Transcript IMMUNOLOGY SIMPLIFIED

IMMUNOLOGY
SIMPLIFIED
Barb Bancroft, RN, MSN, PNP
www.barbbancroft.com
[email protected]
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.
3 general principles…
• Recognition of self versus non-self
• MHC (major histocompatibility complex)—a
section on chromosome # 6 containing a group
of genes that produce molecules marking our
own tissues as “self” (referred to as “selfantigens.”) These are referred to as HLA
(human leukocyte antigens) because…
HLA antigens…
• They were first studied on our WBCs by
transplant surgeons
• 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
• HLA-A, HLA-B, HLA-C—Class I antigens
• HLA-DP, HLA-DQ, HLA-DR—Class II
antigens
• Class II antigens are the immune
response antigens
Autoimmune disease…
• Certain diseases are immune based and the risk is
associated with specific HLA antigens
• For example…Type 1 diabetes—HLA-DR3, HLA-DR4
Scandinavian background,
Blonde-hair
Blue-eyed with…
Polyuria (excessive urination), polydipsia (excessive
drinking), polyphagia (excessive eating), weight loss,
fatigue
Named…
General principles
• Autoimmune diseases associated with specific HLAantigens: Rheumatoid Arthritis (HLA-DR1, HLA-DR4);
Multiple sclerosis (HLA-A8, B8, DR3); Celiac
Disease (DQ2, DQ8)
• What triggers autoimmune disease? 75% are
women-• Something from outside the body? (exogenous
agent)—virus, bacteria, sunlight, cow’s milk
2nd general principle
SELECTIVITY
and
SPECIFICITY—
The immune system is highly selective and
specific for each pathogen
1 pathogen=1 response
1 pathogen=1 response=1
antibody=MONOclonal
• Monoclonal antibodies as “biological response
modifiers”
• Infliximab (Remicade)
• Adalimumab (Humira)
• Rituximab (Rituxan)
• Trastuzumab (Herceptin)
• Cetuximab (Erbitux)—colon cancer (Martha
Stewart)
• Bevacizumab (Avastin)—inhibits angiogenesis
• Omalizumab (Zolair)—mab to IgE
2nd general principle
• How many types of strep are there?
• Over 200 (Group A thru O + hemolytic
properties—
alpha, beta, gamma)
• GABHS (Group A beta hemolytic strep—the
bad guy)—Antistreptolysin O titers (ASO
titers)
• RHD, Streptococcal TSS, and “the flesheating” disease (necrotizing fasciitis)
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.
So, how do you acquire memory?
• You either suffer the infection…
OR…
• VACCINATE, VACCINATE, VACCINATE!
Vaccines…
• Kids receive a plethora of oral or
parenteral vaccines prior to the age of 2 to
prevent a plethora of childhood diseases…
In the future…
• Shampoos as vaccines
In the future…?? using foods as
vaccines…
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Potatoes
Tomatoes
Bananas
Spinach
Why do we need booster vaccines?
• To boost the immune system’s memory…
• Pneumococcal vaccine at age 50-65; repeat in 5-7
years
• Tdap is recommended now…Adacel (11-64);
Boostrix (10-18) (acellular pertussis)
• Tetanus boosters—every 10 years, don’t forget!
• Highest risk group for tetanus—over 40
• Fishing and gardening in the elderly—big risks
With such a fabulous memory we should
never get the same disease twice!
Exceptions…
The Herpes “Family”
• HSV-type 1
• HSV-type 2
• VZV (varicella vaccine)
• Epstein-Barr
• CMV
• HHV-6, HHV-7
• KSHV (HHV-8)
• HUH?
• HSV-1
• Cold sores
• Usually above the belt
The Herpes family…
• HSV-Type 2—below the belt (STD vs. VD)
The Herpes family…
• VZV—varicella zoster virus
• “Shingles”—Hell’s fire
• Can shingles be prevented by
administering the varicella vaccine to the
elderly?
