Diseases of the Immune System Flashcards
1
Q
What is the principal morphologic manifestation of immune complex injury (i.e. injury from type III hypersensitivity rxn)?
A
Acute vasculitis with associated necrosis.
Necrotic tissue appears fibrinoid in histologic slides (fibrinoid necrosis)
2
Q
Isotype switching is induced by what cytokines?
A
IFN-Υ
IL-4
3
Q
Immune-complex mediated diseases tend to be systemic, but often prefernetially involve what areas of the body?
A
Kidneys
Joints
Small blood vessels
4
Q
In the spleen, where are B cells and T cells located?
A
B cells located within follicles
T cells are concentrated in periarteriolar sheaths surrounding small arterioles
5
Q
Where are TLRs located and what are their functions?
A
In the plasma membrane and endosomal vesicles
Recognize different sets of microbes
6
Q
What is the clinical presentation of a patient who has progressed to the development of AIDS
A
Fever
Fatigue
Weight loss
Diarrhea
Opportunistic infections
Secondary neoplasms
Neurological deficits
7
Q
Function of type I interferons in the antiviral defense initiated by innate immunity
A
Act on infected and uninfected cells to activate enzymes that degrade viral nucleic acids and inhibit viral replication, inducing the antiviral state
8
Q
What accounts for the majority of deaths in untreated AIDS patients?
A
Opportunistic infections
9
Q
What type of mutation in TLRs is associated with rare but serious immunodeficiency syndromes?
A
Germline loss-of-function mutation
10
Q
Clinical manifestations of DiGeorge syndrome
A
Facial abnl
Cleft palate
Tetany 2/2 hypocalcemia
Immune deficiency 2/2 T cell deficiency as a result of thymic hypoplasia
11
Q
Type I hypersensitivity rxns have two phases, what are they?
A
Immediate reaction
Late-phase reaction
12
Q
infants affected by SCID present with
A
thrush, diaper rash and failure to thrive
13
Q
How does UV irradiation exacerbate SLE in certain individuals?
A
UV light may induce apoptosis in cells
May stimulate keratinocytes to produce IL-1
14
Q
How do the two types of dendritic cells help to maintain the HIV infection?
A
Mucosal dendritic cells are used to transport infection to lymph nodes
In the lymph nodes, follicular dendritic cells act as additional reservoirs of infection
15
Q
Drug-incuced lupus has what positive ab test?
A
ANA
Anti-histone Ab
16
Q
How is it possible to detect polyclonal (nonneoplastic) lymphocyte proliferation from monoclonal (neoplastic) lymphoid tumors?
A
Each T cell or B cell and its clonal progeny have a unique DNA arrangment and a unique Ag receptor which can be detected by molecular analysis
17
Q
What type of cells are effectively destroyed via the MAC, generated through the activation of the complement system?
A
Cells with thin walls, such as Neisseria bacteria
18
Q
What causes most type I hypersensitivity rxns?
A
Excessive Th2 cell responses
19
Q
Although macrophages allow for viral replication of HIV, they are resistant to the cytopathic effects of the virus. Instead, macrophages act as a ___ of infection
A
Reservoir
20
Q
RIG-like receptor location and function
A
Cytosol of most cell types
Detect nucleic acids of viruses and replicate in the cytoplasm of infected cells
Stimulate production of antiviral cytokines
21
Q
Clinical manifestations of chediak-higashi syndrome
A
Increased susceptibility to infection
Neutropenia
Giant granules within leukocytes
Albinism 2/2 defects in melanocytes
22
Q
What gene is responsible for initiating transcription and binds TFs?
A
LTR (long terminal repeat)
23
Q
C-type lectin receptor location and function
A
Plasma membrane of macrophages and DCs
Detect fungal glycans and elicit inflammatory rxns to fungi
24
Q
What is the most common form of parenteral transmission of HIV?
A
Intravenous drugs, through sharing of needles
25
What are the major components of innate immunity
Epithelial barriers
Phagocytic cells (neutrophils, MΦ)
Dendritic cells
NK cells
Plasma proteins, including complement
26
What leukocyte is seen in abundant amounts during a late-phase rxn?
Eosinophils
27
Function of CD4+ T-cells
secrete cytokines that assist macrophages and B lymphocytes in combatting infection
28
Acute cellular rejection, often seen within the initial months post-transplantation, is mediated by what cell type?
CD4+ T-cells, generating cytokines that promote an inflammatory response and graft injury via activated macrophages
29
What are the subtypes of CD4+ T-cells
TH1
TH2
TH17
30
What function do integrins have in T-cell activation?
Promote the attachment of T-cells of APCs
31
Arthus reaction
localized area of tissue necrosis resulting from acute immune complex vasculitis, usually elicited by the skin
32
Where are dendritic cells located and what is their function?
Epithelia, lymphoid organs, most tissues
Capture antigens and display peptides for recognition by T-cells
33
SLE predominantly affects what gender?
Females
34
What is characteristic of the limited scleroderma, CREST syndrome?
Calcinosis (in skin)
Raynaud's
Esophageal dysfunction (GERD, decreased motility)
Sclerodactyly
Telangiectasis (dilated capillaries)
35
What are the classic primary innate immunodeficiency disorders associated with leukocytes?
Chediak Higashi syndrome
Chronic granulomatous disease
36
What occurs in central tolerance?
Immature self-reactive B and T cell clones that recognize self-Ags during their maturation in primary lymphoid organs are killed or rendered harmless
37
Function of IL-1
Mediator of inflammation, recruiting leukocytes to site of infection
Induction of fever
38
A patient's serum will show what is they have Hyper-IgM syndrome?
High levels of IgM
No IgA or IgE
Extremely low levels of IgG
39
What cytokine is involved in the antiviral defense
Type I Interferons
40
Ab-mediate inflammation is the mechanism responsible for tissue injury in what types of disorders?
Glomerulonephritis
Vascular rejection in organ grafts
41
Affinity maturation
When helper T-cells stimulate the production of antibodies with high affinity for Ag
42
How does a T-cell become anergic?
