Immunology Flashcards
1
Q
Describe the flow of lymph through a lymph node.
A
from the afferent vessel to a subcapsular sinus to a trabecular sinus in the cortex to a medullary sinus and then out the efferent vessel
2
Q
What are the major components of the cortex, paracortex, and medulla of a lymph node.
A
- cortex: B-cell follicles
- paracortex: T-cells
- medulla: cords of plasma cells and sinuses containing histiocytes and reticular cells
3
Q
Give the structures drained by each of the following lymph node clusters:
- cervical
- hilar
- axillary
- mediastinal
- celiac
- superior mesenteric
- inferior mesenteric
- internal iliac
- para-aortic
- superficial inguinal
- popliteal
A
- cervical: head and neck
- hilar: lungs
- axillary: upper limb, breast, skin above umbilicus
- mediastinal: esophagus and trachea
- celiac: liver, spleen, pancreas, stomach, upper duodenum
- superior mesenteric: lower duodenum, jejunum, ileum, colon to splenic flexure
- inferior mesenteric: splenic flexure to upper rectum
- internal iliac: lower rectum to pectinate line, bladder, middle ⅓ vagina, cervix, prostate
- para-aortic: ovaries, testes, kidneys, uterus
- superficial inguinal: vulva, scrotum, anal canal below pectinate line, skin below umbilicus
- popliteal: posterior calf and dorsolateral foot
4
Q
The stomach and upper duodenum are drained by which lymph node cluster?
A
the celiac
5
Q
Splenic dysfunction leaves one susceptible to which group of organisms? Which organisms in particular?
A
encapsulated organisms (Please SHINE my SKiS):
- P. aeruginosa
- Streptococcus pneumoniae
- H. influenza type b
- N. meningitidis
- E. coli
- Salmonella spp.
- Klebsiella pneumoniae
- Group B Strep
6
Q
What are Howell-Jolly bodies? What do they usually indicate?
A
basophilic nuclear remnants found in erythrocytes, often indicative of splenic dysfunction
7
Q
List 4 hematologic findings consistent with splenectomy.
A
- thrombocytosis
- lymphocytosis
- target cells
- Howell-Jolly bodies
8
Q
What is the splenic marginal zone?
A
an area between the red pulp and white pulp, which contains macrophages and specialized B cells, where APCs capture blood-borne antigens for recognition by lymphocytes
9
Q
The thymus is derived from which embryonic structure?
A
the third pharyngeal pouch
10
Q
The innate immune system relies on what system for pathogen recognition?
A
TLRs that recognize PAMPs
11
Q
HLA genes encode what?
A
MHC molecules
12
Q
Which HLA genes encode which MHC-I molecules? Which encode MHC-II?
A
- MHC-I are encoded by HLA-A, B, C
- MHC-II are encoded by HLA-DP, DQ, DR
13
Q
Which cells express MHC-I and MHC-II?
A
MHC-I are expressed by all nucleated cells while MHC-II are expressed only by antigen presenting cells
14
Q
What is B2-microglobulin?
A
a protein without a transmembrane domain that is found in association with MHC-I alpha chains
15
Q
What is invariant chain?
A
a protein that binds MHC-II prior to loading in order to prevent loading endogenous antigens during trafficking
16
Q
Describe the process of loading MHC-I.
A
- MHC-I is synthesized in the RER
- TAP in the cytosol escorts endogenous antigens to the surface of the RER
- at the surface, TAP delivers the antigen to MHC-I
- now loaded, MHC-1 is trafficked to the plasma membrane
17
Q
Describe the process of loading MHC-II.
A
- MHC-II is synthesized and bound to invariant chain
- MHC-II is delivered to an endosome where invariant chain is cleaved to form CLIP
- in the endosome, exogenous antigens outcompete CLIP for binding to MHC-II
- MHC-II is loaded with exogenous antigen and trafficked to the plasma membrane
18
Q
Give the major disease associated with each of the following HLA subtypes:
- A3
- B8
- B27
- DQ2/8
- DR2
- DR3
- DR4
- DR5
A
- A3: hemochromatosis
- B8: addison disease, myasthenia gravis
- B27: seronegative arthropathies (psoriatic arthritis, ankylosing spondylitis, IBD-associated arthritis, reactive arthritis)
- DQ2/8: celiac disease (“I 8 2 much gluten at DQ)
- DR2: MS, SLE, goodpasture
- DR3: DMT1, SLE, Grave’s, Hashimoto thyroiditis, Addison disease
- DR4: rheumatoid arthritis, Addison disease
- DR5: pernicious anemia, Hashimoto thyroiditis
19
Q
What is the strongest HLA-disease association?
A
HLA-B27 and ankylosing spondylitis
20
Q
What is CD16?
A
an Fc receptor expressed by NK cells
21
Q
What are the two targets/mechanisms through which NK cells kill?
A
- ADCC of IgG-bound targets
- perforin/granzyme induced apoptosis of cells lacking MHC-I
22
Q
List four cytokines that enhance the activity of NK cells.
A
- IL-2
- IL-12
- IFN-a
- IFN-B
23
Q
Describe positive and negative selection of T cells.
A
- in the thymic cortex, T cells expressing TCRs capable of binding self-MHC on cortical epithelial cells survive (positive selection)
- in the thymic medulla, T cells with a high affinity for self antigens expressed by epithelial reticular cells using AIRE undergo apoptosis (negative selection)
24
Q
What is autoimmune polyendocrine syndrome 1? How does it present?
A
- an autoimmune condition that results due to an AIRE loss of function mutation (a transcription factor needed for the expression of certain self-antigens by epithelial reticular cells in the thymus)
- presents with hypoparathyroidism, adrenal failure, and chronic candida infections
25
What is AIRE? A loss of function mutation causes what disease?
- a transcription factor needed by epithelial reticular cells in the thymus in order to express some self-antigens for the negative selection of T-cells
- deficiency results in autoimmune polyendocrine syndrome 1
26
What is the purpose of regulatory T cells? How do they carry out this function and how can we identify them?
- they help maintain peripheral tolerance by suppressing CD4 and CD8 T-cells
- once activated they secrete two anti-inflammatory cytokines: IL-10 and TGF-B
- they express the CD25 and FOXP3 immunophenotype
27
CD25 and FOXP3 are makers for what kind of immune cell?
regulatory T cells
28
List the three cell types that serve as APCs?
- B cells
- macrophages
- dendritic cells
29
In addition to binding MHC-I/II, T-cells require what other signal in order to become activated?
B7 expressed by the APC must bind CD28 expressed by the T cell
30
What cell type expresses CD80/86 and what is it's function?
