IMMUNOLOGY SIMPLIFIED
—from AIDS to ZZZZZZ
Barb Bancroft, RN, MSN, PNP
www.barbbancroft.com
BBancr9271@aol.com
Immunology…
• Definition: The study of the physiologic
mechanisms that allow the body to
recognize materials as foreign or
abnormal and to neutralize or eliminate
those foreign materials.
MHC (major histocompatibility complex)
• A small section on chromosome 6 containing
a group of genes that produce molecules that
mark a cell as “self”
• Histocompatibility testing, or tissue typing,
involves matching these molecules (antigens)
• Because tissue typing is usually performed on
White Blood Cells (WBCs), or leukocytes,
these self-antigens are called HLA-antigens
HLA antigens…
• They were first studied on our WBCs by renal
transplant surgeons in the 1960s
• All tissues have HLA antigens on them except
red blood cells with ABO antigens
• Of course, the HLA antigens weren’t put on
tissues solely for the convenience of
transplant surgeons…
General principles
• HLA antigens help the immune system
to recognize pathogens and to mount an
immune response
• All body cells (except RBCs) have HLA-A,
HLA-B, HLA-C—known as Class I
antigens
• HLA-DP, HLA-DQ, HLA-DR—Class II
antigens
Class II antigens
• Class II antigens are the immune response antigens
and are located on only on monocytes (in blood),
macrophages (in tissues—APCs*), dendritic cells (in
tissues just beneath the epithelial cells—APCs*), B
lymphocytes (effector cells of the immune system) ,
activated T lymphocytes (effector cells of the
immune system)
• *Antigen processing cells—process the “foreign”
substance to present to the immune system
Class II HLA antigens
• These antigens are essential for immune function
and survival
• They determine which foreign antigens an
individual responds to as well as the strength and
type of response
• These are also “secreted” in body fluids in lower
forms of animals—you want to select a mate based
on “strength” of the immune system—how do
lower forms of animals meet?
• Clonal selectivity
Clonal selectivity
• They stick their nose where the “sun don’t
shine” and say… “You’re the one for me…”
• Why don’t humans do that?
• Well, we kind of do…
When the immune system attacks “self”…specific
HLAs are associated with autoimmune disease
• For example…Type 1 diabetes—HLA-DR3 (5% risk),
HLA-DR4 (6% risk), both? (20% risk)—more
prevalent in Scandnavians
Blonde-hair, blue-eyed with…
Polyuria (excessive urination), Polydipsia (excessive
drinking), polyphagia (excessive eating), weight
loss, fatigue
Named…
Over 80 autoimmune diseases
• Most autoimmune diseases associated
with specific HLA-antigens include:
• Rheumatoid Arthritis (HLA-DR1, HLADR4)
• Multiple sclerosis (HLA-A8, B8, DR3—
10x greater risk)
• Celiac Disease (DQ2, DQ8)
• What about narcolepsy?
Narcolepsy
• Narcolepsy—HLA-DR2
• Stanford University and a breed of
Doberman’s
Other HLA and disease associations
• Inflammatory diseases such as ankylosing
spondylitis and other postinfectious
arthropathies (Reiter’s syndrome—HLA-B27
(90-100%)
• Inherited errors of metabolism—HLA-A and
hereditary hemochromatosis
One more interesting note about autoimmune
disease
• One in 20 Americans have an autoimmune disorder;
10 times more likely to be female (75%)
• RA (7:1); Sjögren’s (9:1); SLE (9:1); MS (3:1);
Hashimoto’s (10:1)
• Presentation tends to be between 25-45
• Men have an overall increased risk of infectious
disease, women have an increased risk of
autoimmune disease
• Any theories as to why?
Autoimmune disease—loss of selftolerance
• MS—antibodies attack myelin basic protein
in the CNS
• Guillain-Barré—antibodies attack peripheral
nervous system myelin
• Systemic Lupus Erythematosus—antibodies
attack nuclear proteins—tested by measuring
anti-nuclear antibodies (ANAs)
• Celiac disease—antibodies attack microvilli of
small intestine (especially the duodenum)
Triggers for genetically-predisposed individuals
• Some type of trigger – from the outside?
(exogenous agent); from the inside?
(endogenous agent)
• Lack of vitamin D for certain autoimmune
diseases (T1 DM, MS?)
• Inside triggers? Colonic bacteria and Crohn’s
disease/ulcerative colitis?
• Outside triggers? Viruses for T1 DM?
• Outside triggers? Bacteria (Campylobacter
pylori) for Guillain-Barre syndrome?
