CHAPTER 4 - DISEASES Flashcards
(232 cards)
1
Q
A breakdown in any part of what can lead to disease?
A
the immune mechanism
2
Q
Disorders with an immunologic origin can involve what?
A
progenitor cells phagocytosis T cells B cells or complement
3
Q
Immunologic disorders can be divided into what processes?
A
primary and acquired or secondary
4
Q
Primary immunodeficiency is what?
A
dysfunction in the immune organ itself
5
Q
Acquired or secondary immunodeficiency is what?
A
disease or therapy causing an immune defect
6
Q
What is discussed separately in Chapter 25 due to its complexity and contemporary importance?
A
AIDS
7
Q
Other immunoproliferative and autoimmune disorders are discussed in what Chapters?
A
27 to 30
8
Q
Immunodeficiency disorders may be caused by defects in what?
A
the quality or quantity of lymphocytes
9
Q
Immunodeficiency disorders may be what?
A
congenital or acquired
10
Q
These conditions may be what?
A
combined disorders or may involve T cells or B cells
11
Q
Primary immunodeficiencies (PID) are what?
A
rare genetic disorders of the innate and adaptive immune system
12
Q
Classic primary immunodeficiency disorders (PIDs) are usually what?
A
monogenic (mendelian) disorders affecting host defenses
13
Q
How many clinical phenotypes of PID have been described?
A
More than 200
14
Q
How many different gene mutations have been identified which cause impairment in the differentiation and/or function of immune cells with different degrees of severity?
A
Over 120
15
Q
Diseases associated with a primary defect in the immune response are comprised of what?
A
about 40% T cell disorders 50% B cell disorders 6% phagocytic abnormalities and 4% complement alterations
16
Q
The most common T cell deficiency states are those associated with what?
A
a concurrent B cell abnormality
17
Q
Primary immunodeficiency disorders are predominantly seen in whom?
A
children younger than 5 years (75%)
18
Q
What is a therapeutic strategy for the treatment of several forms of primary immunodeficiency?
A
Gene therapy with hematopoietic stem cells (HSC)
19
Q
Current approaches for gene therapy use what?
A
gene transfer of the therapeutic gene into autologus HSC by retroviral vector-mediated gene transfer
20
Q
What diseases has this method been successful in treating?
A
severe combined immunodeficiencies (SCID-1) and chronic granulomatous disease (CGD)
21
Q
What syndrome is another good candidate for gene therapy treatment?
A
Wiskott-Aldrich syndrome
22
Q
What is DiGeorge’s Syndrome?
A
A congenital anomaly that represents faulty embryogenesis of the endodermal derivation of the third and fourth pharyngeal pouches which results in aplasia of the parathyroid and thymus glands
23
Q
At autopsy what may be found in ectopic locations?
A
parathyroid and vestigial thymus glands
24
Q
The newborn with DiGeorge’s syndrome may exhibit what?
A
various facial and vascular anomalies collectively referred to as pharyngeal pouch syndrome
25
In addition to the established embryonic cause of DiGeorge’s syndrome what has been suggested as a cause of this process?
a nutrient (zinc) deficiency in utero
26
Initial manifestations of DiGeorge’s syndrome can include what?
hypocalcemic tetany unusual facies and congenital heart defects
27
What infections does an increased susceptibility result from in DiGeorge's syndrome?
viral fungal and disseminated bacterial infections
28
Infants with DiGeorge's syndrome usually die of what?
sepsis during the first year of life
29
What does peripheral lymphoid tissue appear to be in DiGeorge's syndrome?
normal except for the depletion of T cells in thymus-dependent zones
30
In the circulating blood of patients with DiGeorge's syndrome what is generally present?
lymphopenia
31
In the circulating blood of patients with DiGeorge's syndrome what is present due to a decrease in CD8+ cells?
an abnormally high CD4+/CD8+ ratio
32
Most patients with DiGeorge’s syndrome have a decreased percentage of cells expressing what antigen?