- also known as B7.1/2
| - it binds CD28 expressed by T cells and serves as the second signal for activation in addition to binding MHC
31
What cell type expresses CD28 and what is it's function?
expressed by T cells, it binds B7.1/2 (aka CD80/86) expressed by an antigen presenting cell, and serves as the second signal for activation in addition to binding MHC
32
What induces B-cell class switching?
- B cell expresses MHC-Ag which is bound by TCR
| - the T-cell also expresses CD40L, which binds CD40 expressed by B-cells and serves as the second signal
33
What cell type expresses CD40 and what is it's function?
expressed by B cells, it binds CD40L expressed by T cells and serves as the second signal required for class switching
34
Immunoglobulins can be divided up into what two regions?
Fab (antigen binding fragment) and Fc (constant fragment)
35
Give four characteristics of the Fc region.
The 4 C's:
- constant
- carboxy terminal
- carbohydrate side chains
- complement binding
36
Through what two mechanisms do we generate antibody diversity?
- random combination of VJ (light-chain) and V(D)J (heavy-chain) genes
- random addition of nucleotides to DNA during recombination
37
What is terminal deoxynucleotidyl transferase?
an enzyme that randomly adds nucleotides to DNA during recombination of the VJ and V(D)J genes to improve immunoglobulin diversity
38
Which immunoglobulin isotypes fix complement? Which region of those immunoglobulins does complement fix to?
- IgM and IgG fix complement
| - it fixes the Fc region of those immunoglobulins
39
Mature, naive B cells express what immunoglobulin isotypes on their surfaces?
IgM and IgD
40
IgG functions as an immune factor through what three mechanisms?
- opsonizes bacteria
- fixes complement
- neutralizes bacterial toxins and viruses
41
How does IgA protect it's host?
by preventing attachment of bacteria and viruses to mucous membranes
42
What is J chain?
a protein that binds the Fc region of IgA and IgM to form dimers and pentamers, respectively
43
IgA crosses epithelial cells by a process known as what?
transcytosis
44
What is secretory component?
a molecule, acquired from epithelial cells, that protects the Fc portion of IgA from proteases in the gut lumen
45
Which isotype of immunoglobulin is produced at the highest level in the human body? Which isotype reaches the highest serum concentrations?
- IgA is most produced by doesn't reach serum
| - IgG is the most abundant isotype in serum
46
What is the purpose of IgE?
binds mast cells and basophils and cross-links when exposed to an allergen, thereby mediating a type I hypersensitivity
47
What are thymus-independent antigens?
those lacking a peptide component which cannot be presented by MHC to T cells and are therefore weakly immunogenic
48
Which isotype of immunoglobulin readily crosses the placenta?
IgG
49
What are acute-phase reactants? Where are they produced? They are notably induced by which cytokine?
- factors whose serum concentrations change significantly in response to inflammation
- produced in the liver
- induced by IL-6
50
What is c-reactive protein? What is it's immunologic function?
a positive (upregulated) acute-phase reactant that serves as an opsonin and fixes complement
51
List the five positive and two negative acute phase reactants.
- positive: c-reactive protein, ferritin, fibrinogen, hepcidin, serum amyloid A
- negative: albumin, transferrin
52
What purpose does ferritin serve as an acute phase reactant?
it is upregulated, binding and sequestering iron to inhibit microbial iron scavenging
53
What purpose does hepcidin serve as an acute phase reactant?
it reduces iron absorption (by degrading ferroportin) and reduces iron release from macrophages, thereby inhibiting microbial iron scavenging
54
The membrane attack complex is effective against which types of organisms?
gram negative bacteria, most notably Neisseria
55
What are the three complement pathways and what activates each?
- classic: IgG or IgM mediated
- alternative: microbe surface molecules
- mannose: mannose or other sugars on microbe surface
56
Which complement components contribute to anaphylaxis via activation of mast cells?
C3a, C4a, C5a
57
Which complement components are part of the MAC?
C5b, C6-C9
58
What are the functions of C3b?
- opsonization
| - clear immune complexes
59
What are the functions of C5a?
- anaphylaxis
| - neutrophil chemotaxis
60
What are the two primary opsonins in the human body?
IgG and C3b
61
Describe the basic steps along the complement pathway.
- a C3 convertase is formed which converts C3 to C3b
- C3b helps form a C5 convertase
- C5 convertase converts C5 to C5b
- C5b joins with C6-C9 to form the MAC
62
What is decay-accelerating factor?
a glycophosphatidylinositol-anchored enzyme, aka CD55, that inhibits complement activation on self-cells
63
What is C1 esterase inhibitor?
an enzymes, that inhibits complement activation on self-cells
64
Review the full complement cascade.
See Lecture Notes
65
What is C1 esterase inhibitor deficiency? Describe the pathogenesis? What is the primary contraindication?
- an AD disorder known as hereditary angioedema resulting form loss of the complement regulator
- there is unregulated activation of kallikrein, leading to increased levels of bradykinin, as well as accumulation of anaphylatoxins, which results in swelling
- ACE inhibitors are contraindicated because they can lead to bradykinin accumulation
66
Why are ACE inhibitors contraindicated in those with C1 esterase inhibitor deficiency?
- the deficiency results in the accumulation of bradykinin, which then contributes to episodes of swelling
- ACE inhibitors also lead to accumulation of bradykinin
67
C3 deficiency increases a person's risk for what two things?
- severe, recurrent, pyogenic sinus and respiratory infections
- type III hypersensitivity reactions
68
A deficiency in C5-C9 increases one's risk for what?
Neisseria bacteremia
69
How does decay-accelerating factor deficiency manifest?
- DAF normally protects self-cells from complement fixation
| - DAF deficiency causes complement-mediated lysis of RBCs and paroxysmal nocturnal hemoglobinuria
70
What is lactoferrin? Where is it found?
a protein found in secretory fluids and neutrophils that inhibits microbial growth via iron chelation
71
What are interferons and specifically what are they important for defending against?
- they are glycoproteins part of the innate host defense against RNA and DNA viruses
- they are synthesized by virus-infected cells and signal via autocrine and paracrine mechanisms to induce transcription of antiviral proteins that selectively degrade viral nucleic acid and inhibit viral protein synthesis
- it up regulates RNase L, an endonuclease that degrades RNA and protein kinase R, which inactivates eIF-2 and inhibits initiation of translation
72
What pneumonic helps recall the functions of IL-1 through IL-6?
Hot T-bone stEAK
- 1: hot (fever)
- 2: stimulates CD8 T cells
- 3: stimulates bone marrow (like GM-CSF)
- 4: IgE production
- 5: IgA production
- 6: aKute-phase protein production
73
What is the function of IL-8?
recruit neutrophils
74
What are the two major functions of IL-12?
