Exam 3 - The Immune Response - STUDY THIS CARD DECK Flashcards
Tell me what the immune system is doing at rest.
Barrier establishment and evolution and pre-emotive immunity at mucosal surfaces
WBC proliferation, development, recirculation
Complement production and circulation
Tell me three things the immune system does during infection.
-Immediate innate response
—Antimicrobial peptides
—Complement
-Induced innate response —Macrophage and DC activation —Acute phase and interferon response —PMN infiltration —NK cell response
-Adaptive immune response
—B and T cell activation and differentiation
—Antibody production by plasma cells
—CD8 T cell cytotoxicity
Tell me what happens if antimicrobial peptides and complement fail to destroy invading microorganisms.
DC migrate to lymph nodes
Phagocytes action
NK cells activated
Cytokines and chemokines produced
Where are pathogens trapped and phagocytosed?
Lymphoid tissue
-Adaptive immunity initiated by migrating DCs
—Infection cleared by specific antibody, T cell dependent macrophage activation and cytotoxic T cells
T/F - Mucosal barriers protect internal tissues.
TRUE
-Sinuses, trachea, lungs, bladder, vagina, mammary glands, intestines, stomach, esophagus, GI
What are the three compartments of mucosal tissues?
Epi
-Intraepithelial lymphocytes (IEL) - gamma:delta T cells, CD8 T cells, and memory CD8 cells
Lamina propria -Lymphatic tissue -Gamma:delta T cells -CD8 cells -CD4 T cells —TH1 —TH17 -Plasma cells and memory B cells -Macrophages -DCs
Mucosal-associated lymphoid tissue (MALT)
- Specialized
- Lymph node like
What peptides are in mucosal/glandular secretions?
Lysozyme
Lactoferrin
-Milk
What peptides are in skin, mucosal/glandular secretions?
-Secretory leukocyte protease inhibitor
-S100 proteins
—Psoriasin - Disrupts membranes
—Calprotectin - Bind diva lent cations
What peptides are at the mucosal epithelia?
-Defensins (alpha/beta)
—Disrupts membranes, creates pores
—Alpha: PMNs
—Beta: Epithelial cells
-Cathelicidin
—Disrupts membranes
The surfactant proteins are found where?
Secretions of respiratory tract
Alpha:Beta T cells - Bind what?
Gamma:delta T cells - Bind what?
MHC-like ligands
—Peptides
CD1
—Lipids
TH17 releases what and recruit what?
Cytokines
PMNs
—IL-17, IL-22
What are the 3 main granulocytes?
PMNs
Eosinophils
Basophils
*Mast cells come from an unknown precursor, but related to the granulocyte-macrophage progenitor
Monocytes become?
Macrophage
DC
Common cells found in blood serum?
Never Let Men Eat Burritos
N - Neutrophils
L - Lymphocytes
M - Monocytes
E - Eosinophils
B - Basophils
Tell me about lymphocyte circulation.
Maximizes likelihood of antigen encounter
~24 hrs for a single lymphocyte to completely circulate
1:100k lymphocytes bind a presented antigen
DCs probed by 5000 T cells/hr
What is positive selection?
Selecting for a cell that reacts how its supposed to
B cell
- Negative selection first, then positive selection
- Positive selection in periphery
- Follows cytokines to LN
- Interacts with follicular DC
T cell
- Positive selection first, then negative selection
- T cell receptor can bind to proper MHC class
- Positive selection will determine CD4 or CD8
What is negative selection?
Making sure it doesn’t react to self.
When in its organ or maturation, if it reacts to self, it goes through apoptosis
When in the periphery, if it reacts to self, it goes through anergy
What is differentiation?
B cells differ into plasma and memory cells
CD8 T cells - Cytotoxic or Memory cell
ALL CELLS HAVE MEMORY
CD4 T cells - Thx (Th1/Th2/Th17, etc)
Which cells are the bridge b/t innate and adaptive systems?
DCs
DRAW out complement.
DO IT
T/F - Activated macrophages secrete a range of cytokines.
TRUE
What cytokines, released via activated macrophages, are pro-inflammatory?
IL-1beta (systemic and local) - FEVER
TNF-alpha (systemic and local) - Inflammation, fever, shock
IL-6 (systemic and local) - FEVER
CXCL8 (local) - Recruit PMNs
IL-12 (local) - Activate NK cells
Acute phase proteins are produced in what organ?
LIVER
What are some acute phase proteins?
C reactive protein
Mannose binding lectin
LPS-binding protein
Complement
Granulocyte colony-stimulating factor, serum amyloid A, phospholipase A2
Fibrinogen, plasminogen, tissue plasminogen factor
T/F - Most infections are STOPPED at the epithelium.
TRUE
Why is inflammation harmful at mucosal surfaces?
If barrier integrity is lost, then pathogens are close to the vasculature and can get into the body unrestricted
Tell me how a PMN extravasates.
Rolling adhesion
Tight binding
Diapedesis
Migration
When is the interferon response?
When infection establishes
What cells release interferon?
Virus-infected cells
IFN-alpha, IFN-beta
What does interferon do?
Induce resistance to viral replication in all cells
Increase expressions of ligands for receptors on NK cells
Activate NK cells to kill virus-infected cells
T/F - Activated NK cells destroy target tissues.
TRUE
What are the FOUR antigen presenting cells?
DCs
Macrophages
B cells
Gamma:delta T cells
What does a normal cell do when interacting with an NK cell?
Presents peptide and this is the inhibitory signal
Has stimulatory ligand
-NK cell does NOT kill the cell as the inhibitory signal overrides the stimulatory ligand
What happens when an NK cell interacts with a cell missing MHC?