When an Ag is presented to a T-cell but there is inadequate level of co-stimulation
43
How can an amyloid be differentiated from other hyaline materials?
Through the use of Congo red stain
44
Polymorphisms in what gene are associated with rheumatoid arthritis, type 1 DM and other diseases?
PTPN22
45
Stages of the innate immune response
recognition of microbes and damaged cells
activation of various mechanisms
elimination of unwanted substance
46
What is the hallmark of AIDS?
profound immune deficiency, specifically a marked reduction of CD4+ T-cells
47
What is the life cycle of HIV?
Infection
Integration of provirus into host cell genome
Activation of viral replication
Production and release of infectious virus
48
What tumors are of high incidence in patients with AIDS?
Kaposi sarcoma
B-cell lymphoma
Cervical CA in women
Anal CA in men
49
Explain the process of clonal selection of lymphocytes
Lymphocytes specific for a large number of Ags exist before exposure to Ag, and when an Ag enters, it selectively activates the Ag-specific cells
50
What types of preformed mediators are released during an immediate hypersensitivity rxn?
Vasoactive amines (histamine)
Enzymes, including neutral proteases and acid hydrolases
Proteoglycans including heparin and chondroitin sulfate
51
The innate immune system provides host defence through two main reactions, what are they?
Inflammation
Antiviral defense
52
CD8 T cells bind what class of MHC molecules?
Class I
53
Injury associated with type II hypersensitivity rxns occurs from?
IgM and IgG Abs through promotion of phagocytosis or lysis and induction of inflammation
54
How are immunodeficiencies manifested clinically?
increased infections
55
What protein is critical in the deletion of immature T-cells that recognize peripheral tissue-restricted self-Ags in the thymus?
AIRE
56
Of the forms of HIV, which is most commonly associated with AIDS in the US, Europe and Central Africa?
HIV-1
57
What is the earliest response of an activated CD4+ T-cell?
Secretion of IL-2 and expression of high affinity receptors for IL-2
58
What do patients with hyper-IgM syndrome present with clinically?
Recurrent pyrogenic infections
59
Cytokines produced by Th2 cells
IL-4
IL-5
IL-13
60
Why might a lupus patient have a false positive test result for syphilis?
Abs against phospholipid-β2-glycoprotein complex also bind to cardiolipin antigen, which is used in syphilis serology
61
Secondary antiphospholipid syndrome occurs when?
When patients with antiphospholipid antibodies develop venous and arterial thromboses, associated with spontaneous miscarriages and cerebral or ocular ischemia in associated with lupus
62
GPCRs located on what cell types recognize N-formylmethionyl resides?
Neutrophils, macrophages, other leukocytes
63
Define anergy
lymphocytes that recognize self-Ags may be rendered functionally unresponsive
64
Through what mechanisms can a mother transmit HIV to her infant?
In utero through the placenta
During delivery through an infected birth canal
After birth via breast milk
65
What is characteristic of innate immunity?
It is always present
It is mediated by cells and molecules that respond to the products of microbes and dead cells and induce rapid protective host reactions
66
How is inflammation triggered in type III hypersensitivity reactions?
Ab-Ag complexes deposit in tissues, recruit leukocytes which release enzymes and produce ROS
67
What is the mechanism behind drug reactions?
How do these rxns manifest?
The drug alters self proteins, including MHC molecules, and the new Ags are recognized as foreign by T-cells, leading to cytokine production and inflammation.
Manifest as skin rashes
68
Hyperacute rejection is characterized by
marked inflammation and thrombotic microvasculopathy within minutes to hours after transplant 2/2 preformed anti-donor abs (ABO blood group)
69
What are the clinical manifestations associated with Ataxia telangiectasia
Ataxia
Vascular malformation, telangiectasias, often see in the eyes
Immune deficiency, specifically of IgA and IgG leading to respiratory infections, autoimmune diseases and an increased risk of developing CA (lymphomas)
70
Chediak-Higashi syndrome is an autosomal recessive disorder characterized by
defective fusion of the phagosome with the lysosome, therefore not generating the phagolysosome required to kill bacteria
71
What forms the peptide binding cleft in an MHC II molecule?
the α1 portion and β1 portion of the EC aspect of the molecule
72
Persons with SCID are susceptible to severe infections by what pathogens
Candida albicans
Pneumocystis jiroveci
Pseudomonas
cytomegalovirus
73
What types of Ags are trapped by dendritic cells and MΦ in the spleen?
Bloodborne Ags
74
What antibodies are prsent on all mature, naive B cells and are the Ag-binding component of the B-cell receptor
IgM and IgD
75
Polymorphisms in what gene are associated with Crohn's disease?
NOD2
76
Among the genes associated with autoimmune diseases, the greatest contribution comes from which ones?
HLA genes
77
What are MHC molecules called in humans?
Human leukocyte antigens (HLA)
78
Why is lymphocyte circulation important to T cells?
Naive T cells have to circulate through peripheral lymphoid organs (spleen and LN) where Ags are concentrated
79
Morphologic changes in the MSK system of patients with sjogren syndrome
inflammation of synovium, associated with hypertrophy and hyperplasia of the synovial soft tissues occurs first
Fibrosis develops later without joint destruction
80
What is the function of macrophages in T-cell activation?
They phagocytose microbes, presenting peptide fragments to T-cells
81
What changes that contribute to autoimmunity are thought to occur as a result of susceptibility genes and environmental triggers?
Defective tolerance or regulation
Abnormal display of self-Ags
Inflammation or an intital innate immune response
82
What cytokine is produced by NK cells?
IFN-Υ
83
What other conditions can develop from human herpesvirus 8?
Primary effusion lymphoma
Castleman's disease
84
Acute ab-mediated rejection is characterized by
Ab production after transplantation
Injury 2/2 complement dependent cytotoxicity, inflammation and ab-mediated cytotoxicity
initial target = graft vasculature
85
86
What is the final phase of HIV infection characterized by?
Progression to AIDS with the breakdown of host defense, a dramatic increase in plasma virus and severe life-threatening clinical disease
87
What clinical test is essential for the diagnosis of sjogren syndrome?
biopsy of the lip to examin minor salivary glands
88
What immune complexes are found to be the most pathogenic?
