Innate Immunity (Lecture 2) Flashcards

1
Q

Innate lymphoid cells (ILCs)
• ILCs are the most recently identified family of innate immune cells.
• Although they belong to the ____ lineage (lymphocytes), they lack T- or B-cell antigen receptors and thus cannot respond in an ____ manner.

  • ILCs are predominantly found at ____ surfaces (e.g., skin, airways, and intestine), where they regulate immunity, inflammation, and tissue repair.
  • ILCs can additionally maintain immune tolerance toward the ____ in the gut.
A

lymphoid
antigen-specific

barrier
commensal microbiota

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2
Q

Innate lymphoid cells (ILCs) cont

• Different groups of ILCs express distinct sets of ____ and thus are responsible for ____ functions.

A

cytokines

specialized

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3
Q

ILCs are the innate counterparts of specific T cell subsets

NK (CD8+) > ____, ____
ILC1 (Th1) > ____
ILC2 (Th2) > ____, ____, ____, ____
ILC3 (Th17) > ____, ____

A
IFNgamma
perforin
IFNgamma
IL-4
IL-5
IL-13
AREG
IL-17
IL-22
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4
Q

ILCs are the innate counterparts of specific T cell subsets

NK/ILC1:
Type I
Defense against \_\_\_\_ pathogens and \_\_\_\_.
Adverse outcomes:
Inflammatory, \_\_\_\_ diseases.
ILC2:
Type 2
Defense against \_\_\_\_ and \_\_\_\_. 
Homeostatic funcIon: \_\_\_\_ repair. 
Adverse outcomes: \_\_\_\_, \_\_\_\_.

ILC3:
Type 3
Defense against extracellular organisms (____ and extracellular ____). Homeostatic function: ____ maintenance.
Adverse outcomes: Inflammatory, ____ diseases.

A

intracellular
tumors
autoimmune

helminths
venoms
tissue
asthma
allergy

fungi
bacteria
epithelial barrier
autoimmune

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5
Q

Interferons
• Two types, produced in response to inflammation or infection
• Type1 or ____–produced by ____ cells and ____
• Type2 or ____–produced by mainly by ____.

• Responsible for much of host control of viral replication in ____ and other infections

A
alpha/beta
epithelial
fibroblasts
gamma
lymphocytes

colds

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6
Q

Interferons alpha/beta

induce resistacne in cells so they resist ____ synthesis, and increase ____ and activate ____ cells to kill virus-infected cells

A

viral
MHC class I
NK

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7
Q

Interferons alpha/beta induce antiviral proteins that suppress viral replication

cell infected with virus > leads to produce of ____ interferons; has been secreted and activated second cell (now prepared > induces production of antiviral proteins); virus wil not be able to esrtablish ____ like in first cell now

A

alpha/beta

infection

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8
Q

Time course of antiviral reaction

time course of antiviral response

first ____; and activation of ____ cells (from IFN); if NK cells are not enough, then induction of ____ immunity

as immmunity progresses, virus titer plateuas and goes down

A

alpha/beta IFN
NK cells
adaptive

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9
Q

Complement
• Group of proteins that circulate in the blood
• Important role in host defense but also implicated in inflammatory immunopathology (eg, ____).

– Help ____ phagocytes to site of inflammation and activate them
– ____ bacteria which are targeted to receptors on ____, for clearance
– Form ____ in targeted susceptible microbes
– Activate ____ to release histamine and other factors

A

sepsis

recruit
opsonize
phagocytes
pores
mast cells
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10
Q

Functions of Complement

lectin/alternative you don’t need ____

lectin > MBL (is PRM)
doesn’t matter which mechanism
everything goes through ____ (central complement compoentn) two products > ____ = opsonin; ____ = inflam molecule, binds to receptors on phaocytes/inflam cells > C5 is the same > helps inflam cells (macro’s neutros) to get to a tissue > leads to chemotaxis/vascular perm > ____

downstreamf rom C5 > complexes with 6, 7, 8 and 9 > ____ (membran-ettack complex); when binds bacterium > casues its ____

A
adaptive
C3
C3B
C3A
inflammation

C5b-9
lysis

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11
Q

The complement system “complements” the ability of antibodies and phagocytic cells to clear pathogens

C5A > bring ____ > recognize bacteria that has been decorated by ____; if not opsonized doesn’t mean it can’t get phagocytosis

A

phagocytes

C3B

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12
Q

Cytokines
• Secreted ‘messenger’ proteins that mediate communication between cells and regulate immune and inflammatory responses.
• Induced during both ____ and ____ immune responses.
• Have many activities, either ____ or ____ inflammatory.
• Generally follow an ____ appearance, with important roles both in the ____ and ____ phases of the response.

