Immunology week 2 Flashcards
Organization of the Immune System
2 catagories, what are they?
Innate immunity-first line of defense (non-specific)
Adaptive immunity-second line of defense (specific)
what are the 2 types of innate immunity?
cellular component
humoral component
what are teh 2 types of adaptive immunity?
humoral component and cellular component
The Immune System
Innate Immunity
what is the requirement of prior contact with the AG?
Protects the body from injury
without prior contact with an
AG
The Immune System
Innate Immunity
rapid or slow?
Rapid
The Immune System
Innate Immunity
what is the timing for immediate?
● Immediate: 0-4 hrs
The Immune System
Innate Immunity
what is the timing for induced?
● Induced 4-96 hrs
The Immune System
Innate Immunity
with induced is there memory?
● Induced 4-96 hrs
○ NO MEMORY
The Immune System
Innate Immunity
● Induced
what are the 3 types of barriers?
● Physical barriers
● Humoral barriers (complement)
● Cellular barriers
The Immune System
Adaptive
rapid or slow?
● SLOW
The Immune System
Adaptive
relationship to AG?
● Response to AG
The Immune System
Adaptive
Is memory present?
● Memory is present
The Immune System
Adaptive
does it require exposure to the AG
● Requires exposure to AG
The Immune System
what happens after the body when exposed to hundreds of billions of microbes?
Barriers:
mechanical
chemical
biological
(first line of defense)
The Immune System
Barriers:
mechanical
chemical
biological
(first line of defense)
what happens next inside the body?
2nd line of defense
innate immune system
The Immune System
2nd line of defense
innate immune system
what happens next within the body?
Addaptive immune system
3rd line of defense
Innate Immunity- present from birth!
what are the physical barriers?
● Physical barriers- skin & mucosal areas
Innate Immunity- present from birth!
● Physical barriers- skin & mucosal areas
what are the 3 catagories?
○ Mechanical factors: mechanically remove infectious microbes & prevents invasion
○ Chemical
○ Microbiological
Innate Immunity- present from birth!
● Physical barriers- skin & mucosal areas
○ Mechanical factors: mechanically remove infectious microbes & prevents invasion
5 examples:
■ Skin
■ Ciliary movement
■ Peristaltic movement
■ Flushing
■ Mucus
Innate Immunity- present from birth!
● Physical barriers- skin & mucosal areas
○ Chemical
4 examples and what they do:
■ Fatty acids- inhibit growth of bacT
■ lysozyme & phospholipase- inhibit growth of pathogens
■ Low pH- antibacT effects
■ Surfactants-enhance phagocytosis
Innate Immunity- present from birth!
● Physical barriers- skin & mucosal areas
○ Microbiological
what is it and what does it do?
■ Normal biota prevents infection by secreting inhibitory substances
Innate Immunity
● Humoral barrier has 6 defense mechanisms: complement system, coagulation system, lactoferrin, lysosome, interferon and interleukin. How do each help?
Innate Immunity
● Humoral barrier- complement system
○ Complement system- enzymes/ proteins that prevent infections
○ coagulative system- blood coagulation to prevent pathogen entry also can be a
chemotactic
○ Lactoferrin & transferrin- sequesters iron
○ Lysozyme- digests the bacterial cell wall
○ Interferons
■ Type 1= inhibit infection and replication of viruses
○ Interleukin 1- increase temp to induce acute phase proteins
Innate Immunity
● Humoral barrier- complement system
what is Complement system-
enzymes/ proteins that prevent infections
Innate Immunity
● Humoral barrier- complement system
what is coagulative system-
blood coagulation to prevent pathogen entry also can be a
chemotactic
Innate Immunity
● Humoral barrier- complement system
what is Lactoferrin & transferrin-
○ Lactoferrin & transferrin- sequesters iron
Innate Immunity
● Humoral barrier- complement system
what is Lysozyme
○ Lysozyme- digests the bacterial cell wall
Innate Immunity
● Humoral barrier- complement system
what is Interferons
○ Interferons
■ Type 1= inhibit infection and replication of viruses
Innate Immunity
● Humoral barrier- complement system
what is Interleukin 1
○ Interleukin 1- increase temp to induce acute phase proteins
Innate immunity
● Cellular barrier
what is it?
