3
Q
What is the display of new antigens by a pathogen that are not recognized by immune responses formed in response to previous infection?
A
Antigenic Variation
4
Q
What does antigenic variation enable the pathogen to do?
A
To evade pre-formed memory immune responses.
5
Q
What is antigenic drift?
A
Introduction of point mutations that result in minor alterations of the antigenicity of a particular protein.
6
Q
What is the reassortment of genes that results in major changes in the antigenicity of a given protein?
A
Antigenic shift
7
Q
How do the many different serotypes of S. pneumoniae differ?
A
In their capsular polysaccharides.
8
Q
How many distinct serotypes are there of S.pneumonaie?
A
84
9
Q
T/F The same organism can cause disease in the same host many times.
A
TRUE
10
Q
What is latency?
A
A state adopted by some viruses in which they have entered cells but do not replicate. Viral genome is integrated into the host cell DNA.
11
Q
What is a superantigen?
A
Molecules that stimulate a subset of CD4 T cells by simultaneously binding to MHC class II molecules and the B-chain of the TCR. Initiates massive production of cytokines. (toxic shock syndrome)
12
Q
What are the African Trypanosomes?
A
Insect-borne protozoa that replicate in extracellular tissue spaces in the body; cause sleeping sickness.
13
Q
What are trypanosomes coated with?
A
The variant-specific glycoprotein
14
Q
How many different VSG genes are there that encode a VSG protein that is antigenically distinct?
A
1000
15
Q
What type of system is used to express a VSG?
A
A cassette system; to express only one of the different VSGs at a time.
16
Q
What is are some examples of viruses that often enter a latency phase?
A
Herpes simplex virus; varicella zoster; Epstein-Barr Virus.
17
Q
Why do sensory neurons remain infected?
A
Very few viral peptides are available for presentation to CTLs; Neurons express very low levels of MHC class I molecules, making it harder for CTLs to recognize infected neurons.
18
Q
What does the Epstein-Barr Virus cause in adolescents and adults?
A
Mononucleosis
19
Q
What is mononucleosis characterized by?
A
B cell becoming infected and then proliferating, leading to activation of T cells.
20
Q
What are the pathogens that are most likely to subvert immune responses?
A
Viruses
21
Q
What are some of the viral strategies used to subvert the immune response by pathogens?
A
Inhibition of humoral immunity; inhibition of inflammatory response; Blocking of antigen processing and presentation; Immunosuppression of host.
22
Q
What does leprosy involve?
A
Pathogen-induced immunosuppression.
23
Q
What is lepromatous leprosy?
A
Cell-mediated immunity is profoundly depressed, and infection is not controlled.
24
Q
What is are characteristics of lepromatous leprosy?
A
Highly infectious and replicates freely in macrophages; infection is disseminated widely in the body; hypergammaglobulinemia; low or absent T cell responsiveness; leaves host in an anergic state.
25
Q
What is tuberculoid leprosy?
A
Potent cell-mediated immunity with macrophage activation.
26
Q
What are some characteristics of tuberculoid leprosy?
A
Bacteria is not very infectious and are present at low to detectable levels; granulomas and local inflammation; normal serum levels of immunoglobulins and normal T cell responsiveness.
27
What is HIV characterized by?
Susceptibility to opportunistic infections; a profound decrease in CD4 T cell numbers.
28
What does the envelope protein complex of HIV bind to with high affinity?
CD4 molecules
29
How long after the infection of HIV does seroconversion occur?
2-6 weeks post-infection
30
When does the asymptomatic (latency) phase of HIV begin?
Around the same time that seroconversion occurs; lasts for 10 yrs.
31
When does the symptomatic phase of HIV begin?
When the numbers of functional circulating CD4 cells gets very low; high incidence of opportunistic infections.
32
What methods does HIV used to evade immune responses?
Antigenic drift, latency, molecular mimicry, induction of acquired immunodeficiency
34
What is vaccination?
