Ch 4 - Immunopathology Flashcards
1
Q
seasonal conjunctivitis is typically caused by
A
allergies to pollens that are released during a particular time of the year.
2
Q
What is the most common type I hypersensitivity disease in adults?
A
Allergic rhinitis (hay fever)
3
Q
Allergic rhinitis (hay fever) may be caused by;
A
pollen, house dust, animal dandruff, and many other allergens.
4
Q
Antigens inhaled react with what?
A
IgE
5
Q
IgE is attached to
A
basophils in the nasal mucosa
6
Q
Antigen + IgE attached to basophils in the nasal mucosa triggers
A
the release of vasoactive substances stored in cytoplasmic granules.
7
Q
the main mediator released from mast cells?
A
Histamine,
8
Q
Histamine released from mast cells does what?
A
increases the permeability of mucosal vessels, causing edema and sneezing.
9
Q
What are Type III hypersensitivity reactions are characterized by?
A
1) immune complex deposition, 2) complement fixation, 3) localized inflammation.
10
Q
What can give rise to a type III response?
A
Antibody directed against either a circulating antigen or an antigen that is deposited in a tissue
11
Q
What are some diseases that seem to be most clearly attributable to the deposition of immune complexes?
A
1) systemic lupus erythematosus 2) rheumatoid arthritis 3) varieties of glomerulonephritis.
12
Q
How can Streptoccocal infection lead to nephritic syndrome?
A
deposition of antigens and antibodies in glomerular basement membranes
13
Q
clinical features of nephritic syndrome
A
hematuria, oliguria, and hypertension
14
Q
Systemic lupus erythematosus
A
(SLE) is an autoimmune, inflammatory disease that may involve almost any organ
15
Q
What does SLE characteristically affect?
A
the kidneys, joints, serous membranes, and skin.
16
Q
In SLE what are autoantibodies formed against?
A
a variety of self-antigens.
17
Q
What are the most important diagnostic autoantibodies in SLE?
A
those against nuclear antigens
18
Q
What are the autoantibodies in SLE against nuclear antigens that are most important diagnostically?
A
antibody to; 1) double-stranded DNA 2) Sm (Smith) antigen - a soluble nuclear antigen complex that is part of the spliceosome
19
Q
High titers for what two autoantibodies (termed antinuclear antibodies) are nearly pathognomonic for SLE?
A
Those against nuclear antigens - antibody to; 1) double-stranded DNA 2) Sm (Smith) antigen
20
Q
Antibodies to rheumatoid factor are seen in patients with
A
rheumatoid arthritis.
21
Q
Antineutrophil cytoplasmic antibodies are seen in patients with;
A
small vessel vasculitis (e.g., Wegener granulomatosis).
22
Q
Acquired deficiencies of early complement components occur in patients with
A
autoimmune diseases - especially those associated with circulating immune complexes (e.g., systemic lupus erythematosus [SLE]).
23
Q
hypocomplementemia and autoimmune diseases such as SLE
A
Antigen-antibody complexes formed in the circulation during the active stage of these diseases lead to a marked reduction in circulating levels of complement proteins (hypocomplementemia).
24
Q
Scleroderma is
A
an autoimmune disease of connective tissue
25
How is scleroderma similar to graft versus host disease?
Circulating male fetal cells have been demonstrated in blood and blood vessel walls of many women with scleroderma who bore male children many years before the disease began. Accordingly, it has been suggested that scleroderma in these patients is similar
26
Antinuclear antibodies for SLE versus scleroderma.
They are common but are usually present in a lower titer than in patients with SLE.
27
Antibodies virtually specific for scleroderma include:
(1) nucleolar autoantibodies (primarily against RNA polymerase); (2) antibodies to Scl-70, a nonhistone nuclear protein topoisomerase; and (3) anticentromere antibodies, which are associated with the “CREST” variant of the disease.
28
The Scl-70 autoantibody
is most common and specific for the diffuse form of scleroderma and is seen in 70% of patients.
29
Autoantibodies to double-stranded DNA are seen in patients with
SLE.
30
Autoantibodies to SS-A/SS-B are seen in patients with
Sjögren syndrome.