● Cellular barrier- phagocytic system & NK cells
Innate immunity
● Cellular barrier- phagocytic system & NK cells
Neutrophils-what are they?
phagocytose microorganisms
Innate immunity
● Cellular barrier- phagocytic system & NK cells
Macrophages-what do they do?
what do they possess, what dont they possess?
Macrophages-ingest & kill micros intracellularly, phagocytosis, APC, aid in wound healing
(respond to the SOS)
■ They do not possess granules but they have lysosomes that contain factors required
for intracellular killing mechs
Innate immunity
● Cellular barrier- phagocytic system & NK cells
NK- what does it do?
○ NK- kill infected/ tumor cells
Innate immunity
● Cellular barrier- phagocytic system & NK cells
Eosinophils-what do they do?
Eosinophils- eliminate parasites
Innate immunity
● Cellular barrier- phagocytic system & NK cells
Name 4 types of cells
Innate immunity
● Cellular barrier- phagocytic system & NK cells
○ Neutrophils- phagocytose microorganisms
○ Macrophages-ingest & kill micros intracellularly, phagocytosis, APC, aid in wound healing
(respond to the SOS)
■ They do not possess granules but they have lysosomes that contain factors required
for intracellular killing mechs
○ NK- kill infected/ tumor cells
○ Eosinophils- eliminate parasites
what are the 4 most important cells of the innate immuniyt?
Neutrophils
macrophages
dendritic cells
natural killer cells
the most important cells of the innate immunity?
Neutrphils
what is the function?
Phagochtosis
Reactive oxygen and nitrogen species
antimicrobial peptides
the most important cells of the innate immunity?
Macrophages
what is the function?
phagocytosis
inflammatory mediators
antigen presentation
reactive oxygen and nitrogen species
cytokines
complement protiens
the most important cells of the innate immunity?
Dendritic cells
what is the function?
antigen presentation
costimulatory signals
reactive oxygen species
interferon
cytokines
the most important cells of the innate immunity?
natural killer cells
what is the function?
Lysis of viral-infected cells
interferon
macrophage activation
NB cells for phagocytosis
● Neutrophils
5 facts:
are they numerous?
immature=?
what do they do, where do they hang out, why?
How do you ID?
how many types of granules?
● Neutrophils
○ Most numerous innate cell
○ immature=banded neutrophils
○ Circulate in the BS looking for things to
eat :)
○ ID by expression of CD66
○ Contain 2 types of granules
■ Azurophilic
● Defensins
● Proteolytic enzymes
● Lysozyme
●** Myeloperoxidase**
■ Secondary granules
● Lysozyme
● Lactoferrin
● NADPH oxidase
components (toxic radicals)
NB cells for phagocytosis
● Neutrophils
what are the 2 types of ganules called?
Azurophilic
Secondary granules
NB cells for phagocytosis
● Neutrophils
○ Contain 2 types of granules
■ Azurophilic
4 examples are:
■ Azurophilic
● Defensins
● Proteolytic enzymes
● Lysozyme
● Myeloperoxidase
NB cells for phagocytosis
● Neutrophils
○ Contain 2 types of granules
■ Secondary granules
3 examples are?
■ Secondary granules
● Lysozyme
● Lactoferrin
● NADPH oxidase
components (toxic radicals)
NB cells for phagocytosis
● Macrophages
3 facts:
How do you ID?
What don’t they possess, what do they have, why?
what do they react to, how?
● Macrophages
○ ID by expression of CD14,Cd11b, F4/80
○ Do not possess granules but have
lysosomes that contain factors required
for intracellular killing mechs
○ React to SOS signals that induce
chemotaxis of macs towards the site of
microbe entry
Phagocytosis- background info
What are phagocytes?
what do they have?
what do they do?
why?
