A) Drain interstitial fluid
B) Dietary lipid absorption/transport
C) Intitiate & regulate immune responses
II. General Anatomy -
A) Lymphatic capillaries and lacteals
B) Lymphatic vessels & ducts
1)
what happens if lymph vessels or ducts
are blocked? 
C) Lymph nodes
1)
what is the function of lymph nodes? 
D) Flow of lymph
1)
where does lymph fluid come from?
2) where
does lymph fluid go?
III. Lymphoid Tissues and Organs -
A) Primary organs
1) major functions
2) red bone marrow
a) site of hematopoiesis
3) thymus
a) know anatomic location (review from lab)
b) most important function: site of T-cell maturation
c) age-associated thymic atrophy
B) Secondary organs
1) major functions
2) lymph nodes
a) general anatomy
1) cortex containing follicles
a) outer T-cell areas
b) inner germinal centers (B-cell areas)
c) macrophage and dendritic cell activity
2) flow of lymph through node
a) afferent >>> efferent vessels
b) lymph node hilus
b) Hodgkin's lymphoma
1) signs, symptoms and stages
c) metastatic cancers and lymphatic vessels
3) spleen
a) general anatomy
b) white pulp
1) site of B-cell proliferation
c) red pulp
1) RBC removal
2) platelet storage
d) injuries to spleen
4) Mucosal-Associated
Lymphoid Tissue (MALT )
a) tonsils
b) Peyer's patches
c) veriform appendix
The Immune System:
I. Cells of the Immune System: (also
covered in hematology outline)
A) Leukocytes: 5-10,000cells/mm3
in blood
B) Granulocytes:
1) Neutrophils
(50-70%); 3 day lifespan; major phagocyte & granulocyte; attracted
by inflammatory factors and complement; granules with hydrolytic enzymes;
cell dies after degranulation/phagocytosis
a) "Band" is immature neutrophil (band-shape nucleus);
b) "Seg" is mature neutrophil (segmented nucleus).
c) Neutrophilia: increase %; common with acute bacterial infections
d) Neutropenia: decrease %; common with anemias, viral infections,
radiation/chemotherapy;
1) what is the danger for patients having neutropenia?
2) Eosinophils
(2-4%); major anti-helminth protection (myelin basic protein released);
also contributes to some hypersensitivity reactions and phagocytosis of
bacteria
3) Basophils
(<1%); granulocytic, nonphagocytic; major inflammatory cell, releases
histamines, proteases and granulocyte-attracting factors.
4) Mast cells;
non-circulating, reside in connective tissues, similar function as basophils,
initiate inflammatory reactions
C) Monocytes (2-8%); only last 8-12
hrs in circ. then migrate to tissue = major function to become macrophage
in tissue; play key role in "antigen presentation".
D) Platelets (240-400,000/mm3);
crucial to help activate blood clot formation; spleen acts as reserve site;
E) Lymphocytes (20-30%) mononuclear
cells; mediate/regulate specific immune responses (antibody formation,
anti- viral and anti-tumor protection)
a) B-cell:
produce immunoglobulins (mature in bone marrow)
b) T-cell:
activate/regulate B-cells, major immune regulatory cells (mature in thymus)
c) NK cell:
natural killer cell; non-specific anti-tumor cytolytic cell
II. Inate Immunity:
A) Anatomic barriers include: keratinized
skin, mucus, cilia, hairs, sebum, sweat, cerumen, tears, lacrimal apparatus,
B) Physiologic barriers include: low pH,
temperature, lysozyme, peroxidase, complement, transferrin (binds up Fe+),
phagocytosis, inflammation.
III. Two Arms of Specific Immune Response: Humoral and Cellular Immunity
A) Humoral Immunity:
1) Immunoglobulin
(Ig) production by activated B-cells
2) Antigen
(Ag): any molecule capable of illiciting a specific immune response
3) Antigen
presentation: macrophage (or B-cell) ingests antigen, degrades into
fragments, re-expresses antigen fragments on surface in context of major
histocompatibility complex II (MHC class II). During this process,
macrophage release Interleukin 1, a potent cytokine which acts as
a pyrogen and activator of T-helper cells.
4) T-helper
(CD4+) cell specific for that antigen binds to MHC-Ag using T-cell
receptor (TCR) and is stimulated by binding and by Interleukin-1 released
from antigen-presenting cell. This presentation usually occurs in lymph
node or spleen. T-cell clone is activated, proliferates, secretes Interleukin-2
which enhances T-cell activation. B-cell bearing Ig specific for that antigen
binds antigen, and presents it to T-cell in context of MHC-II. Binding
of activated T-helper cell to B-cell and release of B-cell growth factors
including Interleukins 4 and 6 from T-cells activate B-cells to
proliferated and produce more Ig.
5) Clonal
selection of Ag-specific T-cell (with TCR) and B-cell (with Ig) provides
specific immune response.