• Zostavax (Merck)-a stronger version (14x) of Varivax (for
kids)
The Herpes family…
• EBV (Epstein-Barr **virus)
• MONO, Lymphoma
• ? MS
• (Dr. Tony Epstein and his lovely assistant,
Ms. Yvonne Barr)
The Herpes family…
• And don’t forget:
• CMV (cytomegalovius)—gastroenteritis,
retinitis, pneumonitis—wreaks havoc in
immunocompromised patients
• HHV-6 (Roseola)(?MS)
• HHV-7 (??)
The Herpes family…
• HHV-8 (1995)
Kaposi’s Sarcoma
Herpes Virus (KSHV)
OTHER EXCEPTIONS TO THE
RULE..
• Tuberculosis
Exceptions to the rule…
• HPV
• Vaccine for HPV-16 and 18
• Gardasil (Merck)
Exceptions to the rule…Hepatitis C
• How often do adults clear hepatitis C?
• Blood transfusions prior to 1992 (July)—1 in
3000 prior to 1992; 1 in 276,000 today
• Sharing needles
• Multiple sex partners
• Intranasal cocaine use
• Body piercing
• Tattoos
Guy’s tattoos—out there,
everywhere
• Gals are a bit more subtle…
Exceptions to the rule…Hepatitis B
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How often do adults clear Hepatitis B?
How often do infants clear Hepatitis B?
Hepatitis B vaccine
Should patients with hepatitis C get the
hepatitis A and B vaccine?
INNATE IMMUNE RESPONSE…Barrier defense
mechanisms
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Skin and mucous membranes
Open wounds/ulcerative lesions
Bleeding gums, sores or lesions in mouth
Saliva—protective factors—IgA, low
salinity
ph of body fluids…
• Estrogen plays a role in maintaining the
healthy pH of the vagina—4.5
• Vaginal lactobacillus as normal microflora
• Teenagers and sex
• Menses
• Exocervix vs. endocervix
“You have a yeast infection.”
• Yeast infections
• When the estrogen levels are low or nonexistent
• Young girls
• Elderly women
• Antibiotics change the normal flora
pH of body fluids…
• Urine pH4 (estrogen receptors on the
urethra)
• E. Coli and UTIs
• Young gals, and old gals
pH of body fluids…
• semen (pH—7); anything with an H_V
lives in it—alkaline to alkaline transmits
disease
• Do condoms protect? YES
But not the “natural feel”
condoms
“You want to do what
with my intestines?
To circumcise or not to
circumcise…that is the question…
• YES!
• Not only protect themselves but also their
partners
• If all men were circumcised around the
world--↓ cervical cancer by up to 60%
pH of body fluids…
• Gastric pH2
• H. pylori and ulcers
• Consider the patient on PPIs and
continuous H2 blockade for GERD at highrisk for food-borne illnesses
Innate defense: acute inflammation
• Vasodilation
• Increased permeability of vascular
membranes
• Arrival of WBCs—first the segs and then
the macrophages
Acute inflammation
• Segs are the cells of acute inflammation
• Respond to tissue necrosis and bacterial
invasion
• Also respond to a signal from the specific
immune response
• Play a major role in destruction of tissues such
as the joints in patients with rheumatoid arthritis;
the kidneys in patients with lupus
SEGS…normal function and the
role of Prednisone
• Margination, pavementing, migration and
engulfment (degranulation)
Yum.
Prednisone and the neutrophil
• Inhibits migration and degranulation, hence it’s
anti-inflammatory properties
• 1st 24 hours after prednisone = neutrophillia
• Prednisone also increases blood sugar; high
blood sugars can inhibit the function of segs
• Diabetes– Blood sugars greater than 180 mg/dL
inhibits seg migration
• Elderly with decreased migration of segs,
increases infection susceptibility
• Fever increases the migration of segs—is fever
good for you? YES!
