innate immunity II Flashcards
describe the human lymphatic system
similar to the circulatory system, lined with endothelial cells
parallel to the circulatory system, they don’t touch or connect
lymphatic vessels come together in places called lymph nodes
lymph nodes can be found in the back of your throat (tonsils), under your arms, groin area, lower body
what are lymph nodes?
where lymphatic vessels come together
lymph nodes are known to have a “focusing” ability that draws immune cells to them – this is where an immune response is generated
describe the structure of a lymph node
these organs are packed with white blood cells, specifically lymphocytes
highly organized structure
center is referred to as the medulla and it’s surrounding area is called the cortex
APCs, antigen-presenting cells (e.g. dendritic cells, macrophages, and monocytes) present antigens to the T cell here
follicles are very rich in B cell, hence also referred to as B cell zones
the area surrounding the B cell zones (and the medulla) is called the paracortex; also referred to as the T cell zone because it’s filled with T cells
REFER TO DIAGRAMM!!
describe the structure of the spleen
red pulp is important for the recycling of RBCs
—— specialized macrophages will eat dying RBCs
—— prevents iron from leaking out of RBCs – iron is used by pathogens to function and replicate
white pulp is where WBCs are located – like other lymph nodes, it is highly organized
the follicle/B cell zone of the white pulp is the area that brings cells of the immune system together - where an immune response is initiated
what are pathogens?
anything that generates sickness - “sickness generator”
how do cells “sense” the presence of pathogens
by receptors! which then transmits a signal that induces changes within the cell - including in gene expression, cell division status, etc. - which induces phagocytosis or production of growth factors
the receptor is a transmembrane protein
—– has a transmembrane component and intracellular component (that transmits the signal)
differentiate between innate recognition and adaptive recognition
innate recognition
—- germ line encoded receptors that recognize conserved molecular patterns in microorganisms
adaptive recognition
—- uses somatically generated antigen receptors which are distributed on the two types of lymphocytes, T cells and B cells
describe the intracellular signalling pathway
signal molecule non-covalently (and with high-affinity) interacts with the receptor, inducing conformational changes in the receptor, allowing it to transmit signals from membrane to interior of the cell
—— the signal molecule could be the pathogen itself or a molecule derived from it
signal initiated via signal transduction pathway
—— there is a large diversity of signal transduction pathways
—— some signal transduction pathways are “on” signals (turns it on) and some are “off” signals (turns it off)
pathways can overlap and interact with each other
—— pathways are not usually mutually exclusive
—— one can affect another - e.g. one can turn on/off another
what are PRRs? what do they do?
pattern recognition receptors
used in innate immunity
PRRs are expressed at the cell’s surface and within (in the cytoplasm/endosomes - their surrounding lipid membrane) many cell types
—– if found on the cell surface, they induce phagocytosis by extending its pseudopods (this is part of the signal transduction pathway). once in the cell, the PRRs will additionally activate the cell
they recognize molecules in evolutionary conserved and invariant regions of pathogens (PAMPs)
they can also recognize damage or infection signals (DAMPs)
the specificity of the receptor is germ-line encoded – meaning from parents
they are critical for initiating immune responses
what do PRRs recognize?
they recognize molecules in evolutionary conserved and invariant regions of pathogens (PAMPs)
they can also recognize damage or infection signals (DAMPs)
other than innate immune cells, where can PRRs be found?
some WBCs have PRRs, for example Toll-like receptors in B cells and also in some epithelial cells
what are the (4) families of PRRs?
Toll-like receptors (TLR)
C-type lectin receptors (CLR)
—- found on the cell surface
Nucleotide oligomerization receptors (NLR)
RIG-I like receptors (RLR)
where are TLRs found and describe its diversity
can be on the cell surface or in the endosome (after material has already been engulfed, so this would be seen in highly phagocytic cells - like macrophages and dendritic cells)
humans have many of these genes due to duplications of the family, now able to recognize a variety of patterns
—– different types of TLRs recognize different types of PAMPs
in an experiment with toll-deficient fruit flies, what occurred?
Toll-deficient fruit flies weren’t able to prevent fungal infection, thus, developing a fungal infection
what are PAMPs?
Pathogen Associated Molecular Patterns
what can be recognized by PRRs!
what are some PAMPs for bacteria?
peptidoglycan and lipoteichoic acid are found in the cell walls of gram+ bacteria and gram- bacteria
lipopolysaccharide is found in the cell walls of only gram- bacteria
flagellin found on bacteria
what are some PAMPs for viruses?
viral nucleic acids and coat proteins (capsid/surface) of viruses
viruses have many types of nucleic acids – so if it’s not double-stranded DNA, they know it’s foreign!
what are some PAMPs for parasites?
GPI anchors on parasitic surfaces
what are some PAMPs for fungi?
glucan in the cell walls of fungi
zymosan / mannan in the cell walls of yeast
what are DAMPs?
Damage-Associated Molecular Patterns
self-molecules released as a consequence of cellular damage
what are examples of DAMPs?
when ATP is outside the cell, its sensed by the cell receptors to activate immune response
also applies for uric acid, mitochondrial DNA, free histones (normally found in the nucleus), heat shock proteins, S100, ATP and high-mobility group proteins
WBCs will only be able to detect them if damage has been done! these should all be in the cell or organelles
what are cytokines?
used for extracellular signalling
chemical “messages”: proteins that allow communication between cells of the immune system - some short and some long distances
target cells can only respond to cytokines if they have the receptor for it
what are the different modes of action for cytokines?
pleiotropy
—- same cytokine acts on different cells, evoking different responses
redundancy
—- different cytokines evoke same response in cells
cascade induction
—- action of a cytokine on a cell induces production of one or more additional cytokines. e.g. cold! has numerous effects
what are the 6 major cytokine families?
interleukin family “between WBC”
class 1 - hematopoietin
class 2 - interferon
tumor necrosis factor
interleukin-17
chemokines
what is the interleukin family?
a cytokine family
first non-interferon cytokine (and as a result, interleukin family) to be identified was IL-1
important for inducing inflammation
what are hematopoietins?
a cytokine family
includes cytokines and growth factors important for controlling all aspects of the immune response
what are tumor necrosis factors?
a cytokine family
important for inflammation
works on tumor necrosis factor family receptors to transmit the signal
what are chemokines?
a cytokine family
small molecules that interact thru transmembrane receptors
essential for telling cells where to go in the body (chemoattractant). e.g. to migrate to/from the lymph node
also assist in tissue organization inside the body
both immune and non-immune cells (e.g. epithelial cells) can secrete chemokines
immune cells with chemokine receptors are recruited from the blood into tissues
what does the dissociation constant tell us about receptors (and complexes)?
shows us the different affinities they have,
lower dissociation constant = higher affinity for binding
describe the transduction pathway of JAK/STAT , an interleukin family
IL2R, a growth factor is important for cell division
IL-2R interacts with receptor, inducing signal that recruits JAK, an enzyme
JAK enzymes will phosphorylates one another and also phosphorylate a protein called STAT (“signal transduction and activation of transcription”)
the STAT proteins will dimerize with one another (combines) and cross the membrane of the nucleus, where they will turn some genes on/off (by directly binding to the DNA), activating cellular responses
REFER TO DIAGRAM
what are interferons?
cytokines that are important in directing antiviral responses
virus-infected cells secrete type I interferons, which turn on cells of the immune system
interferons are important for initiating immune responses by activating dendritic cells