6) Memory
B- and T-cells are also produced with ability to be activated easily
upon 2nd exposure to Ag, provide long-term "immune protection", allows
for very large and rapid response to 2nd exposure (2ndary immune response)
7) Immunoglobulins:
"Y" shape monomer, 2 Ag-binding sites, 1 "tail" region (Fc region),
made of 2 heavy chain proteins, 2 light chains proteins,
produced only by B-cells.
a) IgG: most abundant Ig, long-lasting in serum, usually produced upon
2nd exposure to Ag, can cross placenta.
b) IgM: 2nd most abundant Ig, pentamer, produced upon 1st exposure
to Ag,
c) IgA: most abundant Ig in secretions (saliva, tears, mucus...), dimer,
d) IgE: involved in allergic reactions by binding of mast cells &
basophils and triggering to degranulate upon Ag exposure
e) IgD: on resting B-cells, not seen in serum (<0.1%)
f) Neutralization: binding of Ig to virus, toxins, bacteria to block
activity or infectivity
g) Agglutination: clumping of cells by Ig binding, aids in phagocytosis
h) Opsinization = coating cell with Ig, enhances binding of macrophage
by binding to the tail region of Ig (Fc region).
i) Precipitation: clumping of soluble molecules by Ig binding, aids
in phagocytosis
j) Complement activation: Ig bound to cell surfaces activates complement
cascade to attack targeted cell
B) Cellular Immunity:
1) General
Description:
Specific anti-viral, anti-tumor immune response mediated by cytolytic
T-cells (CD8+).
All normal cells express major histocompatibility complex I (MHC-I)
(only antigen presenting cells express MHC-II) MHC-I is your molecular
"ID card" and is used to present antigens produced within the cell (not
brought in from outside). Virus-infected cells express viral antigens in
context of MHC-I T-cytotoxic (CD8+) bearing TCR specific for a particular
antigen bind to Ag/MHC-I on virus-infected cell and is activated T-cytotoxic
cells release cytolytic molecules (lymphotoxin, perforin) to kill
target cell.
Activation of T-cytotoxic cells is enhanced by cytokines released by
T-helper cells (IL-2, gamma interferon) T-cytotoxic cells also act
against tumor cells in similar way; tumor cells express tumor-Ag in context
of MHC-I and become targets for T-cytotoxic cells. The immune system constantly
checks all tissues for "altered cells" (foreign, virus-infected, tumors)
in a process called "immune surveillance". The use (necessity) of
expressing most antigens in the context of MHC (class I or II) to initiate
an immune response is termed "MHC Restriction".
2) Transplant Immunology:
a) Tissue
Typing: Vital to match donor and recipient MHC-molecules (especially
human leukocyte antigens HLA) for tissue transplants: HLA-A,
B, C genes = (MHC-I molecule) and HLA-DP, DQ, DR genes = (MHC-II
molecule) (Tissue must match in HLA-A, B, C and should match in at least
HLA-DR to be considered for transplants)
b) Graft-rejection
is mainly T-cytotoxic response of recipient against donor's tissue (mismatch
in HLA-A, B or C), antibodies may also be illicited which exacerbate rejection.
Blood vessels into the graft are blocked and degraded by activated T-cells
and antibodies, graft becomes necrotic and is destroyed.
c) Graft-versus-host
disease (GVHD) is when bone marrow is transplanted, donor cells attack
recipient tissues as being foreign (mismatch in MHC-II usually).
Immunosuppressive drugs (cyclosporin, corticosteroids usually given
to control rejection or GVHD)
3) Hypersensitivity Reactions of Immune
System:
a) Type I:
Anaphylactic Reactions (typical bee-sting or hayfever allergic responses)
b) Type II:
Cytotoxic Reactions (as in mismatched ABO transfusion reaction)
c) Type III:
Immune Complex Reactions (as in rheumatoid arthritis or in "serum sickness")
d) Type IV:
Cell-mediated Reactions (seen with positive tuberculin(TB)-skin test reaction)
4) Autoimmunity:
a) General
Description: "Self/Non-self" discrimination (self tolerance)
of immune system developed during thymic maturation (Positive and Negative
selection processes resulting in clonal deletion or clonal anergy
of auto-reactive T-cells)
b) Graves
Disease: Autoantibody activates thyroid stimulating hormone receptors
c) Rheumatoid
Arthritis: Circlulating immune complex of IgM (rheumatoid factor)
binding to IgG Fc regions
d) Systemic
lupus erythematosus (SLE): Variety of autoantibodies with multiple
organs involved
e) Myasthenia
Gravis: Autoantibody blocks acetylcholine receptors at neuromuscular
junctions
f) Insulin-dependant
Diabetes: Auto-reactive T-cytotoxic cells destroy pancreatic beta-cells
(the insulin producing cells).