31
Scleroderma is characterized by
1) vasculopathy 2) excessive collagen deposition in the skin and internal organs, such as the lung, gastrointestinal tract, heart, and kidney.
32
Scleroderma disease population.
The disease occurs four times as often in women as in men and mostly in persons aged 25 to 50 years.
33
Progressive systemic sclerosis is characterized by
widespread excessive collagen deposition.
34
In progressive systemic sclerosis there is emerging evidence for what?
the expansion of fibrogenic clones of fibroblasts.
35
In Progressive systemic sclerosis what do the fibrogenic clones display?
augmented procollagen synthesis, including increased circulating levels of type III collagen aminopropeptide. Tissue levels of the other proteins are not significantly altered in patients with scleroderma.
36
Delayed-type hypersensitivity is defined as
a tissue reaction involving lymphocytes and mononuclear phagocytes,
37
What does delayed-type hypersensitivity occur in response to?
a soluble protein antigen and reaches greatest intensity 24 to 48 hours after initiation.
38
What happens in the initial phase for delayed-type hypersensitivity?
foreign protein antigens or chemical ligands interact with accessory cells bearing class II HLA molecules.
39
What happens to protein antigens?
they are actively processed into short peptides within phagolysosomes and are presented on the cell surface in conjunction with the class II HLA molecules.
40
The protein antigens are recognized by?
CD4+ T cells
41
What happens to the CD4+ T cells upon binding to the class II HLA?
they become activated to synthesize an array of cytokines.
42
What do the cytokines released from CD4 activation do?
The cytokines recruit and activate lymphocytes, monocytes, fibroblasts, and other inflammatory cells.
43
Suppressor T cells are
CD8+
44
Class I HLA molecules provide targets for
cell-mediated cytotoxicity.
45
GlyCAM-1 is
a cell adhesion molecule involved in lymphocyte trafficking.
46
What are Type II hypersensitivity reactions mediated by?
Antibodies directed against fixed antigens. For example, preformed antibodies in the patient’s blood attach to foreign antigens (oligosaccharides) on the membranes of the transfused erythrocytes. At sufficient density, bound immunoglobulins fix complement
47
Once activated what does the complement cascade lead to?
destruction of the target cell through formation of a membrane attack complex.
48
Type II hypersensitivity leading to complement-mediated cell lysis occurs in what?
autoimmune hemolytic anemia.
49
Antibody-dependent cell mediated cytotoxicity (ADCC) involves
cytolytic leukocytes that attack antibody-coated target cells.
50
ADCC may be involved in the pathogenesis of
some autoimmune diseases (e.g., autoimmune thyroiditis).
51
Delayed-type hypersensitivity occurs over a period of
days and does not involve preformed antibodies.
52
Humoral immune responses to specific viral antigens involve?
the activation and differentiation of B lymphocytes into antibody-secreting plasma cells.
53
Analogous to T cells, B cells express what?
an antigen-binding receptor, namely mIg.
54
How does the immunoglobulin mIg on the B cell compare to the immunoglobulin that is secreted?
This immunoglobulin bears the same antigen specificity as the soluble immunoglobulin that is ultimately secreted.
55
Class I HLA molecules provide targets for
CD8+ T cells in cell-mediated cytotoxicity.
56
Class II HLA molecules are recognized by
CD4+ T cells, which become activated to synthesize an array of cytokines.
57
Class I molecules of the major histocompatibility complex present what?
foreign peptides and are recognized by cytotoxic T lymphocytes during graft rejection or during cell-mediated killing of virus-infected cells.
58
What expresses class I?
All tissues express class I molecules, whereas class II molecules are displayed primarily on macrophages and B lymphocytes.
59
CD4 and CD8
are cell surface markers of helper and killer T lymphocytes, respectively.
60
GlyCAM-1
facilitates lymphocyte recirculation by providing a receptor for leukocyte attachment to high endothelial venules.
61
Sjögren syndrome (SS) is
an autoimmune disorder
62
Sjögren syndrome (SS) is characterized by
keratoconjunctivitis sicca and xerostomia in the absence of other connective tissue disease.
