Exam 4 Flashcards
1
Q
Serotypes
A
numerous strains of the same pathogen existing as a means to evade the immune system
2
Q
S. pneumoniae
A
has 90 different serotypes that differ in capsular polysaccharide but only one antibody can recognize one serotype capsule
3
Q
epidemics
A
local population spread
4
Q
influenza virus
A
displays genetic variation since antibodies rise against is tend to bind to hemagglutinin and neuroamindiase (glycoprotein of viral coat)
5
Q
antigenic drift
A
RNA replication is error prone and can introduce mutations; this evolution through mutation allowing for survival is this.
6
Q
pandemic
A
world wide spread i.e. viruses that emerge and are quite different from predecessors that can infect almost everyone
7
Q
antigenic shift
A
strains that cause pandemics are recombinate viruses that derive from some RNA genome from a human influenza virus and some from an influenza virus that infects a different species
8
Q
Trypanosomes
A
protozans like trypanosma brucei (sleeping sickness), S. typhimurium, N. honorrhoease.
9
Q
gene conversion
A
what happens when a variable surface glycoprotein is produced one at a time but rearrangment makes the expression site into requred for synthesis
10
Q
VSG gene
A
variable surface glycoproteines….for T. brucei there are more that 100 genes encoding this weird trypanosome surface glycoprotein
11
Q
hemagglutinin and neuraminidase
A
glycoproteins of influenza’s viral envelope and where antibodies tend to bind
12
Q
Trypanosome life cycle
A
involves both insect and human host where the insects transmit it to humans through bite.
13
Q
Trypanosome surface
A
made of glycoprotein and has 1000 genes encoding for varibale surface glycoproteins (VSGs), but only produce one at a time. Need rearrangement into the expression site for synthesis, VSG genes are moved into this expression site by gene conversion. Different human antibodies have to be made every time the VSG switches.
14
Q
Normal virus elimination
A
established viral infections are terminated by CD8 cytotoxic T cells after MHC class I presentation. Great for handling rapidly replicating viruses since there are more proteins around.
15
Q
Viral latency
A
dorment non-replicating state of virus where they do not produce enough proteins form MHC class I presentation
16
Q
M. tuberculosis and L. monocytogenesis
A
bacteria that live intracellularly after phagocytosis
17
Q
Toxoplasma gondii
A
creates a specialized intracellular environment
18
Q
Treponema pallidum (syphilis) and schistosome
A
coat themselves with human proteins
19
Q
Ways viruses subvert immune system
A
capuring cytokine genes, inhibition of complement, and inhibition of MHC class 1 presentation and synthesis
20
Q
Human Cytomegalovirus (HCMV)
A
Makes proteins aimed at MHC class 1 molecules. Some of the proteins lower MHC class 1 at the surface (should increase NK action) and other proteins block NK inhibitory receptor action responsible for sensing MHC class I
21
Q
Staphylococcal enterotoxins and toxic shock syndrome toxin-1
A
These are superantigens
22
Q
Superanitgens
A
Bind MHC class II and T-cell receptors together in absence of a specific antigen. This causes T cells to divide and differentiate randomly (polyclonal response) so the adaptive immune response is not specific or functioning. Causes a lot of IL-1, IL-2, TNF-a and thus systemic shock
23
Q
Normal monomeric Iga
A
normally functions as an opsonin for delivery to phagocyte
24
Q
Staphylococcal superantigen-like protein 7
A
(SSLP7) protein made by S. aureus which has binding sites for IgA and C5. Prevents IgA and C5 from working and stops bacteria from being phagocytosed
25
Pathology
the disease symptoms
26
Respiratory syncytial virus
(RVS) all of the symptoms are caused by T(h)2 cells responding to the infection and causing wheezing bronchiolitis. Vaccine just makes it worse by activating T(h)2 cells that produce cytokines on subsequent infection thus exacerbating the disease
27
Schistosoma mansoni
parasite who lays eggs which can get stuck in the liver. T(h)2 cells cause inflammation, hepatic fibrosis, and liver failure
28
Which of the following explains why Streptococcus pneumoniae can infect an individual recurrently?
Immune responses against S. pneumoniae are serotype-specific and protect only against strains that possess the same capsular polysaccharide antigens
29
The mode of evolution responsible for the production of recombinant influenza viruses composed of a genome derived from two different influenza variants is called .
antigentic shift
30
Which of the following contribute to new epidemics and the long-term survival of the influenza virus in the human population? (Select all that apply)
a. New viral strains possess epitopes not recognized by antibodies made in the previous epidemic
b. The first influenza strain provoking a primary immune response constrains the types of antibodies made during a subsequent encounter with a different strain
c. The RNA genome of the influenza virus is subject to point mutations during viral replication
d. The virus loses the capacity to express hemagglutinin, thereby rendering neutralizing antibodies useless
e. The virus uses gene rearrangement to achieve antigenic variation, which creates new epitopes
a, b, c
31
Trypanosomes escape from adaptive immunity by altering the type of expressed on the parasite surface.
variable surface glycoprotein
32
Which of the following are used by the herpes simplex virus to subvert host immune responses? (Select all that apply)
a. a virus-encoded Fc receptor
b. a virus-encoded complement receptor
c. inhibition of MHC class I expression
d. inhibition of peptide transport by transporter associated with antigen processing (TAP)
e. inhibition of ICAM-1 expression
a, b, c, d
33
Herpes simplex virus favors neurons for latency because of the low level of ____, which reduces the likelihood of killing by CD8 T cell.
a) LFA-3
b) Tool-like receptors
c) MHC Class I
d) MHC Class II
c) MHC Class I
34
The process whereby random mutations lead to viral evasion from previously developed immune responses, leading to epidemics is:
a) antigentic shift
b) antigentic drift
c) serotype switching
d) gene conversion
b) antigenic drift
35
"good" of inherited immunodeficiencies
There are over 150 with some more sever then others. However, their study and treatment has revealed a lot about the immune system
36
Inherited Immunodeficiency classification
dominant, recessive, or x-linked
37
Normal INF-gamma
major cytokine that activates macrohpages, induces phagocytosis, important in intravesicular infections (mycobacterial) is made by NK cells, T(h)1 CD4 T cells, and cytotoxic CD8 T cells.
