molecules can fail to present oligopeptide due to loss of
beta2
TAP1
explain tumor immunoevasion by Tregs
tumor cells release chemokine (CCL22) which binds to Treg resulting in suppression of effector T cells
what surface antigens expressed by Treg inhibits Tc cells
CD25 and FOXP3
what is an indicator of long term survival in ovarian cancer patients?
increased concentrations of Treg
precancerous inflammation can cause
- increased genetic damage
give examples of the genetic damage that can occur due to inflammation
- point mutations
- AID activity
- decreased oncogene methylation
- DNA breaks
- DNA damage
- tumor suppressor methylation
what can induce inflammation
aberrant oncogenic signaling
what are the 2 paths that cancer inflammation can take?
- extrinsic
- intrinsic
explain the extrinsic mechanism
chronic inflammation that leads to increased cancer risk
explain the intrinsic mechanism
DNA damage activated oncogenes leading to tumor development
tumor cell behavior depends on
- characteristics of cancer cells
- cancer cells interactions w/ normal cells
tumor cells secrete _______ that recruit _________ and promote _______.
chemokines
TAM
angiogenesis
TAMs can produce _________ and ______ which can mutate ________
cytokines
ROD/NOS
DNA
what pathway is a key mediator of the inflammatory response
NF-kB pathway
when NF-kB enters the nucleus it targets genes that lead to what 3 responses
- inhibition of apoptosis
- inflammatory response
- metastasis and angiogenesis
inhibition of apoptosis is done by what gene
Bcl-XL
inflammatory response is done by what gene
cytokines (TNFa)
metastasis is done by what gene
MMP9
angiogenesis is done by what gene
VEGF
list some upstream initiator of the NF-kB pathway
- bacteria
- viruses
- stress
- inflammatory agents
- carcinogens
downstream effectors of the NF-kB pathway lead to
tumorigenesis
what are the main 3 focuses for immunotherapy
- enhancing antigen presentation
- suppressing immunological checkpoints
- Enhancing T cell migration
What are the 2 types of immunization strategies
- passive
- active
passive immunization include
- tumor-specific antibodies
- engrafting histo-incompatible marrow
active immunization includes
- activated tumor-infiltrating lymphocytes (TILs)
- dendritic cells w/ tumor specific oligopeptide antigen
- tumor blocking of CD47
- inhibiting Treg cells
- blocking CTLA-4 function
what happens when p53 inhibitors are prevented from inhibiting p53?
tumor-suppressing protein releases endogenous retroviruses
helps immune system spot cancer cells