Those that are medium sized and formed in slight Ag excess
89
What is characteristic of adaptive immunity?
It is a delayed reaction, developing after exposure to microbes and other foreign substances.
It is even more powerful than innate immunity in combating infections
90
What population is more likely to develop systemic sclerosis?
African american women
91
what are the most potent vasoactive and spasmogenic agents known?
Leukotrienes C4 and D4
92
Tissue injury resulting from a type IV hypersensitivity rxn occurs from what cells?
T-cells
93
Ab-mediated inflammation occurs through what mechanism?
Activation of complement
94
What category of immunity is the first line of defense?
Innate immunity
95
Describe the direct pathway of allorecognition
T cells from the transplant recipient recognize the allogeneic (donor) MHC molecules as foreign and mount an immune response against it (with CD8 and CD4 T-cells) leading to damage to renal tubule by inflammation and death of graft cells
96
T-cells activate both B-cells and macrophages through what cell surface molecules?
CD40L on the T-cell
CD40 on the B-cell or MΦ
97
What autoantibodies are involved in SLE?
Antinuclear antibodies (ANAs)
98
What inhibitory receptors can send inhibtory signals to T-cells that are recognizing self-Ags?
CTLA-4
PD-1
99
What is the association between ankylosing spondylitis and HLA-B27?
Individuals who inherit this HLA-B27 allele have a 100-200 fold higher chance of developing the disease
100
What are the sites of continuous HIV replication and cell destruction during the late phase of the disease?
lymph nodes
spleen
101
What type of helper T-cell is involved in the isotype switching and affinity maturation that occurs within lymphoid organs?
Follicular helper T-cells (TFH)
102
A mutation in Foxp3 in humans results in what systemic autoimmune disease?
IPEX (**i**mmune dysregulation **p**olyendocrinopathy, **e**nteropathy, **X**-linked)
103
Describe the indirect pathway of allorecognition
The host dendritic cell recognizes the graft as foreign, uptakes it as an EC Ag, processing it and presenting it to host CD4 cells.
CD4 cells induce delayed type hypersensitivity inflammatory rxn
CD4 cells also help to activate B-cells to produce Abs against graft Ag
104
Why is the chronic phase of HIV termed the clinical latency period?
There are no clinical manifestations of the infection during this time
105
Treatment for hyper-IgM syndrome
IVIg
Stem cell transplant
106
Regulatory T-cells also express CTLA-4, what is the purpose of this receptor?
Bind B7 molecules (CD80/CD86) on APCs, reducing their ability to activate T-cells
107
In addition to fibrosis of skin and other organs, what other clincial manifestations are seen with systemic sclerosis (scleroderma)?
GERD
Esophageal ulceration
Renal vascular disease
Pulmonary HTN
Pulmonary fibrosis
108
What cell surface molecules are present on NK cells?
CD16
CD56
109
AIDS is characterized by
Profound immunosuppression that leads to:
Opportunistic infections
Secondary neoplasms
Neurological manifestations
110
What are complications seen in patients who are taking immunosuppressive drugs s/p transplantation?
Increased susceptibility to opportunistic infections, most commonly polyoma virus
Increased risk of developing EBV-induced lymphomas, HPV induced squamous carcinomas, and kaposi sarcoma
111
What is present in the bone marrow or in other organs and strongly indicative of SLE?
LE cells or hematoxylin bodies
112
What is the most important mast-cell derived amine?
Histamine
113
Pharyngeal tonsils and Peyer's patches are examples of what kind of lymphoid tissues?
Mucosal
114
IgG4-related disease is characterized by
a constellation of disorders with tissue infiltrates dominated by IgG4 Ab-producing plasma cells, T-lymphocytes, and fibrosis
115
What Ab acts as an opsonin?
IgG
116
Systemic anaphylaxis is characterized by
vascular shock, widespread edema, difficulty breathing
117
A patient is likely to develop a drug-induced lupus after receiving hydralazine if they have what allele type?
HLA-DR6
118
Amyloidosis is a condition characterized by the deposition of fibrillar proteins that cause tissue damage, what causes the formation of the fibrils?
Aggregation of misfolded proteins
119
What are the structural components share among related microbes, are essential for infectivity, and are recognized by cells of the innate immune response?
Pathogen-associated molecular patterns (PAMPs)
120
X-linked agammaglobinemia is characterized by
failure of B-cell precursors to develop into mature B-cells
121
What does the viral load at the end of the acute phase reflect?
The equilibrium reached between the virus and the host response; this is the viral set point and it is the predictor of the rate of decline of Cd4+ T-cells
122
Autoimmune disorders arise as a result of
failure of tolerance to self Ags
123
What cardiovascular condition is seen in young patients with SLE who have been treated previously with corticosteroids?
coronary artery disease
124
What ethncities have a 2 to 3 fold higher prevalence of SLE than caucasians?
African americans
Hispanics
125
What are the functions that have been attributed to innate lymphoid cells?
Early defense against infection
Recognition and elimination of stressed cells
Shaping the adaptive immune response by providing cytokines that influence T-cell differentiation
126
Autoantibodies specific for RBCs, WBCs, and platelets ____ these cells, promoting phagocytosis and lysis
Opsonize
127
Function of interferon regulatory factors
Stimulation of the production of antiviral cytokines, type I interferons
128
Type I hypersensitivity reactions are often termed allergic reactions, what triggers these reactions?
The binding of an Ag (allergen) to an IgE Ab
129
Patterns of nuclear fluorescence
Homogenous or diffuse nuclear staining
Rim or peripheral staining
Nucleolar pattern
Centromeric pattern
130
What are the best defined regulatory T-cells?
CD4+ T-cells with high expression of CD25 and Foxp3
131
If amyloidosis occurs in the kidney, what occurs?
Disruption of glomeruli which can lead to proteinuria and eventually edema
132
What effect do the preformed enzyme mediators have in an immediate hypersensitivity reaction?
They cause tissue damage and lead to the generation of kinins and activated components of complement
133
What is the most common cause of autosomal recessive SCID?