The deliberate administration of killed or non-pathogenic forms of the pathogen, or antigens derived from that pathogen in an effort to elicit protective immune responses specific for that pathogen.
35
What did the 1st smallpox vaccine consist of?
Dried pustules collected from individuals that experienced mild infections (variolation).
36
What is variolation?
Delivery of initial smallpox vaccine either intranasally or intradermally
37
What is immunization?
The deliberate prevocation of an acquired immune response by introducing antigen into the body.
38
What is any vaccine that employs killed pathogens as the antigen?
Killed or inactivated vaccines
39
What is an attenuated vaccine?
Any vaccine protocol that employs "weakened" pathogens as the immunogen.
40
What is a subunit vaccine?
Vaccines that employ only part of the pathogen as the vaccine immunogen.
41
What is an inactivated toxin that is used as a vaccine immunogen whose toxic activity has been destroyed?
Toxoid
42
What are the different forms of vaccines that are routinely administered?
Killed subunits; toxiods; whole killed virions; live attenuated viruses; Heptavalent; diptheria protein conj; conjugated capsule subunit; virus-like particles
43
What constitutes an effective vaccine?
Safe, Protective, Gives sustained protection, Induces neutralizing antibody, Induces protective T cells, Practical considerations
44
What is the goal of vaccination?
To trick the immune system; to provoke the immune system to produce responses to vaccine formulation as if it is responding to a pathogen.
45
What is the response that the immune system gives when it encounters extracellular pathogens?
Humoral Th2-driven responses (antibodies) (MHC Class II)
46
What is the response that the immune system gives when it encounters intracellular pathogens?
Cell-mediated Th1-driven responses (CTL-responsiveness) (MHC class I)
47
What route must be used to elicit a mucosal immune response?
A mucosal route
48
T/F Parenteral immunization will not elicit mucosal response.
TRUE
49
What is the worst parenteral route of immunization?
Intravenous
50
What are the two broad classiication of vaccines?
Whole pathogen (smallpox, live-attenuated, whole killed); and Subunit vaccines (pathogen-derived components, live vectors).
51
What is an adjuvant?
A substance that is used to enhance the adaptive immune response to a vaccine immunogen. Typically co-administered with the vaccine immunogen.
52
What is Freund's adjuvant composed of?
Oil-in-water emulsion
53
What is Alum adjuvant composed of?
Aluminum hydroxide gel.
54
What are ISCOMs?
Immune stimulatory complexes; Matrix of lipid micelles containing viral proteins
55
What is a liposome?
A highly stable closed vessicle formed by a single bilayer of phospholipids; can fuse with cellular membranes dumping their contents into the cytoplasm of the host cell.
56
What are adjuvants for the potentiation of mucosal responses?
Cholera toxin; E.coli; pertussis toxin
57
What is an attenuated pathogen?
A strain of a pathogen that will grow in the host and induce immunity without causing disease.
58
T/F Attenuated vaccines are typically more effective than killed vaccines.
TRUE
59
What are the safety issues that accompany the attenuated vaccine format?
Possible reversion of the virus to a virulent form; can result in iatrogenic disease
60
Which is safer - a mutated virulence gene or a deleted virulence gene?
A deleted virulence gene
61
How is a rotovirus similar to influenza virus?
1) it has a segmented genome (11dsRNAs) that can be exchanged in a superinfected cell (antigenic shift); 2) Immune protection via envelope glycoprotein-specific neutralizing Abs; 3)High mutation rate of envelope glycoproteins (VP4 and VP7) gives rise to distinct serotypes (antigenic drift).
62
How many known serotypes of Rotovirus are there?
42
63
What is Rotarix?
An attenuated human rotavirus that expresses common variants of VP4 VP7.
64
What is RotaTeq?
A mixture of 5 bovine strains of Rotavirus that are non-pathogenic in humans; genetically engineered to express common human variants of VP4 and VP7.
65
Which strategy would you use to vaccinate against the intracellular bacterium Listeria monocytogenes?
LMAg w/ ISCOMS and killed by B.pertussis sub-Q
66
Which method are DNA vaccines delivered by?