● phagocytes= have many receptors that
they can bind to microbes with to eat
them
Phagocytosis- background info
● phagocytes
what are teh 4 kids of receptors?
- Complement receptor
- Scavenger receptors
- Fc receptors
- Toll-like receptors TLR
Phagocytosis- background info
What are complement receptors and what do they do?
- Complement receptors=C3b
a. Binds to the AG then AG binds to the
phagocyte
Phagocytosis- background info
What are Scavenger receptors and what do they do?
Scavenger receptors= SRA,CD68,Lox-1,
CD36 bind directly to polyamines (on
bacT surface)
Phagocytosis- background info
what are Fc receptors and what do they do?
Fc receptors- on macs bind to the FC
regions on Ab that are bound to AG
Phagocytosis- background info
Toll-like receptors TLR what do they do?
Toll-like receptors TLR-
Recognize PAMPS
Phagocytosis- background info
What is the definition and what are the 4 functions?
Def: active process of capturing and
ingesting foreign objects/ microbes by
phagocytes (ex
neutrophils and macs)
○ Detects and destroys microbes
○ Removes damaged cells & foreign
objects
○ Induce productions of cytokines for
inflammation
○ Process and present AG to induce IR
Phagocytosis
what are the 2 ways various receptors bind to microbes?
Phagocytes have various receptors to bind to microbes directly or through
opsonization (basically marks the pathogen to induce phagocytosis)
Phagocytosis-
explain direct recognition?
● Direct recognition is performed by PRR recognizing PAMPS
Steps of phagocytosis
what are the 7 steps?
- Chemotaxis move towards the target/phagocytes move toward SOS signal
- Phagocytes detect and bind to said
target/object through appropriate receptors - They surround the captured object with pseudopodia and engulf objects through endocytosis
- EndocytosedObject is enclosed in the phagosome
- Phagosome + lysosome=
phagolysosome - Lysosome releases its contents in the
phagolysosome - Digestion of the endocytosed object
Steps of phagocytosis
Example beginning with Bacterium becoming attached to the membrane evaginations called Pseudopodia…next?
Bacterium is ingested forming phagosome
phagasome fuses with lysomsome
lysosomal enzyme digests captured material
digestion products are released from cell
Process of Phagocytosis (more detailed)
purpose:
*Purpose: DETECT and DESTROY microorganisms, REMOVE damaged cells and foreign objects,
INDUCE cytokines, PROCESS and PRESENT antigens and induce immune response
The 2 killing pathways
● Oxidative pathway ROS and RNS
● Non-oxidative (enzymatic)
The 2 killing pathways
● Oxidative pathway ROS and RNS
● Oxygen dependent intracellular killing
explain ROS
what happens?
how is it activated?
what is the result?
how did it occur?
○ ROS
■ Glucose->NADPH
■ NADPH-> activated by cytochrome
oxidase
■ Result: superoxide anion
■ Basically the reactive O2 spp. will
change the chemical structure of
the cell and the bacT will be
destroyed.
The 2 killing pathways
● Oxidative pathway ROS and RNS
● Oxygen dependent intracellular killing
○ RNS
what result?
○ RNS
■ Results in cell death
The 2 killing pathways
● Oxidative pathway ROS and RNS
● Oxygen dependent intracellular killing
○ Myeloperoxidase dependent killing
what is it?
○ Myeloperoxidase dependent killing
■ essentially using bleach
(hypochlorous acid) to kill bacT
w/n the neutrophil
The 2 killing pathways
● Non-oxidative (enzymatic)
how does this occur?
(4 steps)
● Non-oxidative (enzymatic)
○ Cationic proteins- damage bacT cell wall
○ Lysozyme- damages mucopeptides in
cell wall
○ Lactoferrin- sequesters iron
○ Proteolytic/ hydrolytic enzymes- digest
killed bacT
Pathogen recognition
● Sentinel cells
what are they?
