Download Lymphatic/Immune - Pasadena City College

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Maintain fluid balance
Protect body from infection and disease
21-1
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Immunity
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Lipid absorption
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fluids from all capillary beds are filtered
immune cells stand ready to respond to foreign cells or
chemicals encountered
Lacteals in small intestine absorb dietary lipids
Fluid recovery
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absorbs plasma proteins and fluid (2 to 4 L/day) from tissues
and returns it to the bloodstream
 interference with lymphatic drainage leads to severe edema
21-2
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Lymph is a clear, colorless
fluid, similar to plasma but
much less protein
Lymphatic capillaries are
closed at one end and much
‘leakier’ than blood
capillaries
21-3
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Larger lymphatics have 3
layers
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tunica interna: endothelium
and valves
tunica media: elastic fibers,
smooth muscle
tunica externa: thin outer
layer
21-4
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Lymphatic capillaries
Collecting vessels: course through many
many lymph
lymph nodes
nodes
Lymphatic trunks: drain major portions of body
Collecting ducts :
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right lymphatic duct – receives lymph from R arm, R side of
head and thorax; empties into R subclavian vein
thoracic duct - larger and longer, begins as a prominent sac in
abdomen called the cisterna chyli; receives lymph from below
diaphragm, L arm, L side of head, neck and thorax; empties into
L subclavian vein
21-5
21-6
21-7
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Lymph flows at low pressure and speed
Moved along by rhythmic contractions of lymphatic
vessels
Flow aided by skeletal muscle pump (like veins)
Thoracic pump aids flow from abdominal to thoracic
cavity (also like veins)
Valves prevent backward flow
The rapidly flowing blood in subclavian veins draws
lymph into the vascular system
Exercise significantly increases lymphatic return
21-8
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Natural killer (NK) cells
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can find and destroy tumor cells
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T lymphocytes (mature in thymus)
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B lymphocytes (mature in bone marrow)
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activation makes cells that produce antibodies
Antigen Presenting Cells - APCs
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macrophages (from monocytes)
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dendritic cells (in epidermis, mucous membranes and
lymphatic organs)
21-9
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Diffuse lymphatic tissue
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lymphocytes in mucous membranes and connective
tissues of many organs
Mucosa-Associated Lymphatic Tissue (MALT): prevalent in
passages open to exterior
Lymphatic nodules
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dense oval masses of lymphocytes, congregate in
response to pathogens
Peyer patches: more permanent congregation, clusters
found at junction of small to large intestine
21-10
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At well defined sites; have connective tissue capsules
Primary lymphatic organs
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site where T and B cells become immunocompetent
red bone marrow and thymus
Secondary lymphatic organs
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immunocompetent cells populate these tissues
lymph nodes, tonsils, and spleen
21-11
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Lymph nodes – are the only organs that filter lymph
Fewer efferent vessels, slows flow through node
Lymph nodes are divided into compartments containing
stroma (reticular CT) and parenchyma (lymphocytes and APCs)
Lymph nodes are subdivided into cortex and medulla
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reticular cells, macrophages phagocytize foreign matter
lymphocytes respond to antigens
lymphatic nodules-germinal centers for B cell activation
21-12
Fig. 21.12 a and b
21-13
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Collective term for all lymph node diseases
Lymphadenitis
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swollen, painful node responding to foreign antigen
Lymph nodes are common sites for metastatic
cancer
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swollen, firm and usually painless
21-14
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Palatine tonsils
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Lingual tonsils
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pair at posterior margin of oral cavity
most often infected
pair at root of tongue
Pharyngeal tonsil (adenoid)
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single tonsil on wall of pharynx
21-15
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Very large in babies. Begins to involute at about 14 years
T lymphocytes mature here.
Secretes thymopoietin, thymulin and thymosins.
21-16
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Parenchyma appears in fresh specimens as
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red pulp: sinuses filled with erythrocytes
white pulp: lymphocytes, macrophages
21-17
Why is the ‘white
pulp’ blue?
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Functions
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blood reservoir
RBC disposal
immune reactions: filters blood, quick to detect antigens
21-18
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Your immune system’s structure and function is
much like that of an earth army fighting alien
invaders.
It is there in times of peace and in times of war.
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To distinguish ‘self’ from ‘non-self’
to destroy ‘non-self’
The fortifications
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The human body’s first line of defense is a set of
physical barriers and chemical agents that prevent
foreign invaders from getting inside.
