Foundations in

Microbiology
Sixth Edition
Chapter 16
Disorders in Immunity
Lecture PowerPoint to accompany
Talaro
Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
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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 dont 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 B-
cell 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) self-
contained; 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.