● Sentinel cells= DC, Macs, Mast cells
Pathogen recognition
● Sentinel cells= DC, Macs, Mast cells
what do they contain? what do they do?
○ Contain Pattern Recognition Receptors(PRR) which will be able to recognize PAMPS and
DAMPS
Pathogen recognition
● Sentinel cells= DC, Macs, Mast cells
○ Contain Pattern Recognition Receptors(PRR) which will be able to recognize PAMPS and
DAMPS
what are PAMPS? how are they expressed?
○ PAMPS- expressed by microbes and not host tissue
Pathogen recognition
● Sentinel cells= DC, Macs, Mast cells
○ Contain Pattern Recognition Receptors(PRR) which will be able to recognize PAMPS and
DAMPS
What are DAMPS? where do they come from?
○ DAMPS- released by damaged host cells
Pathogen recognition
● Sentinel cells= DC, Macs, Mast cells
○ Contain Pattern Recognition Receptors(PRR) which will be able to recognize PAMPS and
DAMPS
○ PAMPS- expressed by microbes and not host tissue
○ DAMPS- released by damaged host cells
○ There are 5 types of PRR, what are they?
■ Toll- like TLR
■ NOD like- NLR
■ RIG Like- RLR
■ C-type lectin CLR
■ Peptidoglycan- recognition proteins
PRR
● Toll-like
where are they located?
how are they signaled?
what is the final result?
● Toll-like
○ Located on host cell membranes or
within the host cells
○ Signal through MyD88 except TLR3 TRIF
and TLR4 can do both
○ The end game: proinflammatory
cytokine production
PRR
● NOD- like
what do they do, how?
what can it lead to?
● NOD- like
○ Detects intracellular pathogens via either
PAMPS or DAMPS
○ Detection of PAMPS= activation of
transcription factor NF-kB (very
important will come back again) which
results in expression of proinflammatory
cytokines
○ Can also lead to production of type 1
interferons
PRR
● RIG- like
what do they detect?
how?
what do they do?
● RIG- like
○ Detect VIRUSES (viral RNA)
○ Induce production of type 1 interferons
and imflam. Cytokines
PRR
● C- type Lectin
what is an example?
why is it important?
● C- type Lectin
○ Think fungi!
○ Side note: th17= is important for fungal
infections as well
PRR
● Peptidoglycan recognition proteins
examples?
where are they found?
what do they produce?
● Peptidoglycan recognition proteins
○ NAG/NAM
○ Localized in granules of neutrophils
(acute bacT infection)
○ Produces defensins- antimicrobial
peptides
Receptors
what are the 4 kinds?
● Scavenger receptors
● Toll-like receptors
● Fc receptors
● Complement
Receptors
● Scavenger receptors
what do they do?
examples?
● Scavenger receptors
○ directly bind to polyamines on bacT
surfaces
○ SRA, CD68, Lox-1, CD36
Receptors
● Toll-like receptors
where are they located?
what do they do?
what happens?
● Toll-like receptors
○ On the cell membrane or within the cell
○ Recognize PAMPS & DAMPS
○ Aid in secretion of inflammatory
cytokines
Receptors
● Fc receptors
what happens?
what does it require?
● Fc receptors
○ When a phagocyte binds to the Fc region
of an AB it enhances the metabolic
activity of the phagocyte
○ Requires AB!
Receptors
● Complement
what happens, what result?
**see slide to small to read.
● Complement
○ C3b binds to the AG which then results
in phagocytosis
Natural
Killer
cells
What are NK cells?
They kill infected or tumor cells
What are NK cells?
what are they also known as and what do they contain?
● Aka large granular lymphocytes (LGL) and contain granules
What are NK cells?
where do they originate?
● Origin: bone marrow
What are NK cells?
where are they located?
● Location: blood, spleen, liver
What are NK cells?
Do they migrate? when?
● Migrate in lg #’s when inflammatory rxn is occurring
What are NK cells?
Do they have AG specific receptors?
● No AG specific receptors like t&b cells
What are NK cells?
what do they do?