Cook your chicken!
• White meat—170° F
• Dark meat -- 180° F
• Whole chicken – 180
2nd general principle—selectivity and
specificity
• The immune system is highly selective and
specific for each pathogen
• 1 pathogen=1 response
• “monoclonal”
For example…
• How many types of strep are there?
• Over 200 (Group A thru O + hemolytic properties—
alpha, beta, gamma)
GABHS (Group A beta hemolytic strep—
(anti-streptolysin O titers are antibodies made to group A
strep)
ASO titers and strep throat
Rheumatic heart disease and molecular
mimicry
• Some infections share epitopes with selfantigens, an immune response against such
microbes may produce tissue –damaging
reactions that cross react with self-antigens;
group A beta hemolytic strep cross reacts
with cardiac glycoproteins (myosin-like);
takes 7 to 21 days to make antibodies; acute
rheumatic heart disease usually occurs 2 to 3
weeks after strep throat—murmur, joint pain,
rash
Monoclonal antibodies made in the
laboratory— “magic bullets”
• Trastuzumab—Herceptin targets the HER/2neu gene
in breast cancers; this gene amplifies the growth of
the tumor
• Rituximab—Rituxan targets a specific protein on B
lymphocytes; used for non-Hodgkin’s lymphoma, MS,
DM
• Cetuximab (Erbitux)—targets epidermal growth
factors (Martha Stewart)
• Bevacizumab (Avastin)—inhibits angiogenesis (TAF—
tumor angiogenesis factor)
• Infliximab (Remicade)—targets an inflammatory
protein (TNF-a)—Crohn’s disease, rheumatoid
arthritis, more…
General Principles
3) MEMORY—
• Once having met a pathogen, the immune system never
forgets it.
• If you are re-challenged with the same pathogen the memory
response will recognize it immediately-and destroy it or neutralize it.
With such a fabulous memory we should never get
the same disease twice! BIG exception to the rule…
The Herpes “Family”
• HSV-type 1
• HSV-type 2
• VZV (varicella vaccine)
• Epstein-Barr
• CMV
• HHV-6, HHV-7
• KSHV (HHV-8)
• HUH?
You can’t kill herpes…you can “live
with it”…
• 3 herpes viruses live in the dorsal root
(sensory root) of the peripheral nerves
• “What’s the difference between herpes and
love?”
Herpes simplex virus--type 1
• HSV-1 typically lives in the dorsal root of the
trigeminal nerve
• Cold sores
• Usually above the belt
Herpes simplex virus—type 2…
• HSV- 2—below the belt (STD vs. VD)
• “Hey nurse, can I get hairpiece from a toelet
seat?”
Varicella zoster virus—
(chickenpox/shingles)
• VZV—varicella zoster virus
• Primary infection is chickenpox—crawls up the
sensory nerve and lives in dorsal root of the
trigeminal nerve (V)
• If your immune system is “competent” , the
virus remains dormant in the sensory root
Immunocompromised? Shingles is the
secondary manifestation
• Hematologic malignancy; rate of HZ is 5-25%
• Lupus—3.2-21%
• HIV/AIDS increases risk by 12-17 fold (T cell
deficiency)—multidermatomal shingles
• Depression and significant stress within past
6 months increases risk
• The elderly
Shingles and the elderly population
• With aging population, the absolute # of
herpes zoster cases is increasing dramatically;
Why?
• Because the type of immunity that keeps
latent herpes in a “latent” state wanes with
aging—this type of immunity is called cellmediated immunity (CMI); killer T cells are
responsible for CMI and their action decreases
with age
FYI: Percent of individuals with shingles, by
age
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10—0.5%
20—1.3%
30—2.7%
40—4.8%
50—7.5%
60—11.9%
70—19.7%
80—31.8%
90—46.1%
Donahue JG, et al. Archives of Internal Medicine, 1995.
Locations of Herpes Zoster or
“shingles”
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•
•
•
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•
•
4% sacral
11% cervical
13% cranial
13% lumbar
56% thoracic
3% other
Ophthalmic complications 10-25% (keratitis, iritis,
retinitis, optic neuritis with vision loss and blindness)
• AIRBONE precautions for disseminated herpes zoster
Herpes Zoster
• Acyclovir (Zovirax)—800 mg/day po 5x/day x 7-10 days;
significant reduction in severity, duration and relative risk
of postherpetic neuralgia
• Famciclovir (Famvir)—500 mg po 3x/day x 7 days—as
effective as Zovirax in reducing acute pain and preventing
PHN
• Valacyclovir HCl (Valtrex)—1000 mg/po 3x/d x 7 days
provides an improved benefit over acyclovir in reducing
the severity and duration of PHN in patients over 50
• Start treatment within 48 to 72 hours of rash onset;
nerve block?