Intramuscularly or intranasally
67
Which subunit strategy would you use to generate mucosal protection against S.pneumo (extracellular bacterium)?
SpAg w/ cholera toxin B intranasal
68
T/F Injection of antibody specific for a particular cytokine alters response produced
TRUE
69
What are the potent adjuvant properties of cytokines?
They promote development of immune responses; help shape the immune response that is produced.
71
What is Asplenia?
An inherited disorder; patients have elevated susceptibility to encapsulated bacterial pathogens; susceptible to septic infections.
72
What is acquired asplenia?
Due to splenectomy following traumatic injury. Similar susceptibilities
73
What is the clinical intervention for Asplenia?
vaccination; phophylactic anibiotic treatment
74
What are phagocyte defects?
Defects in the recruitment of phagocytes to the extravascular sites of infection; can cause severe immunodeficiency; result in infections that are antibiotic resistant and persist
75
What are some examples of phagocyte defects?
Leukocyte adhesion deficiency; chronic granulomatous disease; myeloperoxidase deficiency; Chediak-Higashi syndrome
76
What occurs in chronic granulomatous disease?
Phagocytes cannot produce reactive oxygen compound; impaired ability to kill bacteria; patients have chronic bacterial infections, lead to the formation of granulomas
77
What is the mode of inheritence in chronic granulomatous disease?
X-linked trait; autosomal recessive
78
What is myeloperoxidase deficiency?
Patient's macrophages are unable to efficiently kill phagocytosed microbes; impaired ability to produce hypochlorous acid and toxic oxygen species; defective respiratory burst
79
What are the characteristics of Chediak-Higashi syndrome?
Partial albinism, abnormal platelet function, severe immunodeficiency
80
What is Chediak-Higashi syndrome result from?
A defective gene encoding a protein involved in intracellular vesicle formation that causes a failure of lysosome:phagosome fusion; impaired ability of phagocytes to kill pacteria
81
What disorders are characterized by low numbers of granulocytes?
Neutropenias (<500 cells)
82
What are the three most common types of Neutropenias?
Severe congenital neutropenia; cyclic neutropenia; benign chronic neutropenia
83
Which neutropenia is an autosomal recessive disorder associated with a gene abnormailty of G-CSF or G-CSFR?
Severe congenital neutropenia
84
Which neutropenia is an autosomal dominant disorder in which the neutropenia occurs every 2-4 weeks and lasts about a week; associated with ELA-2?
Cyclic neutropenia
85
Which neutropenia has low but not life-threatening neutropenia and is often asymptomatic?
Benign chronic neutropenia
86
Which primary immunodeficiencies have an associated neutropenia?
X-linked hyper-IgM syndrome, X-linked agammaglobulinemia (XLA), WHIM syndrome, Griselli syndrome
87
What are the 3 categories of NK cell defects?
Absolute NK cell deficiency (ANKD), Classical NK cell deficiency (CNKD), Functional NK cell deficiency (FNKD)
88
Which NK cell deficiency involves either the complete absence of NK cells and NKT cell, or total lack of NK cell function?
ANKD
89
What is CNKD?
Lack NK cells and NK cell function; presence of NKT cells
90
Which NK cell deficiency has normal NK cell numbers, but absent or severely decreased NK cell function?
FNKD
91
What is the clinical presentation of NK cell deficiencies?
Increased incidence and severity of viral and other infections esp. varicella zoster; mycobacterium avium; Trichophyton; and genetic deficiency.
92
What are some of the genetic deficiencies exhibited in patients with NK cell defects?
Defective formation of cytoplasmic granules; defective perforin; defects in development in bone marrow.
93
What is NEMO?
X-linked hypohydrotic ectodermal dysplasia and immunodeficiency; a genetic defect in a protein (IKKy or NEMO) required for NFkB activity
94
What type of developmental defects do patients with NEMO typically have?