63
In patients with Sjögren syndrome (SS) what are typically produced?
the production of autoantibodies, particularly antinuclear antibodies directed against DNA or nonhistone proteins, typically occurs in patients with SS.
64
What are found in half of patients with primary SS and what are they associated with?
1) Autoantibodies to soluble nuclear nonhistone proteins, especially the antigens SS-A and SS-B, and 2) are associated with more severe glandular and extraglandular manifestations.
65
In SS are autoantibodies to DNA or histones common?
They are rare.
66
What are autoantibodies to centromere proteins seen in?
the CREST variant of progressive systemic sclerosis.
67
In SS are organ specific antibodies common?
Organ-specific autoantibodies, such as those directed against salivary gland antigens, are distinctly uncommon.
68
Bruton X-linked agammaglobulinemia
congenital disorder that appears in male infants at 5 to 8 months of age,
69
In Bruton X-linked agammaglobulinemia, why does it appear at 5 to 8 months of age?
the period during which maternal antibody levels begin to decline
70
In Bruton X-linked agammaglobulinemia what does the infant suffer from?
1) recurrent pyogenic infections 2) severe hypogammaglobulinemia.
71
In Bruton X-linked agammaglobulinemia where are the mature B cells?
There is an absence of both mature B cells in peripheral blood and plasma cells in lymphoid tissues.
72
In Bruton X-linked agammaglobulinemia where and what is the genetic defect?
Its located on the long arm of the X chromosome, it is an inactivating mutation of the gene for B-cell tyrosine kinase, an enzyme critical to B-lymphocyte maturation.
73
DiGeorge syndrome
is a developmental disorder characterized by thymic and parathyroid aplasia.
74
Wiskott-Aldrich syndrome
an X-linked genetic disease but is characterized by defects in both B-cell and T-cell functions (i.e., humeral and cellular immunity).
75
Hyperacute rejection
occurs within minutes to hours after transplantation.
76
Hyperacute rejection is manifested clinically as
a sudden cessation of urine output, along with fever and pain in the area of the graft site.
77
In hyperacute rejection the immediate rejection is mediated by
preformed antibodies and complement activation products.
78
Are lymphocytes and macrophages associated with acute and chronic graft rejection?
yes
79
Myasthenia gravis is
a type II hypersensitivity disorder caused by antibodies that bind to the acetylcholine receptor.
80
In Myasthenia gravis what do the antibodies interfere with?
the transmission of neural impulses at the neuromuscular junction, causing muscle weakness and easy fatigability.
81
In Myasthenia gravis what are affected?
External ocular and eyelid muscles are most often affected, but the disease is often progressive and may cause death by respiratory muscle paralysis.
82
Autoantibodies to desmoglein-3
they are found in patients with pemphigus vulgaris, an autoimmune blistering skin disorder.
83
Antibodies to the TSH receptor
are seen in patients with Graves hyperthyroidism.
84
Antibodies to calcium channels
are found in patients with Eaton-Lambert syndrome. This paraneoplastic syndrome also manifests as muscle weakness but is usually associated with small cell carcinoma of the lung.
85
Rheumatoid factor
represents multiple antibodies directed against the Fc portion of IgG and is seen in patients with rheumatoid arthritis and many other collagen vascular diseases.
86
The relentless progression of HIV infection is now recognized as
a continuum that extends from an initial asymptomatic state to the immune depletion that characterizes patients with overt AIDS.
87
Patients with AIDS die from
opportunistic infections.
88
The fundamental lesion FOR HIV is?
infection of CD4+ (helper) T lymphocytes, which leads to the depletion of this cell population and impaired immune function.
89
Does HIV infect the monocyte/macrophage lineage?
but infected cells exhibit little if any cytotoxicity.
90
Does HIV affect NK cell activity?
Yes it is also decreased in AIDS. This defect may contribute to the appearance of malignant tumors and the viral infections that plague these patients.
91
In AIDS, the suppression of NK cell activity has been related to what?
a decrease in the number of NK cells and to a reduction in IL-2 levels due to the loss of CD4+ cells.
92
HIV-1
The primary etiologic agent of AIDS, it is an enveloped RNA retrovirus that contains a reverse transcriptase (RNA-dependent DNA polymerase).