CD3+ (mature T cell)
33
Lymphocytic responsiveness to antigenic and mitogenic stimulation in patients with DiGeorge's syndrome can be what?
absent reduced or normal depending on the degree of thymic deficiency
34
Cell-mediated immune reactions such as delayed hypersensitivity and skin allograft rejections in patients with DiGeorge's syndrome are what?
absent or feeble
35
What are serum Ig concentrations in patients with DiGeorge's syndrome?
near normal
36
Levels of what may be diminished in patients with DiGeorge's syndrome?
IgA
37
Levels of what may be elevated in patients with DiGeorge's syndrome?
IgE
38
Antibody response to primary antigenic stimulation in patients with DiGeorge's syndrome may be what?
unimpaired
39
What is Nezelof Syndrome?
Cellular Immunodeficiency With Immunoglobulins
40
What kind of inheritance is often seen in Nezelof syndrome?
An autosomal recessive pattern
41
The defect in Nezelof syndrome appears to exist on what?
chromosome 14q13.1
42
What PID is most likely to be confused with AIDS in the pediatric age group?
Nezelof syndrome
43
Infants with Nezelof syndrome have what?
failure to thrive recurrent or chronic pulmonary infections oral or cutaneous candidiasis chronic diarrhea recurrent skin infections gram-negative sepsis urinary tract infections and severe varicella
44
Nezelof syndrome is characterized by what?
lymphopenia neutropenia and eosinophilia
45
In addition to blood abnormalities what is observed in Nezelof syndrome?
diminished lymphoid tissue and abnormal thymus architecture
46
What are Peripheral lymphoid tissues like in Nezelof syndrome?
hypoplastic and demonstrate paracortical lymphocyte depletion
47
Lymphocyte responses in patients with Nezelof syndrome to what are profoundly depressed but not totally absent?
mitogens antigens and allogeneic cells
48
Serum levels of what are normal or increased in Nezelof syndrome?
most of the five Ig classes
49
Antibody-forming capacity has been reported as normal in what fraction of Nezelof syndrome cases?
one third
50
Severe combined immunodeficiency (SCID) is caused by what?
the inappropriate development of progenitor cells into lymphocyte precursors
51
What kind of disorder is SCID?
hereditary and invariably fatal disorder in infants
52
SCID results from what?
the lack of both T and B cells and the consequent inability to synthesize antibody
53
Mutations in what have been shown to cause X-linked SCID in humans?
the IL-2 receptor complex a hematopoietic growth factor
54
What modes of inheritance are known for SCID?
autosomal recessive and X-linked recessive
55
What form of SCID is thought to be the most common in the United States?
X-linked recessive
56
What percentage of patients with autosomal SCID have a concomitant deficiency of adenosine deaminase (ADA)?
0.5
57
ADA converts what to what?
adenosine to inosine
58
Analysis by complementary (copy) DNA (cDNA) probe has revealed that the deficiency results from what?
a hereditable point mutation in the ADA gene
59
Another variant with a severe deficiency in T cell immunity but normal B cell concentrations is associated with what?
purine nucleotide phosphorylase deficiency
60
What are the two main forms of defective expression of MHC antigens?
MHC class I antigen deficiency (bare lymphocyte syndrome) and MHC class I antigen deficiency plus the absence of class II antigens
61
Patient lymphocytes with defective expression of MHC antigens cannot be typed by what?
standard serologic cytotoxicity tests
62
What initial manifestations are seen in SCID?
repeated debilitating infections beginning within the first 6 months of life
63
What are these infections dominated by?
bacterial viral and fungal infections of the respiratory and intestinal systems and skin
64
Infants with SCID usually die from what?
lung abscesses Pneumocystis pneumonitis or a common viral disorder such as chickenpox or measles
65
What happens to the thymus and other lymphoid organs in SCID?
they are severely hypoplastic
66
What happens to the bone marrow in SCID?
it is devoid of lymphoblasts lymphocytes and plasma cells
67
What happens to lymphoid tissues in SCID?
lymphocytes are also absent
68
What kind of features are present in SCID?
Variable hypogammaglobulinemia with decreased serum IgM and IgA levels and poor to absent antibody production
69
What is detectable early in infancy in SCID?
