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58 Cards in this Set

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Name and describe the 7 cell types of the innate immune system
these are broadly speaking white blood cells called Leukocytes
a. Neutrophils aka granulocytes or PMN (most common type of leukocyte)
b. Eosinophils (kills parasites)
c. Basophils and Mast Cells are least common
d. Monocytes/Macrophages
e. DC are the sentinel cells and activate the adaptive response
f. NK cells are large granular lymphocytes
g. deltagamma lymphocytes and NKT lymphocytes can interface with both innate and adaptive immunity
Describe the two pathways by which the innate immune system recognizes danger
1. The mannose binding protein from the liver binds to mannose in bacterial cell walls resulting in the uptake by phagocytic cells.
2. Innate immune cells have Toll-like receptors TLR that detect pathogen-associated molecular patterns PAMPs. TLR is the on switch for the innate immune response. Once turned on the cytokines act as the messenger to activate others.
What are the 4 cardinal characteristics of the adaptive immune system?
1. recognizes antigens on pathogens (very specific)
2. can tell self from non-self
3. clonal expansion after antigen recognition
4. has memory
what are the cells of the adaptive immune system
1. macrophages and dendritic cells - phagocytize antigen and processes portions to be displayed as a red flag triggering the immune response
2. Small Lymphocyte - generates specific antigen receptors
communicate with other cells
proliferate and amplify a response and remembers the encounter.
Describe the characteristics of SC
Stem cells are cells in G0 stage of cell cycle that can be induced to divide to produce more of itself or differentiate.
SC are pluripotent- can give rise to all the somatic cell types. Only embryonic SC are totipotent- can give rise to whole organism. SC become multipotent after they have committed to becoming a particular tissue type.
Describe the structural and fx characteristics of stem cells and compare them with progenitor, precursor and mature circulating blood cells
SC
totipotent (can produce entire embryo)
pluripotent(can give rise to all somatic cells)
multipotent (can give rise to all cell types of tissue or organ)
progenitor (can give rise to more than 1 type of a specific kind of tissue)
Precursor (acquires cell traits for a single cell line)
Differentiation (acquiring phenotypic and genotypic traits of a cell type)
What are PHASC and where are they found?
PHASC are Pluripotent HemAngiogenic Stem Cell
PHASC are found in blood islands of the embryo's yolk sac at 2 weeks of development
How do the dendritic cells initiate adaptive immune response?
DC take up macropinocytosis and receptor-mediated endocytosis. DC cells are stimulated -> travel through the lymphatics to regional lymph nodes -> by then they are mature nonphagocytic DCs that express both antigen and the necessary surface molecules to stimulate clonal expansio also activates antigen-specific naive T lymphocytes.
How are B cells activated when they encounter antigen?
B cells encountering antigens in secondary lymphoid tissues form germinal centers and undergo differentiation to plasma cells.
The B cell is activated by CD4 helper T cells in the T-cell areas to form a primary focus of dividing cells. B cells then migrate directly to the medullary cords secreting plasma cells other B cells migrate into primary follicle to form a germinal center. B cells continue to divide and differentiate within the germinal center into either antibody-secreting plasma cells or memory B cells. Activated B cells migrate to the medulla or to the bone marrow to complete differentiation into plasma cells.
What is the fx of M cells in the GI tract?
M cells are present in the dome shaped covering of Peyer's patches.
M cells take up antigens from the lumen of the gut by endocytosis.
Describe the path of Lymphocyte traffic.
Lymphocytes leave the blood thru High Endothelial Venules in lymph nodes and Peyer's Patches -> enter efferent lymphatics and the thoracic duct system which joins the left subclavian and internal jugular veings.
Lymphocytes enter the white pulp of the spleen from the marginal zone blood sinuses. They eventually find their way into the red pulp blood sinuses and leave via the splenic vein.
How are erythrocytes formed from stem cells?
Erythropoietin from the kidney causes CFC-GEMM to become CFC-erythroid -> Proerythroblast -> Erythrocyte
How are Platelets formed?
Thrombopoietin from the liver causes CFC-GEMM to become CFC-Megakaryote -> Megakaryoblast -> Megakaryoctye -> Platelets
How are Basophils formed?
CFC-GEMM is stimulated by IL-4 to become CFC-Basophil -> Myeloblast -> B. Stab -> Basophil
How are Eosinophils formed?
CFC-GEMM is stimulated by IL-5 to become CFC-Eosinophil -> Myeloblast -> E. Stab -> Eosinophil
How are Neutrophils formed?
CFC-GEMM is stimulated by GM-CSF to become CFC-NM.