● Recognize and kill virally infected or cancer cells
What are NK cells?
what do the granules do?
● Contain granules which induce apoptosis
What are NK cells?
what 2 types of immunity do they aid in?
● Nkt cells aid in both innate and adaptive immunity
What are NK cells?
Humans & mice=?
● Humans & mice= express CD56, CD16 and LACK CD3
What are NK cells?
● Pigs=?
● Pigs= no exclusive marker
What are NK cells?
Cattle & Horses=?
Cattle & Horses= CD335
NK Functions
Innate immunity
what are the 2 functions?
Innate immunity
○ Killing stressed/ infected/ tumor cells=
“abnormal”
■ abnormal= no MCH1 and/ or
express stress signals too
○ Aid in cytokine and chemokine
production
NK Functions
Innate immunity
○ Killing stressed/ infected/ tumor cells=
“abnormal”
what is “abnormal”
■ abnormal= no MCH1 and/ or
express stress signals too
NK Functions
what do inhibitory signals recognize? where?
● Inhibitory signals recognize MHC1
molecules found on ALL NORMAL
nucleated cells
NK Functions
what are activating receptors
examples?
**● Activating receptors- bind to
stressed/ infected/ tumor cells (ex.
MICA & MICB)
NK Functions
how are they regulated?
● Nk cells are regulated by a balance
between activating and inhibitory signals
○ Inhibitory signal is dominate
NK Functions
how are they regulated?
which signal is dominant activating or inhibitory?
Nk cells are regulated by a balance
between activating and inhibitory signals
○ Inhibitory signal is dominate
NK Functions
● KIRs=?
● KIRs= humans, cattle, cats, dogs,& pigs
NK Functions
● KIRs= humans, cattle, cats, dogs,& pigs
explain:
3 facts
they are highly..
how are they expressed?
● KIRs= humans, cattle, cats, dogs,& pigs
○ Highly polymorphic
○ LILRs= expressed on NK cells &
leukocytes
○ NKp46= expressed only by NK cells!
NK Functions
● KLRs=
● KLRs= mice, rates,& horses
● KLRs= mice, rates,& horses
what do they express? how is it recognized?
what result?
● KLRs= mice, rates,& horses
○ NK express NKG2D which recognizes
MICA & MICB and results in apoptosis
○ NKG2D is also on gamma delta t cells
(will talk about later)
NK Functions
In virto NK cells are activated by what?
what do they become?
how are they used?
● Side note:(will touch on again later)
○ In virto NK cells activated by IL2
and INFy become lymphokine activate
killer cells (LAK) which are
cutotoxic cells and can be used in
immunotherapy
How do they know who to kill & how do they kill?
● Abnormal cells
most of the time they don’t express much ?
what do they express?
what result?
● Abnormal cells
○ Most of the time don’t express MCH1
○ Also express stress signals like MICA and
MICB
● Results in killing of the abnormal cell
How do they know who to kill & how do they kill?
● Normal cells
How are they different?
● Normal cells
○** Strong inhibitory signals**
■ Normal MCH1 and absence of
stress hormones
How do they know who to kill & how do they kill?
what signal is dominent? why does that matter?
Inhibitory signals are dominant and
will result in a do not kill signal
How do they know who to kill & how do they kill?
● Perforin dependent- innate
what happens?
what result?
what does this induce?
● Perforin dependent- innate
○ Perforin granules are released
○ It creates a hole in the cell
○ Granzymes & proteases enter through
the hole
○** Induces apoptosis**
How do they know who to kill & how do they kill?
● Fas/ FasL CD95/ CD95L- innate
what is expressed, by who? what result?
● Fas/ FasL CD95/ CD95L- innate
○ NK express CD95L and abnormal cells
express CD95 (death receptor) and will
result in apoptosis
How do they know who to kill & how do they kill?
● CD16 pathway ADCC-adaptive
what is responding to what, how?