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An outer layer of
intact skin
Hair in the nostrils
Mucous membranes
Cilia
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Tears
Sweat
Mucous
Oils
Acid in stomach
Urine
The soldiers and their weapons
Non-specific (innate)
 Neutrophils
Make antibodies
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Macrophages
Natural Killer Cells
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Specific (adaptive)
 Lymphocytes
B cells make antibodies
T cells help them
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If something gets past the external barriers, the
second line of defense are ‘innate’ immune
defenses, primarily white blood cells.
Page 530
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Nonspecific defenses - broadly effective, no prior
exposure
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first line of defense
 external barriers
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second line of defense – innate immune system
 phagocytic cells, antimicrobial proteins, inflammation and
fever
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Specific defense - results from prior exposure,
protects against only a particular pathogen
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third line of defense – adaptive immune system
21-27
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Phagocytize bacteria
These are most likely to dramatically increase in
numbers during bacterial infection
Create a killing zone
 degranulation
 antimicrobial proteins are discharged into tissue fluid
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respiratory burst
 toxic chemicals are created (O2.-, H2O2)
21-28
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Phagocytize antigen-antibody complexes
Antiparasitic effects
Promote action of basophils, mast cells
Enzymes block excess inflammation, limit action of
histamine
21-29
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Aid mobility and action of WBC’s by release of
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histamine (vasodilator)
  blood flow to infected tissue
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heparin (anticoagulant)
 prevents immobilization of phagocytes
21-30
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Circulating precursors to macrophages
Specialized macrophage-like cells are found in specific
localities
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Dendritic cells
 epidermis, oral mucosa, esophagus, vagina, and lymphatic organs
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Microglia (CNS)
Alveolar macrophages (lungs)
Kupffer cells (liver)
21-31
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There are 3 types but they look
identical under a microscope!
Act to destroy cancer cells
Kill virus-infected cells
Make antibodies
The lymphocytes circulating in human
blood are
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80% T cells
15% B cells
5% NK cells
These are the cells that
confer immunity
through a vaccination!
21-32
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Interferons
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Made by cells when they are invaded by a virus
Induce neighbor cells to activate anti-viral defenses
Can stimulate destruction of some cancer cells
Complement system
More than 20 different proteins
 Are activated by the presence of pathogens
(like a booby trap)
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21-34
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Mechanisms of action
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enhanced inflammation
phagocytosis
 promoted by opsonization
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cytolysis
 membrane attack complex forms on target cell
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immune clearance
 RBCs carry Ag-Ab complexes to macrophages in liver and
spleen
21-35
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NK cells (Natural Killer Cells)
destroy bacteria, cells infected by viruses,
and cancer cells
 also destroy transplanted cells
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21-36
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Swelling
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Pain
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Redness & heat
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Purulence
hyperemia
Page 531
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Three major processes
mobilization of body defenses
2. containment and destruction of pathogens
3. tissue clean-up and repair
1.
21-38
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Kinins, histamine, and leukotrienes are secreted by
damaged cells
 stimulates vasodilation that leads to hyperemia
 causes redness and heat
  local metabolic rate, promotes cell multiplication and
healing
 dilutes toxins, provides O2, nutrients, waste removal
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stimulates  permeability of blood capillaries
 allows blood cells, plasma proteins (antibodies,
complement proteins, fibrinogen) into tissue
21-39
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Leukocyte
Deployment
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margination
 selectins cause
leukocytes to adhere
to blood vessel walls
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diapedesis (emigration)
 leukocytes squeeze
between endothelial
cells into tissue space
21-40
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Chemotaxis
leukocytes are attracted to chemotactic chemicals
Neutrophils are quickest to respond
 phagocytosis
 respiratory burst
 secrete cytokines for recruitment of macrophages and
neutrophils
 macrophages and T cells secrete colony-stimulating factor
to stimulate leukopoiesis
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21-41
Total WBC: 4,500 - 10,000
Bands or stabs: 3 - 5 %
Granulocytes
Neutrophils (or segs): 50 - 70% relative value (2500-7000
absolute value)
Eosinophils: 1 - 3% relative value (100-300 absolute value)
Basophils: 0.4% - 1% relative value (40-100 absolute value)
Agranulocytes (or mononuclears)
Lymphocytes: 25 - 35% relative value (1700-3500 absolute
value)
Moncytes: 4 - 6% relative value (200-600 absolute value)
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Defense mechanism: does more good than harm
promotes interferon activity
 accelerating metabolic rate and tissue repair
 inhibiting pathogen reproduction
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A cytokine named interleukin 1
called a pyrogen
 secreted by macrophages
 stimulates anterior hypothalamus to secrete PGE2
 Prosatglandin E2 resets the body’s thermostat higher
> 105F may cause delirium, 111F- 115F, coma-death
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Stages of fever
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onset (spiking a fever)
stadium
defervescence (breaking a fever)
What if your patient is
shivering with a normal or
very slightly raised temp?
