Transcript Immune disorders

Immunology
Immunologic Disorders
Chapter 18
Nester 4th. Ed.
Immunological Disorders
The immune system is incredibly efficient.
It protects us from microorganisms, larger
parasites and viruses.
Without immunity we would all die.
Immunological Disorders
Sometimes immunity works to eliminate
the Ag but inappropriately.
Hypersensitivity (tissue damage)
Autoimmune disease
Sometimes it does not work, or some
piece is missing.
Immunodeficiency diseases
Hypersensitivity
An exaggerated immune response
An inappropriate immune response
Occurs in two stages, a sensitization stage
and then the hypersensitivity reaction
4 categories (Table 18.1)
Based on the parts of the immune system
involved
Based on the speed of the response
Type I Hypersensitivity
Mechanism
Sensitization
first exposure to antigen in which IgE is produced
Triggering
second or any subsequent exposure to Ag after
sensitization
Figure 18-1, page 445
Type I Hypersensitivity
Figure 18.1
IgE bound on the surface of mast cells
Chemical mediators
histamine, serotonin, leukotrienes, bradykinins
all lead to:
•
•
•
•
inflammation
smooth muscle contraction leading to airway constriction
smooth muscle contraction of the GI tract
smooth muscle contraction of vessels
Type I Hypersensitivity
Localized Type I Hypersensitivity reactions
Also known as atopic reactions or as
allergies
Allergic rhinitis
hay fever
itching, teary eyes, sneezing, runny nose
histamine activity is blocked by anti-histamine
Type I Hypersensitivity
Localized Type I
Urticaria
hives
wheals, itchy red swellings
one consequence of food allergies
histamine activity is blocked by anti-histamine
Figure 18- 2
Type I Hypersensitivity
Localized Type I
Food allergies
shell fish, wheat, milk protein, etc.
diarrhea
painful cramping
hives
anti-histamine helps as stated previously
Type I Hypersensitivity
Localized Type I
Asthma
mostly airborne allergens
Leukotrienes, prostaglandins and protein
cytokines are the main mediators
anti-histamine will not work
Type I Hypersensitivity
Why do we have IgE?
Mucous membranes have many B-cells
committed to making IgA and IgE
people with allergies have more IgE producing
cells than other people
both of these Ab are needed for protection
against certain bacteria and definitely parasites
Type I Hypersensitivity
The tendency to have allergies is
inherited.
About 20-30 % of the U.S. population has
Type 1 allergies.
There is a direct correlation in increasingly
large allergic populations and pollution in
the western world.
Type I Hypersensitivity
Immunotherapy
 Desensitization or hyposensitization
Inject very small doses of allergen
Do this over a period of months
Gradually increase the dose with time
Increases IgG response
Increases Ts cells
Decreases IgE production
Figure 18.2
Figure 18-3, page 445
Type I Hypersensitivity
Immunotherapy
Antibodies to IgE (anti-IgE)
Monoclonal antibody produced in mouse
Hybrid recombinant molecule rhuMab
(recombinant human Monoclonal antibody)
Type I Hypersensitivity
Generalized Type I hypersensitivity is
anaphylaxis (shock)- rare, serious
Systemic release of histamine and other
mediators
Extensive blood vessel dilation
Decreased organ perfusion
Blood pressure drops dramatically leading to
shock
Fatal in minutes
Bee venom, penicillin (hapten) injection, peanuts
Angioedema in anaphylaxis
Edema of Anaphylaxis
Type II Hypersensitivity
Table 18.1
Response is to a cellular antigen
Foreign antigen
Haptens (some drugs bind to RBC’s)
Mechanisms
Cytotoxic by opsonization or ADCC
Cytolytic by complement fixation
Stimulation or inhibition of cell function
Figure 16.16
Type II Hypersensitivity
Transfusion reaction
Normal RBC’s have many antigens
600 known Ag’s
23 major blood groups
ABO blood group is of most concern
Type II Hypersensitivity
Transfusion reaction
ABO system (Table 18.2)
genes on chromosome 9
A gene product makes A antigen
B gene product makes B antigen
O gene makes neither
AB gene makes A and B antigen
Naturally occurring IgM antibodies
If an ABO mismatch occurs, IgG is made to
the Ag
Blood
Group
Antigens
Antibodies
Can give
blood to
Can
receive
blood
from
A
A
B
A and AB
A and 0
B
B
A
B and AB
B and 0
AB
A and B
None
AB
AB, A, B, 0
0
None
A and B
AB, A, B, 0
0
Type II Hypersensitivity
Hemolytic disease of the newborn
Rhesus (Rh) blood group
Rh+ = D antigen on RBC’s
Rh- = D antigen is missing from RBC’s
Figure 18.4
Type II Hypersensitivity
Hemolytic disease of the newborn
Disease not usually seen until shortly after
birth
mother’s enzymes that removed toxic products of
RBC destruction are gone
36 hours
jaundice
severe anemia
brain damage
death
Type II Hypersensitivity
Hemolytic disease of the newborn
Treatments
exchange transfusions
light treatment
• detoxifies the RBC breakdown products
• 420-480 nm (in the ultra violet range)
RhoGam - anti-Rh antibodies
• given to mom within a few hours of abortion or
delivery
• 24-48 hours is OK but not preferable
Type II Hypersensitivity
Cytotoxic effect by alteration in cell
function
Stimulation of cell function
Grave’s disease of the thyroid gland
• Autoantibody binds to a receptor on the outside of the
cell and increases activity causing hyperthyroidism
Inhibition of cell function
Myasthenia gravis
• Autoantibody against the acetylcholine receptor on the
motor end plate causes muscle weakness
Grave’s disease
Myasthenia Gravis
Type III Hypersensitivity
Immune complex formation
Mechanism- Figure 18-5
Blood clotting
Attracts neutrophils
Type III Hypersensitivity
Immune complex formation
Mechanism- Figure 18-5
Localized reaction- Arthus reaction
Antigen is present in excess over antibody
Produce large complexes that don’t travel far
in circulation
Example is Hypersensitivity pneumonitis such
as Farmer’s Lung.
