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FS I, Module III > Innate Immunity (Lecture 2) > Flashcards

Innate Immunity (Lecture 2) Flashcards

1
Q

Immunity:
Protection from pathogens and disease

• Mechanical Barriers
– ____
– ____ surfaces

• Innate and Acquired (adaptive) defense mechanisms

A

skin

mechanical

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2
Q

Pathogens cause tissue damage directly or indirectly

• Direct Mechanisms

  • ____
  • Degradative ____
•  Indirect Mechanisms
 (host-mediated damage to host)
- Destructive \_\_\_\_ (locally or systemically) 
- \_\_\_\_ (Ag-Ab; blood vessel damage) 
- \_\_\_\_ (cross-reactive with microbes)
A

toxins
enzymes

inflammation
immune complexes
anti-host antibody

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3
Q

The immune system protects against four classes of pathogen

Bacteria > salmonella enteritidis > ____

Viruses > influenza > ____

Fungi > candida albicans > ____, systemic ____

Parasites > protozoa > plasmodium falciparum > ____

A 
food poising
flue
thrush
candidiasis
malaria
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4
Q

Self vs Non-self
• The immune system needs to distinguish foreign (‘non-self’) material from self–tissues and –cells.
• Moreover, the immune system needs to neutralize or eliminate ____ while sparing ____ from immune attack.
• The latter concept is known as ____, in that the body needs to ‘tolerate’ its own tissues.
• If immune tolerance breaks down, the resulting aberrant immune response against self-tissues may cause disorders known as autoimmune diseases.

A

non-self
self
immune tolerance

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5
Q

Self vs Non-self cont.
• The self/non-self paradigm provided a useful conceptual framework on how the immune system responds to exogenous pathogens (non-self).
• However, it could not explain immunity to all types of ‘threats’.
• For instance, immunity to cancer could not readily fit into the self/non-self concept because ____ are not actually ‘non- self’ but rather represent ‘altered self’.
• Furthermore, immune responses are activated also to cope with tissue damage that is caused by ____ (____ damage).

A

tumor cells
mechanical injury
sterile

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6
Q

Detecting Danger
• The immune system has primarily evolved to discriminate between ____ and ____ rather than between ‘self’ and ‘non-self’.
• According to the so-called ____ model,the immune system is alarmed by signals released from ____ cells (due to injury or infection), such as nucleic acids, heat-shock proteins and other intracellular molecules, collectively known as ____.

A 
safe
dangerous
danger
damaged
alarmins
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7
Q

Examples of self and non-self entities and possible outcomes of the immune response or lack thereof

Take a look at table

respond to normal self > don’t want to respond > ____

____ > altered self > want to respond
damaged self > want to respond

symbiotic microbes > don’t want to respond to commensal bacteria > if you do, there will be a lot of ____ (unncessary)

food antigens (innocuous substances) > do not want to respond > can develop into ____

A

self-tolerance
tumors
inflammation
allergies

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8
Q

The immune players

Innate

  • ____ barriers
  • ____
  • ____ cells
  • ____
  • ____ cells

innate > VERY ____, deployed hours/minutes

adaptive > ____, days/weeks

A 
epithelial
phagocytes
dendritic
complement
NK

fast
slow

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9
Q

Two arms of immunity

When preformed or constitutive defense mechanisms are not adequate to control an invading pathogen, the innate immune system needs to mobilize ____.

Initially, this involves only innate immune cells but, if necessary, ____ immune cells will also be recruited in a few days

0-4 hours: ____ responses of ____ immunity
4-96 hours: ____ responses of ____ immunity
>= 96 hours: ____ response

A

reinforcements
adaptive

ubiquitous
innate
induced
innate
adaptive
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10
Q

Innate vs. adaptive immunity

Innate

  • ____ response (hours)
  • ____
  • ____ number of specificites
  • ____ during response

Adaptive

  • ____ response (days to weeks)
  • ____
  • ____ highly selective specifities
  • ____ during response
A

rapid
fixed
limited
constant

slow
variable
numerous
improve

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11
Q

All innate and adaptive immune cells are derived from ____ cells in the ____

common myeloid progenitor and lymphoid progenitor

lymphoid pro > T cells and B cells and ____ cells

myeloid pro> ____ pro, or the ____ pro

A

hematopoietic stem
bone marrow

innate lymphoid
megakaryocyte/erythroid
granulocyte/macrophage

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12
Q

The players in innate and adaptive immunity

NEUTROPHIL > 3 ____, they arrive ____ than macro’s, ____

eosinophil > killing of ____ through release of granule contents

macrophages > ____, activation of ____ cells and initiation of immune responses

basophil > role in ____ infections

dendritic > activating ____ cells and activating ____ immune response

A 
lobes
faster
antibody-coated parasites
phagocytosis
T
parasitic
T
adaptive
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13
Q

How does innate immunity recognize microbial targets?