Moderate lymphocytopenia
70
What happens to T cell functions in SCID?
they are decreased
71
What cells are absent from the circulating blood in SCID?
CD4+ CD8+ or CD3+ cells
72
What is usually normal in SCID?
the percentage of B cells
73
Patients with what form of SCID usually appear similar to those with the autosomal recessive form?
X-linked
74
What do patients with the X-linked form of SCID tend to have?
an increased percentage of B cells
75
The defect in the X-linked form of SCID affects what cells?
B-lineage cells as well as T-lineage cells
76
Chronic mucocutaneous candidiasis (CMC) results from what?
a primary defect in cell-mediated immunity
77
In CMC what do T cells specifically fail to recognize?
only the Candida antigen
78
Patients with CMC usually survive to when?
adulthood
79
The characteristic manifestation of CMC is what?
Candida infection of the mucous membranes scalp skin and nails
80
What abnormalities are frequently associated with fungal manifestations in CMC?
Endocrine abnormalities often polyendocrinopathies
81
What has been reported in patients with CMC?
Sudden death from adrenal insufficiency
82
Patients with CMC demonstrate normal skin reactions to testing with what?
all antigens except Candida
83
Because the primary function of B cells is to do what?
produce antibody
84
What is the major clinical manifestation of a B cell deficiency?
an increased susceptibility to severe bacterial infections
85
Selective IgA deficiency is what?
the most common B cell disorder affecting 1 in 400 to 800 persons
86
Because IgA is the primary immunoglobulin in secretions a deficiency contributes to what?
pulmonary infections gastrointestinal (GI) disorders and allergic respiratory disorders
87
What percentage of selective IgA deficiency cases are autoimmune in nature?
0.5
88
What autoimmune diseases are associated with Ig deficiencies?
rheumatoid arthritis (RA) systemic lupus erythematosus (SLE) thyroiditis and pernicious anemia
89
What is Bruton’s X-Linked Agammaglobulinemia?
a classic example of an X-linked agammaglobulinemia in which a disease-causing variant in the gene coding for Bruton’s tyrosine kinase (BTK) leads to the arrest of B cell development at the pre–B cell stage
90
X-linked agammaglobulinemia occurs primarily in whom?
young boys but scattered cases have been identified in girls
91
When do manifestations of X-linked agammaglobulinemia begin?
in the first or second year of life
92
Why does Hypersusceptibility to infection not develop until 9 to 12 months after birth in X-linked agammaglobulinemia?
because of passive protection by residual maternal immunoglobulin
93
Thereafter patients with X-linked agammaglobulinemia repeatedly acquire infections with what?
high-grade extracellular pyogenic organisms such as streptococci
94
This disorder is characterized by what?
sinopulmonary and central nervous system (CNS) infectious episodes and severe septicemia
95
What are patients with X-linked agammaglobulinemia not abnormally susceptible to?
common viral infections (excluding fulminant hepatitis) enterococci or most gram-negative organisms
96
What infections are not usually present in X-linked agammaglobulinemia?
Chronic fungal infections
97
What autoimmune phenomenon has been associated with X-linked agammaglobulinemia?
a juvenile RA type of disease
98
In addition patients with X-linked agammaglobulinemia are highly vulnerable to what?
a malignant form of dermatomyositis that eventually involves destructive T cell infiltration surrounding the small vessels of the CNS
99
In addition to infections and connective tissue disorders what other disorders do agammaglobulinemic patients have?
hemolytic anemia drug eruptions atopic eczema allergic rhinitis and asthma
100
The diagnosis of X-linked agammaglobulinemia is suspected if what?
serum concentrations of IgG IgA and IgM are notably below the appropriate level for the patient’s age
101
What tests are useful in distinguishing X-linked agammaglobulinemia from transient hypogammaglobulinemia of infancy?
tests for natural antibodies to blood group substances and for antibodies to antigens given during standard courses of immunization (e.g. diphtheria)
102
What is the status of B cells in X-linked agammaglobulinemia?
