11. White Blood Cell Phagocytes

Life of neutrophil.........5) Killing

Three ways to kill: 1) Phagocytosis and Degranulation = ingested into vacuule------ROS, lysozyme, hydrochlorous acid digests pathogen 2) Degranulation = frustrated phagocyte-----releases digestive agents to the interstitium (outside cell) 3) Neutrophil Extracellular Traps (NET)---throws nuclear material, DNA net, to trap whatever is there

What is a TLR?

Toll-like receptor = type of PRR

What is the function of Th2 cells?

activation of B cells

B memory cells still have the same (with some modifications) _________ bound to its surface as the original B cell that created it

antibody

What is part of the MHC II complex?

antigen + MHC II

How do dendritic cells and macrophages act in adaptive immunity?

antigen presenting cells

Life of neutrophil........3) Chemotaxis

attracted to agents: -LPS (lipopolysaccharides, gram negative bacteria) -N-Formylmethionine (all bacteria have this) -LTB4 (leukotriene B4, made by other PMNs) -C5a (from complement cascade)

origin of LBS and N-Formylmethionine

bacteria -LPS (lipopolysaccharides, gram negative bacteria) -N-Formylmethionine (all bacteria have this)

What is released by a macrophage or dendritic cell (APC)?

cytokines IL-1 (Interleukin-1) IL-6 TNF-alpha (Tumor Necrosis Factor-alpha)

How does IL-1 and TNF -alpha affect neutrophils?

diapedesis IL-1 also stimulates development of more neutrophils (PMNs) from bond cells in bone

Where are B cells created?

in bone marrow

Life of neutrophil......1) Circulating

in peripheral blood

Where is an alveolar macrophage located?

lung

What are the least numerous wbc?

lymphocytes

What kind of immune cell is an osteoclast?

macrophage in bone that also has function in degradation and laying of new bone

What is a microglia?

macrophage in brain and optic cells

What is a sinus histocyte?

macrophage in spleen

What is a kupffer cell?

macrophage in the liver

What are monocytes called when they enter tissue?

macrophages

What is the function of plasma cells?

make more of the antigen specific IgM or IgG that was bound to the b cell that produced the plasma cell

Name of macrophages in blood

monocytes

Life of neutrophil ..........2) Diapedesis

move through blood vessel attracted by IL-1 and TNF-alpha

What secretes IL-2 and what does IL-2 stimulate?

naive T helper self stimulation T helper 2 stimulation of naive B cell

What is the first responder for acute inflammation?

neutrophil

What is the most abundant white blood cell (phagocyte or otherwise)?

neutrophil

Three types of wbc phagocytes:

neutrophils, macrophages, dendritic cells

origin of C5a and LTB4

our immune system

What is an epitope?

part of an antigen capable of eliciting an immune response also where antibody can bind

Where in the body does an antigen for B cells typically come from?

part of bacteria that ended up in blood after being shed somewhere in the body

Life of neutrophil.........4) Recognition

pathogen/infected cell tagged with... -LPS (lipopolysaccharides, gram negative bacteria) -N-Formylmethionine (all bacteria have this) -Opsonins (IgG, IgM, CRP, C3b)

What is somatic hypermutation and affinity maturation?

plasma cells have small genetic mutations during replication = hypermutation some will have a higher affinity for a pathogen = affinity maturation

Why is the development of an autoimmune disease common after a severe infection?

plasma cells hypermutating may produce antibodies that are 'self' coding resulting on an attack on the body

Where are dendritic cells and macrophages typically located?

points of entry

What is a heat killed virus vaccine?

proteins of virus administered

What is a therapeutic that decreases division and movement of wbc in an effort to decrease immunity?

steroids/corticosteroids/glucocorticoids

Function of IL-6

stimulates acute phase reactant production in liver pyrogen

Function of IL-1

stimulates generation of new immune cells causes fever = pyrogen diapedesis (when with TNF-alpha)

Functions and characteristics of IgA

-found in body fluids -neutralizes antigen (binds to prevent action/infection by pathogen) -NOT opsonin

Functions and characteristics of IgM

-neutralizes antigen -activates complement -opsonin -first in immune response

Functions and characteristics of IgG

-neutralizes antigen -activates complement -opsonin -second in immune response -stable, lasts long time -crosses placenta -lives in bone marrow

Functions and characteristics of IgE

-protects against helminths (parasitic worms) -allergy related

Life of neutrophil....6 steps

1) Circulating 2) Diapedesis 3) Chemotaxis 4) Recognition 5) Killing 6) Hematopoiesis

What are the steps of B cell activation?

1) Naive B cell binds antigen 2) Th2 binds B cell 3) Th2 releases IL-2--->B cell 4) B cell becomes active 5) B cell divides into plasma cells and memory cells

What are the six steps of antigen presentation?