- induce Th1 phenotype
| - activate NK cells
75
Which cytokine mediates septic shock?
TNFa
76
What is the major function of TNFa?
- it mediates septic shock by activating the endothelium for recruitment of WBCs and vascular leakage
- responsible for cachexia in malignancy
77
What are the two major anti-inflammatory cytokines?
IL-10 and TGF-B
78
What is the major function of IL-10?
it is anti-inflammatory: decreases expression of MHC-II and Th1 cytokines, inhibits activated macrophages and dendritic cells
79
List the cell type(s) that express each CD:
- CD3
- CD16
- CD21
- CD25
- CD28
- CD34
- CD40
- CD40L
- CD80/86 (B7.1/2)
- CXCR4
- CCR5
- FOXP3
- CD3: T cells
- CD16: NK cells
- CD21: B cells
- CD25: regulatory T cells
- CD28: T cells
- CD34: hematopoietic stem cells
- CD40: B cells
- CD40L: helper T cells
- CD80/86: APCs
- CXCR4: T cells
- CCR5: T cells and macrophages
- FOXP3: regulatory T cells
80
What is the purpose of CD3 and which cells express it?
found on T cells, it is associated with the TCR for signal transduction
81
What is the significance of CXCR4 and CCR5?
they are the co-receptors for HIV found on T cells
82
What is the signficiance of CD34?
it is a marker of hematopoietic stem cells
83
Do B cells express CD40 or CD40L? CD28 or CD80/86?
they express CD40 and CD80/86
84
What is the clinical significance of CD21?
it is a B-cell marker and the receptor for EBV
85
What are superantigens?
bacterial antigens that cross-link the beta-region of the TCR to the MHC-II on APCs, causing a massive release of cytokines
86
What is the receptor for LPS that mediates toxic shock?
LPS binds CD14 (aka TLR4) on macrophages
87
What is CD14?
aka TLR4, it is an LPS receptor found on macrophages that mediates toxic shock
88
Name three viruses that are classic examples of antigenic variation.
- HIV
- Hib
- HCV
89
What is passive immunity? Give examples of how it is acquired.
immunity conveyed by the receipt of preformed antibodies (e.g. IgA from breast milk, IgG via the placenta, antitoxin, humanized monoclonal antibodies)
90
After exposure to what five microbes are unvaccinated patients given preformed antibodies?
"To Be Healed Very Rapidly"
- tetanus toxin
- botulinum toxin
- HBV
- varicella
- rabies virus
91
Which kind of vaccination is capable of inducing both a cellular and humoral response?
live attenuated vaccination
92
Which common vaccines are inactivated or killed vaccine?
"R.I.P. Always"
- R: rabies
- Influenza
- Polio
- Hep A
93
Which four common vaccines are live attenuated vaccines?
"May You Be Vivacious"
- MMR
- yellow fever
- BCG
- varicella
94
What defines acute and chronic inflammation?
- acute: neutrophil infiltrate
| - chronic: lymphocyte infiltrate
95
Acute inflammation arises in response to what two things?
- infection
| - tissue necrosis (neutrophils clear necrotic debris)
96
What is the downstream effect of activating a TLR?
up regulation of NF-kB, which leads to production of many more immune mediators
97
What is the role of arachidonic acid metabolites and how are they produced?
- metabolites that mediate acute inflammation
- AA is released from the cell membrane by phospholipase A2 and then acted upon by either COX or 5-lipoxygenase
- COX produces prostaglandins while 5-lipoxygenase produces leukotrienes
98
How are prostaglandins produced?
AA is released from a cell membrane by phospholipase A2 and then acted upon by COX
99
How are leukotrienes produced?
AA is released from a cell membrane by phospholipase A2 and then acted upon by 5-lipoxygenase
100
What role do prostaglandins play in acute inflammation?
they mediate arteriolar vasodilation and increase vascular permeability in the post-capillary venule
101
What role do leukotrienes play in acute inflammation?
they are slow reacting substances of anaphylaxis and mediate vasoconstriction, bronchospasm, and increased vascular permeability (all things that involve smooth muscle contraction)
102
Describe the function of arachidonic acid metabolites.
- they mediate acute inflammation
- prostaglandins are produced by COX and mediate vasodilation of the arteriole as well as increase vascular permeability of the post-capillary venule
- leukotrienes attract and activate neutrophils in addition to mediating vasoconstriction, bronchospasm, and increased vascular permeability
- specifically, PGE2 also mediates pain and fever while LTB4 attracts and activates neutrophils
103
What are pericytes?
contractile cells that sit under endothelial cells in capillaries and post-capillary venules and open spaces to increase vascular permeability
104
What is the significance of PGE2 in acute inflammation?
it mediates pain and fever
105
What is the significance of LTB4 in acute inflammation?
it attracts and activates neutrophils
106
List three things that activate mast cells.
- IgE cross-linking by antigen
- C3a and C5a
- tissue trauma
107
What are the fast and slow mediators of anaphylaxis?
- fast: histamine, released from preformed granules
| - slow: leukotrienes produced after mast cell activation
108
What is Hageman factor?
- also known as FXII, it is a pro inflammatory protein produced by the liver, which activates coagulation and fibrinolytic systems, complement, and kinin systems
- FXII defects cause hereditary angioedema because they activate kinin, which yields bradykinin
109
What is bradykinin and how is it produced?
kinin cleaves high-molecular-weight kininogen (HMWK) to bradykinin, which then mediates vasodilation, increased vascular permeability, and pain
110
What are the five cardinal signs of inflammation?
- warmth
- redness
- pain
- swelling
- fever
111
What causes the warmth and redness of inflammation? What are the primary mediators of this mechanism?
arteriolar vasodilation mediated by histamine, prostaglandins, and bradykinin
112
What causes the swelling associated with inflammation? What are the primary mediators of this mechanism?
leakage of fluid from post capillary venules mediated by histamine and tissue damage (endothelial disruption)
113
What causes the pain associated with inflammation? What are the primary mediators of this mechanism?
PGE2 and bradykinin sensitize sensory nerve endings
114
What mediates the fever associated with inflammation?
pyrogens trigger release of IL-1 and TNF by macrophages, which increase COX activity in perivascular cells of the hypothalamus where the internal temperature is regulated, increasing PGE2 and raising the set point
115
List the primary mediators of each of the following in association with inflammation:
- redness
- warmth
- swelling
- pain
- fever
- redness: vasodilation - histamine, bradykinin, prostaglandins
- warmth: vasodilation - histamine, bradykinin, prostaglandins
- swelling: leakage of fluid from postcap venules - histamine and tissue damage
- pain: sensitization - PGE2 and bradykinin
- fever: pyrogens trigger IL-1 and TNF release, increasing PGE2 in the hypothalamus
116
What are the 7 steps of neutrophil arrival and function during acute inflammation?