• What about Prednisone?
Vaccine to prevent shingles--Zostavax
• Vaccine approval May 2006
• 500,000 to 1 million episodes per year
• PHN – vaccine reduces incidence of HZ by 51%
and decreases incidence of PHN by 66%;
decreases morbidity by 61%
• Patients older than 50 have a 14.7-fold higher
incidence of chronic pain 30 days after the
onset of rash than patients under age 50
The Epstein-Barr* virus (EBV) is a
member of the Herpes “family”
• *Dr. Tony Epstein and his lovely assistant, Ms.
Yvonne Barr; Denis Burkitt and Burkitt’s
lymphoma
• Lives in your B lymphocytes
• MONO
• B-cell Lymphoma (the boy in the bubble—
David Vetter)
• Nasopharyngeal carcinoma
• ? MS
Cytomegalovirus …
• CMV (cytomegalovius)—gastroenteritis, retinitis,
pneumonitis, adrenalitis, pancreatitis, encephalitis,
polyneuritis—wreaks havoc in immunocompromised
patients (transplant and HIV+ patients)
• Crosses the placenta and can cause cytomegalic
inclusion disease in developing babies
• ? Trigger of glioblastoma multiforme?
Human herpes virus -6, and Human
herpes virus -7
• HHV-6—roseola
• HHV-7--???
Human herpes virus-8, or KSHV…
• HHV-8 (1995)
Kaposi’s Sarcoma
Herpes Virus (KSHV)
• STD
• Rarely found in blood transfusions (only 3
known cases)
So let’s go back to the MEMORY of the immune
system…how do you acquire memory?
• You either suffer the infection…
• OR YOU…
• Vaccinate, vaccinate, vaccinate
How does the immune system develop
memory?
• It meets a pathogen, responds to it, and that
response can be measured as a memory
response
• Antibodies are made to some pathogens and
we measure those as “titers”—
• Memory T cells directly respond to certain
pathogens
How do we test memory?
• Antibody titers can do a couple of things:
1) tell us if you have EVER been exposed to a
specific pathogen—varicella titers, CMV titers
2) tell us if you have responded to a
pathogen/vaccine and how strong that
response was/or currently is—levels of titers
3) these titers tend to wane as we age—we
just can’t remember like we used to…
TB skin test
• Tests whether or not you have been exposed to
TB
• OR you can have a positive test if you have had
the BCG vaccine
• High risk groups for TB are patients and
healthcare workers from other countries—India,
China are the two top countries
• Having had the BCG vaccine as a child in another
country does NOT mean that you are protected
from TB
• Quantiferon Gold test for TB in BCG+ pts.
TB and LTCF (long-term care facilities)
• All newly admitted residents should receive
two-step mantoux/purified protein derivative
(PPD) test unless a physician’s statement has
been obtained that the resident had a past
positive reaction to tuberculin
• A PPD is considered positive and a chest X-ray
is indicated when a resident has:
TB and LTCF
• ≥10 mm of induration
• ≥ 5 mm for residents with organ transplants,
other immunosuppressed conditions, HIV +,
recent contact of an active TB case or fibrotic
changes on CXR
• TB requires airborne precautions, Use of N-95
respirators when entering the room
Let’s get back to vaccines for a
moment…historical highlights
• Chinese vaccines—11th century B.C. –
“sowing the pox”—injecting pus from the
smallpox pustules into a cut on the hand of a
healthy person; “snorting” the pox was
another way of inoculating against small pox
• Lady Mary Wortley Montegu, wife of the
British ambassador to Turkey in the early
1700s, saw it in action and brought the idea
back to England from Turkey
Historical Highlights…
1796—English country doctor, Edward Jenner
and the milkmaid--cowpox (“vacca” is the
Latin word for cow) offering protection
against smallpox; “vaccinia”=cowpox
His prediction?
1976…last case of smallpox in Somalia
• Small pox
• Great pox
• Chicken pox
World Health Organization and “herd” immunity
• Vaccinating 70% of the world’s
population against smallpox developed
“herd” immunity
• Why were we able to totally eradicate
smallpox from the face of the earth?