93
HIV-1 enters the cytoplasm of what cell?
T lymphocytes
94
What does HIV-1 do after it enters into the cytoplasm of a T lymphocyte?
the virus is uncoated, and its RNA is copied into double-stranded DNA by retroviral reverse transcriptase.
95
For HIV-1, what happens to the DNA derived from the virus?
it is integrated into the host genome by the viral integrase protein, thereby producing the latent proviral form of HIV-1. Viral genes are replicated along with host chromosomes and, therefore, persist for the life of the cell.
96
Immediate-type hypersensitivity is manifested by
a localized or generalized reaction that occurs within minutes after exposure to an antigen or “allergen” to which the person has previously been sensitized.
97
In its generalized and most severe form, what are immediate hypersensitivity reactions associated with?
bronchoconstriction, airway obstruction, and circulatory collapse, as seen in anaphylactic shock.
98
What do Type I hypersensitivity reactions feature the formation of?
IgE antibodies that bind avidly to Fc-epsilon (Fc-å) receptors on mast cells and basophils.
99
What accounts for the term cytophilic antibody?
The high-avidity binding of IgE in Type I hypersensitivity reactions.
100
For Type I hypersensitivity reactions, when is a person sensitized?
Once exposed to a specific allergen that has resulted in the formation of IgE, a person is sensitized.
101
For Type I hypersensitivity reactions what do subsequent responses to the allergen induce?
an immediate release of a cascade of proinflamatory mediators.
102
What are the proinflammatory mediators released in Type I hypersensitivity responsible for?
smooth muscle contraction, edema formation, and the recruitment of eosinophils.
103
Aside for IgE, what other immunoglobulin classes mediates immediate hypersensitivity.
none
104
Graves disease is
a type II hypersensitivity disorder
105
What is graves disease caused by?
antibodies to the TSH receptor on follicular cells of the thyroid.
106
In Graves disease antibody binding to the TSH receptor results in what?
stimulates a release of tetraiodothyronine (T4) and triiodothyronine (T3) from the thyroid into the circulation.
107
In Graves disease what is the effect of Circulating T4 and T3?
suppress TSH production in the pituitary.
108
What is typical of Graves disease?
Sweating, weight loss, and tachycardia are evidence of the hypermetabolism typical of hyperthyroidism. Graves disease also causes exophthalmos.
109
Delayed-type hypersensitivity is seen in patients with
poison ivy and graft rejection.
110
Immune complex disease is caused by
deposition of immune complexes and complement activation.
111
Wiskott-Aldrich syndrome
is a rare syndrome and is characterized by (1) recurrent infections, (2) hemorrhages secondary to thrombocytopenia, and (3) eczema.
112
Wiskott-Aldrich syndrome typically manifests in
boys within the first few months of life as petechiae and recurrent infections (e.g., diarrhea).
113
Wiskott-Aldrich syndrome is caused by
numerous distinct mutations in a gene on the X chromosome that encodes a protein called WASP (Wiskott-Aldrich syndrome protein)
114
Where is WASP expressed?
at high levels in lymphocytes and megakaryocytes.
115
What does WASP bind?
members of the Rho family of GTPases.
116
What does WASP itself control?
the assembly of actin filaments that are required to form microvesicles.
117
Is X-linked agammaglobulinemia of Bruton associated with thrombocytopenia and eczema?
No
118
GVHD
1) GVHD occurs when lymphocytes in the grafted tissue recognize and react to the recipient. 2) GVHD can also occur when an immunodeficient patient is transfused with blood containing HLA-incompatible lymphocytes. 3) The advent of transplantation of bone marrow
119
What are the major organs affected in GVHD?
the skin, gastrointestinal tract, and liver.
120
Clinically, GVHD manifests as what?
rash, diarrhea, abdominal cramps, anemia, and liver dysfunction. None of the other cells mediates GVHD.
121
“Poison ivy” is what type of reaction?
a type IV hypersensitivity reaction to plants of the Rhus genus.
122
Poison ivy (a type IV hypersensitivity reaction) is mediated by what?
This T-lymphocyte–mediated allergic contact dermatitis
123
What does poison ivy present as?
presents as urticaria and bullous eruption. Blisters rupture and heal with crusts, usually without scarring.