Deep-set eyes, sparce/fine hair, conical or missing teeth, unusual blistering, changes in skin color
95
What are the clinical manifestions that patients suffer from?
Recurrent bacterial and viral infections (Mycobacterium avium)
96
What is the treatment for NEMO?
Biweekly injections of gamma globulin from healthy donor; bone marrow transplant
97
What do deficiencies of complement regulatory proteins cause?
Susceptibility to encapsulated bacteria (depletion of C3), autoimmune-like disease-complement activity destroys RBCs
98
What is an effect of a deficiency of C3?
Susceptibility to encapsulated bacteria
99
What is an effect of C5-C9 deficiency?
Susceptibility to Neisseria
100
What is an effect of Factor D and properdin (factor P) deficiency?
Susceptibility to capsulated bacteria and Neisseria
101
Which complement protein has a effect of deficiency similar to C3?
Factor I
102
What is the effect of a deficiency in DAF, CD59?
Autoimmune-like conditions including paroxysmal nocturnal hemoglobinuria
103
What deficiency causes HANE?
C1INH
104
What does C1INH do?
Binds to activated C1r:C1s forcing them to dissociate from C1q; controls spontaneous activation of C1 that always occurs.
105
What is a rare, acquired, potentially life-threatening disease characterized by complement-induced intravascular hemolytic anemia, red urine, and thrombosis?
Paroxymal Nocturnal Hemoglobinuria (PNH)
106
What is required for surface expression of CD59 and DAF?
Glycophosphatidylinositol
107
What is the only curative therapy for PNH?
Allogeneic bone marrow transplantation
108
What are some inherited antibody deficiencies?
X-linked agammaglobulinemia (XLA), pre-B cell receptor (gamma-5) deficiency, X-linked hyper IgM syndrome, selective IgA deficiency, selective IgG deficiency
109
What is XLA caused by?
A defect in B cell development
110
What is XLA?
A defect in Bruton's tyrosine kinase that is involved in signal transdution of B cell development
111
What are patients with XLA susceptible to?
Extracellular bacterial pathogens; many viruses
112
What is the cause of Pre-B cell receptor deficiency?
Mutation of gamma5 gene
113
What is gamma5?
A component of the surrogate light chain that pairs with the mu heavy chain during somatic recombination of light chain genes.
114
What happens if the surrogat light chain is not functional?
Inability of developing B cells to produce a pre-B cell receptor; all undergo apoptotic death; profound B cell deficiency results
115
What can X-linked hyper IgM syndrom be caused by?
A defect in T cell function, defect in CD40 ligand expression-B cells cannot receive 2nd activation signal. Also by activation-induced cytidine deaminase (AID) deficiency.
116
What is AID required for?
Isotype switching and somatic hypermutation.
117
What is characteristic of people with IgA deficiency?
Make higher leels of other Ab isotypes.
118
T/F IgG1 deficiency is vary rare; susceptibility ot many bacterial and viral pathogens.
TRUE
119
Who is IgG2 deficiency most common in?
Kids
120
What are kids with IgG2 deficiency susceptible to ?
Encapsulated bacteria
121
Who is IgG3 deficiency most common in?
Adults
122
What is Common Variable Immunodeficiency (CVID)?
A group of 150 primary immunodeficiencies that have common features that typically include reduced levels of antibodies, but different etiologies; Most common primary immunodeficiency disorder.
123
When does diagnosis of CVID typically occur?
2nd or 3rd decade of life
124
What is the clinical presentaion of CVID?
Recurring infections with vacterial and viral pathogens involving the ears, eyes, sinuses, nose, bronchi, lungs, skin, GI tract, joints, bones, CNS, parotid glands.
125
What results in very low levels of MHC class I molecules and defective responses to intracellular pathogens due to CD8 T cell deficiency?
TAP peptide transporter deficiency
126
What is the CD8 alpha chain defect?
Lack of CD8 expression; same phenotype as a TAP transporter deficiency
127
Dramatically or totally reduced CTL activity is a result of what?
Non-sense mutation of perforin
128
What can CD4 T cell defects result in?