- margination
- rolling
- adhesion
- transmigration (aka diapedesis) and chemotaxis
- phagocytosis
- destruction of phagocytosed material
- resolution
117
What causes margination of neutrophils?
vasodilation slows blood flow in the post-capillary venules, causing cells to marginate from the center of flow
118
What causes rolling of neutrophils?
- endothelial cells up regulate selectins which bind sialyl Lewis X on leukocytes
- P-selectins are released form Weibel-Palade bodies in response to histamine
- E-selectins are induced by TNF and IL-1
119
Weibel-Palade bodies contain what two things?
- von Willebrand Factor for platelet adhesion
| - P-selectins for neutrophil rolling
120
What is sialyl Lewis X?
a selectin receptor expressed by leukocytes
121
What role do selectins and integrins play in neutrophil recruitment to the site of inflammation?
- selectins mediate rolling
| - integrins mediate adhesion
122
Describe the process of neutrophil adhesion.
- TNF and IL-1 up regulate cellular adhesion molecules on endothelial cells (e.g. ICAM)
- C5a and LTB4 up regulate integrin expression on leukocytes, specifically CD11/18 known as LFA-1 and Mac-1
- the interaction results in firm adhesion to the vessel wall
123
What role do C5a and LTB4 play in neutrophil recruitment?
they induce expression of integrins important for neutrophil adhesion to endothelial walls
124
Neutrophils are attracted by what four things?
- bacterial products
- C5a
- IL-8
- LTB4
125
Describe the enzymatic steps of O2-dependent killing of phagocytosed microbes.
- NADPH oxidase converts O2 to superoxide (O2.-)
- superoxide dismutase converts superoxide to hydrogen peroxide
- myeloperoxidase converts hydrogen peroxide to bleach (HOCl)
126
What are the two mechanisms of O2-independent killing of phagocytosed microbes?
uses enzymes present in secondary granules
- lysozyme in macrophages
- major basic protein in eosinophils
127
Neutrophils undergo apoptosis and disappear within what period following resolution of the inflammatory stimulus?
24 hours
128
While neutrophils utilize O2-dependent killing of phagocytosed microbes, macrophages rely more on what?
O2-independent killing in the form of lysozyme released from secondary granules
129
Macrophages predominate at what point during the course of inflammation?
after neutrophils, about 2-3 days after inflammation begins
130
What is the role of macrophages in acute inflammation?
arrive after neutrophils and manage the next step of the inflammatory process whether that be resolution, abscess formation, chronic inflammation, etc.
131
How do macrophages induce resolution and healing, continued acute inflammation, abscess formation, or chronic inflammation depending on the situation?
- resolution: secrete anti-inflammatory IL-10 and TGF-B
- continue acute: secrete IL-8 to recruit more neutrophils
- abscess: secrete fibrogenic growth factors and cytokines
- chronic inflammation: activate CD4 helper T cells
132
What induces the Th1 phenotype and what is the role of these helper T cells? What do they secrete to do so?
- induced by IL-12 and IFNy
- they promote cytotoxic T cell functioning
- by secreting IL-2 as a CD8 activator and growth factor
- and by secreting IFNy to activate macrophages and inhibit the Th2 phenotype
133
What induces the Th2 phenotype and what is the role of these helper T cells? What do they secrete to do so?
- induced by IL-4
- they promote B cell functioning and a humoral response
- secrete IL-4 to promote IgE class switching
- secrete IL-5 to promote IgA class switching
- secrete IL-10 to inhibit the Th1 phenotype
134
CD8 T cells kill via what two mechanisms?
- perforin/granzyme
| - Fas/FasL
135
CD8 cells require what two signals to become activated?
- bind MHC-I
| - bind IL-2
136
What is the defining feature of granulomatous inflammation?
the presence of epithelioid histiocytes
137
Describe the histology of a classic granuloma.
a collection of epithelioid histiocytes and giant cells surrounded by a rim of lymphocytes
138
How do non-caseating and caseating granulomas differ in their appearance and in their causes?
- non-caseating lack central necrosis and are caused by a reaction to foreign material, sarcoidosis, beryllium exposure, Crohn disease, and cat scratch disease
- caseating have central necrosis and are characteristic of TB and fungal infection
139
How can you differentiate a TB caseating granuloma from a fungal caseating granuloma?
- TB stains AFB positive
| - fungal stains GMS positive
140
Describe how granulomas form.
- macrophages become activated and secrete IL-12, which induces Th1 differentiation
- Th1 cells then secrete IFNy, which converts macrophages to epithelioid histiocytes
- macrophages secrete TNFa which induces and maintains granuloma formation
141
What is autoimmune lymphoproliferative syndrome? How does it present?
- mutations in the Fas apoptosis pathway impair peripheral tolerance mechanisms for T and B cells such that they self-reactive lymphocytes proliferate
- it presents with symptoms of autoimmune dysfunction as well as lymphadenopathy and an increased risk of lymphoma
142
Describe the negative selection of T cells. Where does it occur? What other cells are involved? What is being tested?
- negative selection takes place in the medulla
- dendritic cells express self antigens and medullary epithelial cells express peripheral antigens
- cells that have an affinity for self-antigens undergo apoptosis
143
Describe B cell negative selection. Where does it occur? What is being tested? What happens when cells fail?
- it takes place in the bone marrow
- B cells are tested for recognition of self-antigens
- if they do bind self-antigens, they undergo either receptor editing or apoptosis
144
What is B cell receptor editing? What genes must be re-expressed? What portion of the BCR undergoes further recombination?
- a process B cells can undergo rather than apoptosis if they fail negative selection
- the cell re-expresses the RAG genes
- the light chain undergoes recombination again
145
What is IPEX syndrome? What causes it? How does it present?
- results from a FOXP3 mutation that causes dysfunction of regulatory T cells
- IPEX stands for immune dysregulation, polyendocrinopathy (thyroiditis or type I DM), enteropathy, X-linked
146
Why is it believed that women of childbearing age are most affected by autoimmune disorders?
because estrogen may reduce apoptosis of self-reactive B cells
147
CD25 and FOXP3 polymorphisms result in what conditions?
- both are important for regulatory T cell functioning
- CD25 polymorphisms are associated with Type I DM and MS
- FOXP3 polymophisms are associated with IPEX syndrome
148
Describe peripheral tolerance. How is it mediated?