124
Deposition of antigluten antibodies occurs in patients with what?
dermatitis herpetiformis.
125
How does IgE-mediated mast cell degranulation relate to the response to poison ivy?
It is part of the response to poison ivy (hypersensitivity reactions overlap), but this immediate response does not explain the pathogenesis of delayed hypersensitivity
126
SCID Severe combined immunodeficiency
is a group of disorders of T and B lymphocytes
127
SCID is characterized by what?
recurrent viral, bacterial, fungal, and protozoal infections.
128
What do many infants with SCID have?
severely reduced volumes of lymphoid tissue and an immature thymus that lacks lymphocytes.
129
About one half of these severely immunodeficient children lack what?
adenosine deaminase (ADA).
130
ADA deficiency causes
the accumulation of intermediate products that are toxic to lymphocytes.
131
What happens to children with ADA deficiency secondary to SCID?
they cannot survive beyond early infancy unless they are raised in a sterile environment (“bubble children”).
132
What do immune complex (type III) hypersensitivity reactions cause?
vasculitis.
133
Antigen-antibody complexes are either formed in what locations?
1) in the circulation and deposited in the tissues 2) formed in situ.
134
What do immune complexes induce?
a localized inflammatory response by fixing complement, which leads to the recruitment of neutrophils and monocytes.
135
What does the vasculitis in patients with polyarteritis nodosa involve?
small to medium-sized muscular arteries.
136
What is the most prominent morphologic feature of the affected artery in polyarteritis nodosa?
an area of fibrinoid necrosis
137
How is the diagnosis for polyarteritis nodosa usually made?
by biopsy of the skin, muscle, peripheral nerves, or the most affected internal organ (ex: kidney).
138
What are some examples of type III hypersensitivity reactions?
They include Henoch-Schönlein purpura (vascular IgA deposits) and vasculitis associated with hepatitis C infection.
139
What is DiGeorge syndrome?
a chromosomal defect that results in developmental anomalies of the branchial (pharyngeal) pouches and organs that develop from these embryonic structures (thymus, parathyroids, and aortic arch).
140
What are the organs that develop from the branchial (pharyngeal) pouches?
thymus, parathyroids, and aortic arch
141
What do children with DiGeorge syndrome present with?
1) These children present with tetany caused by hypoparathyroidism and deficiency of cellular immunity. 2) They also have characteristic facial features (“angry look”).
142
What happens in the absence of a thymus?
T-cell maturation is interrupted at the pre-T stage.
143
DiGeorge syndrome has been corrected by what?
transplanting thymic tissue.
144
MCTD
mixed connective tissue disease has features of other common autoimmune diseases (e.g., SLE and scleroderma) but appears to be distinct.
145
Patients with MTCD typically have autoantibodies to what?
ribonucleoproteins
146
How does MTCD compare to SCID?
Has autoantibodies to ribonucleoproteins but unlike SLE, they do not have antibodies to Sm antigen or double-stranded DNA.
147
Some patients with MCTD develop symptoms of scleroderma or rheumatoid arthritis, what does it suggest?
suggesting that MCTD may be an intermediate stage in a genetically determined progression.
148
Raynaud phenomenon
Intermittent episodes of ischemia of the fingers, marked by pallor, paresthesias, and pain
149
What fraction of patients with systemic lupus erythematosus (SLE) possess elevated concentrations of antiphospholipid antibodies?
One third
150
What does having elevated concentrations of antiphospholipid antibodies in SLE patients predispose them to?
This phenomenon predisposes these patients to thromboembolic complications, including stroke, pulmonary embolism, deep venous thrombosis, and portal vein thrombosis.
151
What is the clinical course of SLE?
It is highly variable and typically exhibits exacerbations and remissions
152
What can be done with mild cases of SLE?
With the recognition of mild forms of the disease, improved antihypertensive medications, and the use of immunosuppressive agents, the overall 10-year survival rate approaches 90%.
153
What is the role of antibodies against clotting factors or fibrinolytic enzymes in the clotting tendency associated with SLE?
They are not involved in the clotting tendency associated with SLE
154
What is the most common primary immunodeficiency syndrome?