38
Normal INF-gamma receptor
functions as a dimer to bind to Jak with activates STATs
39
INF-gamma receptor mutations
can be recessive or dominant and cause INF-gamma Receptor Deficiency
40
Recessive INF-g Receptor Mutation
no INF-gamma receptor at the surface leading to complete absence of INFgR1
41
Dominant INF-g Receptor Mutation
leads to no Jak binding and partial INFgR1 chain
42
Antibody deficiency
causes increase in infections by pyogenic bacteria (S. pyogenes, S. aureus)
43
pyrogenic bacteria
encapsulated like S pyogenes and S aureus, that cannot be recognized by professional phagocytes without antibody opsonization
44
X-Linked Agammaglobuinemia
(XLA was first immunodef found) Defective Btk kinase which is needed for growth and development of pre-B cells preventing mature B cells from forming. Females will have normal development in B cells with inactivated mutated X chromosome)
45
X-Linked Hyper IgM Syndrome
lack of functional CD40 needed for isotype switching
46
Complement Deficiency
Also tends to cause pyogenic infections, but can also cause buildup of immune complexes since early components of complement are important in elimination of immune complexes
47
Complement Activation Protein Deficiencies
can lead to increased infections and autoimmune-like states
48
C1, C2, C4 Deficiency
immune-complex disease
49
C3 Deficiency
Susceptibility to pyogenic bacteria
50
C5-C9 Deficiency
Susceptibility to Neisseria
51
Factor D, P Deficeincy
Susceptibility to encapsulated bacteria and Neisseria but no immune-complex disease
52
Factor I Deficiency
similar to C3 with increased pyogentic infections
53
DAF, CD59 Deficiency
Autoimmune-like conditions including paroxysmal nocurnal hemoglobinuria
54
C1INH Deficiency
Hereditary angioedemia (HAE)
55
Hereditary Angioneurotic Edema
HANE is an autosomal dominant disease caused by deficiency in complement regulator C1 inhibitor (C1INH). Causes swelling of face, laryn, abdomen, inactivates C1 protease, inhibits blood clotting proteases.
56
serpin
serine/cysteine protease inhibitor family...C1INH is one
57
Bradykinin
if high levels and fluid leaking out of the blood (edema)...due to C1INH not being around since it inhibits blood clotting proteases
58
Phagocyte Deficiency
Any defect in phagocytosis has a profound effect on infection clearance
59
Leukocyte adhesion deficiency
lack of integrin necessary for phagocyte homing....results in persistent extracellular bacterial infection
60
Chrongic granulomatous disease
CDG - defective NADPH oxidase....results in persistent bacterial infection and granuloma formation
61
Chediak-Higashi Syndrome
defect in vesicle fusion (phagocytosed material not delivered to lysosome)
62
Severe Combined Immune Dificiency
SCID can be caused by many different aspects of bad T cell development. Infants need to be in pathogen free environment and need bone marrow transplant and passive administration of antibodies
63
SCID causes
X-Linked (mutation in common gamma chain cytokine receptor, and Wiskott-Aldrich Syndrome), deficiency in Purine degradation, and Bare lymphocyte syndrome
64
Wiskott-Aldrich Syndrome
mutation in protein involved in cytoskeletal rearrangement needed for sytokine release and signaline
65
Deficiency in Purine Degradation
(adenosine deaminase and purine nucleoside phosphorylase) thought to lead to an increase in dATP whic hindibits nucleotide biosynthesis and thus DNA synthesis needed for proliferation
66
Bare lymphocyte syndrome
lack of MHC molecules from lack of AID or AIRE I think
67
IL-12 receptor deficiency
Also increases intracellular bacterial infections (linked to INF-g defeciecies)
68
Normal IL-12 Receptor
On NK and MO which are activated by IL-12 and leads to secreation of INF-g and macrophage activation. Oh T cells, IL-12 will induce differentiation into T(h)1 cells which then secrete INF-g for MO activation. On cytotoxic T cells, IL-12 activated leading to secretion of INF-g
69
X-Linked Lymphoproliferative Syndrome
immunodeficiency in SH2D1A (unknown function) leading to increased persistence of Epstien Barr Virus (EBV), which can lead to lymphoma
70
Immunodeficiency Treatments
Bone marrow transplant, somatic gene therapy since most immunodeficiencies affect hematopoietic cells
71
Bone Marrow Transplant Process
Patient's bone marrow destroyed by radiation and chemotherapy, followed by transplations of a graft from a healthy donor to reconsitute the entire hematopoiteic system
72
somatic gene therapy
replacing the defective gene is being explored as an option
73
Transplant Considerations
HLA Matching
74
Purpose of HLA matching
reduces graft-versus-host disease, and ensures reconstitution of immune system. The recipient's HLA molecules is what drives positive selection in T cell development, but the donor HLA molecules will be doing the presentation of peptides to T cells by antigen-presenting cells
75
Graft-versus-host disease
response to allogeneic MHC molecules
76
During bone marrow transplant... Positive selection of T cells
driven by recipient HLA molecules
77
During bone marrow transplant....presentation of peptides to T cells by antigen-present cells
due to the donor HLA molecules
78
Which of the following is not an example or mutation found in SCID?