almost absent from bone marrow and lymphoid tissues
103
What is usually noted regarding peripheral B lymphocytes in X-linked agammaglobulinemia?
a deficiency or absence
104
If present what is the state of B cells in X-linked agammaglobulinemia?
unresponsive to T cells and incapable of antibody synthesis or secretion
105
What is the status of surface immunoglobulins in X-linked agammaglobulinemia?
absent
106
What is the status of CD3+ and CD8+ cells in X-linked agammaglobulinemia?
normal numbers
107
What is the status of CD4+ cells in X-linked agammaglobulinemia?
many have normal numbers
108
What is the status of T cell function in male children with X-linked agammaglobulinemia?
normal
109
Therefore what mechanisms are intact in male children with X-linked agammaglobulinemia?
homograft rejection
110
What reaction can be elicited in male children with X-linked agammaglobulinemia?
delayed-hypersensitivity reaction for both tuberculin and skin contact types
111
What is Common variable immunodeficiency (CVID)?
a form of primary acquired agammaglobulinemia occurring equally in males and females
112
The cause of CVID seems to be what?
heterogeneous with abnormalities of B cell maturation antibody production antibody secretion or T cell regulation
113
What has been reported in families with CVID?
family clusters in which first-degree relatives of patients with selective IgA deficiency have a high incidence of abnormal Ig concentration autoantibodies autoimmune disease and malignant neoplasms
114
Findings of what have suggested that the susceptibility gene(s) is (are) on chromosome 6 in CVID?
rare alleles or deletions of MHC class III genes in patients with IgA deficiency of CVID
115
When does CVID usually manifest?
in the second or third decade of life
116
What signs and symptoms are included in CVID?
frequent sinopulmonary infections diarrhea endocrine and autoimmune disorders and malabsorption (e.g. of vitamin B12)
117
What infection is also prevalent in CVID?
Intestinal giardiasis
118
What is thought to represent the most common and well-defined type of PID?
Both the decreased concentration of immunoglobulins and near absence of serum and secretory IgA
119
What does the pattern of inheritance suggest in CVID?
that an autosomal function of antibodies is usually compromised
120
What is the number of B cells like in CVID?
typically normal or mildly depressed
121
Despite a normal number of circulating Ig-bearing B lymphocytes and the presence of lymphoid cortical follicles what happens in CVID?
blood lymphocytes do not differentiate into Ig-producing cells
122
In most patients with CVID the defect appears to be what?
intrinsic to the B cell
123
The primary defect in Ig synthesis in CVID may be caused by what?
the absence or dysfunction of CD4+ cells or by increased CD8+ supressor cell activity
124
Therefore what are impaired by the interaction between helper and suppressor T cell subsets in CVID?
cellular immunity and Ig production
125
What is the state of plasma cells in lymph nodes in CVID?
lack plasma cells but may show striking follicular hyperplasia
126
What may be normal in the total IgG level in CVID?
a subclass (usually IgG2 or IgG3)
127
What may be detectable in CVID but IgM levels may be elevated?
Both IgA and IgM
128
In addition what may some patients with CVID have?
thymoma and refractory anemia
129
Some patients have deficiencies of what despite a normal total IgG serum concentration?
one or more subclasses of IgG
130
Most of those with absent or very low concentrations of IgG2 have been what?
patients with selective IgA deficiency
131
What is the cause of Selective Immunoglobulin A Deficiency?
An isolated absence mode is often seen in pedigrees of individuals with CVID. IgA deficiency has been noted to evolve into CVID and rare alleles and deletions of MHC class III genes in both conditions suggest a common basis
132
Selective Immunoglobulin A Deficiency is typically associated with what?
poor health.
133
What infections occur predominantly in Selective Immunoglobulin A Deficiency?
in the respiratory gastrointestinal (GI) and urogenital tracts
134
Is there any clear evidence that patients with Selective Immunoglobulin A Deficiency have any increased susceptibility to viral agents?
No
135
IgA deficiency has been noted in patients treated with what?
phenytoin sulfasalazine penicillamine and gold
136
As many as what percentage of patients with selective IgA deficiency demonstrate antibodies to IgA?
