Transcript Foundations in Microbiology

Lecture PowerPoint to accompany
Foundations in
Microbiology
Sixth Edition
Talaro
Chapter 16
Disorders in Immunity
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
Immunopathology
• Allergy, hypersensitivity – an exaggerated,
misdirected expression of immune responses to
an allergen (antigen)
• Involves the same types of immune reactions as
those at work in protective immunities
• Autoimmunity – abnormal responses to self Ag
• Immunodeficiency – deficiency or loss of
immunity
• Cancer – results from a lack of surveillance
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Type I Hypersensitivity
Two levels of severity:
• Atopy – any chronic local allergy such as
hay fever or asthma
• Anaphylaxis – a systemic, often explosive
reaction that involves airway obstruction
and circulatory collapse
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Contact With Allergens
• Generalized predisposition to allergies is
familial – not to a specific allergy
• Allergy can be affected by age, infection,
and geographic area.
• Atopic allergies may be lifelong or may be
“outgrown”; may also develop later in life.
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Nature of Allergens and Their
Portals of Entry
• Allergens have immunogenic characteristics.
• Typically enter through epithelial portals –
respiratory, gastrointestinal, skin
• Organ of allergic expression may or may not
be the same as the portal of entropy.
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Mechanism of Type I Allergy
Develop in stages:
• Sensitizing dose – on first contact with allergen,
specific B cells form IgE which attache to mast cells
and basophils; generally no signs or symptoms
• Provocative dose - subsequent exposure with the
same allergen binds to the IgE-mast cell complex
• Degranulation releases mediators with physiological
effects such as vasodilation and bronchoconstriction.
• Symptoms are rash, itching, redness, increased
mucous discharge, pain, swelling, and difficulty
breathing.
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Role of Mast Cells and Basophils
• Mast cells are located in the connective tissue
of virtually all organs; high concentration in
lungs, skin, GI and genital tract.
• Basophils circulate in blood and migrate into
tissues.
• Each cell can bind 10,000-40,000 IgE.
• Cytoplasmic granules contain physiologically
active cytokines, histamine, etc.
• Cells degranulate when stimulated by allergen.
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Insert figure 16.3
Cellular reactions
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Chemical Mediators and Allergic
Symptoms
• Act alone or in combination; account for scope
of allergic symptoms
– histamine, serotonin, leukotriene, platelet-activating
factor, prostaglandins, bradykinin
• General targets include: skin, upper respiratory
tract, GI tract, and conjunctiva.
– responses: rashes, itching, redness, rhinitis, sneezing,
diarrhea, shedding tears
• Systemic targets: smooth muscles, mucous
glands, and nervous tissue
– responses: vascular dilation and constriction resulting in
change in blood pressure and respiration
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• Histamine – most profuse and fastest acting;
stimulator of smooth muscle, glands, and
eosinophils
– response to chemical depends on the muscle
location: constricts smooth muscles of small
bronchi, intestines; relaxes vascular smooth
muscles
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Specific Diseases
• Atopic disease – hay fever, rhinitis; seasonal, inhaled
plant pollen or mold
– asthma – severe bronchoconstriction; inhaled allergen
– eczema – dermatitis; ingestion, inhalation, skin contact
• Food allergy – intestinal portal can affect skin and
respiratory tract
– vomiting, diarrhea, abdominal pain; possibly severe
– eczema, hives, rhinitis, asthma, occasionally anaphylaxis
• Drug allergy – common side effect of treatment; any
tissue can be affected; reaction from mild atopy to
fatal anaphylaxis
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Systemic Anaphylaxis
• Sudden respiratory and circulatory disruption
that can be fatal in a few minutes
• Allergen and route are variable.
• Bee stings, antibiotics or serum injection
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Diagnosis of Allergy
• Important to determine if a person is experiencing
allergy or infection
• Skin testing
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Treatment and Prevention
General methods include:
1. Avoiding allergen
2. Use drugs that block the action of the
lymphocytes, mast cells, chemical mediators –
antihistamines.
3. Desensitization therapy – injected allergens
may stimulate the formation of high-levels of
allergen-specific IgG that act to block IgE;
mast cells don’t degranulate
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Type II Hypersensitivity
• Reactions that lyse foreign cells
• Involve antibodies, complement, leading to
lysis of foreign cells
• Transfusion reactions
– ABO blood groups
– Rh factor – hemolytic disease of the newborn
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Human ABO Antigens and Blood Types
• 4 distinct ABO blood groups
• Genetically determined RBC glycoproteins;
inherited as 2 alleles of A, B, or O
• 4 blood types: A, B, AB, or O
– named for dominant antigen(s)
– type O persons lack both A and B antigens
– Tissues other than RBCs also carry A and B
antigens.