● CD16 pathway ADCC-adaptive
○ NK will respond to an AB that is
responding to an AG using CD16 (Fc
receptor)
ADCC
1-antibody binds what?
where?
2-what do the FC receptors do?
3-cross-linking of what, signals what?
4-what happends to the target cell, how?
1-antibody binds antigen on the surface of teh target cell
2- fc reseptors on NK cell recognise bound antibody
3-cross-linking of Fc receptors signals the NK cell to kill the target cell
4-target cell dies by apoptosis
ADCC
Its NB to know that target recognition through ? only occurs when ? are present?
Its NB to know that target recognition through CD16
only occurs when AB are present ;)
Regulation of NK cells
what are they activated by?
*Activated by IL-1, IL-2, IL-12, IL-15, IL-18, IL-21, and type 1 and 2 interferons
Regulation of NK cells
are they In vitro?
*In vitro
Regulation of NK cells
*Activation via above= what turns to what which result in what?
*Activation via above=Nk cells turn into LAK (lymphokine activated killer cells)
which have increased cytotoxic capacity
Regulation of NK cells
what can LAK be used for?
*LAK can be used for tumor immunotherapy
Regulation of NK cells
what does *LAK—>
*LAK—>highly cytotoxic cell
NK subtypes
4 what are they?
● NK T cells
● NK cells that are similar to t
lymphocytes
● NK DCs
● DC that are similar to NK cells
NK subtypes
● NK cells that are similar to t
lymphocytes
origin?
express?
specific to what?
what are they made of?
How are they activated?
what do they link?
examples (4)?
● NK cells that are similar to t
lymphocytes
○ From thymic origin
○ Express and invariant alpha beta
TCR
○ Only specific to a few pathogens
○ They are CD4+ cells
○ Activated by IL-15
○ Link the t cell system and NK cells
○ Allergies, antitumor immunity,
autoimmunity, and
antimicrobial immunity roles
NK subtypes
● DC that are similar to NK cells
spontaneously what?
can present to ?
produce what?
link what?
● DC that are similar to NK cells
○** Spontaneously lyse tumor cells**
○ Can present to naive T cells
○ Produce larger amounts of INFy
○ Link innate and adaptive immunity
Which of the following is NOt one of the most important
cells of innate immunity?
A. Mast Cells
B. B. NK cells
C. Neutrophils
D. Macrophages
A
Which of the following is a first line of defense?
A.Antibodies
B.Complement
System
C.Phagocytosis
D.Sweat
D
Which of the following Phagocytosis receptors require
AB?
A.Fc receptors
B.Scavenger
Receptors
C.Toll Like
Receptors
D.Complement
Receptors
A
DIn which of the following do endocytosed material occur
during phagocytosis?
A.Pseudopodia
B.Phagosome
C.Endocytosis
D.Phagolysosome
D
Which of the following is true regarding a malfunctioning
phagocytic system?
A.Increase in adaptive immunity
B.Increased inflammatory response
C.Increased infection rate
D.Increased detention and destruction of
pathogenic microorganisms
C
Which of the following PRR binds for viral recognition?
A.RIG-like receptors
B.NOD-like receptors
C.C-type Lectin receptors
D.Peptidoglycan-recognition
receptors
A
Which of the following is released by NK cells to activate
macrophages?
A.Cytokines
B.IL-17
C.IFN gamma
D.Angel Stop
asking me these
things
C
If a NK cell were to come upon this cell, the NK cell would induce
apoptosis. True or False?
A.True
B.False
B
Activating signal is the dominant signal for NK cells.
A.True
B.False
B
Which of the following NK cell pathways works by creating a pore
in the target cell and releasing enzymes to induce apoptosis?
A.Perforin-dependent
Pathway
B.Fas/FasL Binding
C.CD16/ADCCC
D.Idk man
A
What is the end result of the FAs/ FAsl pathway?
Follow up : what is another name for this pathway?
A. It results in activating the
adaptive immune system
B. Bpoptosis
C. It aids in the cells
replicating rapidly
D. Apoptosis
D