0.44
137
Severe or fatal what reactions can occur after IV administration of blood products containing IgA and anti-IgA antibodies (particularly IgE anti-IgA antibodies)?
anaphylactic
138
What is a sex-linked mode of inheritance that has been noted in some pedigrees?
Immunodeficiency With Elevated Immunoglobulin M (Hyper-IgM)
139
The abnormal gene in the X-linked type of Immunodeficiency With Elevated Immunoglobulin M (Hyper-IgM) has been localized to what?
Xq24-Xq27
140
Patients with hyper-IgM defect become symptomatic when?
during the first or second year of life
141
Patients with hyper-IgM defect becomes symptomatic with what?
recurrent pyogenic infections including otitis media sinusitis pneumonia and tonsillitis.
142
What other conditions have been observed in patients with hyper-IgM defect?
Hemolytic anemia and thrombocytopenia
143
What is a common feature of patients with hyper-IgM defect?
Transient persistent or cyclic neutropenia
144
What is characterized by extremely low concentrations of IgG and IgA and most frequently greatly elevated concentrations of polyclonal IgM?
Hyper-IgM
145
What numbers of IgM and IgD B lymphocytes have been observed in patients with hyper-IgM defect?
Normal or slightly reduced numbers
146
Unlike patients with Bruton’s X-linked agammaglobulinemia or CVID patients with transient hypogammaglobulinemia of infancy can do what?
synthesize antibodies to A and B erythrocyte antigens if they lack the antigen(s) and to diphtheria and tetanus toxoids
147
When does antibody production usually occur in patients with transient hypogammaglobulinemia of infancy?
by 6 to 11 months of age
148
What does this antibody production occur before?
Ig levels become normal
149
What is X-Linked Lymphoproliferative Disease (Duncan’s Disease) caused by?
a recessive trait
150
The defective gene for X-Linked Lymphoproliferative Disease (Duncan’s Disease) has been localized to what region?
Xq26-Xq27
151
What is the disease characterized by?
an inadequate immune reaction to infection with Epstein-Barr virus (EBV )
152
What happens to infected patients?
they are apparently healthy until they experience infectious mononucleosis
153
What happened to two thirds of more than 100 patients studied with X-Linked Lymphoproliferative Disease (Duncan’s Disease)?
died of overwhelming EBV-induced B cell proliferation during mononucleosis
154
What did most patients surviving the primary infection with X-Linked Lymphoproliferative Disease (Duncan’s Disease) develop?
hypogammaglobulinemia and/or B cell lymphomas
155
What has been noted in affected patients with X-Linked Lymphoproliferative Disease (Duncan’s Disease)?
A marked impairment in the production of antibodies to the EBV nucleus
156
In contrast what ranges from zero to extremely elevated in patients with X-Linked Lymphoproliferative Disease (Duncan’s Disease)?
titers of antibodies to the viral capsid antigen
157
What has been low in many patients with X-Linked Lymphoproliferative Disease (Duncan’s Disease)?
Antibody-dependent cell-mediated cytotoxicity against EBV-infected cells
158
What cell function is also depressed in patients with X-Linked Lymphoproliferative Disease (Duncan’s Disease)?
NK cell function
159
What is there also a deficiency in patients with X-Linked Lymphoproliferative Disease (Duncan’s Disease)?
long-lived T cell immunity to EBV
160
What is the cause of Wiskott-Aldrich Syndrome?
mutation of the gene encoding Wiskott-Aldrich syndrome protein (WASp)
161
What does Wiskott-Aldrich syndrome protein (WASp) play a critical role in?
actin polymerization in blood cells
162
The mutated gene for Wiskott-Aldrich Syndrome is expressed where?
uniquely in hematopoietic cells
163
What is Wiskott-Aldrich syndrome characterized by?
thrombocytopenic purpura increased susceptibility to infection and eczema (atopic dermatitis)
164
What is the common age of survival of boys with Wiskott-Aldrich syndrome?
rarely survive beyond 10 years of age
165
What are common in Wiskott-Aldrich syndrome?