• The smallpox vaccine contained 200
different smallpox specific antigens—
had the potential to overwhelm the
immune system
• All vaccines today contain
approximately 120 antigens combined
Vaccines…
• Prevention of childhood diseases…(kid
receive 28 doses by the age of 2 if they get
the complete schedule of immunizations
recommended by the CDC)
• The good news—the prevention of childhood
diseases… the bad news? Most of the
vaccines are needles, so…in the future…
• Shampoos as vaccines?
• Foods as vaccines?
Using foods as vaccines…
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•
•
•
•
Potatoes
Tomatoes
Bananas
Spinach
Still working on the possibility…
Vaccine miracles…meningitis in kids
• H. flu meningitis—what are the numbers? 40-100
cases/100,000 of invasive H. flu in 1989; vaccine in
1990—
• 1.4 cases/100,000 today
• Strep pneumoniae meningitis—what are the
numbers? 77% decline in kids; 60% decline in adults
via “herd immunity”
• Lumbar punctures in kids—before, during,
after…too many…
Acetaminophen and vaccine response
• Acetaminophen should not be given
prophylactically as a routine practice with
vaccination
• Reduces the antibody response after
vaccination
• However, does this actually increase the
susceptibility to the infections that the
vaccines protect against? The study did not
answer that question
(Chen RT et al. The yin and yang of paracetamol and
paediatric immunizations. Lancet 2009 Oct 17;
374:1305)
Why do we need vaccine boosters?
• To boost the immune system’s memory…
• Boosters for kids
• One shot, two shots or three shots? Depends on the
response of the immune system
• Pneumococcal vaccine at age 65; repeat in 5-7 years
• Give it earlier in patients with chronic disease
Tetanus/diphtheria booster
• Td (tetanus toxoid, reduced diphtheria toxoid) – every 10
years
• Why every 10 years? The diphtheria portion wears off in 11
years; the tetanus doesn’t wear off for 19 years…but, since
they are given together is better to err on the safe side and
give it every 10
• What are the two most common causes for tetanus (lockjaw)
in the older individual?
• Tdap (Td + and acellular pertussis)Boostrix (ages 10-18) and
Adacel (ages 11 to 64)— one time booster
So how does the immune system
work?
• You actually have 2 “immune” systems…
1) Innate and 2) acquired (adaptive)
• Innate “immune” system—born with certain
abilities to fight invading pathogens
• Acquired or adaptive “immune” system—you
learn from experience—you have to meet the
pathogen and respond specifically to it, and
then…remember it!
INNATE IMMUNE RESPONSE…Barrier defense
mechanisms and acute inflammation
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•
Skin and mucous membranes
Open wounds/ulcerative lesions
CA-MRSA and open wounds in athletes
Toothbrushes and flossing
Gotta hole? We’ll put a tube in it…if you don’t have a hole for
the tube we’re holding—we’ll make a new hole for ya’!
Urinary catheters, Hickman catheters, ports, arterial lines,
venous lines, surgical sites, IV sites.
• Hospital-acquired MRSA, MRSA, MRSA and wound infections
Barrier defenses
• Bleeding gums, sores or lesions in mouth
• Epidemiological synergy—twofold to fivefold
increased risk of HIV infections among persons
who have other STDs
• Saliva—antimicrobial proteins, IgA, low
salinity (1/7th the amount of salt as other body
fluids
• pH of body fluids
pH of body fluids—gastric acid
• acid pH of 2 in the stomach keeps a lot of bugs “out”
• Therapy with PPIs, H2 blockers, and antacids has
been associated with an increased risk of hospitalacquired pneumonia (JAMA 2009;301:2120-2128)
• The incidence of bacterial gastroenteritis caused by
salmonella and Campylobacter may be increased in
patients taking PPIs, but no association with H2
blockers has been found (Clin Gastroenterol Hepatol.
2007;5:1418-1423)
Urinary pH
• acid pH of urine keeps E. coli (and the other
bacteria that live in the bowel) “out”—age of
the woman
Vaginal pH
• acid pH of the vagina keeps yeast “out” and
STDs (pre-teens vs. teens vs. 20-40s vs.
postmenopausal)
“You have a yeast infection.”
• Yeast infections
• When the estrogen levels are low or non-existent
• Antibiotics change the pH and normal flora of the
vagina
pH of body fluids…
• semen (pH—7); anything with an H_V lives in
it—alkaline to alkaline transmits disease
• Do condoms protect from STDs? YES, for most
STDs; not 100% but better than nothing
• What about those “natural feel” condoms?
To circumcise or not to circumcise…that is
the question…
YES!
