Innate Immunity (Lecture 2) Flashcards
Immunity:
Protection from pathogens and disease
• Mechanical Barriers
– ____
– ____ surfaces
• Innate and Acquired (adaptive) defense mechanisms
skin
mechanical
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)
toxins
enzymes
inflammation
immune complexes
anti-host antibody
The immune system protects against four classes of pathogen
Bacteria > salmonella enteritidis > ____
Viruses > influenza > ____
Fungi > candida albicans > ____, systemic ____
Parasites > protozoa > plasmodium falciparum > ____
food poising flue thrush candidiasis malaria
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.
non-self
self
immune tolerance
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).
tumor cells
mechanical injury
sterile
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 ____.
safe dangerous danger damaged alarmins
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 ____
self-tolerance
tumors
inflammation
allergies
The immune players
Innate
- ____ barriers
- ____
- ____ cells
- ____
- ____ cells
innate > VERY ____, deployed hours/minutes
adaptive > ____, days/weeks
epithelial phagocytes dendritic complement NK
fast
slow
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
reinforcements
adaptive
ubiquitous innate induced innate adaptive
Innate vs. adaptive immunity
Innate
- ____ response (hours)
- ____
- ____ number of specificites
- ____ during response
Adaptive
- ____ response (days to weeks)
- ____
- ____ highly selective specifities
- ____ during response
rapid
fixed
limited
constant
slow
variable
numerous
improve
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
hematopoietic stem
bone marrow
innate lymphoid
megakaryocyte/erythroid
granulocyte/macrophage
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
lobes faster antibody-coated parasites phagocytosis T parasitic T adaptive
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 ____.
eyes germ-line LPS LTA microbe-associated molecular patterns (MAMPs)
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).
general
non-specific
specific
pattern-recognition receptors (PRR)
toll-like receptors
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
LPS LTA lipoproteins zymosan fungi
flagellin
TLR10
TLR3
TLR7/TLR8
TLR9
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
evolutionarily
adaptive
multicellular
vertebrates
toll receptor
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)

microbe-associated molecular patterns (MAMPs)
danger
damaged
stressed
non-infectious
asbestos
uric acid
amyloid-beta
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 ____.
damage-associated molecular patterns (DAMPs) alarmins nucleic histone heat-shock
PRRs
tissue repair
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’).
heterogenous
pentraxins
ficolins
carbohydrate
damaged
apoptotic
agglutination opsonization complement Fcgamma pentraxins
predecessors
Antibody-mediated immune functions
- ____ activation
- ____ neutralization
- ____
- ____ cytotoxicity
- ____ mediated inflammation
- inhibition of bacterial ____
complement virus opsonization antibody-dependent cellular fc-receptor adherence
In contrast to PRMs, antibodies have ____ specificity
exquisite
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
mechanical
chemical
peptides
lysozyme
phagocytosis
complement
complement
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)
defensins cationic broad-spectrum epithelial macrophages mucosal skin
membranolytic
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)
mast
dendritic
NK
dendritic
neutrophil
monocyte