A deficiency in the enzyme adenosine deaminase
134
Describe the structure of the HIV virion
Spherical
Electron-dense, cone-shaped core surrounded by a lipid envelope derived from the host cell membrane
Glycoproteins coat the virion (gp120, gp41)
135
Injury associated with Type I hypersensitivity rxns is caused by what?
Th2 cells
IgE Abs
Mast cells
other leukocytes
136
Where are pattern recognition receptors located?
in cellular compartments where microbes may be present
137
Susceptibility to immediate hypersensitivity rxns is ______ determined.
Genetically
138
What drugs have been found to induce an SLE-like response in humans?
Hydralazine, procainamide and D-penicillamine
139
Describe the contents of the HIV virion
Core contains:
major capsid protein p24
viral enzymes including protease, reverse transcriptase and integrase
HIV-1 RNA genome including gag, pol, env retroviral genes
140
What type of virus is HIV?
Retrovirus that is part of the lentivirus family (slow virus)
141
What is the mechanism behind the transmission of HIV?
Breaching the mucosal barriers introduces the virsu to the bloodstream or infects mucosal dendritic cells
142
What is the most common secondary immunodeficiency?
AIDS
143
What other proteins are commonly found on T-cells?
CD4, CD8, CD28
144
Cell-mediated (cellular) immunity is mediated by what cell types?
T-lymphocytes (T cells)
145
What chemokine is responsible for drawing eosinophils to the site of immediate hypersensitivity?
Eotaxin
146
where are Υδ T-cell receptors commonly found?
epithelial surfaces, including skin and mucosa of the GI tract and urogential tract
147
What is a common clinical example of a delayed-type hypersensitivity rxn (type IV)?
Tuberculin rxn
| (PPD test)
148
Antiphopholipid antibodies are present in 30-40% of lupus patients, what are these Abs directed against?
Epitopes of plasma proteins that are revealed when the proteins are in complex with phospholipids
149
Wiskott Aldrich syndrome is an X-linked disease caused by a mutation in what gene?
WASP
150
What is the function of peripheral lymphoid organs?
Concentrate Ags, APCs, and lymphocytes in order to optimize interactions and develop the adaptive immune response
151
Most common COD in patients with SLE?
renal failure
intercurrent infections
152
What are the three major populations of T-cells
Helper T cells
Cytotoxic T cells
Regulatory T cells
153
Severe combined immunodeficiency (SCID) represents a constellation of syndromes that all have common defects in
humoral and cell-mediate immune responses (both B-cell and T-cell)
154
During T-cell activation, some APCs produce IL-12, which signals the differentiation of CD4+ T-cells into what subset?
Th1
155
Explain the process of negative selection that occurs during central tolerance of developing T-cells
Some T-cells express TCRs that have high affinity for self-Ags, when they encounter self-Ags in the thymus, these T-cells die by apoptosis to rid these cells from the T-cell pool
156
Most autoimmune disorders are considered to be what type of genetic disorder?
complex multigenic
157
What is the function of MHC molecules?
Display peptide fragments of protein Ags for recognition by Ag-specific T-cells
158
Morphologic changes of the kidney in patients with SLE
Deposition of immune complexes along the basement membrane and glomerulus
159
How do infections trigger autoimmune reactions?
Upregulation of costimulators on APCs
Some microbes may express Ags that have the same AA sequence as self Ags (molecular mimicry)
160
What is seen in drug-induced lupus erythematous that is also seen in SLE?
Arthralgias
Fever
Positive ANA
Discoid rash
Hematologic disease
Positive immunofluorescence
161
What type of mutation in NOD-like receptors leads to fever syndromes known as autoinflammatory syndromes?
Gain-of-function mutation
162
If a B cell has responded to an Ag within the lymph node, what is present within the follicle?
Germinal center
163
What antibody, directed against DNA topoisomerase I, is highly specific for systemic sclerosis and is found in immunofluorescent *speckled* staining?
anti-Scl 70
164
Typical presentation of a patient with SLE
**young female** with some, but not necessarily all of these features:
butterfly rash, fever, joint pain, pleuritic CP, photosensitivity
165
What mechanisms are involved in peripheral tolerance?
Anergy
Suppression by regulatory T-cells
Deletion by apoptosis
166
What cytokine is the most potent eosinophil activator known?
What is the source of this cytokine?
IL-5
Th2 cells
167
What signals are released from injured or necrotic cells and are recognized by leukocytes?
Damage-associated molecular patterns (DAMPs)
168
What is responsible for the depletion of cells coated with abs?
Phagocytosis
169
Morphologic changes in the skin of patients with sjogren syndrome
diffuse sclerotic atrophy of skin, beginning in the fingers (sclerodactyly) and extending proximally up the arms toward the neck and face
170
What is the mechanism behind the late-phase rxn of a type I hypersensitivity rxn?
The immediate rxn induces the release of various cytokines and chemokines, including TNF and IL-1, these cytokines recruit leukocytes which act to sustain the inflammatory response without further exposure to the Ag
171
What cells are the only ones in the body capable of producing antibodies?
B lymphocytes
172
Various protein Ags that form immune complexes and result in serum sickness lead to what clinicopathologic manifestations?
Arthritis
Vasculitis
Nephritis
173
Where are naive T lymphocytes activated and where do they end up?
In peripheral lymphoid organs
Anywhere that the Ag is present
174
Release of what transcription factor leads to the viral transcription of HIV through LTR?
NF-kB
175
MHC I molecules are made up of a polymorphic α chain and a nonpolymorphic β2-microglobulin. The α chains are encoded by three genes, what are they?
HLA-A
HLA-B
HLA-C
176
What proteins are critical for HIV infection of host cells by helping with attachment?
gp120
gp41
177
Morphologic changes in the kidneys of patients with sjogren syndrome
Vascular lesions
Thickening and fibrinous deposition in aa
Fibrinoid necrosis can develop in patients with HTN
178
What proteins do eosinophils contain that induce tissue damage?
**Major basic protein**
eosinophil cationic protein
179
What is a major barrier to transplantation?
