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