a) Mutation in adenosine deaminase
b) Hereditary Angioneurotic Endema (mutation of C1INH)
c) Wiskott-Aldrich syndrome (mutation in WASP - cytoskeletal protein)
d) Mutation in common gamma chain cytokine receptor
b) Hereditary Angioneurotic Endema (mutation of C1INH)
79
Symptoms of AIDS first recongnized
Early 1980s characterized by a large reduction in CD4 T cells and subsequent infection by pathogens that normally don't infect healthy individuals, or by very aggressive lymphomas
80
Human Immunodeficiency Virus
isolated in 1983 (actually two types HIV-1 and HIV02 but HIV-1 is the principal cause
81
Early evidence of HIV
Late 1950s, its believed that the virus was caused by antigenic shift from primate virus
82
HIV infection number
WHO estimated 33 million people are infected
83
Characteristics of HIV
RNA virus with ribonucleoprotein core, Retrovirus, nucleocapsid proteins (protease, reverse transcriptase, integrase) uses host cells transcription and translatio machinery to make virions
84
Retrovirus
uses an RNA genome to direct synthesis of a DNA intermediate
85
Protease
HIV nucleocapsid protein, cleaves glycoprotein to produce gp41 and gp120 at surface
86
Reverse Transcriptase
converts viral RNA genome into a complementary DNA (cDNA)
87
provirus
cDNA is integrated into the genome
88
General Life cycle of HIV
1) virion binds to CD4 and co-receptor on T cell
2) Viral envelope fuses with cell membrane, and viral genome enters cell
3) reverse trascriptase copies viral RNA genome into double-stranded cDNA
4) Viral cDNA enters nucleus and integrates into host DNA
5) T-cell activation induces some transcription of provirus
6) RNA trascriptions are spliced to allow synthesis of early proteins Tat and Rev
7) Tat amplifies transcription of viral RNA. Rev increases transport of RNA to cytoplasm
8) Gag, Pol, and Env are made and assembled with viral RNA into virions which bud from the cell
89
Cells HIV infects
CD4 T cells, dendritic cells, and macrophages since they all express CD4
90
gp120
is on outside of HIV and binds tightly to CD4 and a co-receptor (CXCR4(lymphocyte) or CCR5(MO))
91
gp41
mediates fusion of the viral envelope with the host cell plasma membrane
92
Virion production
requires T cell activation since T-cell activation causes activation of transcription factor NF-kB which binds the promoter of the provirus, thus directing RNA transcription of viral RNAs
93
Tat
viral protein that binds long terminal repeat of viral mRNA known as the trascriptional activation region (TAP) to increases viral RNA transcription
94
Rev
viral protain that controls supply of viral RNA to the cytoplasm and RNA splicing
95
Rev early action
RNA to encode viral proteins
96
Rev late action
viral genomes
97
gp160
made from provirus and is the precursor to gp41 and gp120 after protease cleaves it.
98
HIV Infection Immediately
either asymptomatic or flu-like, but dramatic decline of CD4 T cells, possible immune response with antibodies and cytotoxic T cells activation
99
Seroconversion
2-6 weeks after initial HIV infection, when first exhibition of anti-HIV antibodies inblood serum. Slight rebound of CD4 T cells and patient is asymptomatic. Lasts 2-15 years (average 10) and the CD4 T cell population steadily declines until half of normal levels making effeciive immune response unlikely (sympotmatic phase)
100
Symptomatic phase
Effective immune response does not exist, lasts until 20% of CD4 T cells remain...after full blown AIDs
101
HIV-infected progession prognosis
Most HIV-infected individuals will progess to AIDs without medical treatment (seen by studying infection of hemophiliacs with contaminated blood.
102
Seronegative
Very small group of HIV infected people who do not progress to AIDs even with extensive exposure to virus like sex workers. Some even have cytotoxiv lymphocytes and T(h)1 cells directed against infected cells.
103
CCR5 Deficiency
Causes resistance to HIV infection. Causes mild immunodeficenty. Might have come from selection for this mutation during plague and smallpox
104
CCR5 normal
plays a role as a chemokine receptor (also the MO co receptor that tightly binds to gp41 of HIV)
105
CCR5-delta32
the mutation that causes the CCR5 deficiency. Only found in caucasians, and 10% of the population is heterozygous, 1% homozygous)
106
HLA homozygosity and AIDs
speeds up the progession to AIDs but there are some allotypes that slow the progression (present HIV peptides and activate NK cells)
107
HIV Therapy Targets
Reverse transcriptase inhibitors, Protease inhibitors, Fusion/Entry inhibitors, Integrase inhibitors, multi-drug combinations, maturation inhibitors...31 FDA-approved drugs on market (ish)
108
Reverse Transcriptase Inhibitors
nucleoside and non-nucleoside...prevent action of reverse transcriptase
109
Protease Inhibitors
prevents production of infectious viral particles
110
Fusion/Entry Inhibitors
prevents viral fusion with host cell membrane
111
Integrase Inhibitors
blacks integrase, required for viral cDNA incorporation
112
Multidrug Combination Products
combines more than one drug class into a single product to prevent resistance...HAART
113
maturatio inhibitors
in development, prevent virion assembly and then prevent HIV outer coat assembly or viral budding)
114
HAART
highly active antiretrovial therapy...combo of antiretorviral drugs
115
HIV mutation rate
very high since RNA has lack of proofreadind of reverse transcriptase. complicates vaccine development and effectiveness of antiviral drugs.
116
Antiviral Failure
when drugs target a specific HIV viral process, the drug will lose effectivness as the virus mutates to be resistant to the drug. Resistance to protease drugs can start within days but then months for reverse transcriptase.
117
General action of antiviral drugs
1) productive infection of CD4 T cells accounts for more than 99% of virus in plasma
2) Infected cells are short-lived (3-4days) so HIV must continually infect new cells
3) if virus production is blocked by a drug, the virus is rapidly cleared from the blood (neutralizing antibodies, complement, phagocytes)
4) CD4 T cell numbers will rapidly increase to replace those lost by infection
118
Clinical latency
When during therapy the CD4 T cell numbers increase.. During this, a vast number of viruses and CD4 cells are produced and dying
119
Onset of AIDs
Even with clinical latency, CD4 T cells will continue to decline until adaptive immune response is not effective and individuals are susceptible to other infections (resembles SCID)
120
Common AIDs onset infections
usually from opportunistic infections with infectious agents already present in our body but normally under conrol.