Pattern-recognition receptors (PRRs) ‘The ____ of innate immunity’

  • ____ encoded receptors
  • Detect and respond to conserved microbial structures, such as bacterial ____ or ____ acid, known as ____.
A 
eyes
germ-line
LPS
LTA
microbe-associated molecular patterns (MAMPs)
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14
Q

Is innate (inborn) immunity really ‘non-specific’?

Since this type of immunity appeared to provide a ____ defense against classes of microorganisms and without being directed at any one in particular, it was historically seen as ____; we now know that innate immunity has ____ recognition elements:

Different ____ recognize different classes of microbial molecules and activate the expression of appropriate immune-response genes.

____, an important PRR family, offers a good example (next slide).

A

general
non-specific
specific

pattern-recognition receptors (PRR)

toll-like receptors

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15
Q

Different toll-like receptors (TLR) recognize distinct classes of microbial molecules

TLR4 > ____ (common on gram-neg bacteria)

TLR2 > ____ (gram-pos); partners with other TLRs (with TLR1 it reognizes ____, and with TLR6 it recognizes ____ from ____)

TLR5 > ____

don’t know what ____ recognizes

also intracellular pathogens (viruses) there is a TLR for them, dsRNA > ____; ____ > ssRNA; CpG rich of DNA, ____ is much more likely

A 
LPS
LTA
lipoproteins
zymosan
fungi

flagellin
TLR10

TLR3
TLR7/TLR8
TLR9

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16
Q

The innate immune response is a universal and ____ conserved mechanism of host defense against infection.

! Predates the ____ immune response

  • –! Found in all ____ organisms
  • –! Adaptive immunity only in ____

Lack of ____ expression in flies leads to death from fungal infection

A

evolutionarily

adaptive
multicellular
vertebrates

toll receptor

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17
Q

Pattern-recognition receptors: More than sensing microbes

! PRRs recognize conserved structural features of microbes, termed ____).
! The immune system needs to detect and respond to ____ in general rather than to non-self, which might not always entail danger.
! Besides infectious agents, danger can be represented by the presence of ____ or ____ host cells.

! Inflammation can be induced by ____ causes such as:
! Trauma,
! Inhalation of ____ and silica,
! ____ crystals (cause of gout, a form of arthritis)
! ____ formed in the central nervous system
(implicated in Alzheimer’s disease)


A

microbe-associated molecular patterns (MAMPs)
danger
damaged
stressed

non-infectious
asbestos
uric acid
amyloid-beta

18
Q

Pattern-recognition receptors: More than sensing microbes (cont)

! Endogenous stress signals are called ____ or ____, and include:
! ____ acids,
! ____ proteins
! ____ proteins

! Once released in the extracellular space, DAMPs act as generic markers for cell damage or death by binding and activating ____.

! PRRs/DAMP receptors stimulate immunity to clear damaged/dead cells and promote ____.

A 
damage-associated molecular patterns (DAMPs)
alarmins
nucleic
histone
heat-shock

PRRs
tissue repair

19
Q

Soluble pattern-recognition molecules (PRMs)

  • The humoral arm of innate immunity contains a ____ group of PRMs, such as, ____, collectins, and ____.
  • PRMs collectively detect unique ____ motifs on bacteria, fungi, and viruses. Additionally, they can recognize ____ and ____ cells.

• PRMs perform diverse host-defense functions,
including:
– Microbial ____ and neutralization,
– ____,
– Control of inflammation
– ____ activation and regulation
– Interact with ____ receptors and activate phagocytosis and cytokine secretion (____).

• PRMs appear to act as functional ____ of antibodies (‘ante-antibodies’).

