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Dr. Barnum
Immunology
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Specific Description of the Topic Being Discussed Today
I. Hematopoiesis [S1]:
a. Hematopoietic stem cell: a pluripotent cell that differentiates into RBCs and WBCs, is a self-renewing cell that
maintains numbers throughout life by making a copy of the original cell along with daughter cells. The
progenitor cells that follow do not have unlimited renewal potential [S1].
b. Hematopoiesis occurs in the embryonic yolk sac then moves to the fetal liver and spleen at 3 months into
development and finally at 7 months the process occurs in the bone marrow
c. Asynchronous – the term that refers to the first division that deals with self renewal
d. 2 major lineages: the lymphoid committed and the myeloid committed. Lymphoid gives rise to NK cells T and B
lymphocytes. Myeloid gives rise to granulocytes monocytes and megakaryocytes. Look at slide [S1] to see the
further differentiation of these cells
e. Regulated by amount of space in bone marrow, for T/B cells controlled by the peripheral population or space of
secondary lymphoid organs, during infection for neutrophils there are feedback systems of cytokines that drive
the production. Bottom line is that this process is highly regulated and maintained by physical limitations, and
availability of soluble factors like cytokines.
FUN2: 10:00-11:00
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Dr. Barnum
Immunology
II. Normal adult blood cell counts [S2]
a. Largest number of WBCs are neutrophils
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III. Granulocytes [S6]
a. Important in the innate immune response
b. 3 types based on staining properties: neutrophils that have neutral granules, eosinophils that have acidic
granulues and basophils that have basic granules; can also distinguish by nuclear morphology
c. Neutrophils mediate the innate immune response by being recruited to sites of infection, enter the site, and
phagocytize bacteria. Short lived cell type. 1st cell recruited to inflammation site so they are the 1st line of
defense.
d. Eosinophils are also phagocytic cells important for parasitic infections
e. Basophils are non-phagocytic cells that play a role in allergies and asthma and are found in blood. Their
counterparts in tissue are called mast cells and have the same role. Both basophils and mast cells express Fc
receptors on their surface that bind to the Fc region of IgE produced by the immune system. IgE is made in
response to allergy to some antigen like pollen or ragweed and the basophils and mast cells then express those
IgE Abs on their surface. Upon binding of an allergen, 2 IgE Abs in Fc receptors are cross-linked which causes
degranulation and release of histamines and other anaphylactic agents causing an allergic reaction [S6].
f. When allergen is encountered T cells respond by activating B cells, B cells turn into plasma cells that make IgE
specific fro allergen and those IgE coats the surface or afore mentioned cells[S7].
[S6]
[S7]
IV. Inflammatory response [S4]
a. Innate immune response knows if the body is damaged/infected by bacteria by the presence of PAMPs
(pathogen associated molecular patterns)
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Immunology
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b. The inflammatory process will lead to increased vasodialation, increased vascular permeability, up regulation of
adhesion molecules along blood vessel endothelium. All this sends signals to neutrophils telling of an
inflammation detected by chemotactic factors, complement factors and anaphylactic factors. This detection of
factors causes the neutrophil to up regulate its integrin receptors and roll along the endothelium and then stop at
the site and migrate into the tissue
c. The neutrophil then recognizes bacteria by PAMP presence and grab the bacteria via complement and Fc
receptors and phagocytize
d.
V. Macrophages [S 9&10]
a. Important in innate immune response
b. Monocytes circulate in blood, migrate into tissues and differentiate into macrophages; called different names in
different tissues for example Kupffer cells in liver (see outline for more examples). Going from monocyte to
macrophages causes an increase in cell size, receptors, opsonizing proteins, phagocytic activity and granules
present.
c. Opsonization – when a bacteria is covered by complement, serum proteins and natural Ab. Receptors of
neutrophils and macrophages bind to these and phagocytize bacteria.
d. Proteolytic enzymes destroy the bacteria once inside the phagosome. Phagosome fuses with lysosome to form
phagolysosome, this is where the bacteria is degraded.
e. When the bacteria is degraded it produces peptides that are transferred to MHC class II molecules.
f. MHC class II molecules give the macrophage the ability to present these peptides on its surface to activate T
cells
g. Macrophages are important in the innate immune response by destroying bacteria, elaborating inflammatory
cytokines and antibacterial products, and controlling tissue remodeling but also form a bridge to the adaptive
immune response by presenting peptides to activate T cells leading to T cell activation.
h. Recruiting of macrophages takes 24 hours, but do not die as rapidly as T cells
VI. NK cells
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Immunology
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a. Important in innate immune system
b. Main role is to recognize virally infected cells and destroy them
c. Work with CD8+ T cells
d.
VII. Cells of the adaptive immune system [S14]
a. 3 types: B cells, T cells and Ag presenting cells (APCs)
b. Work together to generate immune response
c. Macrophages, B cells and dendritic cells are all APCs
d.