121
First opportunistic infections
Tend to be in oral and respiratory tract (Candida, M, tuberculosis)
122
Late onset of AIDs infections
herpesvirus reactivation can lead to shingles, B cell lymphoma (EBV), and Kaposi's sarcoma (endothelial tumor)
123
AIDs Pneumonia
very common caused by Pneumocystis carinii
124
Broadly Neutralizing Antibodies
Tend to recognize one or four epitopes on gp120 (all epitopes are in functinally relevant locations) and can be polyractive between two different antigens (gp120 and CD4)
125
Elite Neutralizers
1 in 500 make antibodies that neutralize a broad range of HIV-1. Targeting this natural production or using passive immunization could be HIV treatments.
126
Hypersensitivity (allergic) reactions
overreactions of the immune system to harmless environmental agents
127
Allergens
environmental agents that drive hpersensitivity reactions
128
Who has allergies?
10-40% of the population in developed countries
129
Common allergens
Inhaled (pollen, dust mite feces), Injected (insect venom, drugs), Ingested Material (peanuts, shellfish), Contacted Material (plant oil, metal)
130
Type 1
binding of antigen to IgE, principally on mast cells (typically inhaled antigens) – sometimes referred to as immediate hypersensitivity
131
Type 2
covalent binding of small molecules producing foreign-looking particles – B cell response leads to IgG production (e.g. penicillin allergy)
132
Type 3
immune complexes deposit on tissue walls and cause damage (e.g. nonhuman antibodies and proteins used in therapy)
133
Type 4
lipid-soluble antigens covalently bind to intracellular proteins, yielding abnormal peptides during MHC presentation – thus effector T cells are involved (also called delayed-type hypersensitivity)
134
IgE and multicellular parasite infections
Too large to be easily phagocytosed so expulsion is the major immune response. IgE is protective in multicellular parasite infections and central component of T(h)2 response.
135
Helminth parasite infection
Helminth stimulates T(h)2/IgE to aid in poly clonal response. Adaptive immune further kicks in the cytokines, IgG, expanded eosinophil, basophil, mast cell populations. 1.5 billion people persistently infected)
136
Hygiene Hypothesis
vaccination, improved, hygiene and antibiotics are great but might hold back a child's developing immune system. Could lead to immune system being poorly educated and overreacting to false dangers...like allergies
137
Why Mast cells and not B cells?
B cells have highly specific immunoglobulins on the surface but are committed to only one. Mast cells bind soluble antibodies to their receptors in a non antibody-specific way....leads to polyspecific mast cells
138
Fc(e)RI
Expressed on mast cells, eosinophils, basophils which all have granules containing inflammatory mediators. When IgE binds to its antigen, degranulation causes release of inflammatory mediators.
139
IgE and Fc receptors
IgE has an extremely high affinity for the Fc receptor Fc(e)RI and binds even in the absence of antigen. IgE can also bind to the Fc(e)RII receptor
140
Difference between IgE bound cells and antigen receptors of B and T cells
Action is immediate (no cell proliferation needed) and cells can have multiple IgE receptors bound.
141
Normal Mast Cell Action
present in mucosal tissue, spithelial tissues, and vascularized tissue. There to alert the immune system to local trauma and help repair damage from wounds and infection. Contain 50-200 inflammatory mediator filled granules. Can also use cytokines to recruit other cells to infected tissued
142
Mast Cell Granules Contain
Histamine, Heparin, TNF-a, Proteases, other degenerative enzymes
143
Speed of mast cell degranulation
happens withing seconds of IgE molecules crosslinking
144
Histamine
Exerts a variety of responses included vessel permeability and smooth muscle contraction. Depending on the effected tissue, can induce sneezing, caughing, wheezing, vomiting, and diarrhea.
145
TNF-a in mast granules
promotes leukocyte homing
146
Synthesized by mast cells
prostaglandins and leukotrienes which both come from arachidonic acid
147
leukotrienes
will act similar to histamine
148
prostaglandins
promotes dilation and vessel permeability. enzyme that produces is target for aspirin and thus inactivates the prostaglandin.
149
Eosinophil Action
most reside in tissue, gruanules contain arginine-rich basic proteins and toxic molecules aimed at microorganisms and parasites, also make prostaglandinss, leukotrienes, and pro inflamm cytokines, controlled by presence at low levels and modulation of Fc receptor presence
150
Hyperesosinophilia
presence of high numbers of eosinophils which can cause heart damage and neurophathy
151
Basophil Action
Granules similar to mast cells, <1% WBC, seems important for T(h)2 response (secretes Th2 cytokines), activated via TLR, express CD40 lignad to allow for B cell activation and driving of isotype switching to IgE and IgG4
152
IgE Allergic Reactions
Systemic anaphylaxis intravenous or after rapid absorption or drugs, serum, venom, peanutes. Wheal and flare from subcutaneous insect bites or allergy testing. Allergic rhinitis (hy fever) from inhaled pollens. Bronchial asthma from inhaled pollens. Food allergy for oral eating.
153
Inhaled Allergens
Most are small, soluble proteins on dried up particles of plants or animals (pollen or cat dander). Inhalation and association with mucus rehydrates dried particle releasing antigen. Takken up by APC, then Th2 response. This promotes IgE response
154
D. pteronyssimus
The dust mite that produces a protease which is related to proteases used in meat tenderizing, laundrgy detergent, and medicine. 20% of allergies in North America caused by this.
155
Atopy
the predisosed state to allergies. up to 40% of the population is more likely to develop allegies.
156
Atopy genetics
only 50% of atopy is due to genetics but is very complicated with different polymorphisms in many different genetic loci. 6 loci in asthma predisposition are involved in stimulation of antigen-specific IgE while others are tissue specific.
157
Wheal and Flare Allergy Testing
Produced within a few minutes of immediate reaction from allergen injection. Caused by IgE-mediated degranulation of mast cells causing local swelling. Last up to 30 minutes for Immediate-Phase Response.
