Exam 3 - The Immune Response - STUDY THIS CARD DECK Flashcards by Brennan Stringam

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

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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

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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

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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

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T/F - Mucosal barriers protect internal tissues.

TRUE

-Sinuses, trachea, lungs, bladder, vagina, mammary glands, intestines, stomach, esophagus, GI

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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

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What peptides are in mucosal/glandular secretions?

Lysozyme

Lactoferrin
-Milk

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What peptides are in skin, mucosal/glandular secretions?

-Secretory leukocyte protease inhibitor

-S100 proteins
—Psoriasin - Disrupts membranes
—Calprotectin - Bind diva lent cations

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What peptides are at the mucosal epithelia?

-Defensins (alpha/beta)
—Disrupts membranes, creates pores
—Alpha: PMNs
—Beta: Epithelial cells

-Cathelicidin
—Disrupts membranes

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The surfactant proteins are found where?

Secretions of respiratory tract

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Alpha:Beta T cells - Bind what?

Gamma:delta T cells - Bind what?

MHC-like ligands
—Peptides

CD1
—Lipids

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TH17 releases what and recruit what?

Cytokines

PMNs
—IL-17, IL-22

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What are the 3 main granulocytes?

PMNs

Eosinophils

Basophils

*Mast cells come from an unknown precursor, but related to the granulocyte-macrophage progenitor

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Monocytes become?

Macrophage

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Common cells found in blood serum?

Never Let Men Eat Burritos

N - Neutrophils

L - Lymphocytes

M - Monocytes

E - Eosinophils

B - Basophils

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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

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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

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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

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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)

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Which cells are the bridge b/t innate and adaptive systems?

DCs

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DRAW out complement.

DO IT

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T/F - Activated macrophages secrete a range of cytokines.

TRUE

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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

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Acute phase proteins are produced in what organ?

LIVER

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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