- occurs when T cells bind an antigen via the TCR, but this event doesn't coincide with the second activation signal of B7/CD28 binding
- repeated instances of this triggers expression of FasL by the T cell
- FasL then binds Fas and induces apoptosis of the T cell and other nearby, self-reactive T cells
149
What is PTPN22?
- a tyrosine phosphatase that affects B and T cell receptor signaling
- polymorphisms can lead to a gain of function with inhibits the signaling needed for peripheral tolerance and anergy, increasing the risk of autoimmunity
150
What is bystander activation?
incidental activation of a self-reactive lymphocyte by cytokines released in response to a genuine microbe (infection leads to release of cytokines and up-regulation of the necessary activation signals, allowing a self-reactive lymphocyte to leave a state of anergy)
151
Describe the pathogenesis of SLE.
- UV damage to keratinocytes causes apoptosis
- the apoptotic debris isn't cleared effectively and it activates self-reactive lymphocytes
- these lymphocytes then produce antibodies to host nuclear antigens
- antigen-antibody complexes are generated at low levels and taken up by dendritic cells
- these DNA antigens activate TLRs in dendritic cells, amplifying the immune response
- higher levels of antigen-antibody complexes are generated and deposited into multiple tissues
- complement is activated, causing tissue damage
152
What is CH50?
a test of complement function that measures complements ability to lyse RBCs
153
What are the classic findings of SLE.
- non-specific: fever, weight loss, Raynaud phenomenon
- malar or discoid rash, especially upon exposure to sunlight
- painless nasopharyngeal ulcers
- arthritis
- serositis
- psychosis
- renal damage (diffuse proliferative glomerulonephritis is the most common nephritic syndrome, membranous glomerulonephritis the most common nephrotic syndrome)
- anemia, thrombocytopenia
- Libman-Sacks endocarditis (small vegetations on both sides of the mitral valve)
- ANA (sensitive but not specific)
- anti-dsDNA (specific, indicates poor prognosis) or anti-Sm antibodies (specific, not an indicator of prognosis)
154
Name a very sensitive antibody found in SLE patients? What about a very specific one?
- ANA is very sensitive
| - anti-dsDNA or anti-Sm antibodies are very specific
155
What is Libman-Sacks endocarditis?
a form of endocarditis characteristic of SLE in which vegetations are found on both sides of the mitral valve
156
What is an anti-phospholipid antibody? Give three examples.
- an autoantibody direct against proteins bound to phospholipids
- anti-cardiolipin, anti-B2-glycoprotein I, and lupus anticoagulant are all examples
157
Anti-cardiolipin anti-phospholipid antibodies can cause what clinical confusion?
they can produce a false-positive syphilis test
158
Antiphospholipid Antibody Syndrome
- a hypercoagulable state due to antiphospholipid antibodies, primarily lupus anticoagulant
- associated with SLE but more often a primary disorder
- results in arterial and venous thrombosis, recurrent pregnancy loss, and cerebral thrombosis (stroke)
- treat with lifelong systemic anticoagulation
159
Drug-Induced Lupus
- it is a drug-induced form of SLE defined by antihistone antibodies
- procainamide, hydrazine, and isoniazid are common causes
- presents like SLE but CNS and renal involvement are rare, removal of the drug usually results in remission
160
Mortality due to SLE is usually the result of what complications?
- renal failure
- infection (from immunosuppression and complement depletion)
- accelerated coronary atherosclerosis
161
What is the most common renal complication in someone with SLE?
diffuse proliferative glomerulonephritis
162
Sjogren Syndrome
- a type IV HSR and autoimmune destruction of lacrimal and salivary glands with fibrosis
- presents with dry eyes, dry mouth, recurrent dental carries and complaints of "can't chew a cracker" or "dirt in my eyes"
- may progress to ulceration of corneal epithelium
- unilateral enlargement of the parotid gland often occurs late and carries a risk for B-cell lymphoma (marginal zone)
- can be primary or associated with another AI disorder, especially RA
- characterized by ANA and anti-ribonucleoprotein antibodies (anti-SSA and anti-SSB)
- SSA and SSB are associated with extra glandular manifestations and SSA poses a risk for delivering babies with neonatal lupus and congenital heart block
- lymphocytic sialadenitis on lip biopsy is very specific
163
What is SSA? What diseases is it associated with? What risk does it pose?
- a self-reactive anti-ribonucleoprotein antibody that is seen in Sjogrens and SLE
- it can cross the placenta and cause neonatal lupus or congenital heart block
- therefore, screen pregnant SLE and Sjogrens patients
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Scleroderma
- an autoimmune disorder characterized by sclerosis of the skin and visceral organs
- autoimmune damage to mesenchyme triggers endothelial dysfunction, which leads to inflammation, vasoconstriction, and secretion of fibroblast growth factors (TGF-B and PDGF)
- fibrosis is initially perivascular but extends to cause organ damage with time
- limited type: skin involvement is limited to the hands and face with late visceral involvement; CREST syndrome is the prototype
- diffuse type: skin involvement is diffuse with early visceral involvement; can involve any organ but most often presents with esophageal dysmotility and reflux, interstitial fibrosis and pulmonary hypertension, or sclerodermal renal crisis
- highly associated with antibodies to DNA topoisomerase I also known as anti-Scl-70
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What is CREST syndrome? What are the features?
- the prototype limited scleroderma
- CREST: Calcinosis/anti-Centromere antibodies, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasias of the skin
166
What is mixed connective tissue disease?
an auto-immune disease with mixed features of SLE, diffuse scleroderma, and polymyositis characterized by ANA and serum antibodies to U1 ribonucleoprotein
167
Tissues can be divided into what three types based on their regenerative capacity?
- labile (stems cells continuously cycle)
- stable (cells are quiescent but can reenter the cell cycle)
- permanent (permanent lack of regenerative potential)
168
What is a classic example of tissue with stable regenerative potential?
regeneration of the liver by compensatory hyperplasia after partial resection as each hepatocyte produces additional cells
169
What kind of wound healing follows MI?
repair (not regeneration)
170
Describe the process of wound healing by repair.
- granulation tissue forms first, consisting of fibroblasts, capillaries, myofibroblasts, and type III collagen
- type III collagen is replaced with type I by collagenase
171
What is granulation tissue and what is it composed of?
- it is the first phase of wound healing by repair
| - formed by fibroblasts laying down type III collagen, myofibroblasts, and dense capillaries
172
What is collagenase? What cofactor does it require?
an enzyme that removes type III collagen in granulation tissue and replaces it with type I, requiring zinc
173
What are the four types of collagen used for?
