Transcript ImmunLec22

Lecture 22
December 7th 2010
Hypersensitivity Reactions
Domains of the thymus
In cortex, thymic epithelial cells presents 2X the
amount of MHC2 molecules as MHC1 molecules. This
determines the ratio of Th to Tc as 2:1.
They present all the alleles in the persons genome: 6
MHC class 1 molecules and 12 different MHC class 2
molecules. This determines that only T cells with a
TCR receptor that recognizes the persons own MHC
survives the cortex.
Delta
Three outcomes with regard to what the TCR
chosen sees:
TCR does not recognize any of your own MHCI
or MHCII molecules
TCR recognizes but reacts to one of your own
MHCI or MHCII molecules by proliferating even
when unoccupied by antigen
TCR recognizes as self one of your own MHCI or
MHCII molecules but does not proliferate to the
unoccupied MHC molecule.
Now those T cells that survive the cortex
move to the medulla,
they upregulate the number and affinity of
their TCRs and become committed as either
CD4 or CD8 positive.
In medulla they express either CD4 or CD8
not both.
Three outcomes with regard to what the TCR
chosen sees:
TCR does not recognize any of your own MHCI
or MHCII molecules (cortex, positive selection)
TCR recognizes but reacts to one of your own
MHCI or MHCII molecules by proliferating even
when unoccupied by antigen (medulla, negative
selection)
TCR recognizes as self one of your own MHCI or
MHCII molecules but does not proliferate to the
unoccupied MHC molecule (only these cells get
.
Routes of entry
antibody mediated
Ig E
antibody mediated
antibody mediated
Ig M or IgG
Ig M or IgG
Immediate
Immediate
Fastest (sec)
4-6 hrs
Immediate
w/i 4-6 hrs
cell mediated
T lymphocyte
Delayed
48-72 hrs.
Type 1 hypersensitivity
• All hypersensitivity reactions require a first
asymptomatic exposure to antigen
• Second exposure manifests a exaggerated and
extensive reaction
• In type one reactions, these are very fast
within secs and usually but not always can
resolve not causing permanent damage. They
can during the reactive phase however cause
death.
Type 1 hypersensitivity
• A. Systemic anaphylaxis
• B. Local Anaphylaxis-atopic allergies
– 1.
– 2.
– 3.
– 4.
Allergic rhinitis 20% of the population
Asthma
Food allergies
Atopic dermatitis
First exposure
All type 1 Rxs.
Second exposure
HS1
A. Systemic anaphylaxis
• Portier and
Richet Nobel
1913
• Dogs with jelly
fish toxins
• Guinea pigs with
penicillin
Systemic Analyphaxis-Shock
• Within secs of second exposure to drugs, venoms or
specific foods (peanuts).
• Mast cells degranulate.
• GI tract –increased fluid (edema), increased peristalsis
= severe diarrhea and vomiting.
• Lungs- this is life threatening . Every time the person
exhales, SMC constrict causing further decreased
diameter of bronchi, increased mucous secretion and
swelling of connective tissue closes airways
completely. Within minutes they cant take a breathe
in = asphyxiation.
Upper and lower respiratory
At multiple sites
Tract,
GI tract, skin reaction.
simultaneouslyGI tract, upper and lower
respiratory tract, skin
Severe
constriction
Severe
permeability
Severe
secretion
Severe
Histamine release
1. Processing of antigen
2. T help that produces a Ig E response
3. 2- 10 X more mast cells
4. Mast cells with 10 x higher affinity
receptors
What is different about an allergic individual and a non-allergic individual.
5. Mast cells with 10-100 x more histamine per cell
6. More and higher histamine receptors on SMC
7. Mast cells with 10 x higher affinity
receptors
If you suspect that you or someone you are with is having an
anaphylactic reaction, inject epinephrine immediately. The shot is given
into the outer thigh and can be administered through light fabric. Rub the
site to improve absorption of the drug. An Epi Pen kit is shown.
Epinephrine antagonist of histamine and causes EC tight junction to reformation and SMC relaxation.
Type 1 hypersensitivity
Systemic anaphylaxis-severe.
• Local Anaphylaxis-mild-severe
– Allergic rhinitis 20% of the population.
hay fever, animal dander.
– Asthma (Extrinsic not Intrinsic)-pollen, dust
mites, fumes, insect products.
– Food allergies-hives, anaphylaxis.
– Atopic dermatitis-fabric softeners, wool.
B. Local anaphylaxis
1. Allergic rhinitis
Milder forms of HS1. Upper airways
only.
Ragweed 16 tons of pollen per sq. mile
Antigens are complex. Enzymes break
them down. 5 fractions 2 are allergens
E and K – 95% of HS1
RA3, RA4 and RA 5 5-20% of HS1
rhinitis
Allergic individuals process the
antigen in a different way.
Animal dander is a protein
deposited on hair.
Upper respiratory only
Upper airways only
Local not systemic Type 1 Hypersensitivity
reactions
The first generation antihistamines (e.g., trade
names Benadryl, Chlor-Trimetron, and Dimetapp)
bind to histamine receptors, preventing the
allergic response. Dosages vary depending on
the medication.
Type 1 hypersensitivity
Systemic anaphylaxis-severe.