VIII. B lymphocytes [S15&18]
a. Mediate humoral immune response. Can recognize any type of Ag protein, carb, lipid, etc. and do this by
themselves
b. Respond to Ag differentiate into plasma cells which secrete a soluble Ab.
c. Circulate throughout the body in a Go state, if the encounter an Ag they are specific for the Ag binds the
membrane Ig which drives the initial activation response. If the B cell gets additional help from T cells and
additional cytokine stimuli it can differentiate into a plasma cell that secretes Ab.
d. Each B cell expresses a unique receptor for a specific Ag which allows for only the clones of that specific cell to
proliferate. This is called clonal expansion. This is important because we have few cells in our bodies that can
recognize any given Ag
[S18]
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Immunology
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IX. T lymphocytes [S15]
a. 2 main categories: CD4+ helper and CD8+ cytotoxic cells
b. CD4+ produces cytokines that promote activation of B cells and promotes activation of CD8+. It’s the
commander of the adaptive immune response and can shift the response to either a humoral or cytolytic
response
c. CD8+ destroy virally infected or intracellular bacterially infected cells
d. Have Ig in membrane consisting of an αβ T cell receptor (TCR). The TCR consists of 2 polypeptide chains
disulfide bonded together that make a single Ag binding site; these simply recognize the Ag. There are CD3
complex and zeta chain homodimer that drive the signal of activation.
e. T cells are restricted in the Ag they bind; for example αβ T cells recognize peptides presented by MHC class II
(CD4 T cell) only. The MHC class II molecules come from the APCs.
[S15]
X. Surface markers [S16]
a. On T and B cells there are unlimited unique receptors for a Ag, for innate system there are a limited number of
receptors that recognize PAMPs.
b. B cells express membrane bound IG molecules with 2 light and 2 heavy chains disulfide bonded together. Each
heavy chain inserts into the membrane and terminates into a cytoplasmic tail. Have 2 Ag binding sites.
c. The Ig transduces signal to the B cell by being non-covalently linked to the Igα-β heterodimer which mediates
the signaling to activate the cell
d.
XI. Major histocompatability complex molecules[S22]
a. MHC class II come from the ingestion of an Ag by an APC and the subsequent presentation of the Ag peptide in
the molecule on the surface of the APC. CD4+ T cells recognize these
b. MHC class I comes from a cell that is virally or intracellularly infected with bacteria. Peptides from these
infections get presented by MHC class I. when these are presented they are recognized by CD8+ T cells
c. MHC II is expressed mainly on APCs while MHC I can be expressed on inflamed cells. Most cells do not have
MHC II molecules but almost every cell has MHC I on it because it can become inflamed
d. CD4 and CD8 act to stabilize their respective MHC.
XII. Primary immune organs[S24,25,26,27,28]
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a. Main function is the generation of T and B cells
b. Bone marrow: hematopoiesis occurs in bone marrow as well as where B cell maturation occurs. Committing to
the B cell pathway occurs by rearranging the genes that encode the heavy and light chains of Ag receptor.
c. Thymus: precursors to T cell migrate to thymus. T cell development takes place in cortex of thymus.
Precursors enter into medulla, go to cortex, mature and migrate back out. Precursors (thymocytes) go through
positive and negative selection that positively selects T cells that can detect self MHC but not too strongly.
Those thymocytes that do not recognize self MHC or recognize it to strongly get negatively selected and die.
d.
XIII. Secondary lymphoid organs[S30 til the end]
a. Lymphatic system is a parallel system to the blood system. Leakge of plasma from capillaries is taken up by
lymphatic capillaries and becomes lymph. Ag and immune cells are in lymph. Muscle contraction moves lymph
in only one direction. The afferent lymphatic vessel leads to the lymph node and the efferent vessel leads out of
the node. This is a passive process that concentrates the Ag and immune cells recovered from lymph into the
lymph nodes. Nodes are located all over at strategic locations. Langerhans cells in skin are examples of an
APC that migrates out of the skin and into the lymphatic system to get to a lymph node and present Ag to T/B
cells. Lymph node is divided into the cortex paracortex and medulla. Cortex contains B cells, paracortex
contains T cells and the medulla contains APCs and activated cells. Main point is that lymph nodes and system
collect Ag from tissue and concentrate it so it can be effectively presented
b. Spleen has red pulp consisting of RBCs and macrophages and the white pulp that contains T/B cells and APCs.
T cell area surrounds the splenic artery and around the T cells are the B cells. Ag go into marginal sinuses
where they are presented to T cells which drives interaction between T and B cells.
c. Main point is that the role of the spleen is to respond to Ag that are in the blood.
d. There are also huge networks of pseudoimmune organs in the mucosa (gut lung mouth). Respond to Ag
encountered at mucosa. Also have separation of T and B cells. Peyer’s patches are in the gut.
e. [end 50 min]
Note: at the end of lecture I asked him what we needed to know from his outline. Disregard the portion
on NK cells but be familiar with the rest including the specific surface markers.