CFC-NM is stimulated by G-CSF to become CFC-Neutrophil -> Myeloblast -> N. Stab -> Neutrophil
How are Monocytes formed?
GM-CSF stimulates CFC-GEMM to become CFC-NM which is stimulated by M-CSF to become CFC-Monocyte -> monoblast -> Monocyte
How are dendritic cells formed?
GM-CSF, IL-4, Flt3-ligand cause CFC-NM to become CFC-Dendritic Cell -> Immature Dendritic Cell (Langerhan's Cell of Skin)
How are T cells formed?
IL 7& IL 2, 6 CAUSES CFC-Ly to become CFC-T/NK -> preT -> Thymus -> T-cell
How are NK cells formed?
IL 7 & IL 2, 12 causes CFC-Ly to become CFC-T/NK ->preNK -> NK cell
How are plasma cells formed?
IL-7, SCF causes CFC-Ly to become CFC-B ->pro B -> pre B -> immature B -> mature B.

IL 4, 5, 6 helps an ACTIVATED B cell mature into a PLASMA CELL
Define Innate Immunity
our non-adaptive, global host defense against pathogens.

Key cells are phagocytes -> macrophages and neutrophils
Describe the recognition mechanisms used by leukocytes to ID pathogens
TLR on DC binds PAMPs activate an immune response
ID the key components of the inflammatory process
1. increased blood flow -> vasodilation = more serum mediators and white cells
2. Increased vascular permeability -> endothelia contract causes widened intracellular junctions which cause injury and increased leakage of serum into tissue space

3. Infiltration of WBC into affected area -> increase amt. of neutrophils in the area and later macrophages
Understnd how the innate and the adaptive system interact to produce optimal immune responses
1. Dendritic cells: phagocytize antigens, signal adaptive system based on TLR activation, secretes cytokines

2. NK cells: derived from lymphoid progenitors, samples environ looking for cells with altered self-expression

3. Lymphocytes ->NK-Tcell (produce cytokines and are restricted to glycolipid antigens) and γδ Lymphoctyes(at host environ interfaces)
What is opsonization?
coating of particles by molecules that enhance recognition by phagocytes.
anatomic course of adaptive immunology ... ie the path of antigen introduction to end result
1. Antigens derived from pathogens are either delivered to the lymph nodes/spleen system by DC or via the blood.
2. Once there, the antigens activate the adaptive system of B and T cells residing in the lymphoid tissue.
3. The adaptive response culminates in activated T cells and antibodies.
4. The activated T cells and antibodies exit the Node/Spleen and migrate to area of infection and eliminate the infection.
Describe usual routes of immunization and adjuvant for B cell immunity
Route of immunization and adjuvant
subcutaneous (produces increased immunogenicity)
intradermal, intramuscular, intravenous, intramucosal
Describe T cell-dependent antigens
Surface Ig serves as BCR -> interacts with antigen -> internalized -> BCR + antigen degraded intracellularly.
Then
Proteins are degraded into peptides
which associate with MHC class II -> go to the surface of the B cell
Then
T cell antigen receptor recognizes the peptide in the context of MHC class II molecules -> stimulated to provide "help" ->activates the B cell to prolif. and diff. into an antibody-producing plasma cell
Describe T cell-independent antigens
some examples are bacterial lipopolysaccharide, polymerized flagellin, Pneumococcal polysaccharides, dextrans, levans, and hyaluronic acid
-many are bacterial products or components
comprised of repetitive units that can cross link the BCR thereby activating B cells
do not promote generation of memory B cells
Describe the mechanism by which antibodies protect the host from pathogens
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Describe the function of germinal centers in humoral immunity
Germinal centers form in secondary lymphoid tissue during immune responses
are the site of B cell proliferation and differentiation
site of isotype switching, somatic hypermutation of Ig genes and the development of memory B cells and antibody-secreting plasma cells

After somatic hypermutation, high affinity cells receptors for foreign antigen bind antigen bound to DC cells and present antigen to T cells.

Primary B cell blasts enter the germinal center and then exit as memory B cells or antibody-secreting plasma cells
Describe the sequence of events that occur in germinal centers during T cell-dependent immune repsonses
BCR binds antigen
TCR binds to antigen-class II MHC complex
CD40 binds to CD40L
cytokines IL4, 5, 6 RELEASED

Somatic hypermutation of Ig v regions in rapidly proliferating germinal center B cells

Germinal center B cell with mutated low-affinity surface Ig dies by apoptosis

Germinal center B cell with mutated high-affinity surface Ig
can cross link and present antigen so proliferation and maturation occurs

Memory B cell produced and Plasma cell
Describe the sequence of events leading from interaction of a B cell with a T cell-dependent antigen to production of high affinity IgG antibody.
-
Compare and contrast primary and secondary immune responses
-
Describe how Fc and complement receptors participate in immune responses
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Describe how ITAMs of the BCR contribute to B cell activation
-
what
size
dose
route
composition
adjuvant
should be used to increase immunogenicity
large size
intermediate dose
subcutaneous>intrperitoneal>intravenous or intragastric
complex composition
denatured particulate form
with slow release bacterial adjuvant
with multiple differences from self proteins
should produce effective interaction w/ host MHC
What are some adjuvants used to enhance immune responses?
what are they made of and how do they work?
Alum plus Bordetella pertussis
- made of ALOH gel with killed B. pertussis
-delayed release of antigen; enhanced uptake by macrophages; induction of co stimulators