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Antibodies Against A and B Antigens
• Serum contains pre-formed antibodies that react
with blood of another antigenic type-agglutination;
potential transfusion complication
• Type A contains Abs that react against B antigens.
• Type B contains Abs that react against A antigens.
• Type O contains Abs that react against A and B
antigens.
• Type AB contains no Abs that react against A or B
antigens.
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Rh Factor and Hemolytic Disease of
the Newborn
• RBC antigen – type results from combination of 2
alleles
• Inheriting one dominant gene results in the production
of the Rh antigen; no pre-formed antibodies exist;
must have exposure.
• Hemolytic Disease of the Newborn (HDN) – an Rh
mother forms antibodies to her Rh+ fetus; usually
requires subsequent exposure to the antigen to be
hemolytic
• Prevention requires the use of passive immunization
with antibodies against the Rh antigen; prevents
sensitization of mother.
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Insert figure 16.12
Development and control of Rh
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Type III Hypersensitivity
• A large quantity of soluble foreign Ag
stimulates Ab that produce small, soluble
Ag-Ab complexes.
• Immune complexes become trapped in
tissues and incite a damaging inflammatory
response.
– arthus reaction – local reaction to series of
injected Ag to same body site
– serum sickness – systemic disease resulting
from repeated injections of foreign proteins
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Type IV Hypersensitivity
• T cell-mediated
• Delayed response to Ag involving activation of
and damage by T cells
• Delayed allergic response – skin response to
allergens – tuberculin skin test, contact dermititis
from plants, metals, cosmetics
• Graft rejection – reaction of cytotoxic T cells
directed against foreign cells of a grafted tissue;
involves recognition of foreign HLA
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T Cells and Organ Transplantation
• Graft/transplantation rejection – host may
reject graft; graft may reject host
• MHC markers of donor tissue (graft) are
different; T cells of the recipient recognize
foreignness.
• Release interleukin-2 which amplifies
helper and cytotoxic T cells which bind to
donor tissue and release lymphokines that
begin the rejection
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Classes of Grafts
Classified according to the degree of MHC
similarity between donor and host:
autograft – recipient also serves as donor
isograft – tissue from identical twin is grafted
allograft – genetically different individuals but of
the same species (humans)
xenograft – individuals of different species
• Rejection can be minimized by tissue matching
HLA antigens, immunosuppressive drugs, and
use of tissue that does not provoke a type IV
response.
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Autoimmunity
• In certain type II & III hypersensitivities, the
immune system has lost tolerance to autoantigens
and forms autoantibodies and sensitized T cells
against them.
• More common in females
• Disruption of function can be systemic or organic
specific:
–
–
–
–
–
systemic lupus erythematosus
rheumatoid arthritis
endocrine autoimmunities
myasthenia gravis
multiple sclerosis
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Immunodeficiency Diseases
• Components of the immune response system are
absent. Deficiencies involve B and T cells,
phagocytes, and complement.
• 2 general categories:
– primary immunodeficiency – congenital;
usually genetic errors
– secondary diseases – acquired after birth;
caused by natural or artificial agents
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• Primary immunodeficiency - lack of Bcell and/or T cell activity
– B cell defect – agammaglobulinemia – patient
lacks antibodies
– T cell defect – thymus is missing or abnormal
– severe combined immunodeficiency (SCID)
- both limbs of lymphocyte system are missing
or defective; no adaptive immune response
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• Secondary diseases - due to damage after
birth
– caused by: infection, organic disease,
chemotherapy, or radiation
– AIDS most common – T helper cells are
targeted; numerous opportunistic infections and
cancers
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The Immune System and Cancer
• Overgrowth of abnormal tissue arises due to
malfunction of immune surveillance.
• Tumors may be benign (nonspreading) selfcontained; or malignant that spreads from tissue
of origin to other sites.
• Cancers occur in nearly every cell type.
• Appear to have genetic alteration that transforms a
normal cell
• Possible causes include: errors in mitosis, genetic
damage, activation of oncogenes, or retroviruses.
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