A
innate
adaptive
pro-
anti-
ordered
early
late
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13
Q

Cytokines are messengers in the immune system

Induction and regulation of inflammatory responses
is just one of their functions.

Other functions include the development, differentiation, and proliferation of ____ cells

Cytokine ____
Do not have to learn this! Just appreciate
the intricate complexity
(in fact, quite simplified here).

A

immune

networks

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14
Q

Inflammation

Homeostatic process aiming to:
• Isolate and destroy the initial insult (e.g., infectious agent)
• Mitigate tissue damage
• Remove necrotic cells and tissue, repair damage
• Restore normal function

Also a potentially harmful process
• Components of inflammation capable of destroying microbes may also cause ____ injury
• Serious consequences if not properly controlled and ____

A

bystander tissue

self-limited

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15
Q

Cardinal signs of inflammation (inflammare: latin for set on fire)

Characterized by:
Increase in temperature \_\_\_\_
\_\_\_\_
\_\_\_\_
\_\_\_\_
Loss of \_\_\_\_
A
heat
redness
swelling
pain
function
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16
Q

when you have inflam; if persistent infection > ____ inflammation > common denimoator of ____, ____ loss (rheumatoid arthritis), ____ (neurological diseases), ____ diseases (artheroscleoris, stroke), ____ disease (asthma, COPD), ____ disorders (multiple sclerosis)

A
chornic
periodontitis
bone
alzheimers
cardiovascular
pulmonary
autoimmune
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17
Q

Example of inflammation (skin)

bacteria enter skin; through a wound; bacteria detected by local macro’s > ____ > activte endothelium > ____ and also ____ of junction bt endo cells > faciliate the recruitment of neutrophils/macro’s into the tissue

A

cytokines
vasodilation
loosening

18
Q

Inflammation and associated symptoms at the molecular level

pain also occurs > ____and ____ (why you take NSAIDs, inhibit the function)

A

prostaglandins

histamines

19
Q

Inflammation: Effects on Vascular Endothelium

  • ____ – vessel enlarges and gets greater blood flow, but lower ____
  • Expression of receptors – endothelial cells upregulate ____ proteins specific for interactions with leukocytes (e.g., selectins, ICAMs and VCAMs)
  • Loosening of cell junctions – ____ open up to allow passage of leukocytes
  • Clotting of microvessels – restricts exit of ____ agents from the area to prevent ____ dissemination
A

vasodilation
velocity

adhesion

tight junctions

infectious
systemic

20
Q

Complement involvement in inflammation

The anaphylatoxin receptors ____ and ____ mediate most of complement’s inflammatory responses.
C3a and C5a contribute to ____ degranulation and inflammation during ____-dependent anaphylaxis.

A

C3aR
C5aR

mast cell
IgE

21
Q

Complement is involved in the recruitment of ____, such as neutrophils

Complement amplifies the production of inflammatory ____ potentially leading to tissue damage

too much inflam > complement can be invovled in cytokine ____ > tissue damage, organ failure

A

inflammatory cells
cytokines
storm

22
Q

Inflammatory Cytokines

All are produced by ____, IL-1 the only one also produced by ____. All the others are also produced by ____.

IL-8 > chemoattractant for ____
IL-12 > activated naive ____ to be activate
IL-1/6 > active in ____ and activate lymphocytes; activate ____ proteins
TNFalpha > acts on ____; induces changes

A

macrophages
keratinocytes
dendritic

neutrophils
T cells
liver
acute-phase
vasco endo
23
Q

Inflammasomes

• Inflammasomes are multiprotein complexes that assemble in the ____ after exposure to certain PAMPs or DAMPs and result in the activation of ____, which cleaves the inactive cytoplasmic precursor pro-IL-1β to the mature form of proinflammatory ____, which can then be secreted.