A

heterogenous
pentraxins
ficolins

carbohydrate
damaged
apoptotic

agglutination
opsonization
complement
Fcgamma
pentraxins

predecessors

20
Q

Antibody-mediated immune functions

  • ____ activation
  • ____ neutralization
  • ____
  • ____ cytotoxicity
  • ____ mediated inflammation
  • inhibition of bacterial ____
A 
complement
virus
opsonization
antibody-dependent cellular
fc-receptor
adherence
21
Q

In contrast to PRMs, antibodies have ____ specificity

A

exquisite

22
Q

The innate (inborn) immunity

• Barriers

  • ____ (skin, hair, mucosae)
  • ____ (sweat, tears, saliva, stomach acid)
  • – For instance, tears and saliva contain antimicrobial ____ and ____ that attack bacterial cell walls

• Cellular response
– ____ (neutrophils, macrophages)
– NK (natural killer) and mast cell responses

• Soluble factors (e.g,____)

  • microbiological barriers > commensal bacteria that are present in mouth/gut > do not allow pathogens to get established > ____ resistance
A

mechanical
chemical
peptides
lysozyme

phagocytosis
complement

complement

23
Q

Antimicrobial peptides (____)

• Short, generally ____, ____ antimicrobial proteins
• Secreted by ____ cells, neutrophils, alveolar ____
• Found at ____ surfaces
– trachea, small intestine, female reproductive tract in mammals
– ____ secretions in fish and amphibians

They have ____
activity against targeted
pathogens
(microbial cell is punctured)

A 
defensins
cationic
broad-spectrum
epithelial
macrophages
mucosal
skin

membranolytic

24
Q

Cells of the innate immune system

Phagocytic cells: 
neutrophils
monocytes/macrophages 
\_\_\_\_ cells
immature \_\_\_\_ cells

Non-phagocytic cells:
____ cells
mature ____ cells

Most common leukocyte: ____ (____ are next most common)

A

mast
dendritic
NK
dendritic

neutrophil
monocyte

25
Q

Phagocytic Cells

• Polymorphonuclear leukocytes(PMNs)/neutrophils
– Abundant, ____ lived
– Elevated numbers in blood indicate ____

• Professional antigen-presenting cells(APC)
– ____ lived, lower frequency
– Dendritic cells /Langerhans cells (____)
– Monocytes (____)
– Macrophages (motile or stationary), which can be ____ specific (i.e. alveolar – lung)

A

short
infection

longer
skin
blood
tissue

26
Q

Macrophages are everywhere….

macrophages in lung > ____
macrophages; in brain > ____

also ____; found in intestine, lymph node

in liver > ____ cells

A

alveolar
microglia
osteoclasts
kupfer

27
Q

Phago-lysosomal killing

• Phagosome-membrane bounded vesicle that becomes
____
• Lysosome-granules that contain products that damage or kill pathogens
– Enzymes
• ____ - dissolves cell walls of some bacteria
• ____ - digests bacteria
– Proteins
• ____ - binds and removes Fe++ needed for bacterial
growth
• ____-binding protein
– Peptides
• ____ and cationic proteins - direct antimicrobials

Phago-lysosome = phagosome that has fused with ____

A 
acidified
lysozyme
acid hydrolase
lactoferrin
vitamin B12
defensins

lysosome

28
Q

Phagocytic killing of microbes
• Oxygen-dependent: The respiratory burst and enzymes such as ____ produce multiple forms of ____ that are toxic to bacteria and other ingested microbes.
• The generation of reactive oxygen species (eg, superoxide anion) in the respiratory burst is mediated by the ____. Much of the superoxide anion formed is dismuted by superoxide dismutase (SOD) to produce oxygen and hydrogen peroxide, which is converted by ____(MPO) to hypochlorous acid and chloramines inside the phagosome.

  • Oxygen-independent (____): Granules within phagocytes contain ____ enzymes that digest microbial components.
  • Non-oxidative mechanisms to eliminate pathogens, such as granule proteases or antimicrobial peptides which can be delivered to the ____ or released to the ____.
A

myeloperoxidase
oxygen radicals
NADPH oxidase
myeloperoxidase

degranulation
lytic
phagosome
extracellular space

29
Q

Neutrophils

neutrophils produced in ____ > move into circ > stay unless called to a tissue due to an infection (when they die they are degraded by ____)

CR3, CR4
glycan receptors
LPS receptor (____, not CD14)

A

bone marrow
macrophages
TLR4

30
Q

How do circulating neutrophils know when to exit the blood and migrate to an infected tissue?