- type 1: bone, skin, tendon, dentin, fascia, cornea, late wound repair
- type 2: car"two"lage, vitreous body, nucleus pulposus
- type 3: granulation tissue, uterus, embryonic tissue, keloids (flexible), blood vessels
- type 4: basement membranes, basal lamina, lens
174
List the function of each of the following growth factors in wound healing:
- TGF-a
- TGF-B
- platelet derived growth factor
- fibroblast growth factor
- vascular endothelial growth factor
- epidermal growth factor
- TGF-a: epithelial and fibroblast growth factor
- TGF-B: fibroblast growth factor, cell cycle arrest
- PDGF: growth factor for endothelium, smooth muscle, and fibroblasts
- FGF: important for angiogenesis
- VEGF: important for angiogenesis
- EGF: stimulates cell growth via TKs
175
What are healing by primary and secondary intention?
- primary: wound edges are brought together
- secondary: edges are not approximated, granulation tissue fills the defect, myofibroblasts contract the wound, forming a scar
176
Granulation tissue forms in what type of healing, that by primary or secondary intention?
secondary intention only
177
Name five causes of delayed wound healing.
- infection is the most common
- vitamin C, copper, or zinc deficiency
- foreign body
- ischemia
- diabetes
178
Why do vitamin C, copper, and zinc deficiencies all impair wound healing?
- vitamin C is important in the hydroxylation of proline and lysine pro collagen residues, which are later needed for cross-linking
- copper is a cofactor for lysol oxidase, which cross links lysine and hydroylysine to form stable collagen
- zinc is a cofactor for collagenase, which replaces type III collagen
179
What is the difference between a hypertrophic scar and a keloid?
- hypertrophic: excess production is localized to the wound and formed by excess type I collagen and there is the possibility for spontaneous remission
- keloids are composed of excess, disorganized type III collagen and are out of proportion to the wound; they are likely to regrow if removed
180
Where are keloids classically found?
on the ear lobs of African Americans
181
Type I hypersensitivities are mediated by what?
IgE on presensitized mast cells and basophils
182
Atopic disorders like rhinitis and hay fever are what kind of hypersensitivity reaction?
type I
183
Describe the mechanism behind type II hypersensitivity reactions.
IgM or IgG bind to fixed antigens on "enemy" cells and trigger cytotoxic events (phagocytosis, complement fixation, or antibody-mediated cellular dysfunction)
184
What is the difference between a direct and an indirect Coombs test?
- direct: detects antibodies that have adhered to patient's RBCs
- indirect: detects antibodies in serum that can adhere to other RBCs
185
Describe the mechanism of type III hypersensitivity reactions.
- IgG-antigen complexes activate complement, which attracts neutrophils
- these neutrophils release lysosomal enzymes, causing tissue damage
186
Serum Sickness
- a type III hypersensitivity in which antibodies to foreign proteins are produced
- most cases caused by drugs acting as haptens
- presents with fever, urticaria, arthralgia, proteinuria, and lymphadenopathy 5-10 days after antigen exposure
187
Arthus Reaction
- a local, subacute type III hypersensitivity
- caused by injection of antigen into a presensitized individual (IgG already formed)
- manifests with edema, necrosis, and activation of complement
188
How does serum sickness compare to an arthus reaction?
- both are type III hypersensitivities mediated by IgG
- however, an arthus reaction has a more rapid onset because it is mediated by circulating IgG (the individual has already been sensitized)
- an arthus reaction is more localized than serum sickness
189
Name the three major diseases that are type IV hypersensitivities.
The 3 T's
- TB
- Transplant rejection
- Touching (contact dermatitis)
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Allergic Transfusion Reaction
- a reaction to transfused plasma proteins (so risk is plasma>SDP>pooled platelets>RBCs)
- presents with urticaria, local erythema, pruritis, fever, and wheezing
- treat with antihistamines and restart the transfusion slowly
191
Anaphylactic Transfusion Reaction
- usually a reaction of IgA-deficient patients to blood products containing IgA
- presents with dyspnea, shock, and respiratory arrest
- treat with epinephrine
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Febrile, Nonhemolytic Transfusion Reaction
- a type II hypersensitivity reaction of host antibodies against donor HLA antigens/WBCs and the presence of cytokines in the product
- presents with fever, chills, and flushing
- prevent with leukoreduction
- treat with tylenol
193
Acute Hemolytic Transfusion Reaction
- a type II hypersensitivity due to ABO incompatibility
- causes an intravascular hemolysis
- presents with fever, hypotension, tachypnea, tachycardia, and hemoglobinuria
194
List the disorder(s) associated with each of the following antibodies:
- anti-ACh receptor
- anti-basement membrane
- anticardiolipin or lupus anticoagulant
- anticentromere
- anti-desmoglein
- anti-hemidesmosome
- anti-dsDNA or anti-Sm
- ACh receptor: myasthenia gravis
- BM: good pasture syndrome
- cardiolipin or lupus anticoagulant: SLE or anti phospholipid syndrome
- centromere: limited scleroderma (CREST)
- desmoglein: pemphigus vulgaris
- hermidesmosome: bullies pemphigoid
- dsDNA/Sm: SLE
195
List the disorder(s) associated with each of the following antibodies:
- anti-glutamic acid decarboxylase (GAD-65)
- anti-histone
- anti-jo-1, anti-SRP, or anti-Mi-2
- anti-microsomal or anti-thyroglobulin
- anti-mitochondrial
- anti-nuclear
- anti-parietal cell
- GAD65: type 1 DM
- histone: drug-induced lupus
- jo-1, SRP, Mi-2: polymyositis and dermatomyositis
- microsomal, thyroglobulin: Hashimoto thyroiditis
- mitochondrial: primary biliary cirrhosis
- ANA: SLE, nonspecific
- parietal cell: pernicious anemia
196
List the disorder(s) associated with each of the following antibodies:
- anti-phospholipase A2 receptor
- anti-Scl-70 (aka anti-DNA topoisomerase I)
- anti-smooth muscle
- anti-SSA, anti-SSB
- anti-TSH receptor
- anti- U1 RNP (ribonucleoprotein)
- phospholipase A2 receptor: primary membranous nephropathy
- topoisomerase I: diffuse scleroderma
- smooth muscle: autoimmune hepatitis type I
- SSA/SSB: sjogren syndrome
- TSH receptor: Graves
- U1 RNP: mixed connective tissue disease
197
Celiac disease is characterized by the presence of which autoantibodies?
anti-endomysial or anti-tissue transglutaminase IgA
198
Rheumatoid arthritis is characterized by the presence of which autoantibodies?