• Inflammasome complexes typically consist of:
– ____ (NLR or ALR sensor protein)
– ____ (ASC)
– ____ (in inactive form prior to activation: pro-caspase-1)

• A number of distinct inflammasome complexes have been identified (different activation triggers and PRRs); the best characterized is the ____ complex.

A

cytosol
caspase-1
IL1B

cytosolic PRR
adaptor protein
caspase-1

NLRP3

24
Q

NLRP3 inflammasome

The NLRP3 inflammasome is activated in a 2-step process:
– Signal 1 (priming step): ____ activation (e.g., by bacterial LPS) results in increased expression of ____ and ____.
– Signal 2: Activation of NLRP3 occurs by different triggers* that lead to the assembly of the complex and activation of ____.

Triggers: Whole pathogens; PAMPs/DAMPs; potassium efflux; lysosomal-damaging ____ factors [uric acid, silica, alum]; endogenous factors [amyloid-β, cholesterol crystals]; mitochondrial damage which releases ____.

A

NF-kB
NLRP3
prol-IL-1beta
caspase-1

environmental
reactive oxygen species

25
Q

Anti-inflammatory Cytokines

____ and ____ are anti-inflammatory cytokines produced by several cell types including macrophages and ____ cells.

These cytokines act as ‘brakes’ to restrain the host inflammatory response. For instance, Treg-derived IL-10 and TGFβ can control inflammatory responses by ____, eosinophils or ____ effector cells.

A

IL-10
TGFbeta
regulatory T helper cells

basophils
T helper effector

26
Q

Acute phase proteins
– Proteins in the ____ that increase during infection and inflammation
– Can be used ____ to give an indication of acute inflammation

produced in liver; activated by ____ and ____; icnrease in plasma during infect/inflam; cxn go VERY high during these

A

plasma
diagnostically
IL1
IL6

27
Q

Acute Phase Proteins

IL6 acting liver cells (MBP [one of substances that activated complement]) > binds to residue on bacteria, activates ____ pathway and ____

C-reactive is similar; binds ____ on bacterial cells, acting as an opsonin and a complement activator

Also ____

A

complement
opsonization

phosphorylcholine

fibrinogen

28
Q

Inflammation: Could protect or kill you

Although the inflammatory response contributes to immunity against infection, excessive and/or sustained inflammation contributes to ____ and ____.

A

immune pathology

disease

29
Q

inflam must be regulated; helpful if ____

when systemic inflammation > systemic edema causes decreased ____; causes vessel to ____, and disseminated intravasculature ____ > can result in death (local clotting is good, but coagulation everywhere > bad news)

A

localized

blood flow
collapse
coagulation

30
Q

Inflammation underlies the pathogenesis of many diseases

LOOK OVER THE IMAGE

\_\_\_\_ infection
\_\_\_\_
\_\_\_\_ disease
\_\_\_\_ arthritis
\_\_\_\_
A
myocardial
stroke
chohn's or alzheimers
rheumatoid
periodontitis
31
Q

Mast cells & allergy

mast cells > activated like basophils (with ____); pollen can activate receptors that have already bound IgE

antigens that activate mast > inhaled ____, or material (____), food (____), insect ____, and material we contact (____)

A
bacteria
pollen
peanuts
venom
poison ivy
32
Q

Mast cells
• Found in tissues such as the skin, near ____.
• Activated after antigen binds to a specific type of antibody called ____ that is attached to receptors on the mast cell.
• When activated, mast cells release substances that contribute to inflammation, such as ____.
• Important in ____ responses but are also part of the ____ immune response, helping to protect against infection.