In response to infection, vascular endothelial cells express ____ molecules (selectins, ICAM-1) that interact with complementary adhesion molecules on neutrophils.
These interactions initially slow down the neutrophils (“rolling”; mediated by ____) which then come to a complete stop (‘tight binding’; mediated by ____).

The neutrophils then exit through ____ into the tissue to fight an infection.
For tight binding (firm adhesion), ICAM-1 interacts with the integrin ____ on neutrophils.

Individuals with ____ mutations have ‘leukocyte adhesion deficiency’ and fail to recruit neutrophils to infected tissues.

A

adhesion
selectins
ICAM-1

diapedesis
LFA-1 (CD11a/CD18)

CD18

31
Q

Neutrophil chemotaxis

Neutrophils recognize chemicals produced by bacteria or the host (e.g., ____ or ____) and migrate “toward the smell”.

Here, neutrophils were placed in a gradient of a chemical that is produced by bacteria.

The cells are seen to move in the right direction chasing the bacteria through a process known as ____.

A

FMLP peptide
chemokines
chemotaxis

32
Q

Neutrophil killing yeast

One way that neutrophils kill is by producing an anti- bacterial compound called ____, through a process called ____ burst.

Here, a human neutrophil senses, moves toward, and ingests a yeast. Oxidation can be visualized by means of a ____.

A

superoxide anion
oxidative
dye

33
Q

Neutrophil NETs Trap and Kill Bacteria

In response to certain pathogens, neutrophils release ____ and ____ from their granules. (The DNA is not ____)
These form the so-called ____ which trap and kill bacteria.

A

DNA
antimicrobial proteins
naked
neutrophil extracellular traps (NETs)

34
Q

Macrophages

macro’s > bind to bacteria; which are opsonized; and they kill into phagosomes, fuse with lysosome, and killing in phagolysosome

can respond to isolated bacterial components > produce ____ (also produced via phagocytosis)

A

cytokines

35
Q

Macrophage ingesting yeast

Macrophages, like the neutrophils, are professional ____ or eating cells (phago = “eating”, cyte = “cell”).

Here, a macrophage is eating Candida albicans. After ingestion, it must kill the yeast by some means, such as via the ____ burst.

A

phagocytes

oxidative (respiratory)

36
Q

Summary: Antimicrobial mechanisms associated with phagocytosis

GO THROUGH TABLE

____ > in phagosome before fuses with lysosome; when phagolysosome you have oxygen-derived products that can come into play

NO > is good in ____ specifically

A

acidification

macrophages

37
Q

Other Innate Immune Cells Specialists for some Pathogens

  • Both eosinophils and NK cells attack by ____ means
  • Eosinophils–specialized with granules of substances toxic to ____ and other pathogens – kill by release of Major Basic Protein, Eosinophil Cationic Protein and Eosinophil-derived Neurotoxin; partners with ____.
  • NKcells–”Natural killer”-specialized large granulocytic lymphocyte (LGL) recognize “funny looking” cells - ____ or ____; partners with ____. Proliferate in response to ____.
  • Both can perform ____
A

non-phagocytic
worms
IgE antibody

tumors
virus-infected
interferons
IL-15

antibody-dependent cell cytotoxicity (ADCC)

38
Q

ADCC by Eosinophils

IgE act as an ____ antibody mediating the attachment of eosinophils to helminths for killing. The ____ portion of IgE reacts with antigenic epitopes on the helminth whereas the Fc portion binds to Fc receptors of activated ____. The lysosomal proteases of eosinophils are released and destroy the tough integument of helminths. Released major basic protein binds to and directly damages helminths. IgE also promotes ____ to recruit phagocytes.

A

opsonizing
Fab
eosinophils
inflammation

39
Q

ADCC by natural killer cells (NK cells)

  • Rather than attacking the invaders, they attack the body’s own cells that have become infected by ____.
  • They also attack potential ____, often before they form tumors.
A

viruses

cancer cells

40
Q

ADCC by NK cells

• NK cells bind to target cells using an ____, then kill it by secreting a chemical (perforin) that makes ____ in the cell membrane of the target cell. With enough holes, the cell will die, because water rushing inside the cell will induce ____, and an influx of calcium may trigger ____.

binds via ____ (not IgE)

A 
antibody "bridge"
holes
osmotic swelling
apoptosis
IgG
41
Q

Necrosis vs Apoptosis

In contrast to necrosis which may cause ____, apoptosis is a ____ mechanism for the disposal of dying cells

A

inflammation

safe

FS I, Module III (12 decks)

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