SCID
129
What is bare lymphocyte syndrome?
A lack of expression of MHC class II molecules
130
What does adenosine deaminase (ADA)/purine nucleotide phosphorylase deficiency result in?
Accumulation of toxic nucleotide catebolites that kills developing B and T cells
131
What is the effect of the common gamma chain deficiency?
Impaired signaling results in failure of T cells to proliferate; no effector cells
132
What is the role of the common gamma chain?
It is the signaling component of several cytokine receptors and interacts with Jak3 to initiate signaling.
133
What is a mis-sense mutation that results in partially active RAG enzymes?
Omenn Syndrome
134
What does lack of RAG activity result in?
An absence of B cells and low numbers of oligoclonal autoreactive T cells. Patients develop fungal, bacterial, and viral infections typical of SCID.
135
What does DiGeorge Syndrome result from?
A small deletion in chromosome 22.
136
What is Complete DiGeorge Syndrome?
Much more rare malady in which the patient has absent or underdeveloped (nonfunctional) thymus and makes very few T cells.
137
What develops in patients with Complete DiGeorge Syndrome?
They develop fungal, bacterial, and viral infections typical of SCID
138
What is the treatment for Complete DiGeorge Syndrome?
Thymic transplant to treat immunodeficiency; no treatment for other features.
139
What is a genetic defect that prevents expression of functional ZAP-70?
ZAP-70 deficiency
140
What is ZAP-70?
A tyrosine kinase that associates with phosphorylated ITAMS during signaling via the T cell receptor complex.
141
What is ZAP-70 required for?
For signaling via the TCR.
142
What do patients with ZAP-70 deficiency have an absence of?
CD8 T cells, but normal numbers of non-functional CD4 T cells
143
What does ZAP-70 deficiency result in?
SCID
144
What is the treatment for ZAP-70 deficiency?
Bone Marrow Transplant
145
What does Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED) result from?
From genetic deficiency of a gene that encodes the autoimmune regulator (AIRE).
146
What is AIRE?
A transcription factor that regulates expression of several hundred host-tissue specific genes by epithelial cells in the thymic medulla.
147
What do the host specific proteins regulated by AIRE serve as?
A source of self-proteins for presentation during thymic negative selection.
148
What are some of the characteristics of APECED?
Problems in numerous glands; hypoparathyroidism; hypogonadism; adrenal insufficiency; type 1 diabetes; latent hypothyroidism; total baldness; keratoconjunctivitis; tooth enamel hypoplasia; candidiasis; juvenile-onset pernicous anemia; GI problems
149
What results from genetic deficiency of FoxP3 expression in regulatory CD4 T cells?
IPEX (Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-linked Syndrome)
150
When does the onset of IPEX occur?
Early onset within the 1st year of life
151
What is the autoimmunity in IPEX due to?
A lack of Treg cell function
152
How does IPEX present?
Water diarrhea, eczematous dermatitis, endocrinopathy.
153
What do children with IPEX display?
Coombs-positive anemia, autoimmune thrombocytopenia, autoimmune neutropenia, and tubular nephropathy.
154
What is the treatment for IPEX?
Aggressive immunosuppression and/or bone marrow transplant.
155
What is a genetic disease that is characterized by lymphadenopathy and splenomegaly?
ALPS (Autoimmune Lymphoproliferative Syndrome)
156
What does ALPS result from?
Immune cells failing to undergo apoptotic death following an immune response; and from a mutation that prevents expression of either Fas, Fas ligand, or caspase 10.
157
How does ALPS present?
Autoimmune hemolytic anemia and neutropenia, thrombocytopenia, lymphadenopathy, splenomegaly, large # of CD4-CD8-T cells.
158
What is the treatment for ALPS?
Immunosuppression and IVIg
159
What are some other immunodeficiencies?
Good's Syndrome; WHIM syndrome; Cartilage Hair Hypoplasia; Fanconi's anemia; Griscelli Syndrome
Immuno Block 2
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