Stimulatory receptor bind the stimulatory ligand
No inhibitory signal b/c MHC is not there
DEATH
What happens when a cell with an intracellular infection interacts with an NK cell?
There are more stimulatory ligands expressed on the stressed cell surface, and those overcome the inhibitory signal
DEATH
DC cells pick up bacterial antigen where?
Skin
Then move to enter a draining lymphatic vessel
DCs with antigen go to draining LN, where they settle in the T cell areas
What do chemokines do?
Recruit stuff
-Especially PMNs
What IL drives the acute phase response?
IL-6
PMNs favorite chemokine is what?
CXCL8
The receptors are CXCR1/2
T cells browse, bind, and are activated by _______ _______.
Dendritic cells
B cells capture antigen from _________ and __________ __________ __________.
Macrophages
Follicular dendritic cells
B and T cells form ________ pairs at the _________ boundary.
Cognate
Follicle
What do perforins do?
Perforate the membrane, allowing granzymes thru those holes
What do granzymes do?
Serine proteases
-Chew things up
NK cells can kill in 3 ways.
Death-receptor (Most specific) - FASL, FAS, TRAIL
Granules exocytosis (medium specific) - release of granules
IFN-gamma, nitric oxide (broadly specific)
-Release nitric oxide
B cells present antigen to what?
T follicular helper cells
Dendritic cells present to what?
T cells
Macrophages present to what?
B cells
B cells grabs a free floating antigen, it is activated thru what?
Thymus-independent
If B and T cells form a cognate pair, then what?
Thymus-dependent pathway
-Forms pair, goes to medulla
—Called primary focus
—Produce IgM
-Then to the germinal center —B cell somatic hypermutation, class switching
What happens to T cells in the lymph node?
APC activation
T cell proliferation and differentiation
-T cells bind DCs to browse
-If activated, it will bind to that DC
—Cluster around the DC
-T cells clonally expand
What are the 3 APC signals?
Activation - TCR MHC I or MHC II
Co-stimulatory signal - CD28
Differentiation - cytokines
What do Tfh cells do to aid in B cell activation? 5 things
Stimulate proliferation
Centroblast formation
Class switching and somatic hypermutation
Provide survival signals to FDC selected centroblasts
Plasma or memory cell differentiation
Where do B cells differentiate into plasma cells?
Primary focus
—Proliferation of IgM secreting B cells for several days
—Driven by IL-5 and IL-6
Secondary focus
—B cells rapidly divide every 6 hrs to form centroblasts and germinal centers driven by: IL-6, IL-15, and BAFF
Antibody neutralization of virus and toxin results in what?
Prevents pathogen-host binding
Antibody Opsonization results in what?
Phagocytosis
Complement results in what?
Phagocytosis
OR
Lysis
Antibody-Dependent Cell-mediated cytotoxicity (ADCC)?
NK-induced apoptosis
T/F - CD8 T cells kill one cell at a time.
TRUE
*Co-stimulation is not req’d, only TCR activation
What does CD8 T look for?
MHC I
- Expressing NON-self antigen
- Only needs T cell receptor to kill
How does the adaptive immune system improve with time?
B cells
- Increased Ab concentration
- Improved Ab affinity
T cells
- Memory T cells
- Population expansion
- Persistence
Inhibition of peripheral ___________ cells induces ___________ cell development.
Th17
Treg
What happens in immune resolution and repair?
Inflammatory cytokine reduction
Anti-inflammatory cytokines
Treg cell signaling and development
-Release TGF-beta
T cell CTLA4 expression
-Leads to the inhibition of activated T cells
—Outcompetes CD28
Th1 cells are induced by what?
And release what?
IL-12
IFN-gamma
IL-12
IFN-gamma
Th17 cells are induced by what?
And release what?
IL-16
TGF-beta
IL-23
IL-17
IL-6
Th2 cells are induced by what?
And release what?
IL-4
IL-4
IL-5
Tfh cells are induced by what?
And release what?
IL-6
IL-21
IL-21
Treg cells are induced by what?
And release what?
TGF-beta
TGF-beta
IL-10
CD8 T cells kill what?
Virus-infected cells
Bacteria interact with what TLRs?
And cause the macrophage to release what IL?
And cause what T helper cell to release what?
TLR4, TLR5
IL-12
Th1, IFN-gamma
Fungi interact with what non-TLR receptor?
And cause the macrophage to release what to ILs?
And cause what T helper cell to release what?
Dectin-1
IL-6, IL-23
Th17, IL-17
Helminths interact with what?
And cause the macrophage to release what?
And cause what T helper cell to release what?
TLR2/1
IL-10
Th2, IL-4, IL-5, IL-13
Fungi also interact with what TLR?
And cause the macrophage to release what?
And cause what T helper cell to release what?
TLR2/6
IL-10, RA, TGF-beta
Treg, IL-10, TGF-beta
Viruses interact with what TLRs?
And cause the macrophage to release what?
And cause what T helper cell to release what?
TLR 3, 7, 9
IL-12
Th1, IFN-gamma
Th1 cells take care of what type of infection?
Intracellular infections
-Usually viruses
Th2 cells take care of which type of infection?
Large, multicellular infections
-Parasites
Tfh cells take care of what type of infection?
NONE
-Help B cells become activated, switch Isotype, and increase Ab affinity
Th17 cells take care of what type of infection?
Fungal
AND
Extracellular bacterial infections
At mucosal surfaces
What do Treg cells do?
Suppress the activities of other effector T cells