158
Late Phase Reaction
6-8 hours after the immediate action during allerby testing, there can be more widespread swelling.
159
Asthma allergy tests
skin tests cannot assess allergens that cause asthma (breathing must be monitored)
160
Factors Mast Cell Allergic Response
depends on the location since only the mast cells at the site of exposure degranulate so that molecules and reactions are short lived. Normally mucus of respiratory and GI tract, blood, or connective tissue. ALso wanting to expulse antigen
161
Systemic anaphylaxis
when allergen in bloodstream causes widespread activation of connective tissue mast cells. Increases vascular permeability and constriction of smooth muscle, loss of fluid from blood, death with asphyxiation by airway constriction and epiglottis swelling. From venoms, drugs, peanuts.
162
Anaphylactic Shock
loss of fluid from blood causing rapid lowering of blood pressure
163
Systemic anaphylaxis treatment
epinephrine, which reduces permeability and relaxes bronchial smooth muscle.
164
Drug reactions from type II cause
hemolytic anemia (destruction of red blood cells) and or thrombocytopenia (destruction of platelets)
165
Penicillin-modified red blood cells
Become coated in C3b since complement is activated from the bacterial infection the penicillin is treating. MO uptake these and present peptides of penicillin-protein conjugate to CD4 T cells which become Th2 cells. Be cells also activated, activate Th2, plasma cells make IgE for penicillin, arm mast cells, anaphylaxis
166
Rhinitis
most common entry of allergens come from inhalation causing this
167
Hay Fever
allergic rhinitis - sneezing and runny nose caused by inhaled allergens that stimulate mast cells in mucosa of nasal passages – can also spread to eyes, ears and throat, leading to accumulation of fluid and potential bacterial infection
168
Allergic Asthma
130 million people world wide. triggered by mucosal mast cells in respiratory tract getting activated by inhaled allergens. Causes mucus secretion and brochial constriction. Can be acute or chronic.
169
Chronic Asthema
Chronic inflammation in asthma patients can cause chronic asthma, where inflammation develops even in the absence of allergen (likely caused by other environmental factors or infections of the respiratory tract)
170
Urticaria/Hives
the itchy swelling things when mast cells in the skin cause histamine release (also if allergen is in the blood)
171
angioneurotic edema allergy
can happen if activation of mast cells in deeper subcutaneous tissue occurs (also if allergen is in the blood)
172
Eczema
more prolonged allergic response that causes skin rash and fluid discharge
173
Food Allergies
Occurs when people that are sensitized to a particular protein eat a food containing it and the degradation of the proteins lead to peptides that can be presented to T(h)2 cells. Very few food peptides recognized by IgE. Reaction from mast cells in GI tract causing fluid leakage, smooth muscle contraction, cramping, vomiting, diarrhea.
174
Three Allergy Treatments
Behavior and environment modification, parmacological, immunological
175
Behavior and Environment Mods
avoid foods, refunish house, pollen avoided
176
Pharmacological Allergy Drugs
Antihistamines, corticosteroids, cromolyn sodium, epinepherine
177
antihistamines
reduce rhinitis and urticaria
178
corticosteroids
suppress asthma, eczema, rhinitis
179
cromolyn sodium
asthmatic inhaler
180
epinephrine
prevent anaphylactic reactions
181
Immunological allergy treatment
shifts antibody response from producing IgE to IgG through desensitization (gradual increase of exposure to and allergen or vaccination or an allergen)
182
Women who are heterozygous for a defective Bruton’s tyrosine kinase (Btk) gene
have a non-random X inactivation in their B cells
183
. results in defective phagocytic processes causing chronic bacterial infections. (Select all that apply)
a. Chediak-Higashi syndrome
b. myeloperoxidase deficiency
c. chronic granulomatous disease (CGD)
d. Wiskott-Aldrich syndrome
e. X-linked agammaglobulinemia (XLA)
a, b, c
184
____participates in the T-cell cytoskeletal reorganization required for T-cell cytokine production and cell-mediated interactions.
Wiskott-Aldrich syndrome protein (WASP)
185
A genetic defect in results in the accumulation of toxic levels of nucleotide metabolites and loss of T-cell function.
adenosine deaminase (ADA)
186
Which of the following statements about human immunodeficiency virus (HIV) is/are correct? (Select all that apply)
a. HIV infects cells expressing CD4
b. HIV requires the CXCR4 or CCR5 co-receptor for internalization by T cells
c. NF-B is a transcription factor that facilitates transcription of proviral RNA
d. HIV has a DNA genome
e. HIV must synthesize reverse transcriptase immediately after infecting the cell
a, b, c
187
Which of the following is required for fusion of the human immunodeficiency viral envelope with the host cell membrane and subsequent internalization?
gp41
188
The high degree of mutation in HIV, the accumulation of variant viruses, and the development of resistance to drug regimes are attributed to
absence of proofreading capability of reverse transcriptase
189
Inhaled allergens possess which of the following features that promote the priming of TH2 cells that drive IgE responses? (Select all that apply)
a. They are proteins
b. Many are proteases
c. They are processed into peptides that bind MHC class I
d. They are encountered at high dose
e. They are of high molecular weight
a, b
190
Aspirin (acetyl salicylate) inhibits prostaglandin synthesis by binding irreversibly to prostaglandin synthase, the first enzyme in the pathway.
cyclooxygenase
191
Which cell is NOT a cell type that contains the receptor FceRI?
A. TH2 CD4 T cells
B. Mast cells
C. Basophils
D. Eosinophils
A
192
Type II and Blood Transfustion
From RBC types having different carbohydrates on glycolipids. ABO.
193
Blood Transfusions
Genetic barriers are not extreme, erythrocytes lack MHC so it is only dependent on ABO and rhesus antigens. Patients and donors typed to see if antibodies react with donor blood
194
ABO Antigens
expressed on endothelial blood vessels which becomes important for solid organ transplant
195
Hyperacute Rejection
ABO reaction that would produce antibodies that fix complement in the vasculature throughout the graft. Similar to a type II hypersensitivity. Can also be caused by HLA class I molecules on vascular endothelium.