Neutropenia
• Defined as an absolute neutrophil count of less
than 1000
• ANC = % segs + % bands x total WBC
• Patient is “leukopenic” with a WBC less than
2,500
• 56% segs + 4% bands = 60% x 2500 WBC =
ANC = 1500 (not neutropenic)
• 36% segs + 4% bands = 40% x 2,000 WBC =
800 (neutropenia)
Monocyte/Macrophage
• Monocyte in blood, macrophage in tissue (Kupffer cell in
liver, microglial cell in brain)
• CD4 receptor on their cell membranes
• Phagocytes that respond much slower than the seg (2-4
days vs. 5-10 minutes for the seg)
• Cell of chronic inflammation
• The macrophage is the antigen processing and
presenting cell
• 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, IL-12, TNF-alpha)
What else does IL-1 do?
• Increases temperature set point by increasing
the production and release of prostaglandins in
the hypothalamus
• Increases serotonin release from brainstem—
vomiting
• Increases serotonin release from the
duodenum—nausea
• Duodenum—the organ of nausea
IL-1 release…
• 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…
Macrophage is the APC--Antigen
processing cell and IL-1 release…
CD4
IL-1 release
TNF-a
macrophage
With CD4 receptor
IL-2
T4 cell
CD4
T4 or helper T cell
“ON”
TNF-alpha (tumor necrosis
factor)
• A cytokine released by the macrophage
• In small amounts it is a potent
inflammatory mediator
• In large amounts it can wreak havoc
• Examples: Crohn’s disease
Rheumatoid arthritis
• TNF-alpha inhibition
Drugs to reduce TNF-alpha
• Infliximab (Remicade)
• Adalimumab (Humira)
• Etanercept (Enbrel)—infusion of TNF-α
receptors to bind excess TNF-α
Chemical events involved in
inflammation— “itis”
• Histamine release—histamine must be a bad
guy
• Prostaglandin production—lots of drugs we take
are “anti-prostaglandin” drugs
• Activation of complement (also known as
complement fixation)—a series of 9 inactive
proteins responsible for inflammation—
complement levels can be measured—example,
lupus and the kidney-- “nephritis”
Inflammation and Immunity
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How do the 2 go hand-in-hand?
Example:
Autoimmune glomerulonephritis
Autoimmune means the immune system
attacks self antigens; glomerulo (kidney)
nephritis (inflammation)
Cells of the immune system-lymphocytes
Cell-mediated immunity
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T4 Helpers—turn the system “on”
T8 Suppressors—turn the system “off”
T4/T8 ratio is 2:1
Fights viruses, fungus’, protozoa,
parasites, cancer, transplant tissue
• AIDS and the T-cells
T-cells release cytokines
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Anti-viral—interferon alpha
Other interferons
Interferon beta (immunosuppressing)
Interferon gamma (immunoenhancing)
Echinacea boosts interferon gamma
(should this be used in your patients with
autoimmune disease?)
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
• Get ‘em dirty!!
B lymphocytes (cells)
• B cell---plasma cell---antibody production
(7-21 days)(except HIV—can take as long
as 1 year)
Y
• Flu vaccine 2-4 weeks before it gets here!
Immunoglobulins
• IgM—1st formed to an infection; fixes
complement (inflammation), agglutinates
(clumps)
• IgG—2nd formed; memory; crosses placenta;
fixes 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?
Boosting immune system
• Humor
• Exercise
• Sex
What about IgD?
• No one knows exactly what it does, so you
don’t have to learn it…
Plasma cells produce
antibodies…
• IgE—antibody of allergies
• Drills a hole in the
mast cell—
releases primary granules
full of histamine
• Antihistamines
• Allergies and anaphylaxis
• What can you do to reduce allergies?
• Get rid of the pet?
Take drugs
• Anti-histamines
• Anti-leukotrienes
• Anti-IgE (monoclonal antibody)—
omalizumab (Zolair)
How about sleeping with the
enemy?
Give ‘ em a bath once a week…
• They love it…
Thanks…and remember,
• “Support
bacteria…they’re the
only culture some
people have…”
• Barb Bancroft, RN,
MSN, PNP
• [email protected]
• www.barbbancroft.com