Immune Stimulatory Complexes
-matrix of Quil A containing viral proteins
-delivers antigen to cytosol; allows induction of cytotoxic T cells

Complete Freunds adjuvant
-oil-in-water emulsion with dead mycobacteria
-delayed release of antigen; enhanced uptake by macrophages; indution of co-stimulators in macrophages
B cell activation requires 2 signals
For T cell-dependent antigens these two signals are:
1) interaction of BCR with antigen
2) interaction of TCR with peptide/MHC complex and interaction between costimulatory molec CD40 on the B cell and CD40L on the T cell

For T cell-independent antigens such as polysaccharides, the 2nd signal can be provided by the antigen- no T cell is required
Activation of TH cells by interaction of TCR with peptide/MHC II complex triggers T cells to:
Activation of TH cells by interaction of TCR with peptide/MHC II complex triggers T cells to:
-secrete B-cell stimulatory cytokines IL-4, IL-5, IL-6
-express CD40L on the cell surface

These cytokines and the interaction of CD40L on the T cell with CD40 on the B cell drive B cell proliferation
What is one this both B and T cell must do in order to work?
For T cell-dependent antigens
the B and T cells must respond to the same antigen
although they do not have to recognize the same epitope
How does the influenza type B vaccine work?
-protective antibody is specific for the bacterial polysaccharides
-the vaccine uses influenza polysaccharide linked to a protein called tetanus toxoid
B cells bind the polysaccharide, internalize the immunogen and present peptides of tetanus toxoid to the T cells
T cells can then interact with and stimulate the polysaccharide-specific B cells which will make antibodies to that specific influenza B antigen.
What are the differences between the primary and secondary antibody response?
Primary antibody responses are slow and mostly of IgM isotype
Secondary antibody responses are rapid and mostly of the IgG isotype

Affinity of antibodies for antigen increases due to somatic hypermutation that occurs at the end of primary antibody responses

Antibody titers are higher in secondary responses
Describe isotype switching
what cytokines play a role
Isotype switching occurs during T-cell dependent antibody responses
Is regulated by ctyokines produced BY T-CELLS
For isotype switching
which Ig isotype is expressed when IL-4 is produced by T-cells
IL-4 causes expression of IgG1 and IgE for secondary response and allergic hypersensitivity
For isotype switching
which Ig isotype is expressed when IFN-γ is produced by T-cells
IFN-γ induces IgG2a and IgG3 expression
For isotype switching
which Ig isotype is expressed when TGF-β is produced by T-cells
Induces IgG2b AND IgA for secondary response and external mucus secretions
Antibody responses to T cell independent antigens include
Antibodies are predominantly IgM isotype
antibodies are not modified by somatic hypermutation of Ig genes
antibodies are of loer affinity for antigen that antibodies generated in T cell-dependent responses as a result
antibodies are important in host defense to certain pathogen, particularly bacterial polysaccharide antigens
What are ITAMs?
Immunoreceptor tyrosine-based activation motifs
BCR signaling
cross-linking of BCRs by antigen triggers a signal transduction cascade
signal initiates w/ phosphorylation of tyrosines in the ITAMs of Igα and Igβ by protein tyrosine kinases of the Src family -Blk, Fyn, Lyn
Signaling cascade leads to new gene turned on driving proliferation and diff of activated B cells
Destruction of Antibody coated pathogens
complement and Fc Receptor mediated clearance of pathogens

if Ab do not neutralize an antigen antibodies can promote other effector mechanisms such as complement and Fc Receptor mediated killing
phagocytic cells, macrophages and neutrophils, NK cells, eosinophils, basophils and mast cells all express cell surface Fc receptors

FcR signaling
triggered by coss-linking of FcRs by aggreggated Ig
FcR signaling initiates by phosphorylation of ITAMs in FcR-associated signaling molecules
-activated the cell to destroy the pathogen by ingestion and killing or by secretion of destructive mediators
which of the following is characteristic of an immune response to protein antigens
a) the secndary response is characterized by high levels of IgM antibody
b) the primary resonse occurs approximately 14 days after immunization
c) memory B cells are not expected to develop
d) germinal centers will develop 2 weeks after secondary immunization
e) The B and T cells will recognize different epitopes of the protein
Answer is E
though the B and T cells have to recognize the SAME ANTIGEN they recognize DIFFERENT EPITOPES on that antigen
Describe the steps by which B cells are activated to proliferate and differentiate in response to T cell -dependent antigens.
-
Describe how B cells are activated in response to T cell-independent antigens
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State the fx of CD40L on T cells and consider the immunologic profile of a person with defective CD40L
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Describe how Fc and complement receptors contribute to destruction of pathogens pneumococcal polysaccharide? with tetanus toxoid?
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How do antibodies contribute to protection against and recovery from bacterial and viral infections?
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