Thrombocytopenia and bleeding
166
What are the platelets like in patients with Wiskott-Aldrich Syndrome?
small with an intrinsic defect
167
What do patients with Wiskott-Aldrich Syndrome usually die from?
sepsis hemorrhage or malignancy
168
What tends to develop in Wiskott-Aldrich Syndrome?
autoimmune disease
169
What leads to a defect in cellular immunity and the attrition of T cell populations from the lymph nodes and spleen in Wiskott-Aldrich Syndrome?
Progressive deterioration of the thymus
170
What is manifested in the blood in patients with Wiskott-Aldrich Syndrome?
Decreased numbers of T cells and alteration in the normal T4:T8 ratio of lymphocytes
171
What are serum levels like in Wiskott-Aldrich Syndrome?
low IgM usually normal IgG normal or elevated IgA and usually elevated IgE
172
What do the lymph nodes and spleen of WAS patients show?
relative depletion of lymphocytes from T cell areas
173
What is characteristic of Wiskott-Aldrich Syndrome and may explain the defective antibody responses particularly to polysaccharide antigens?
Depletion of the splenic and circulating marginal zone B cells
174
What kind of disorder is Hereditary Ataxia-Telangiectasia?
autosomal recessive
175
What does Hereditary Ataxia-Telangiectasia apparently result from?
the coexistence of a T cell deficiency with a defect in DNA repair which leads to extreme nonrandom chromosomal instability
176
What sites are included in the chromosomal breakage in Hereditary Ataxia-Telangiectasia?
chromosomes 7 and 14
177
What is characterized by ataxia and choreoathetosis in infancy?
Ataxia-telangiectasia
178
What appears on exposed oculocutaneous surfaces during childhood in Ataxia-telangiectasia?
Multiple telangiectases
179
What high incidence is also seen in Ataxia-telangiectasia?
malignancy (e.g. lymphoma)
180
What do children with Ataxia-telangiectasia eventually die of?
respiratory insufficiency and sepsis
181
What is present in the thymus in Ataxia-telangiectasia?
hypoplastic or dysplastic
182
What zones of the lymph nodes are void of cells in Ataxia-telangiectasia?
the thymus-dependent zones
183
About what percentage of patients lack serum and secretory IgA in Ataxia-telangiectasia?
0.8
184
What symptoms result from in Ataxia-telangiectasia?
a concomitant T cell deficiency deficiency of DNA repair and disordered IgG synthesis
185
What inheritance does Hyperimmunoglobulinemia E Syndrome have?
a presumed autosomal dominant pattern
186
What is a relatively rare PID characterized by recurrent severe staphylococcal abscesses?
Hyperimmunoglobulinemia E Syndrome
187
From what point have patients with Hyperimmunoglobulinemia E Syndrome had histories of staphylococcal abscesses involving the skin lungs joints and other sites?
from infancy
188
What develop as a result of the recurrent pneumonias in Hyperimmunoglobulinemia E Syndrome?
persistent pneumatoceles
189
What also occurs in Hyperimmunoglobulinemia E Syndrome?
Pruritic dermatitis
190
Patients with Hyperimmunoglobulinemia E Syndrome have elevated levels of what?
serum IgE and IgD
191
Patients with Hyperimmunoglobulinemia E Syndrome usually have what concentrations of IgG IgA and IgM?
normal
192
What are demonstrated in patients with Hyperimmunoglobulinemia E Syndrome?
Poor antibody and cell-mediated responses to neoantigens
193
In addition what has been noted in patients with Hyperimmunoglobulinemia E Syndrome?
a decreased percentage of T cells with the memory receptor CD45RO
194
What have some patients with defective activation of T cells experienced?