• Not only protect themselves but also their
partners
• 20% of men with intact foreskin carry HPV;
only 6% of circumcised men carry HPV
• If all men were circumcised around the
world-- cervical cancer rates would drop by
up to 60%
Innate defense: acute inflammation
• Inflammation is
• Vasodilation
• Increased permeability of vascular
membranes
• Arrival of WBCs—first the neutrophils and
then the macrophages
Acute inflammation
• Segs (neutrophils) are the cells of acute inflammation—
comprise 60% of the total WBC and differential; immature
segs are called “bands”—normal bands comprise 0-4% of the
total white count
• Segs and bands respond to acute tissue necrosis and acute
bacterial invasion within 5 to 10 minutes of tissue damage or
invasion
• Also respond to a signal from the specific immune response—
(more later)
• In autoimmune disease, the segs play a major role in
destruction of tissues such as the joints in patients with
rheumatoid arthritis; in the kidneys in patients with lupus
SEGS…
• Margination,
pavementing, migration
and engulfment and
degranulation (release
of preformed granules)
• Marginating segs
(measured by WBC
count)
• Pavementing segs
(stuck to walls)
Yum
Prednisone and the neutrophil
• Prednisone inhibits migration, engulfment and degranulation,
hence its potent anti-inflammatory properties
• Why do we use Prednisone with autoimmune disease? To
inhibit the damage caused by one’s own segs attacking
various tissues
• 1st 24 hours after prednisone = neutrophillia (segs increase in
the blood due to recruitment of pavementing cells)
• Prednisone also increases blood sugar; high blood sugars can
also inhibit the function of segs
Other conditions with segs
• Blood sugars greater than 180 mg/dL inhibits
seg migration (diabetics, high blood sugars
and infections)
• Elderly with decreased migration of segs,
increases infection susceptibility
• Fever increases the migration of segs—is fever
good for you? YES!
• Neutropenia—an oncologic emergency
The cell of chronic inflammation and the cells
that process antigens are:
• Monocytes in blood, macrophages (big eater) in
tissues
• Macrophages have other names in various tissues—
microglial cells in the central nervous system,
Kupffer cells in the liver, histiocytes in connective
tissue
• Dendritic cells are also specialized antigen
processing cells
The macrophage (CD4)(cell
determinant #4)
• The macrophage (CD4) is the antigen
processing and presenting cell
• These cells respond much slower than the seg (2-4
days vs. 5-10 minutes for the seg)
• Cell of chronic inflammation
• It engulfs the pathogen; chews it up
• Processes it and presents it to the helper T cell
(T4 cell) of the immune system
• Releases cytokines (IFN-gamma, IL-1, Tumor
Necrosis Factor-alpha)
Gulp, chew, process, spit, kick…
“ON”
CD4
IL-1 release
TNF-a
IFN-gamma
macrophage
With CD4 receptor
IL-2
T4 cell
CD4
T4 or helper T cell
B s, Ts
WBCs
How do drugs and bugs influence this
immune response
• Prednisone inhibits IL-1 (interleukin-1) release—
immunosuppressive
• Methotrexate inhibits macrophage function
• Cyclosporine inhibits IL-2—used to reduce tissue
transplant rejection
• Etanercept (Enbrel) binds with excess TNF-a
molecules—anti-inflammatory
Monoclonal antibodies
• Adalimumab (Humira), infliximab
(Remicade), golimumab (Simponi), and
certolizumab pegol (Cemzia) block TNF-a
• Daclizumab (Zenapax)—blocks IL-2 on
activated T cells to prevent organ transplant
rejection
• Basiliximab (Simulect)—prevent organ
transplant rejection
HIV and the CD4 cells
• The AIDs virus (HIV) enters via CD4 receptors—kills cells
after replicating;
• The macrophages are primarily “fixed” in tissues—only small
numbers circulate (4% of the total white count); HIV is
silently destroying the macrophage population in tissues
• HIV also kills the circulating CD4 cells; as they fall to 350 per
cu/mm anti-retroviral therapy will be initiated
• Methamphetamine increases the entry of HIV into CD4+
cells
Vitamin D and the immune system
• Vitamin D boosts macrophage function
• In the old days—the treatment for TB was to…“go
up on the mountain if you have consumption…”—
heliotherapy in 1908 vs. today’s heliotherapy
• Ultraviolet light (UVB rays) and immune boosting
• Ultraviolet lights in EDs and internal medicine clinics
in high-risk hospitals
• Homeless vs. shelters
More on vitamin D and the immune
system
• Dramatically stimulates antimicrobial proteins from
neutrophils, monocytes, NK cells, and epithelial cells
lining the respiratory tract
• Vitamin D deficiency (less than 40 nmol/L) increases
the risk of respiratory tract infections
• Sicker in the winter?