1) Phagocytosis---APC captures piece of pathogen/whole pathogen 2) Degredation---pathogen digested within vesicle of cell 3) Protein Presenter---MHC II added to vesicle, vesicle joins with membrane to present antigen to interstitial space 4) Migration---moves from site of pathogen recognition to lymph tissue 5) Presentation---lymphocytes (CD4+ and CD8+) in lymph tissue exposed to the antigen for matching 6) Activation of lymphocyte---matched antigen and TCR (T cell receptor) activate the lymphocyte

Life of a B cell

1) Stem cell differentiation 2) clonal education 3) clonal selection 4) b cell activation 5)memory cell circulation

Lifetime of a neutrophil

48 hrs

What secretes IL-4 and what does IL-4 stimulate?

APC secreted, stimulates naive T helper

What are the receptors of B cells?

Antibodies IgD and IgM

How does a APC bind to a naive T helper cell?

Antigen on MHC II binds TCR CD4 protein arm of T helper binds MHC II NOTE: simultaneous

Where does IL-1 come from?

Antigen presenting cell

Are there more binding sites for antigens on B cells or T cells?

B cells because of antibody structures

Naive T helper cell = _________

CD4+

What are the acute phase reactants produced by the liver?

CRP Complement Fibrinogen

What is an example of an IL-2 antagonist and what does it do?

Cyclosporin, inhibits an immune response by binding up IL-2

What are the antigen presenting cells?

Dendritic, Macrophage, and B-cell

True or False: T and B cells can be distinguished from one another on a slide.

False, they look the same

True or False: IL-2 and IL-4 secretion happen at different times.

False, this happens simultaneously

True or false: Antigen presentation is part of the innate immune response.

False: phagocytosis is part of the innate immune response, but antigen presentation is considered adaptive

Life of neutrophil..........6) Hematopoiesis

IL -1 increases development of PMNs from bond cells in bone NOTE: IL-1 comes from APC

What are the pyrogens?

IL-1, IL-6, PGE2

After binding to an APC, what does the T helper cell secrete? What does this secretion do?

IL-2 Stimulates cell division

After binding to T helper, what does the APC secrete? What does that secretion do?

IL-4 Stimulates the activation of T helper --> T helper & memory cells

What antibodies are given in passive immunity? Examples?

IgG mom, tetanus, rabies, other venoms

What are the opsonins?

IgG IGM CRP C3b all stimulate phagocytes to eat something

What antibody is produced in the second response?

IgG (longer lifetime, lives in bone marrow)

What antibody is produced in the first response?

IgM (decreased longevity)

What is rapamycin and what does it do?

It is an IL-2 receptor blocker that blocks the receptor for IL-2 on T cells and B cells to inhibit an immune response

Lucentis vs. Avastin

Lucentis = specific for AMD pt to decrease bv growing in retina, Fab portion of antibody only, very expensive Avastin = used for colon cancer treatment to decrease bv in colon cancer, whole antibody, inexpensive

Only APCs have this kind of MHC

MHC II

How do Th2 and B cells bind together?

MHC II complex (antigen + MHC II) presents antigen to TCR of TH2 CD4 protein arm of TH2 binds MHC II

Will B cells recognize antigen without an MHC II protein?

No, all lymphocytes need MHC II----MHC II restricted

Another name for a neutrophil and what it means:

PMN = polymorphyl nuclear cells = three lobed nucleus

What stimulates a dendritic cell or a macrophage (APC)?

PRR + PAMP

What are PAMPs?

Pathogen-Associated Molecular Patterns---patterned antigen of a pathogen that is unique to them

What is a PRR?

Pattern Recognition Receptor on dendritic cell---recognizes PAMP

What is an LPS?

type of PAMP

How do dendritic cells and macrophages act in innate immunity?

Phagocytize and release cytokines

What is an attenuated virus vaccine?

virus administered still alive, but made to not 'work'

Describe isotype switching

when a plasma cell switches what kind of antibody it produces the type of antigen it responds to stays the same

What is the most common way for a B cell to become activated? Describe its epitope binding characteristics, the type of antibody produced, memory or no memory cells?

T cell-Dependent B cell activation -single epitope, binds to antibody ( monomeric IgD or IgM) on cell surface and then phagocytized by cell and presented on MHC II -produces high affinity and long-lived antibody IgD -memory cells produced

What is the less common way for a B cell to become activated? Describe its epitope characteristics, the type of antibody produced, memory or no memory cells?

T cell-Independent B cell activation -chain of epitopes (often from worms), binds several receptors on B cell -produces IgM = not long-lived -no memory cells

Function of TNF-alpha

with IL-1 = stimulates diapedesis of cells stimulates acute phase reactant production in liver

How quickly does a neutrophil respond to inflammation?

within 24 hrs

How soon does a macrophage arrive after neutrophils?

within 24 hrs

What are the receptors of T cells called?

TCR (T Cell Receptors)

Where are T cells created?

The thymus