196
Lysis of lymphocytes
cross-match testing done before transplant to see if any antibodies will induce complement-mediated lyksis of donor lymphcytes
197
Normal anti-HLA antibodies
could be present before a transplant due to pregnancy, blood transfusion, or from a previous transplant
198
Paternal HLA
can stimulate alloreactive immune response – placenta segregates fetal and maternal circulation to prevent maternal B and T cells from being stimulated by fetal alloantigens
199
Fetal origin cells
can enter maternal circulation during birth which can make antibodies against paternal HLA
200
Blood transfusion and HLA
HLA-incompatible leukocytes can promote antibody production
201
Panel Reactive Antibody
PRA assessing sensitization of an individual to population
202
Alloantigens
antigens that vary between members of the same species
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Alloreaction types
depends on the type of tissue. transplant rejection (solid organs targeting of transplanted tissue) and graft-versus-host disease (bone marrow, attack of recipient tissue)
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Acute rejection
when there is an organ transplant performed across HLA differences and the recipient T cells produce a response that destroys organ graft. can be prevented/reduced with immunosuppressive drugs and/or anti-T cell antibodies
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Direct pathway of allorecognition
inflamed state activates donor dendritic cells which drain inot secondary lympoid tissues; alloreactive T cells are activated by donor dendritic cells and directly target graft tissue
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ischemia
loss of blood to organ...seen in inflammed organs. usually already a problem for someone receiveng an organ
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Organ Chronic Rejection
can take months or years to develop and is characterized by thickening of the vasculature vessel walls and narrowing of the lumina, Causes decreased blood supply (ischemia), loss of graft function, and graft death. 50% of kidney and heart transplants within 10 years of transplats. Correlated with antibodies to HLA class I
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Indirect pathway of allorecognition
donor dendritic cells die by apoptosis, membrane fragments (may include donor HLA molecules) taken up by recipient dendritic cells so recipient dendritic cells present HLA fragments via Class II mechanism and activated CD4 T cells which active B cells to produce anti-HLA antibodies
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Corticosteroid Immunosuppressive Drug
Anti-inflammatory properties that change gene expression by binding to intracellular receptors associated with Hsp90 causing release fro Hsp90 so the steroid receptor can travel into nucleus and bind sterouid regulator elements. Inhibits NF-kB
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Immunosuppressive drugs that inhibit T cell Activation
Made of microbial products that inhibit T cell activation. Cyclosporin binds to cyclophilins and inhibits calcineurin so NFAT cannot be activated.
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FK506 (tacrolimus)
immunosuppresive drug with similar action of cyclosporin.
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Cyclosporin and FK506
inhibit T cell activation but also inhibit B cell activation and granulocytes (no t cells to activate these). they dont target dividing cells
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Rapamycin
immunosuppressive drug that block IL-2 signaling and inhibits T/B cell activation
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Type III Hypersentsitivity and antibody therapy
example is serum sickness which used to be caused by horse serum being injected to treat scarlet fever, diptheria, and tetanus.
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Serum sickness cause
deposition of small immune complexes of antibodies against horse protain or if monoclonal antibodies are used as therapeutics and sometimes those who's heart attack is treated with streptokinase to dissolve blood clots
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CTLA4 normal
potent negatice regulator of T-cell activation by binding to B7 on APC
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Belatecept
soluble form of CTLA4 fused to immunoglobulin constant region to block B7 on APC binding to CD28 on T cells ....is immunosuppressive drug
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Anti-CD25 antibodies
block high-affinity IL-2 receptor and blocks T cell activation
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Cytotoxic Drugs
kill prolierating lymphocytes by inhibiting DNA replication by inhibiting purine or pyrimidine biosynthesis, crosslinking DNA molecules, or something else
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Cytotoxix drug targets
Kills all dividing cells so it focuses on bone marrow, intestinal epithelium, and hair follicles, but can also cause tissue damage leading to cancer
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Cytotoxic drug examples
azathioprine, merceptopurine, thioinosinic acid, mycophenolic acid, methotrexate, cyclophophamide, phesphoramid mustard
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Bone Marrow Transplant treats...
inherited genetic diseases of white and red blood cells systems, some cancers are treated with autologus transplants and some with allogentic
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autologous
comes from self
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allogeneic transplant
comes form donor
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Dual need for HLA matching
minimize transplant complications and also vital for normal immune cell function
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Key reminders for HLA matching
all blood cells including APC come from hematopoietic system (donor) and T cells develop in recipien's thymus so HLA molecules in the thyum are responsible for positive selection (revipient) must resemble those of APC (donors)
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Bone marrow graft-versus-host disease
most common alloreaction and acute autoimmunity can be fatal. mature T cells from graft (donor) will interact with recipient dendritic cells where they will be stimulated and differentiated into effector cells. Can create inflammation in tissues including skin, intestinal epithelium, and liver via cytokine storm
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Occurance of GVHD
almost all bone marrow transplants result in graft-versus-host diease but the severity depends on how close the HLA matching is
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autologous bone marrow transplant
removal of patient's own bone marrow cells and saving of non-tumor stem cells for reimplantation
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isolation of marrow now
now we can just isolate hematopoetic stem cells from peripheral blood instead of taking bone marrow
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Minor Histocompatibility Antigens
H-Y antigens derived from proteins on Y chromosome which can lead to GVHD even after HLA cross-matching between siblings (especailly bad for males). Presented by HLA class I
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Reduce GVHD
remove T cells from graft before transplant...will reduce GVHD but increases graft failure and cancer replapse
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Graft-Versus-Leukemia Effect
can be used as an alternative to chemotherapy and irradiation, especaily when patient cannot find HLA-match donor. Alloreactive T cells target the leukemia cells.