• Vitamin D deficiency and autoimmune disease—
correlates positively with latitude from the equator—
MS, Type 1 DM, IBD
• Vitamin D and prostate cancer
Let’s go back to the
cytokines…interleukin 1
• Increases temperature set point by increasing
the production and release of prostaglandins
in the hypothalamus
• A fever recruits white blood cells and makes
them more active
• A fever decreases the ability of pathogens to
utilize iron
IL-1
• Increases serotonin release from brainstem—
vomiting
• Increases serotonin release from the
duodenum—nausea
IL-1 …
• Increases melatonin production and makes
you sleepy
IL-1 release also…
•
•
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Lowers pain threshold—everything hurts
Your hair hurts
Your teeth hurt
Your skin hurts
You’re tired
You’re miserable…
Amphotercin B releases IL-1 from
macrophages;
Tumor necrosis factor - alpha
• Potent inflammatory mediator
• In small doses it’s good for you, in systemic
doses it wreaks havoc with joints (Rheumatoid
arthritis), with intestines (Crohn’s disease),
with skin (psoriasis)
• In AIDS patients it’s responsible for “wasting
syndrome”
Interferons are also produced by various cells
of the immune system
• Interferon alpha—anti-viral cytokine; prevents the
attachment of viruses to cells; blocks viral replication
in infected cells
Intron-alfa + ribivirin for the treatment of Hepatitis C
patients
One of the notorious side effects is depression; do
immune system cytokines trigger depression?
Cytokines can decrease levels of serotonin in the
brain
Interferon beta
• Interferon beta is an immunosupressing
interferon
• Used to treat multiple sclerosis--betaseron
Interferon gamma
• Interferon gamma is an immune-boosting
interferon
• NK cells release interferon gamma to
stimulate macrophages to destroy ingested
microbes
CHEMICAL EVENTS INVOLVED IN
INFLAMMATION in tissues… “itis”
• Histamine release—histamine must be a bad
guy (anti-histamines)
Chemical events involved in
inflammation
• Prostaglandin production—lots of drugs we
take are “anti-prostaglandin” drugs—ASA,
NSAIDS (celecoxib/Celebrex)
• Prostaglandins are produced daily in certain
tissues as a normal part of their function—i.e.,
the stomach—prostaglandins boost mucus
production in the stomach to protect it from
acid
• Prostaglandins are also produced with tissue
damage (inducible prostaglandins) via an
enzyme called cyclo-oxygenase 2
• COX-2 inhibitor—celecoxib (Celebrex)—causes
less gastropathy but over time can cause an
NSAID-induced gastric ulcer
Complement
• Activation of complement (also known as complement
fixation)—consists of more than 20 inactive proteins, some of
which are numbered 1 through 9; most abundant is C3
• Triggered by fixation to antibodies IgG or IgM; or by various
microbes and proteins including venom
• responsible for inflammation when they are activated—
complement levels can be measured—example, lupus and the
kidney-- “lupus nephritis”
• With active kidney involvement the complement levels will
DECREASE as it is being “used up” to cause inflammation
Inflammation and Immunity
•
•
•
•
How do the 2 go hand-in-hand?
Example:
Autoimmune glomerulonephritis
Autoimmune means the immune system
attacks self antigens; glomerulo (kidney)
nephritis (inflammation)
Abdominal visceral fat and
inflammation
• Macrophages in the abdomen recognize excess
adipose tissue in the viscera as “foreign”—results in
an inflammatory response; release IL-6, TNF-a, which
in turn trigger the liver to produce hs-CRP (high
sensitivity C-Reactive Protein, a marker of systemic
inflammation) and a high risk for cardiovascular
disease
• This fat is also insulin resistant—T2 diabetes
• REDUCE ABDOMINAL/VISCERAL FAT—how?