Rejection: recipient's immune system recognizes the graft as foreign and attacks it (host vs graft disease)
180
Morphologic changes seen in the skin of patients with SLE
Butterfly rash (50% of patients) along the bridge of the nose and cheeks
Urticaria, bullae, or maculopapular lesions can develop
Histologically, there is vacuolar degeneration of the epidermis, vasculitis with fibrinoid necrosis
181
Pathogenesis of systemic immune complex disease occurs in three stages:
1. formation of immune complexes
2. deposition of immune complexes
3. inflammation and tissue injury
182
What are the principle costimulators for T cells and what do they bind?
B7 proteins (CD80 and CD86)
Bind CD28 on T cells
183
What clinical measurement is used to determine when to start antiretroviral therapy in patients with HIV?
serum CD4+ counts
184
What is the fundamental defect in SLE?
Failure of the mechanisms that maintain self-tolerance
185
Cells involved in adaptive immunity?
Lymphocytes
Antibodies
186
Polysaccharides and lipids stimulate the secretion of what Ab?
IgM
187
What HIV gene encodes the viral enzymes?
* Pol*
* (polymerase)*
188
Function of helper T cells
Stimulate B lymphocytes to make Abs and activate other leukocytes to destroy microbes
189
The B-cells of lymphomas seen in AIDS patients are commonly infected with what virus?
EBV
190
A patient is likely to develop a drug-induced lupus after receiving procainamide if they have what allele type?
HLA-DR4
191
NK cell inhibitory receptors recognize what molecules and help to prevent what from happening?
They recognize self class I MHC molecules and help to prevent NK cells from killing normal cells
192
Sjogren disease is caused by
immunologically mediated destruction of lacrimal and salivary glands followed by fibrotic destruction
193
What are the three forms of ab-mediated rxns seen in transplant rejection?
Hyperacute rejection
acute ab-mediated rejection
chronic ab-mediated rejection
194
Deficiency in DAF or CD59 will result in what disease?
Paroxysmal nocturnal hemoglobinuria
195
Morphologic changes in the spleen seen in patients with SLE
Splenomegaly
capular thickening
follicular hyperplasia
196
What is the onset of SLE?
Acute or insidious
197
In lymph nodes, where are the B cells and T cells located
B cells are located in follicles along the periphery of the LN
T cells are located in the paracortex of the LN, next to the follicles
198
What molecules do the Υδ TCR recognize?
Does this receptor complex require MHC display?
Peptides, lipids, small molecules
No
199
DiGeorge syndrome occurs 2/2
Failure of the development of the 3rd and 4th pharyngeal pouches, leading to defects in the thymus, parathyroid glands, heart and great vessels
200
Chronic granulomatous disease is a group of genetic disorders characterized by
defects in superoxide production within phagocytes, resulting in subsequent defects in bacterial killing, rendering the patients susceptible to recurrent bacterial infection
201
Humoral immunity is mediated by what cell types?
B-lymphocytes (B cells) and their products, Abs
202
Injury is caused by what in SLE?
deposition of immune complexes and binding of abs to various cells and tissues
203
What is the function of natural killer cells?
to destroy irreversibly stressed and abnormal cells, such as virus-infected cells and tumor cells
204
What is essential in the developement and maintenance of regulatory T-cells?
IL-2
Foxp3
205
Type III hypersensitivity reactions are characterized by
formation of Ag-Ab immune complexes that deposit into vessel walls, causing inflammation at these sites
(can also deposit in tissues)
206
What determines if a lymphocyte is mature or naive?
Whether or not it was encountered a specific Ag
207
The HLA system is highly polymorphic, why is this problematic?
There are many alleles of MHC genes and each individuals alleles differ, therefore a berrier in organ transplantation exists
(i.e. rejection)
208
What two problems are unique to hematopoietic stem cell transplantation?
graft vs host disease
immunodeficiency
209
Cytokine produced by Th1 cells
IFN-Υ
210
How does innate immunity differ from adaptive immunity?
Innate immunity **does not** have memory or fine Ag specificity
211
How is the graft, vs host disease minimized in hematopoietic stem cell transplants?
The donor and recipient are HLA matched prior to transplantation
212
What is the function of a regulatory T-cell?
Prevent immune rxns against self-Ags
213
Why do some patients with IgA defiency develop anaphylaxis after receiving blood transfusion?
IgA behaves like a foreign antigen and patients' immune systems develop immune rxn to it
214
Why are antiphospholipid antibodies sometimes considered lupus anticoagulants?
They interfere with clotting tests, such as aPTT
215
Lymphocytes constantly circulate between tissues and particular sites, where do naive lymphocytes travel to?
They traverse lymphoid organs where immune responses are initiated
216
Where are class I MHC molecules located
All nucleated cells
Platelets
217
What are common complications that can be seen in patients with Sjogren syndrome?
Pulmonary fibrosis
lymphoma 2/2 B-cell proliferation becoming clonal
218
X-linked agammaglobinemia is caused by mutations in what gene?
The Bruton tyrosine kinase gene on the X chromosome
219
How is antigen receptor diversity accomplished?
Somatic recombination of genes that encode receptor proteins
220
What triad is characteristic of Wiskott aldrich syndrome?
Thrombocytopenia
Eczema
Recurrent infections
221
Function of caspase-1
Cleaves precursor form of IL-1, generating the biologically active form
222
How do dendritic cells resemble macrophages and how are they different?
They initiate innate immune responses, but unlike macrophages, they are not key participants in eliminating the offending agent
223
Morphologic changes in the alimentary tract of patients with sjogren syndrome
Atrophy and collagenous fibrosis of musclaris, most severely in the esophagus
GERD
Barrett metaplasia
Strictures
Loss of villi and microvilli leading to malabsorption syndrome
224
Patients with CVID often present with
Recurrent sinopulmonary pyogenic infections
Granulomas
Chronic diarrhea 2/2 *Giardia lamblia*
Autoimmune diseases
225
Infection of what cells are the foundation of the neuropathic effects of HIV?
microglia
226
Where are the genes encoding HLA located?
