innate immunity II Flashcards

1
Q

describe the human lymphatic system

A

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

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2
Q

what are lymph nodes?

A

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

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3
Q

describe the structure of a lymph node

A

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!!

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4
Q

describe the structure of the spleen

A

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

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5
Q

what are pathogens?

A

anything that generates sickness - “sickness generator”

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6
Q

how do cells “sense” the presence of pathogens

A

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)

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7
Q

differentiate between innate recognition and adaptive recognition

A

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

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8
Q

describe the intracellular signalling pathway

A

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

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9
Q

what are PRRs? what do they do?

A

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

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10
Q

what do PRRs recognize?

A

they recognize molecules in evolutionary conserved and invariant regions of pathogens (PAMPs)

they can also recognize damage or infection signals (DAMPs)

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11
Q

other than innate immune cells, where can PRRs be found?

A

some WBCs have PRRs, for example Toll-like receptors in B cells and also in some epithelial cells

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12
Q

what are the (4) families of PRRs?

A

Toll-like receptors (TLR)

C-type lectin receptors (CLR)
—- found on the cell surface

Nucleotide oligomerization receptors (NLR)

RIG-I like receptors (RLR)

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13
Q

where are TLRs found and describe its diversity

A

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

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14
Q

in an experiment with toll-deficient fruit flies, what occurred?

A

Toll-deficient fruit flies weren’t able to prevent fungal infection, thus, developing a fungal infection

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15
Q

what are PAMPs?

A

Pathogen Associated Molecular Patterns

what can be recognized by PRRs!

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16
Q

what are some PAMPs for bacteria?

A

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

17
Q

what are some PAMPs for viruses?

A

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!

18
Q

what are some PAMPs for parasites?

A

GPI anchors on parasitic surfaces

19
Q

what are some PAMPs for fungi?

A

glucan in the cell walls of fungi

zymosan / mannan in the cell walls of yeast

20
Q

what are DAMPs?

A

Damage-Associated Molecular Patterns

self-molecules released as a consequence of cellular damage

21
Q

what are examples of DAMPs?

A

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

22
Q

what are cytokines?

A

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

23
Q

what are the different modes of action for cytokines?

A

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

24
Q

what are the 6 major cytokine families?

A

interleukin family “between WBC”

class 1 - hematopoietin

class 2 - interferon

tumor necrosis factor

interleukin-17

chemokines

25
Q

what is the interleukin family?

A

a cytokine family

first non-interferon cytokine (and as a result, interleukin family) to be identified was IL-1

important for inducing inflammation

26
Q

what are hematopoietins?

A

a cytokine family

includes cytokines and growth factors important for controlling all aspects of the immune response

27
Q

what are tumor necrosis factors?

A

a cytokine family

important for inflammation

works on tumor necrosis factor family receptors to transmit the signal

28
Q

what are chemokines?

A

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

29
Q

what does the dissociation constant tell us about receptors (and complexes)?

A

shows us the different affinities they have,

lower dissociation constant = higher affinity for binding

30
Q

describe the transduction pathway of JAK/STAT , an interleukin family

A

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

31
Q

what are interferons?

A

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