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haploidentical transplant
when family member may share one HLA haplotype
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function of graft-versus-leukemia effect
after T cells are removed and anti-T cells antibodies are infused (prevent GVHD), NK cells can go against leukemia cells needed to prevent relapse based on action of KIR receptors
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Autoimmunity caused by
failures in maintenance of self tolerance and by action of the immune system itself attacking cells of the body but can vary widely in tissues attacked and symptoms caused
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Autoimmunity defining characteristics
autoantibodies, and T cells that recognize autoantigens (reffered to as autoimmune T cells)
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Normal mechanisms of self tolerance
regulatory proteins prevent fixation of compliment on human cells, innate imunity recognition molecules can distinguish between microbial and human componenets, B and T cells are subjected to negative selection or become anergenic, regulatory T cells also actively suppress autoimmune cells, and tissues like the brain, eyes, testies, pregnant uteruses are not accessible to ciruclating leukocytes
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How autoimmune dieases are classified
by the effector mechanisms that cause the disease and three types correspond to types II, III, and IV hypersensitivity in terms of effector mechanisms
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Autoimmune Type II
antibody against cell-curface or matrix antigens
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Autoimme Type III
Immune-complex disease
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Autoimmune Type IV
T cell-mediated disease
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Autoimmune Hemolytic Anemia
corresponds to type II - IgG and IgM bind to components of RBC and activate classical compliment )
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Completion of complement pathway for type II autoimme
cause lysis (membrane attack complex) and or phaocytosis (spleen)
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WBC and autoantibodies
facillitates phagocytosis but WBC can still function with autoantibodies and complement on suface
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splenectomy
treatment for WBCs with autoantibodies and complement
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Normal Endovrine Glands
express tissue-specific proteins and there is vascularization of tissue...makes very prone to autoimmune disease and the majority of autoimmune diseases
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organ-specific autoimmune dieases
when autoimmune diseases affect endocrine glands and target one type of cell in that gland
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AIRE
malfuntion can cause autoimmunity called APECED
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Autoimmune diseases of Thyroid endocrine gland
hashimoto's thryoiditis, Graves' disease, subacute tyroiditis, isiopathic hypothyroidism
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Autoimmune diseases of Islets of Langerhans (pancreas) endocrine gland
Type 1 diabetes, Type 2 diabetes
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Autoimmune diseases of Adrenal endocrine gland
Addison's disease
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APECED diseases
a lot...especailly finish people
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Goodpasture's Syndrome
antibodies against type IV collagen (in basement membranes...extracellular protein...rare) then deposit in renal tubules and glomeruli casing renal inflammation and failure while blood not being filtered. Treatment is plasma exchange and immunosuppressive drugs
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Systemic Lupus Erthrematosus
(systemic autoimmune disease) autoantigens for almost every cell of body specifically ciruclateing IgG for cell curface, cytoplasm and nucleus, including nucleic acids.
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SLE trigger
antibodies against cell surface moelcules cause finlammation, cell destruction, and release of intracellular antigens...exacerbating symptoms.
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Prognosis SLE
majority will have failure of vital tissues like kidneys and brain....the frist system is butterfly rash on face. 1/500 women of african or asian descent affected
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intermolecular epitope spreading
how the broad antibody response in lupus develops - destruction of cells by surface recognition causes release and recognition of intracellular contents
- autoreactive T cells recognize peptides from nucleosomal complex and then activate multiple B cell types that can present the complex
- activated b cells further amplify T cell response by activating different T cells that recongize different nucleosmal components
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Normal Thyroid
regulates basal metabolic rate through the action of two hormones – tri-iodothyronine (T3) and thyroxine (T4) – iodinated derivatives of tyrosine while the epithelial cells make thyroglobulin which needs iodine.
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TSH
normally when metabolic rate increase is needed, the pituitary secretes this
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TSH function
stimulates endocytosis of thryoglobulin which then degrades to release T3 and T4 (then shuts down TSH release)
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Unique thyroid proteins
thyrogolbulin, thyroid peroxidase, TSH receptor, thryoid iodide transporter
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Graves' Disease
– antibodies to TSH receptor – mimics TSH and causes overproduction of thyroid hormones (hyperthyroid conditions) – results in heat intolerance, nervousness, irritability, weight loss – treatment is drugs to inhibit thyroid function
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Hashimoto's Disease
– thyroid loses capacity to produce thyroid hormones (destruction of thyroid tissues) – treatment is replacement of thyroid hormones
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antagonist
block
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aganist
mimick
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Ectopic lymphoid tissue
infiltrating immune-system cells that organize into structures resembling microstructures of secondary lympoid tissue (feature of hashimoto) and even can do similar functions (B and T cell activation, B cell somatic hypermutation and isotype switching)
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Lymphotoxin
drives formation of ectopic lymphoid tissue
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Ectopic lyphoid tissue dieseases
rheumatoid arthritis, graves, MS, and is other chronicaaly infected individuals
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Why is it hard to indentify autoantigens?
healthy people also have autoimunity!
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Prevent autoimmune disease transfer to baby
mother with graves has anti-TSHR antibodies, cross placents, baby has it, plasmapheresis removes maternal anti-TSHR antibodies and cures infant
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Type I Diabetes
insulin-dependent - destruction of insulin producing cells in pancreus ...1/300 europeans
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islets of langerhans
responsible for secretion of pancreas hormones
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How Type 1 diabetes destroys
raises antibodies and T-cell responses to insulin, glutamate decarboxylase, and other specialized proteins of the pancreatic beta cells causing their destruction and insulitis
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Rheumatological diseases
commonly affects joints causing inflammation. the inflammatory response caused by secretion of prostaglandins, leukotrienes, lysosomal enzyems, TNF-a, IL-1, IL-6, IL-17.