On chromosome 6
227
Function of cell-mediated immunity?
Defense against intracellular microbes
228
Type II hypersensitivity reactions occur when
Abs react with Ags present on cell surfaces or in ECM, causing the destruction of cells followed by inflammation OR by interfering with the normal function of cells
229
Sjogren disease is characterized by
dry eyes
dry mouth (xerostomia)
230
What is the purpose of a memory cell?
React rapidly and strongly to combat a microbe it has already been exposed to, if it returns
231
What is the molecular composition of an MHC class II molecule?
a heterodimer with one α chain and one β chain
232
Function of NF-kB
Stimulates the synthesis and secretion of cytokines and the expression of adhesion molecules
233
What peptide inserts into the cell membrane of the target cell, leading to the fusion of the HIV to the host?
gp41
234
Mast cells and basophils involved in the immediate hypersensitivity rxns have what cell surface receptor?
What does this receptor bind?
FcεRI
Fc portion of IgE
235
How many receptors does innate immunity use?
What about adaptive immunity?
100
2
236
What tx options are available for SCID?
Hematopoietic stem cell transplant
Gene therapy
237
What is the most common neoplasm in AIDS patients?
Kaposi sarcoma
238
Because IgA is the major Ab in external secretions, mucosal defenses are weakend. Infections thus commonly occur where?
Respiratory, GI and GU tracts
239
What virus is associated with the development of kaposi sarcoma
Human herpesvirus 8
240
What is the **most important** Ag-presenting cell for initating T-cell responses against Ags?
Dendritic cells
241
What constitutes the initial step in infection by HIV?
Binding of the surface glycoprotein gp120 to CD4 receptor molecule, which leads to a conformational change that allows for a new recognition site on gp120 for coreceptors (CCR5, CXCR4)
242
What are granzymes and what is their function in CTL mediated cell killing?
Granzymes are proteases that cleave and activate caspses which induce apoptosis of the target cell
243
Where is CR2/CD21 located and what is its function?
On B-cells
Recognizes complement products generated during the innate immune response
244
What Ags do MHC II molecules present?
Those that are internalized into vesicles, derived from extracellular microbes and soluble proteins
245
Where is CD40 located and what is its function?
On B-cells
Receives signals from helper T-cells
246
What are the peripheral lymphoid organs?
Spleen
Lymph nodes
mucosal and cutaneous lymphoid tissues
247
Chronic ab-mediated rejection is characterized by
fibrosis with primary effect on vasculature
248
What HIV gene is responsible for encoding the surface glycoproteins, gp120 and gp41, important for HIV infection?
* env*
* (envelope protein)*
249
Th1 cells secrete what cytokine, which promotes further Th1 cell development and thus amplifies the rxn?
IFN-Υ
250
When a lymphocyte differentiates into an effector cell, what is its function?
eliminating microbe for which it is specific for
251
What is the function of IL-2 in respect to T-cells?
IL-2 stimulates proliferation of T lymphocytes
252
What is the most abundant mediator formed in mast cells by the cyclooxygenase pathway?
Prostaglandin D2
253
In immunizations, adjuvants are given with the Ag in or do stimulate an innate immune response, what is the purpose of the adjuvant?
To activate APCs to express costimulators and to secrete cytokines that will stimulate the proliferation and differentiation of T lymphocytes
254
What are the three most common forms of amyloid?
Amyloid light chain
Amyloid-associated type
Beta-amyloid protein
255
What results from inherited defects in RAG proteins?
failure to generate mature lymphocytes
256
The most common form of SCID follows what inheritance pattern and hence is more common in?
X-linked
More common in boys
257
ataxia telangiectasia is an autosomal recessive disorder caused by a mutation in what gene, leading to a defect in?
ATM gene
Defective DNA repair
258
What does innate immunity provide that stimulates the adaptive immune response?
Danger signals
259
What are the 5 groups of adults who are high risk of developing AIDS?
Homosexual or bisexual men
IVDA
Hemophiliacs
Heterosexual contacts of members of other high risk groups
Newborns in areas of high female prevalence
260
Antinuclear antibodies are grouped into four cateogories, what are they?
Abs to DNA
Abs to histones
Abs to nonhistone proteins bound to RNA
Abs to nucleolar ags
261
Two categories of mechanisms of defence against microbes
Innate immunity
Adaptive immunity
262
What is the most abundant viral Ag that is detected via ELISA and used to diagnose HIV infection?
p24
263
What cytokine is produced by CD8+ T-cells and contributes to inflammatory rxns seen in delayed type hypersensitivity?
IFN-Υ
264
What are the common immune-privileged sites?
Why are the immune privileged?
Testis, eye, brain
It is difficult to induce immune response to Ags introduced into these sites
265
What cytosolic receptor recognizes products of necrotic cells, ion disturbances, and some microbial products?
NOD-like receptors
266
Mixed CT disease is characterized by high seriology titers of what antibody?
Anti-ribonucleoprotein (anti-RNP)
267
What cytokines are involved in the regulation of NK cell activity?
IL-2
IL-15
IL-12
268
How do B cells respond when they recognize self-Ags?
They undergo receptor editing, where antigen receptors undergo gene rearrangment to generate new Ag receptors not specific to self-Ags
269
How can CREST syndrome be identified using immunofluorescence?
Staining is centromeric, staining for anticentromere abs
270
Chronic discoid lupus erythematosus is characterized by
presence of skin plaques showing varying degrees of edema, erythema, scaliness, follicular plugging, and skin atrophy surrounded by an elevated erythematous border
271
systemic sclerosis (scleoderma) is characterized by
Chronic inflammation though to be a result of autoimmunity
Widespread damage to small blood vessels
Progressive interstitial and perivascular fibrosis in the skin and multiple organs
272
Class II MHC molecules are encoded in what region?
HLA-D
273
What is the most common form of nephritis associated with SLE?
What is the least common form?
Class IV
Class I
274
Type IV hypersensitivity reactions are mediated by T-cells and result in injury how?
inflammation 2/2 cytokines produced by CD4+ T cells
OR
Cell killing by CD8+ T-cells
275
What are the classic primary adaptive immunodeficiencies associated with lymphocyte activation or function?