Natural Killer lymphocytes are cells of the
innate defense system
• Kill viruses and cancer cells “naturally”—in other
words they are ready to destroy invading viruses and
cancer cells without having to “learn” the response
• These comprise about 4-10 percent of the circulating
lymphocytes
• B and T lymphocytes are the lymphocytes of the
specific or aquired immune response—Bs 16% and
T’s about 70% of the total circulating lymphocytes
Cells of the immune system--lymphocytes
Lymphatic tissues
• Spleen
• Lymph nodes
• Cutaneous lymph tissue just beneath the epithelial
cells
• Mucosal lymph tissue—pharyngeal tonsils and
Peyer’s patches of the intestine—at any given time,
more than half of the body’s lymphocytes are in the
mucosal tissues (reflecting the large size of these
tissues)
Cell determinants
•
•
•
•
CD3 – found on all T cells
CD4—found on Helper T cells
CD8—found on suppressor/cytotoxic (killer T cells)
CD20—found on B lymphocytes; the monoclonal antibody,
rituximab/Rituxan), targets this cell determinant—RX for nonHodgkin’s lymphoma and some autoimmune diseases (lupus)
• CD21—found on B lymphocytes (Epstein Barr virus enters the
B lymphocytes via this cell determinant/receptor)
• CD16 and CD56 are found on NK cells
Cell-mediated immunity (CMI)
• T4 Helpers—turn the system “on” (there are
actually subsets of helper T cells—more later)
• T8 Suppressors—turn the system “off”
• T4/T8 ratio is 2:1
• CMI fights viruses, fungus’, protozoa, TB,
parasites, cancer, transplant tissue
What are the diseases observed in
AIDS patients?
• Viruses—herpes (HSV-1,2, VZV, EBV, HHV-8),
hepatitis C
• Fungus’—candida albicans
• Parasites--toxoplasmosis
• Protozoa—pneumocystis jirovecii pneumonia
• TB
• Cancer—Non-Hodgkin’s lymphoma, Kaposi’s sarcoma
HIV (human immunodeficiency virus) and
CD4 cells
• The AIDS virus – enters dendritic cells and
macrophages (CD4) and T4s initially; portal of entry?
Rectum, blood, vagina
• It replicates itself by making copies via an enzyme
called reverse transcriptase; for every one HIV that
enters a cell, it makes 10,000 copies; once the “copy
machine” has finished, HIV exits the cell to look for
another host cell; as it exits, the cell dies; CD4 cells in
the blood continue to decline
HIV and the CD4 cells
• Treatment for HIV/AIDS is usually started
when the circulating T4 count falls to 350
cells/ml
• Treatment targets various processes that
occur within the T4 cell to replicate and exit
the cell
• Reverse transcriptase inhibitors were the
initial therapies and continue to be used today
with a multitude of other drugs
HIV and the CD4 cells
• Another receptor is necessary for HIV to enter
CD4 cells
• CCR5 receptor is one of them
• Blond-haired, blue-eyed gay men named?
• New class of drugs called entry inhibitors
• A few historical highlights about HIV
TH1 and TH2
• Hygiene Hypothesis; the earlier the exposure
to dirt, the better the TH1 system will be
• TH1 predominance = cell mediated immunity
• TH2 predominance=allergies and autoimmune
disease
• Let them eat dirt!!
B lymphocytes (cells)
• B cell---plasma cell ---antibody (immunoglobulins,
gamma globulins) production (7-21 days)(except
HIV—can take as long as 1 year)
fab
Y
fc receptor
Multiple myeloma
• Multiple myeloma is an uncontrolled proliferation of
plasma cells, also known as a plasma cell dyscrasia
• Produces an overabundance of antibodies; usually
one clone—monoclonal
• Light chains (Bence-Jones proteins excreted in the
urine) and heavy chains
Y
Immunophoresis
• IgM, IgG, IgA, IgD, IgE
Immunoglobulins
• IgM—1st formed to an infection; fixes (activates)
complement (inflammation), agglutinates (clumps)—
cold agglutinins, warm agglutinins
• IgG—2nd formed; memory; crosses placenta;
opsonizes (coats); fixes (activates) complement
(inflammation); reactivated with latent infection
• Antibody testing— “acute vs. convalescent titers”
IgM? Or IgG?
• Have you had this disease or vaccine before? IgG
testing
Plasma cells produce antibodies…
• IgA—barrier antibody; saliva, tears, urine,
breast milk
• How can you boost IgA levels? Humor,
exercise, and a little sex perhaps? 
• IgD--??
Plasma cells produce antibodies…
• IgE—antibody of allergies
• Drills a hole in the
mast cell—releases primary granules full of histamine
• Histamine is responsible for itchy, sneezy, wheezy, coughy,
runny…
• Localized histamine release?
• Systemic histamine release? Anaphylactic shock
Hay fever, asthma, allergic rhinitis—
the allergic salute
What are the triggers?
•
•
•
•
•
Pollen, ragweed and other airborne particles
Wasp venom (fire ants have same venom)
Animal dander—cats and dogs
Roach dander
Certain foods—shellfish, peanuts, tomatoes,
eggs, strawberries, maple syrup
What can you do to reduce allergies?