21-44
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Depends on lymphocytes
Specificity and memory
Cellular immunity: cell-mediated (T cells)
Humoral immunity: antibody mediated (B cells)
This is the half of the
immune system that
confers immunity
through a vaccination!
21-45
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Active immunity produces memory cells
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Natural – you catch the measles
Artificial – you’re vaccinated for the measles
Passive immunity is not long lasting
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Natural - fetus acquires antibodies from mother
Natural – nursing child gets antibodies from colostrum
Artificial - treatment for snakebite or tetanus
21-46
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Trigger an immune response
Complex molecules
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> 10,000 amu, unique structures
proteins, polysaccharides, glycoproteins, glycolipids
21-47
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Stem cells in red bone marrow
Mature in thymus
21-48
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Immature T cells must be able to recognize signals
from other parts of the immune system
If they don’t – they are destroyed
Immature T cells must not recognize proteins on your
tissue cells as ‘foreign’
Only 2% of
If they do – they are destroyed
immature T cells
survive these steps
that are called
‘selection’
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Stem cells in red bone marrow
Mature in thymus
Circulate through blood and lymph
Naïve T cells colonize lymph nodes, Peyer’s patches,
tonsils, spleen
21-50
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Sites of development
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bone marrow
B cells also undergo selection (just not in the thymus)
Self-tolerant B cells form B cell clones
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each cell in a clone has the same antigen receptors
21-51
DCs and macrophages
(some B cells) display
antigens to T cells
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T cells attack foreign cells and diseased host cells;
memory of Ag
Three classes of T cells:
1. Cytotoxic T cells (Tc cells) carry out attack
2. Helper T cells: help promote Tc cell and B cell action
3. Memory T cells: provide immunity from future
exposure to antigen
21-53
T Cells must be
activated by
APCs before
they go to work.
Cytotoxic T cells directly attack enemy cells
Lethal hit mechanism
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1.
2.
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docks on cell with antigen-MHC-I protein complex
releases perforin, granzymes - kills target cell
interferons - decrease viral replication and activates
macrophages
tumor necrosis factor: kills cancer cells
21-55
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Cytotoxic T cell binding to cancer cell
21-56
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Memory T cells
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following clonal selection some T cells become memory
cells
long-lived; in higher numbers than naïve cells
T cell recall response
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upon reexposure to same pathogen, memory cells launch
a quick attack
21-57
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Helper T cells (TH cells) have been informed of the
invader by APCs
Helper T cells (TH cells) stimulate the B cells that
have the right ‘weapon’ for this disease
The B cells turn into Plasma cells
Plasma cells make antibodies that circulate in the
blood and can incapacitate the pathogen
Memory
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some B cells differentiate into memory cells
21-58
21-59
ALL antibodies
are proteins!
Antibodies are
IgG is Y-shaped.
the most
important
80% of your
component
of
circulating
humoral
antibody
is IgG.
immunity!
There are other
classes of Ig
Antibody and immunoglobulin are synonyms
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Immune system capable of as many as 1 trillion
different antibodies
Somatic recombination
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DNA segments shuffled and form new combinations of
base sequences to produce antibody genes
Somatic hypermutation
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B cells in lymph nodules rapidly mutate creating new
sequences
21-61
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Neutralization
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Complement fixation
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antigen binds to IgM or IgG, antibody changes shape, initiates
complement binding; primary defense against foreign cells,
bacteria
Agglutination
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antibodies mask pathogenic region of antigen
antibody has 2-10 binding sites; binds to multiple enemy cells
immobilizing them
Precipitation
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antibody binds antigen molecules (not cells); creates antigenantibody complex that precipitates, phagocytized by
eosinophil
21-62
21-63
21-64
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Excessive immune reaction against antigens that
most people tolerate - allergens
Type I Antibody mediated (IgE), acute reaction
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Type II Antibody mediated (IgG, IgM), subacute
Type III Antibody mediated (IgG, IgM), subacute
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Asthma, Hay fever, Anaphylaxis
glomerulonephritis, systemic lupus
Type IV Cell mediated, delayed (12 to 72 hrs)
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TB test
Poison ivy
21-65
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Failure of self tolerance
cross-reactivity
 abnormal exposure of self-antigens
 changes in structure of self-antigens
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Production of autoantibodies
21-66
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Severe Combined
Immunodeficiency
Disease (SCID)
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hereditary lack of T and
B cells
vulnerability to
opportunistic infection
currently treatable with
gene therapy
21-67