Selective IgA deficiency, with an incidence of 1:700 among Europeans.
155
What is the frequency of symptomatic selective IgA deficiency patients?
patients are often asymptomatic
156
What can patients with selective IgA deficiency occasionally present with?
respiratory or gastrointestinal infections of varying severity. They also display a strong predilection for allergies and collagen vascular diseases.
157
What do patients with IgA deficiency have regarding their immunoglobulins?
normal numbers of IgA-bearing B cells, and their varied defects result in an inability to synthesize and secrete IgA subclasses.
158
What is seen in patients with chronic mucocutaneous candidiasis?
They show an increased susceptibility to Candida infections and also may exhibit various endocrine disorders (e.g., hypoparathyroidism and Addison disease).
159
What have transplant rejection reactions been traditionally categorized into?
hyperacute, acute, and chronic rejection based on the clinical tempo of the response and on the mechanisms involved.
160
What is acute rejection characterized by?
an abrupt onset of azotemia and oliguria, which may be associated with fever and graft tenderness.
161
What would a needle biopsy of acute rejection be expected to show?
(1) interstitial infiltrates of lymphocytes and macrophages, (2) edema, (3) lymphocytic tubulitis, and (4) tubular necrosis.
162
What are seen in hyperacute rejection?
Neutrophilic vasculitis and fibrinoid necrosis
163
What are seen in chronic graft rejection?
Arterial intimal thickening, glomerulosclerosis, and tubular atrophy
164
B and T lymphocytes circulate via
the vascular system to secondary lymphoid organs and tissues.
165
What are some of the tissues that B and T lymphocytes circulate to?
Included among these tissues are lymph nodes, mucosa-associated lymphoid tissues, and spleen.
166
High Endothelial Venules (HEV)
In the case of lymph nodes, lymphocyte trafficking occurs through specialized postcapillary venules termed high endothelial venules (HEVs).
167
What do HEVs express?
an array of specific cell adhesion molecules (e.g., CD31) that allow lymphocyte binding and diapedesis.
168
What does the cuboidal shape of HEV cells do?
Reduces the flow-mediated shear forces and specialized intercellular connections facilitate egress of lymphocytes out of the vascular space.
169
What facilitates egress of lymphocytes out of the vascular space?
1) cuboidal shape of the HEV cells reducing the flow mediated shear forces 2) specialized intercellular connections
170
Do afferent and efferent lymphatic channels possess HEVs?
No
171
Where are Hassall corpuscles found?
in the medulla of the thymus
172
Peyer patches
organized lymphoid tissues found in the small intestine
173
What does the HIV-1 genome consist of?
two identical 9.7-kb single strands of RNA enclosed within a core of viral proteins.
174
What is involved in the core of HIV-1?
enveloped by a phospholipid bilayer derived from the host cell membrane, in which are found virally encoded glycoproteins (gp120 and gp41).
175
What genes are characteristic of all replication-competent RNA viruses?
gag, pol, and env genes
176
In addition to the gag, pol, and env genes what else does HIV-1 contain?
six other genes that code for proteins involved in replication.
177
What are the specific target cells for HIV-1?
CD4+ helper T lymphocytes and mononuclear phagocytes, although infection of other cells occurs.
178
What does the HIV envelope glycoprotein gp120 do?
(either on the free virus or on the surface of an infected cell) binds CD4 on the surface of helper T lymphocytes.
179
Regarding HIV, what binds to the CD4?
Gp120 – the envelope glycoprotein
180
What does the binding of gp120 to CD4 allow?
gp41 to insert into the cell membrane of the lymphocyte,
181
gp41
promotes fusion of the viral envelope with the lymphocyte.
182
In addition to gp120 binding and gp41 insertion, what does the entry of HIV-1 into a target cell in vivo require?
viral binding to a coreceptor, â-chemokine receptor 5 (CCR-5).
183
gp41 and gp120 are involved in
viral replication, they are present on the viral envelope.
184
LFA-1
is a member of the leukocyte integrin family that is involved in cell-cell adhesion.
185
In some patients with SCID
lymphocytes fail to develop beyond pre-B cells and pre-T cells.