Defective surface expression of the CD3-TCR complex caused by mutation in the gene encoding the CD3 γ subunit Defective signal transduction from the TCR to intracellular metabolic pathways and Pretranslational defect in IL-2 or other cytokine production
195
What characterizes these conditions?
the presence of T cells that appear phenotypically normal but fail to proliferate or produce cytokines in response to stimulation with mitogens antigens or other signals delivered to the T cell antigen receptor
196
What do patients’ symptoms resemble?
those of other T cell–deficient individuals
197
What may patients with severe T cell activation defects clinically resemble?
patients with SCID
198
What do several PIDs involve?
the complement system and phagocytic cells
199
These deficiencies are what in origin?
genetic
200
Unusual susceptibility to infection is characteristic of some of these components particularly deficiencies involving what?
C3 C5 C6 and C7
201
What is a functional deficiency of polymorphonuclear neutrophil (PMN) leukocytes?
chronic granulomatous disease (CGD)
202
When does this fatal syndrome usually begin?
with the onset of symptoms during the first year of life
203
What can result from a disease process that causes a defect in normal immune function?
a secondary immunodeficiency
204
What do patients with secondary immunodeficiencies have an increased susceptibility to?
infections as seen in the PIDs
205
What are major causes of secondary immunodeficiencies?
Immunosuppressive agents and burns
206
In varying degrees what have immunosuppressive agents been demonstrated to affect?
every component of the immune response
207
What is a common complication in burn patients who survive the initial period of hemodynamic shock?
septicemia
208
What mechanism seems most critical in thermal injury?
disruption of the skin
209
However what else has been observed in burn patients?
interference with phagocytosis and deficiencies of serum Ig and complement levels
210
What can the nature of the antigen or the genetic makeup of the host cause?
alterations of the immune response that can be injurious and lead to immune-mediated disease
211
In these disorders what is heightened prolonged or inappropriate?
the immune response
212
What is a major concern?
allergic reactions
213
What are allergic reactions characterized by?
an immediate response on exposure to an offending antigen and the release of mediators (e.g. histamine leukotrienes prostaglandins) capable of initiating signs and symptoms
214
Although allergic reactions are associated with what not all allergic reactions are what?-IgE
IgE-mediated
215
What has been shown to release complement C3a and C5a anaphylatoxins which are capable of producing similar reactions?
Complement activation by immune complexes or through the alternative complement pathway
216
Autoimmune disease is thought to be caused by what?
antibody or T cell sensitization with autologous self-antigens
217
Postulated mechanisms of this process include what?
Altered antigen or neoantigen and Shared or cross-reactive antigens
218
What may these antigens be created by?
chemical physical or biologic processes
219
What is an example of this process occurring in RBCs?
Hemolytic anemia caused by a drug interaction
220
Evidence has suggested that what occurs through this mechanism?
poststreptococcal disease
221
What is Autoimmune Lymphoproliferative Syndrome (ALPS)?
a disease in which a genetic defect in programmed cell death or apoptosis leads to breakdown of lymphocyte homeostasis and normal immunologic tolerance
222
ALPS is what?
the first pediatric syndrome described in which the primary defect is in apoptosis
223
Defective apoptosis in lymphocytes leads to what?
accumulation of these cells in the lymphoid organs after they would normally be eliminated
224
As a result what happens?
cells with autoimmune potential are unchecked and can induce a variety of autoimmune diseases
225
What is the risk increased for?
malignant transformation to lymphoma
226
Patients with ALPS have what?
chronic enlargement of the spleen and lymph nodes various manifestations of autoimmunity and elevation of a normally rare population of double-negative T cells (DNTs)
227
When lymphocytes from ALPS patients are cultured in vitro what happens?
they are resistant to apoptosis as compared with cells from healthy controls
228
Most ALPS patients have mutations in what gene?
a TNF receptor gene that is a member of a superfamily (TNFRSF6)
229
This gene encodes what?
the cell surface receptor for the major apoptosis pathway in mature lymphocytes
230
What are other names for this receptor?
Fas
231
What is the Fas apoptotic pathway important for?
eliminating excess T cells after they have been activated and also eliminating antigen-driven and autoreactive T cell clones
232
Fas is what that initiates a proteolytic cascade leading to chromosomal DNA degradation and cell death when engaged by trimeric Fas ligand (FasL)?
a functional trimer residing at the cell membrane