A
blood vessels
IgE
histamine
allergic
innate
33
Q

Innate and Adaptive Immunity work together

good to know that both innate and adaptive wokr together, cannot fight separately

extra bac > present in interstitail spaces or epi surfaces > can be dealt with ____ and ____ > work together to better fight

complement activation > classical pathway, which is activated by ____ (complements antibody functions)

intercell bacteria > cyto or vesicular > both forms; ____ cells with ____ cells

A

complement (innate)
antibodies (adaptive)

antibodies

NK
cytotoxic T

34
Q

Immunity is a double-edge sword: protection vs. harm

tumors and infectious agent you want a ____

3 cases where YOU DONT WANT HTE HOST TO RESPOND > ____, ____, or ____

A

reaction
innocuous substance (peanut)
grafted organ
self-organ

35
Q

Innate:
____
____ recognition
____

First line of defense Necessary for proper function
of adaptive immunity

Adaptive:
Evolutionarily ____
Defined ____ target
____ & custom-made (____ upon repeated infection)
Second line of defense Reinforces innate immunity

A

primitive
pattern
invariant

recent
epitope
variable
improves

36
Q

Innate Immunity
Cells: ____
Receptors for detection of microorganisms: ____: encoded in the ____
Receptor repertoire: ____
Specificity for microbial components: ____ > molecular patterns (shared by classes of microbes)

Adaptive Immunity
Cells: ____
Receptors for detection of microorganisms: ____: generated ____ by gene recombination
Receptor repertoire: ____
Specificity for microbial components: ____ > structural details (specific peptides)

A
monocytes/macrophages, neutrophils (PMN) and dendritic
PRRs
germline
limited
broad
T & B lymphocytes
T cell receptors/B cell receptors
randomly
unlimited
narrow
37
Q

Beyond an initial obstacle to infections

! In recent years, it has been appreciated that innate immunity is not simply a physiological barrier or a set of immune responses aiming to ‘buy time’ until adaptive immunity becomes activated.

! Innate immunity is endowed with adequate ____ to distinguish between different classes of ____ as well as to detect ____ damage.

! Adaptive immunity can elicit a response only after it is informed by the ____ system that the recognized target is dangerous for the host.

! If lymphocytes are instructed that there is no danger, they become ____ to the recognized target.

A

specificity
microorganisms
host cell

innate

unresponsive (tolerant)

38
Q

Beyond an initial obstacle to infections (cont)

! Dendritic cells (DCs) act as sophisticated mediators between detection of infection and induction of the appropriate adaptive immune response.

! This role requires a function known as ____, a process whereby DCs capture microbial antigens, degrade them into small peptides, and couple them with specialized cell surface proteins, termed ____ molecules, for presentation to and recognition by T cells.

! In addition to antigen presentation, DCs provide co-stimulatory signals to ____ cells, thereby activating them and instructing their development in a manner that is tailored to the nature of the infection.

! Antigen presentation alone (without co- stimulation) induces ____ (unresponsiveness).

A

antigen presentation
major histocompatability complex (MHC)

T

T cell tolerance

39
Q

Properties of Adaptive Immune Responses

see same antigen a second time, you respond much ____ > in a more robust way

basis for vaccination; respond much ____ when encounter the infection later

A

faster

quicker

40
Q

No memory in innate immunity?

  • Although innate immune cells lack the exquisite antigen specificity, clonality, and longevity of adaptive lymphocytes, they can be ‘trained to ____’ following exposure to infection or vaccination.
  • Designated ____, this capacity enables innate cells (e.g., monocytes, macrophages, and NK cells) to display enhanced ____ after secondary stimulation with microbial pathogens, which can thereby be eliminated more readily.
  • The molecular basis of ‘trained immunity’ involves sustained changes in their transcriptional programs, known as ____ (as opposed to permanent genetic changes owing to mutations and recombination).
  • Although innate immune memory is ____ lived and less ____ than classical adaptive immune memory, it can contribute to efficient control of many infections.
A

remember
trained immunity
responsiveness

epigenetic reprogramming

shorter
specific

41
Q

What is the relative importance of the innate and adaptive immune systems in infection?

if only going to have one > no innate > ____ immediately > death

if you don’t have adaptive > in beginnign you’ll be okay (bc innate might be able to handle it) > but if it’s more challenging, you will lose control ____ on

A

uncontrolled infection

later