- rheumatoid factor (IgM against the Fc region of IgG)
| - anti-CCP
199
X-linked Agammaglobulinemia
- an X-linked BTK mutation prevents B cell maturation
- presents with bacterial and enteroviral infections after 6 months of age
- see diminished levels of all Ig isotopes and scant/absent lymph nodes and tonsils
200
Selective IgA Deficiency
- unknown mechanism
- typically asymptomatic but with increased risk of airway and GI infections, autoimmune disease, and atopy
- decreased IgA but normal levels of other isotypes
201
What is the most common primary immunodeficiency?
selective IgA deficiency
202
Common Variable Immune Deficiency
- B cell or helper T cell defects impair B-cell differentiation
- often acquired in the 20s-30s with increased risk of autoimmune disease, bronchiectasis, lymphoma, and sinopulmonary infections
- you can observe a decrease in plasma cells and all Ig isotypes
203
DiGeorge Syndrome
- 22q11 deletion causes failure of the 3rd and 4th pharyngeal pouches to develop, leaving the thymus and parathyroids absent
- presents with cardiac anomalies, abnormal facies, thymic aplasia, cleft palate, and hypocalcemia
- measurable reduction in T cells, PTH, and calcium as well as an absent thymic shadow on CXR
204
IL-12 Receptor Deficiency
- loss of the receptor diminishes the Th1 response in an autosomal recessive manner
- presents with disseminated mycobacterial and fungal infections, often after administering the BCG vaccine
- measurable decrease in IFNy
205
Hyper-IgE Syndrome
- an autosomal dominant STAT3 mutation impairs ability of Th17 cells to recruit neutrophils
- manifests with the "FATED" syndrome of coarse Facies, staph Abscesses, retained primary Teeth, increased IgE, and Dermatologic problems (eczema)
206
Describe the defect that leads to chronic mucocutaneous candidiasis.
T-cell dysfunction results in noninvasive candida infections of the skin and mucous membranes
207
Severe Combined Immune Deficiency
- can be X-linked due to an IL-2R gamma chain mutation
- or autosomal recessive due to an adenosine deaminase deficiency which allows the build up of amines toxic to lymphocytes
- presents with failure to thrive, chronic diarrhea, thrush, and recurrent infections ("bubble baby")
- can find diminished TRECs and there is an absence of thymic shadow, germinal centers, and T cells
208
Name two immunodeficiencies that present with an absent thymic shadow on CXR.
- SCID
| - DiGeorge syndrome
209
What is a "sail sign"?
a normal feature of a child's CXR which is also known as the thymic shadow, absent in those with DiGeorge syndrome or SCID
210
Ataxia-Telangiectasia
- ATM gene mutations result in the inability to repair DNA double strand breaks
- presents with a triad of cerebellar defects (ataxia), spider angiomas, and IgA deficiency (the three A's)
- AFP is elevated in serum; IgA, IgG, and IgE are all reduced; and there is lymphopenia as well as cerebellar atrophy
211
Hyper-IgM Syndrome
- an X-linked recessive CD40L defect in Th cells impairs class switching
- presents with opportunistic infections
- IgM is elevated while all other Ig isotypes are absent
212
Wiskott-Aldrich syndrome
- an X-linked recessive mutation in the WAS gene impairs actin reorganization
- presents with "WATER": Wiskott Aldrich, thrombocytopenia, eczema, and recurrent infections
- bleeding is a major cause of death
213
Leukocyte Adhesion Deficiency Type 1
- autosomal recessive defect in LFA-1 integrin (CD18) impairs extravasation of phagocytes
- presents with recurrent skin and mucosal infections without pus formation, impaired wound healing, and delayed separation of umbilical cord
- neutrophil count is elevated because they can't leave circulation
214
Chediak-Higashi Syndrome
- autosomal recessive defect in the lysosomal trafficking regulator LYST which results in a microtubule defect that impairs fusion of phagosomes with lysosomes
- increases one's risk for pyogenic infections by Staph and Strep
- presents with pancytopenia because the microtubule defect impairs mitosis and leads to intramedullary death
- giant granules in leukocytes because they can't be distributed and accumulate at the golgi instead
- presents with defective primary hemostasis due to abnormal dense granules in platelets
- albinism because melanocytes can't hand off pigment to keratinocytes
- peripheral neuropathy because axonal and dendritic transport are impaired
215
Chronic Granulomatous Disease
- X-linked recessive NADPH oxidase deficiency limits oxidative burst in neutrophils
- increased susceptibility to catalase positive organisms (especially Pseudomonas cepacia, serrate, nocardia, and aspergillus)
- abnormal dihydrorhodamine test and no reaction to nitro blue tetrazolium dye
216
Those with chronic granulomatous disease are more susceptible to which organisms?
reduced oxidative burst leaves them more susceptible to catalase + organisms (Cats Need PLACESS to Belch their Hairballs):
- Cat = catalase positive
- Nocardia
- Pseudomonas cepacia
- Listeria
- Aspergillus
- Candida
- E. Coli
- Staph
- Serratia
- B cepacia
- H pylori
217
What is an myeloperoxidase deficiency? How can you distinguish it from chronic granulomatous disease?
- it is an MPO deficiency that prevents conversion of hydrogen peroxide to bleach for O2-dependent killing of phagocytosed microbes
- nitro blue tetrazolium test is normal unlike CGD
218
B-cell deficiencies tend to leave one more susceptible to what kinds of infections? What about T-cell deficiencies?
- B cell deficiencies produce recurrent bacterial infections
| - T cell deficiencies produce more fungal and viral infections
219
T cell deficiencies leave one more susceptible to which bacterial, viral, and fungal infections?
- bacterial sepsis
- CMV, EBV, JCV, VZV, and chronic respiratory/GI viruses
- local candida
220
B cell deficiencies leave one more susceptible to which bacterial, viral, and fungal infections?
- encapsulated bacteria (Please SHINE my SKiS): P. aeruginosa, Strepneumoniae, Hib, N. meningitidis, E. coli, Salmonella spp., K. pneumoniae, Group B Strep
- enteroviral encephalitis and poliovirus
- GI giardiasis (due to lack of IgA)
221
Granulocyte deficiencies leave one more susceptible to which bacterial, viral, and fungal infections?
- Staph, B cepacia, P. aeruginosa, Serratia, Nocardia
| - systemic candida, aspergillus
222
Complement deficiencies leave one more susceptible to which infections?
- early component deficiencies leave one susceptible to encapsulated bacteria (Please SHiNE my SKiS
- late component (MAC) deficiencies leave one susceptible to Neisseria
223
What mediates hyperacute, acute, and chronic transplant rejection? What type of hypersensitivity is each?