Hyper-IgM syndrome
Common Variable Immunodeficiency (CVID)
IgA deficiency
276
What is the major antigenic difference between donor and recipient, resulting in transplant rejection
differences in HLA alleles
277
When abs deposit in fixed tissues, such as the basement membrane or ECM, the resultant injury is due to what?
Inflammation
278
Purpose of immunity
Protection from infectious pathogens
279
Function of humoral immunity
Protect against extracellular microbes and their toxins
280
Mannose receptor function
Recognize microbial sugars and infuce phagocytosis of these microbes
281
What type of peptides are displayed by MHC I molecules?
Peptides derived from proteins of viral and tumor Ags which are located in the cytoplasm and usally produced in the cells
282
What type of immune reaction causes injury?
Hypersensitivity rxns
283
Cause of primary immunodeficiencies
genetics
284
Two types of adaptive immunity
Humoral immunity
Cell-mediated immunity
285
AIDS is caused by
Retrovirus human immunodeficiency virus (HIV)
286
What is the principal mechanism of T-cell mediated killing of targets (via CD8+ CTLs)?
CTLs release a complex of perforins and granzymes, perforin generates a hole in the target cell allowing for granzymes to enter
287
What are the principle generative lymphoid organs?
Thymus
Bone marrow
288
HLA-D has three subregions, what are they?
HLA-DP
HLA-DQ
HLA-DR
289
What are the major lipid mediators of an immediate hypersensitivity rxn?
Arachidonic acid derived products including PGD2, LTB4, LTC4, LTD4
290
Common treatment for autoinflammatory syndromes?
IL-1 antagonist
291
What are the serologic markers for sjogren syndrome?
anti-RO/SS-A and Ati-La/SS-B
292
What opportunistic infections are commonly seen in AIDS patients?
Pneumocystis jiroveci
Cytomegalovirus
Tuberculosis
Toxoplasma
Candidiasis
293
Function of regulatory T cells
Limit immune responses and prevent rxns against self-Ags
294
What are the coreceptors in T-cell activation, as they recognize the same ligand that the Ag receptor sees?
CD4 and CD8
295
Common variable immunodeficiency is a group of disorders with a common feature of
Hypogammaglobulinemia, usually affecting all ab classes but sometimes just IgG
296
What is the **hallmark** of SLE?
Production of antibodies
297
Morphologic changes in the lungs of patients with sjogren syndrome
Pulmonary HTN
Pulmonary fibrosis
298
What makes up the T-cell receptors?
disulfide-linked heterodimer made up of an α and β chain, each having a variable (Ag-binding) region and a constant region
299
Where does isotype switching and affinity maturation occur?
In germinal centers of lymphoid follicles
300
What has been found to be the cause of many chronic inflammatory diseases?
CD4+ T cell-mediated hypersensitivity rxns induced by environmental and self Ags
301
Clinical manifestations of CVID are caused by
antibody deficiency
302
What cell type is central in the development of immediate hypersensitivity?
Mast cells
303
The cause of systemic sclerosis is unknown, but is thought to arise from 3 interrelated processes, what are they?
Autoimmune responses
Vascular damage
Collagen deposition (fibrosis)
304
The EC region of the α chain of MHC I molecule has three domains, α1 α2 and α3.
α1 and α2 form a cleft, what binds in this cleft?
Peptides
305
What are the three requirements in order for a disorder to be categorized as pathologic autoimmunity?
Presense of an immune rxn specific for some self antigen or self tissue
Evidence that such a rxn is not 2/2 tissue damage but is of primary pathogenic significance
The absense of another well-defined cause of disease
306
The immediate rxn of type I hypersensitivity recations is characterized by
Vasodilation
vascular leakage
smooth muscle spasm OR glandular secretion (location dependent)
307
Define epitope spreading
An immune response against one self-Ag causes tissue damage, releasing other ags and resulting in the activation of lymphocytes by these newly encountered epitopes
308
Immature dendritic cells of the epidermis
Langerhans cells
309
What amyloid type constitutes the core of cerebral plaques found in Alzheimer disease?
beta-amyloid
310
Function of CD16 on NK cells?
Allows NK cells to lyse IgG-coated target cells
311
Hyper-IgM syndrome is caused by mutations in a gene encoding what protein?
CD40L
312
What is the acute retroviral syndrome?
The clinical presentation of the intial spread of the virus and the host response; characterized by fever, sore throat, myalgias
313
If amyloid occurs in the heart, what occurs?
Disruption of the myocardium leading to dysrhythmias
314
What is a possible first indicartion of IgA deficiency?
Anaphylaxis s/p blood transfusion
315
The systemic lesions seen in SLE are caused by
immune complexes (type III hypersensitivity rxn)
316
How do NOD-like receptors signal?
Via the inflammasome, which activates caspase-1
317
The enzyme responsible for recombination of gene segments in developing lymphocytes is the product of what genes?
RAG-1 and RAG-2
318
Lymphocytes constantly circulate between tissues and particular sites, where do effector lymphocytes travel to?
To sites of infection and inflammation
319
Morphologic changes of blood vessels in patients with SLE
acute necrotizing vasculitis
fibrinoid deposits in vessel walls
320
What are the two mechanisms of self-tolerance?
Central tolerance
Peripheral tolerance
321
What method is used to detected antinuclear antibodies?
indirect immunofluorescence
322
PAMPs and DAMPs collectively form a group of molecules that are termed
Pattern recognition receptors (PRRs)
323
Morphologic changes seen in delayed type hypersensitivity include
accumulation of mononuclear cells, mainly CD4+ T-cells, and macrophages around venules, producing a "cuffing"
324
Examples of disorders where abs are directed against cell surface receptors, causing a dysregulation in normal function **without** cell injury or inflammation
Graves disease
Myasthenia gravis
325
Inherited defects in leukocyte adhesions is considered a defect in innate immunity and manisfests with
Recurrent bacterial infections d/t inadequate granulocyte function
326
What are the two major targest of HIV infection?
immune system
CNS
327
What HIV gene is responsible for encoding the proteins inside the virus?