Local Anaphylaxis-mild-severe
Allergic rhinitis 20% of the population:
hay fever, animal dander.
– Asthma (Extrinsic not Intrinsic)-pollen, dust
mites, fumes, insect products.
– Food allergies-hives.
– Atopic dermatitis-fabric softeners, wool.
Asthma
• Mild to severe –lower airways .
• Can cause permanent damage because of
eosinophil involvement in lower bronchi.
Eosinophils also possessing high affinity
receptors for Ig E.
• Eosinophils produce leukotrines which recruit
and activate neutrophils to make proteases
that carve up and damage tissue.
Lower bronchi only
Eosinophils cause permanent damage to bronchi
BRONCHODILATORS dilate the small
airways to increase airflow. Long-acting
bronchodilaors are given
prophylactically to prevent asthma
attacks, and may last up to 12-hours.
Rapid-acting bronchodilators have
effects that last 3-4 hours and are used
to relieve a sudden attack. Rapid-acting
bronchodilators may also be used as a
preventative in some cases, as before
exercising to prevent exercise induced
asthma.
ANTI-INFLAMMATORY medications are
used to prevent and/or relieve airway
inflammation, thus reducing the patient's
susceptibility to a sudden attack. Most of
these medications are steroids, although
there are some widely used non-steroidal
anti-inflammatory medications.
The prevalence of asthma has been
increasing since the early 1980s for
all age, sex and racial groups.
• higher among children than
adults
• higher among girls than boys
• higher among blacks than whites
LEUKOTRIENE MODIFIERS are oral
medications that interrupt the body's
allergic response, thus preventing
attacks in some patients. They are more
effective in patients with allergies than in
those with chemical sensitivity.
NEBULIZERS and NEBULIZED
MEDICATIONS are used not only by
EMS and medical facilities, but are not
uncommon in home use. Basically the
same medications as are supplied in
inhalers, nebulization usually results in a
more rapid response to the medications
antibody mediated
Ig E
antibody mediated
antibody mediated
Ig M or IgG
Ig M or IgG
Immediate
Immediate
Fastest (sec)
4-6 hrs
Immediate
w/i 4-6 hrs
cell mediated
T lymphocyte
Delayed
48-72 hrs.
Immediate
6-8 hrs.
6-8 hrs.
48-72 hrs.
Allergic rhinitis
Anaphylaxis
Asthma (extrinsic)
Blood transfusions
rH disease of newborn
Pernicious anemia
Post Strep infection
Arthus reaction
Pigeon Fanciers Syn.
Poison Ivy
Tuberulin Test
Allograft Rejection
Type 1 diabetes
Multiple sclerosis
Blood transfusions
rH disease of newborn
Pernicious anemia
A, B O blood group
antigens are T cell
independent
antigens.
If transfused with
different blood,
immediate
response because
you have been
exposed to A, B due
to symbiotic
microorganisms in
gut possessing
isohemaglutinins
on surface.
Effects of Mis-matched blood
transfusion
• Ig M binds to RBC and complement or innate
cells lyse the RBCs in mass.
• Free hemoglobin goes to kidney and is
converted to bilirubin.
• Bilirubin is toxic and is deposited in skin and
liver and brain capillaries.
• Jaundice, severe anemia, liver failure and
coma can result.
rH disease of the
newborn occurs
Most often
with mothers married to
husbands with
same ABO blood type
as them. Severity only
seen
In rH disease, a Ig G is
produced. How ?
After mother has had a first
Preqnancy whether it goes
to
Term or not.
Dr. Vincent Freda
• Took Sing Sing prisoners (male) and injected
them with different blood types.
• Identified a D antigen, a minor antigen that is
T cell dependent and evokes a Ig G response,
but only if Ig M to major blood group antigens
hasn’t occurred.
• Developed Rhogam , recombinant Ig G to D
antigen. Injected after each pregnancy.
Pernicious
Anemia:
Vitamin B12 cannot be absorbed through
the small intestine unless complexed to
Intrinsic Factor (IF) which transports it
across the intestinal mucosa. Pernicious
anemia (PA) is associated with circulating
antibodies to intrinsic factor (IF). IF
antibodies bind to IF on the surface of gut
epithelial cells and blocks binding of
vitamin B12 to IF in the stomach. This
brings about a deficiency in vitamin B12
that prevents RBC production and thus
causes anemia.
If penicillin becomes bound
to RBC membrane.
Arthus reaction
Post Streptococcal Glomerulonephritis
Pigeon Fanciers Syndrome- excess of
dried pigeon fecal protein.
Farmers Lung- excess of thermophilic
actinomycetes from moldy hay.
Arthus Reaction
Antigen in excess
and in solution when
it binds antibody;
then becomes
associated to tissue.
Tissue damaged by
complement
Poststreptococcal
glomerular nephritis
Rheumatoid arthritis – rheumatoid factor = immune complexes
Poison Ivy
Tuberculin Test
Leprosy
Contact reactions
Leprosy, Tuberculin test
Leprosy
Cannot be grown in the laboratory.
In vivo, it is one of the slowest growing of all organisms and incubations periods
in humans with a minimum of 3-5 years.
The organism is an obligate, intracellular parasite of peripheral nerves, skin cells,
and nasal mucosa.
US Marine
contracting
Leprosy in
Australian
after getting
a tattoo
there.