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Rheumatoid arthritis
most common rheumatological disease affecting 1-3% of US with chronic joint inflammation. Rheumatoid factor normally present
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rheumatoid factor
IgM, IgG, and IgA antibodies sepecific for Fc region of IgG (anti-immunogolbulin antibodies)
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Old RA treatment
combination of phsiotherapy and anti-inflammatory and immunosuppresive drugs
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New RA treatments
infliximab and rituximab (biologics)
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Infliximab
anti-TNF-a monoclonal antibody which eliminates the cytokine and reduces C-reactive protein driven inflammation
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Rituximab (humera)
– anti-CD20 monoclonal antibody which depletes B cells through antibody-mediated cytotoxicity
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Autoimmune diseases of nervous system
MS, Myasthenia gravis
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Multiple sclerosis
autoimmune response against myelin sheath of nerve cells – causes motor weakness, impaired vision, lack of coordination, spasticity
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Effectors of MS
TH1 CD4 T cells and IFN-g which activates macrophages that release proteases and cytokines leading to demyelination
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MS treatment
IFN-b1 injections and high doses of immunosuppressive drugs
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Myasthenia gravis
disruption of neuromuscular junction signalins where autoantibodies to acetylcholine receptors cause internalization and destruction. treat with pyridostigmine
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pyridostigmine
inhibitor of cholinesterase (degrades acetylcholine
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Celiac Disease
immune response to gluten proteins so that CD4 T cells respond to the peptides activate tissue MO thus secreteing pro-inflammatory cytokines into SI. Atrophy of villi, no nutrient absorption, diarrhea
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HLA-DQ Allotype
genetic predisposition to celiacs because peptides with glutamine residues converted to glutamate presented by this allotype
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DNA mutation
drives cancer
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benign
encapsulated tumors
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malignant
continually increase size and invade adjacent tissues
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Metastasis
spreading of cancer in blood/lymph to secondary site
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Oncogene
mutated gene in cancer that normally positively contributes to growth
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Tumor Suppressor
genes that prevent unwanted proliferation of mutatnt cells
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p53
germline mutation that is a genetic factor influencing cancer development
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Environmental factors influencing cancer
chemical agents, UV light, radiation, cigarette smoke
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Chemical agents of cancer
generally cause single base subsititutions
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Radiation and cancer
cause grosser DNA damage by breaking dna, crosslinking nucelotides, and abnormal recomination
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oncogenic viruses
viruses that can transform cells and are thus associated with 15% of human cancers
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Chronic oncogenic viruses
typrical method by being chronic and override normal cell division control (Epstein-Barr drives B cell proliferation)
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Other oncogenic viruses methods
prevent normal tumor suppressor function and thus predispose for cancer (papillomavirus proteins inhibit p53 and Rb) and then other virusus just lead to cancer through tissue damage and renewal
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First response to cancer
there is a lowering of MHC class I which NK cells sense and cytotoxic T cells aid in cancer immunosurveillance
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Cancer different from infection
can go years without imune system noticing since there isn't any tissue damage or inflammation.
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Cancer and bacterial infection
some cancer patients see tumor shrinkage
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Cancer and adaptive response
almost all cancer patients make tumor antigens
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tumor-specific antigens
antigens expressed on tumor cells but not normal cells
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tumor-associated antigens
antigens expressed at higher amounts by tumor cells
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peptide splicing
means of deriving some tumor peptide antigens
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Cancer Evasion of Immune System
- tumor cells normally have increased MIC expression
- NKG2D on NK and gamma:delta T cells bind to MIC, killing the tumor cells
- a variant tumor cell expresses a protease that cleaves MIC from its surface
- soluble MIC binds NKG2D on lymphocytes
- variant tumor not killed and proliferates causing cancer
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Tumors manipulate immune response in their facor
tumor antigens can be presented to T cells by dendritic cells that lack B7 which causes T cell anergy for the T cells that recognize the tumor-specific antigen
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Vaccination with tumor antigens
promotes immune response and degradation of tumor cells causing cancer regression
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Adoptive Transfer
tumor treatment that uses cells engineered to combat tumors or to present tumor-antigens to activate the immune response. either specific target or a 'vaccine' to prime immune response
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Monoclonal Antibodies and cancer
if for tumor-specific antigens, then can be used to diagnose tumors/where they originated but they can also be used to target tumor cells
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antibody-dependent cell-mediated cytotoxicity
use of monoclonal antibodies to target tumor cells
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Monoclonal antibodies conjugated to toxic agents
cytotoxic drugs, biological toxins, radioactive isotopes....aka immunotoxins
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Brentuximab
anti-CD30 antibody that binds to lymphoma, internalization delivers the anti-mitotic drug aurstain to prevent division.
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When an individual receives a kidney transplant, the main concern will be to control the development of .
transplant rejection
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Alloantibodies to blood-vessel endothelium on solid organ grafts .
cause hyperacute rejection
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In general the higher the patient’s panel reactive antibody (PRA), .
the more limited the number of suitable transplant donors
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Acute rejection of a kidney graft involves the activation of recipient T cells by____ of ____ origin.
dendritic cells; donor
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The risk of ______ is the primary complication in bone marrow transplants.
acute graft-versus-host disease
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____ from a bone marrow transplant facilitate alloreactive responses, causing the condition defined as acute graft-versus-host disease.
Mature T cells
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What is the probability that a sibling will be able to provide an HLA-haploidentical kidney for transplantation?
50%
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Human herpes virus 8 (HHV8) is associated with the development of in immunocompromised patients.
Kaposi’s sarcoma
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Burkitt’s lymphoma is a tumor associated with infection, which causes to divide uncontrollably.
Epstein-Barr virus; B cells
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A mechanism by which cancer cells can evade an immune response involves an alteration in the amount of MIC on the cell surface by
cleavage of MIC at the cell surface by a protease
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Thyroid-stimulating hormone is made in the and induces the release of thyroid hormones after proteolytic processing of .
pituitary gland; thyroglobulin
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Another name for anti-immunoglobulin autoantibodies is
rheumatoid factor
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_____autoantibodies enhance receptor function
agonist
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True or False. Autoimmune diseases are rarely resolved
T
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True or False. Autoimmune responses are the result of innate immune responses directed toward self antigens.
F
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True or False. Some forms of autoimmune disease involve IgE autoantibodies.
F