Type III Hypersensitivity
Generalized reaction is serum sickness
Small soluble complexes since antigen is
in excess over antibody
Most often occurs in response to exposure
to an injected foreign protein or to the
continual exposure to an endogenous
antigen such as in autoimmune diseases
Type III Hypersensitivity
Serum sickness mechanism
Deposited in small vessels
Response is seen a week to 10 days following
injection of a foreign antigen
Glomerulonephritis
Arthritis
Skin rash
Disseminated intravascular coagulation
Fever
Lymphadenopathy
Type IV Hypersensitivity
Delayed hypersensitivity
Slow developing response to antigen
Reaction peaks at 2 to 3 days
Cell mediated response T cells are responsible
Occurs anywhere in the body
Tuberculin skin test (Figure 18.8)
Protein Ag from Mycobacterium tuberculosis
Induration occurs if the person has Ab to the Ag
Induration
Sensitized T cells with specific antigen
Followed by release of cytokines and influx of macrophages
Figure 18-7, page 450
Type IV Hypersensitivity
Contact dermatitis
Poison ivy, poison oak (Figure 18.7)
oils of plants induce the allergy
Nickel, chromium salts
Haptens (Figure 18.8)
Detected by a patch test
Type IV Hypersensitivity
In infectious diseases
Leprosy
Tuberculosis
Leishmaniasis
Herpes simplex
Hepatitis B
Fungus diseases
Type IV Hypersensitivity
Transplant rejection
MHC molecules antigens are involved
Tissue typing looks for a match of Ag’s
between the donor and the recipient.
Immunosuppression is needed in most
transplant situations
cyclosporin
• suppresses T-cells but does not kill them
• has no effect on B-cells
• leaves most parts of the immune system intact
Autoimmune disease
Occurs when recognition of self breaks
down
Multiple possible reasons
certain bacteria and viruses have Ag’s similar
to some of ours
tissue damage that results in the release of
self Ag’s
Examples - Table 18.6
Autoimmune disease
Myasthenia gravis
Ab forms to the acetylcholine receptor
Ab blocks the receptors at the neuromuscular
junction
immune complexes have been found at these
junctions
results in muscle weakness
babies with maternal Ab also suffer muscle
weakness temporarily
Autoimmune disease
Sympathetic ophthalmia
penetrating wound in one eye produces
blindness in the healthy eye
Type IV hypersensitivity
Autoimmune disease
Feeding or oral tolerance - ingestion of Ag
induces tolerance
Local intestinal immune response with
release of cytokines
Down-regulation of antigen receptors
Deletion of immune cells
rheumatoid arthritis - collagen
multiple sclerosis - myelin basic protein
Immunodeficiency
Body can’t make or sustain an adequate
immune response.
Primary - congenital
result from genetic or developmental
abnormalities
Secondary - acquired
result of malignancies, advanced age, certain
infections, immunosuppressive drugs,
malnutrition.
Primary - congenital
Severe combined immunodeficiency
SCID
1 in 500,000 live births
no B or T cells
die at an early age without a bone marrow
transplant
Infantile X-linked agammaglobulinemia
(Burton’s agammaglobulinemia)
boys cannot make immunoglobulins
fine until maternal antibody is gone
Staphylococcal and Streptococcal infections
Primary - congenital
DiGeorge’s syndrome
no thymus therefore no T-cells
susceptible to eukaryotic pathogens, viruses,
fungi, intracellular bacteria, fungi
Selective IgA deficiency
most common primary immunodeficiency
repeated bacterial infections
1 in 333 to 700 people
Primary - congenital
Complement deficiencies
no C3 - infections with bacteria with capsules
and pyogenic bacteria
no C5,6,7,8 - more infections with Neisseria
Chediak-Higashi disease
the lysosomes of phagocytes lack some
enzymes
phagocytized bacteria are not killed
Secondary - acquired
Malnutrition
Lymphoid malignancies
Leukemia
Hodgkin’s disease
Infections
AIDS caused by HIV
Secondary - acquired
Measles virus kills many lymphoid cells
Syphilis, leprosy, and malaria affect T-cells
and macrophages
In multiple myeloma, one B-cell clone
multiplies out of control
makes one kind of Ab in such great
quantities that other Ab needed to fight
infection are not made