*gag*
328
Define self-tolerance
Lack of responsiveness to your own antigens
329
After stimulation by Ag, B-cells develop into what cell type?
Plasma cells, which are veritable protein factories for Abs
330
What additional lipid mediator is produced by mast cells, causes platelet aggregation, release of histamine, bronchospasm, increased vascular permeability and vasodilation?
PAF (platelet activating factor)
331
What is typically present in 70% of patients with systemic sclerosis, often manifesting prior to other sxs?
Raynaud's phenomenon
332
Hyper-IgM syndrome is characterized by
inability to class switch d/t the lack of CD40L
333
In class IV nephritis associated with SLE, patients develop lesions in half or more of their glomeruli. These patients often are symptomatic, showing what symptoms?
Hematuria
Proteinuria
HTN
Renal insufficiency
334
Sexual transmission of HIV is enchanced by what?
Coexisiting STIs
335
What are the tree major routes of HIV transmission?
Sexually
Parenteral inoculation
Passage from mother to their newborns
336
What is the best known pattern recognition receptor?
toll-like receptor (TLR)
337
What cells are located within germinal centers of lymphoid follicles in the spleen and lymph nodes that trap Ag bound to Abs or complement proteins
Follicular dendritic cells
338
Where do T cells mature?
In the thymus
339
Where do B cells mature
In the bone marrow
340
If an APC produces IL-1, IL-6 and IL-23, the CD4+ T-cell is stimulated to differentiate into what subtype?
Th17
341
The late-phase rxn of a type I hypersensitivity reaction is characterized by
an onset of 2-24 hours after exposure
infiltration of tissues with eosinophils, neutrophils, basophils, monocytes, CD4+ T-cells and tissue injury
342
Mixed connective tissue disease is a combination of what disorders?
SLE
Scleroderma
Polymyositis
343
Injury to what regions of the body is prominent in SLE?
Skin, joints, kidney, serous membranes
344
What is a common presenting feature of patients with mixed CT disease?
Raynaud's phenomenon
345
Deficiency in the C1 inhibitor leads to what condition?
Hereditary angioedema
346
what types of dendritic cells are important for the initiation and maintanence of HIV infection?
Mucosal
Follicular
347
The TCR is covalently linked to 6 polypeptide chains, forming the CD3 complex and ζ chain dimer, what is the function of these?
Transduction of signals into the T cell that are triggered by Ag binding to TCR
348
What profound B-cell abnormalities are seen in patients with HIV?
Polyclonal activation of B-cells leading to germinal center hyperplasia and possible development of lymphoma
Hypergammaglobulinemia
Reduced isotype switching
Reduced Ab production
349
Define immunologic tolerance
the phenomenon of unresponsivenss to an Ag induced by exposure of lymphocytes to that Ag
350
subacute cutaneous lupus erythematosus has a strong association with what antibodies and what genotype?
Ab to SS-A Ag
HLD-DR3 genotype
351
Morphologically, what defines a natural killer cell?
Larger in size
Azurophilic granules
352
What immunosuppressive drugs are commonly used to increase graft survival after transplantation?
Steroids
Tacrolimus (to inhibit T cell function)
353
Hypersensitivity reactions can be triggered by what types of Ags?
Endogenous self-Ag
Exogenous environmental Ags
354
X-linked lymphoproliferative syndrome is characterized by
the inability to eliminate Epstein-Barr virus (EBV), eventually leading to infectious mono and development of B-cell tumors
355
Tx for Wiskott-Aldrich syndrome
stem cell transplant
356
Function of CD8+ T-cells
They function as cytotoxic T-cells (CTLs), destroying host cells that are harboring microbes
357
What do TCRs recognize?
Peptide Ags that are presented by major histocompatibility complex (MHC) molecules on the surfaces of Ag-presenting cells
358
CD4 T cells bind what class of MHC molecule?
Class II
359
Because of the impaired humoral (B-cell) immunity, patients with HIV are susceptible to infection by what types of organisms?
Encapsulated bacteria (S. pneumoniae, H. influenzae)
360
What is the appearance of amyloid on an H&E stain?
Amorphous, eosinophilic, hyaline extracellular substance
361
What forms the TCR complex?
TCR
CD3
ζ chain
362
Graft vs host disease is mediated by what cell type?
What are the common clinical manifestations of this?
T-cell mediated
Skin rash leading to desquamation, jaundice leading to cholestasis, blood diarrhea leading to bowel strictures
363
Ab-mediated cell destruction and phagocytosis occurs in what situations?
Transfusion rxns
Hemolytic disease of the newborn (erythroblastosis fetalis)
Autoimmune hemolytic anemia, agranulocytosis and thrombocytopenia
Certain drug rxns
364
How is the activity of NK cells regulated?
Through the balance of signals from activating and inhibitory receptors
365
Chronic granulomatous disease attempts to control the bacterial infection through what mechanism, as the normal phagocytic O2-dependent killing is inactive?
Activated macrophages wall off the infection, forming granulomas
366
When a toll-like receptor is activated, regardless of the type, a common pathway culminates in the activation of what transcription factors?
NF-κB
Interferon regulatory factors (IRFs)
367
What are the two major classes of MHC molecules?
Class I
Class II
368
Where are the abnormal amyloid fibrils deposited?
Extracellular space in various tissues and organs of the body
369
IgG4-related disease often affects what population?
middle-aged and older men
370
Isolated IgA deficiency is characterized by
extremely low levels of both serum and secretory IgA
371
What is part of innate immunity, providing protection against inhaled microbes?
Lung surfactant
372
What occurs when there is a deficiency in any complement protein involved in the formation of the membrane attack complex (MAC)
There is no lysis of microbial membrane
increased susceptibility to Neisseria bacteria
373
Cytokines produced by Th17 cells
IL-17
374
Function of cytotoxic T cells
kill infected cells
375
What molecules are essential for signal transduction through B-cell Ag receptor
Igα (CD79a)
Igβ (CD79b)
376
Patients with IgA deficiency present with
recurrent sinopulmonary infections
diarrhea