• Get rid of the roaches
• Get rid of the pet?
Why?
Don’t sleep with the enemy
• Speaking of sleep…People who sleep
less than seven hours are 2.94 times
more likely to develop a cold than those
who sleep eight or more
• Sleep deprivation causes a dip in killer T
cells and lower interleukin-2 levels
Drugs to reduce allergic symptoms
• Oral anti-histamines--cetirizine (Zyrtec), desloratadine
(Clarinex), fexofenadine (Allegra)
• Nasal antihistamines—fluticasone propionate (Flonase);
mometasone furoate (Nasonex); triamcinolone acetonide
(Nasacort-AQ)
• Mast cell stabilizers—cromolyn sodium (Nasalcrom)
• Anti-leukotrienes—montelukast (Singulair)
• Anti-IgE monoclonal antibody—omalizumab (Xolair)
Immune-mediated hypersensitivity reactives—
4 types
• Type 1– Immediate hypersensitivity
• Type II – Antibody-mediated hypersensitivity
• Type III – Immune complex-mediated
hypersensitivity
• Type IV – Cell-mediated hypersensitivity
Type 1 immediate hypersensitivity
• Prototype – Hay fever; asthma; allergic rhinitis;
• IgE—immediate release of histamine and other
vasoactive substances; late phase reaction 2 to 24
hours after repeat exposure
• Anaphylactic shock…the systemic release of
histamine—vasodilation (bright red), blood pressure
drops, bronchoconstriction, may have explosive
diarrhea
• Triggers? Bee stings, penicillin, various foods
(shellfish, peanuts), husbands 
Type 2 – antibody-mediated
hypersensitivity
• Production of IgG, IgM—binds to antigen on
target cell or tissue; phagocytosis or lysis of
the target cell by activated complement or Fc
receptors
• Autoimmune hemolytic anemia—anti-RBC
antibodies (Coomb’s test positive)
Type 3 – immune complex
hypersensitivity
• Antigen/antibody complexes land in small vessels
and fix complement; trigger inflammation wherever
they land
• Prototype—systemic lupus erythematosus; antigen is
the nucleus of cells/antibody formed to it…combines
into an Ag/Ab complex (measured as anti-nuclear
antibodies or ANAs
Type 4—T cell mediated
• Contact dermatitis such as poison ivy; latex;
type 1 diabetes; MS, RA, IBD
• Latex “allergies” are usually contact dermatitis
but can also be type 1 if anaphylaxis is
involved
Bibliography
• Chen RT et al. The yin and yang of paracetamol and
paediatric immunizations. Lancet 2009 Oct 17;
374:1305)
• Dantzer R, et al. From inflammation to sickness and
depression: when the immune system subjugates the
brain.” Nature Reviews Neuroscience. January 2008.
• Fehervari Z, Sakaguchi. Regulatory cells of the immune
system. Scientific American 2006; 57-63.
• Hoffman RL. What lies behind the vitamin D
revolution? The Cinical Advisor 2010 (March); 31-36)
Bibliography
• Garten RJ, et al. Antigenic and genetic characteristics of
swine-origin 2009 A (H1N1) influenza viruses circulating in
humans. Science 2009 May 22.
• Maxmen A. Sick and Down. Science News. 2008 (July 19)
• Report. Arousing the Fury of the Immune System. Howard
Hughes Medical Institute. 1998
• Rituximab Protects Insulin Producing Cells in Diabetes—
www.MedPageToday.com; November 25, 2009.
• Prymula R et al. Effect of prophylactic paracetamol
administration at time of vaccination on febrile reactions and
antibody responses in children: Two open-label, randomised
controlled trials. Lancet 2009 Oct 17; 374:1339
Bibliography
• Schaffner W, Jones, TF. Immunizing older adults against
tetanus and diptheria. Patient Care 2004 (October); 19-22.
• The Strategies for Management of Antiretroviral Therapy
(SMART) Study Group. Major clinical outcomes in
antiretroviral therapy (ART)-naïve participants and in those
not receiving ART at baseline in the SMART study. J Infect Dis
2008 Apr 15;197:1133.
• Wejse C et al. Vitamin D as supplementary treatment for
tuberculosis; A double-blind, randomised, placebo-controlled
trial. Am J Respir Crit Care Med 2009 May 1;179:843.
Thank you…and remember,
• “Support bacteria…they’re the only culture
some people have…”
• Barb Bancroft, RN, MSN, PNP
• bbancr9271@aol.com
• www.barbbancroft.com