- hyperacute: pre-existing recipient antibodies to donor antigen activate complement (type II hypersensitivity)
- acute: CD8 T cells against donor MHC (type IV) and antibodies to donor antigens formed after transplant
- chronic: CD4 T cells against recipient APCs presenting donor peptides (type II and IV)
224
Hyperacute Transplant Rejection
- pre-existing recipient antibodies react to donor antigens and activate complement
- causing widespread thrombosis of graft vessels, ischemia, and necrosis
- must remove the grafted organ
225
Acute Transplant Rejection
- CD8 T cells attack donor MHCs in addition to antibodies forming after transplant to graft antigens
- causes a vasculitis of graft vessels
- can be prevented or reversed with immunosuppressants
226
Chronic Transplant Rejection
- CD4 T cells respond to recipient APCs presenting donor peptides, triggering a cellular and humoral response (type II and IV hypersensitivity)
- cytokine response causes atrophy of the graft, interstitial fibrosis, and arteriosclerosis
227
Describe the mechanism and presentation of GvHD. What kind of transplants are most plagued by GvHD?
- grafted immunocompetent T cells proliferate and reject host cells
- causes maculopapular rash, jaundice, diarrhea, and hepatosplenomegaly
- most often in HSCT or liver transplants because these are rich in lymphocytes
228
Which drugs pose a risk of granuloma break down and disseminated disease?
TNFa inhibitors
229
Why are granulomas associated with hypercalcemia?
they produce calcitriol
230
which bacterial, fungal, and parasitic organisms are likely to cause granulomas to form?
- bacteria: Mycobacteria (TB and leprosy), B. henselae (cat scratch), Listeria, Treponema pallidum (tertiary syphilis)
- fungal: endemic mycoses
- parasites: schistosomiasis
231
Which anti-inflammatory conditions cause granulomas to form?
- sarcoidosis
- Crohn disease
- primary biliary cirrhosis
- subacute thryoiditis
- granulomatosis with polyangiitis
- eosinophilic granulomatosis
- giant cell arteritis
- Takayasu arteritis
232
What is the difference between a transudate and exudate?
- exudates are thicker: they are cellular with high protein and LDH content as well as a higher specific gravity
- transudates are hypo cellular with low specific gravity, protein, and LDH
233
What are the primary causes of transudates and exudates?
- transudates: increased hydrostatic pressure or decreased oncotic pressure (due to cirrhosis or a nephrotic syndrome)
- exudate: lymphatic obstruction, inflammation, or malignancy
234
What is ESR a measure of? What causes it to vary?
- a measure of inflammation
- products of inflammation (mainly fibrinogen) coat RBCs and cause aggregation, and during the test, denser RBC aggregates fall faster which elevates the ESR
235
What would cause an elevated or depressed ESR?
- elevated: most anemias, infections, inflammation, cancer, renal disease, and pregnancy
- depressed: sickle cell anemia (altered shape), polycythemia (increased RBCs dilute aggregation factors), HF, microcytosis, hypofibrinogenemia
236
How is SLE treated?
- NSAIDs
- steroids
- immunosuppressants
- hydroxychloroquine
237
What role do anti-dsDNA, ANA, anti-Sm, and antihistone antibodies play in SLE?
- ANA is a sensitive, but non-specific, marker
- anti-dsDNA are specific and indicative of a poor prognosis
- anti-Sm are specific but don't have any prognostic significance
- antihistone antibodies are sensitive for drug-induced lupus
238
What are anti-Smith antibodies?
specific markers for SLE that are directed against snRNPs
239
What is the purpose of down-regulating albumin as an acute phase reactant?
reduced production conserves amino acids for positive reactants
240
What are the functions of IL-2?
stimulate growth of helper, cytotoxic, and regulatory T cells as well as NK cells
241
What are the functions of IL-4?
- induces the Th2 phenotype
- promotes growth of B cells
- enhances class switching to IgE and IgG
242
What are the functions of IL-5?
- promotes growth and differentiation of B cells with IgA class switching
- stimulates growth and differentiation of eosinophils
243
Cyclosporine (mechanism, use, toxicity)
- blocks T cell activation by binding cyclophilin and inhibiting calcineurin, which causes less NFAT to be produced (a transcription factor for IL-2)
- used for transplant rejection prophylaxis, psoriasis, and RA
- highly nephrotoxic; may also cause HTN, hyperlipidemia, hirsutism, and gingival hyperplasia
244
Tacrolimus (mechanism, use, toxicity)
- blocks T cell activation by binding FK506 binding protein and inhibiting calcineurin, which causes less NFAT to be produced (a transcription factor for IL-2)
- used for transplant rejection prophylaxis
- highly nephrotoxic with increased risk for diabetes and neurotoxicity
245
Sirolimus
- blocks T cell activation and B cell differentiation by preventing a response to IL-2
- it does this by binding FK506 binding protein and inhibiting mTOR, a part of the IL-2R signal cascade
- used for kidney transplant rejection prophylaxis
- causes pancytopenia, insulin resistance, and hyperlipidemia but is not nephrotoxic
246
Daclizumab
- a monoclonal antibody that blocks IL-2R
- used for kidney transplant rejection prophylaxis
- may cause edema, hypertension, tremor
247
Basiliximab
- a monoclonal antibody that blocks IL-2R
- used for kidney transplant rejection prophylaxis
- may cause edema, hypertension, tremor
248
Azathioprine
- an antimetabolite precursor of 6-MP, which inhibits PRPP amidotransferase and thus purine synthesis
- used for transplant rejection prophylaxis, RA, Crohn disease, and other autoimmune conditions
- may cause leukopenia, anemia, or thrombocytopenia
- toxicity is enhanced by allopurinol because 6-MP is degraded by xanthine oxidase as well
249
Mycophenolate Mofetil
- a drug that reversibly inhibits IMP dehydrogenase to prevent purine synthesis in B and T cells
- used for transplant rejection prophylaxis and lupus nephritis
- may cause GI upset or pancytopenia and is associated with invasive CMV infection
250
What is aldesleukin and how is it used clinically?
- it is recombinant IL-2
| - used for renal cell carcinoma and metastatic melanoma
251
What is epoetin alfa and how is it used clinically?
- it is recombinant EPO
| - used to treat anemias in those with renal failure
252
What is filgrastim and how is it used clinically?
it is recombinant G-CSF used to promote the recovery of bone marrow
253
What is sargramostim and how is it used clinically?
it is recombinant GM-CSF used to promote the recovery of bone marrow
254
How do we used IFN-a clinically?
to treat chronic HBV and HCV as well as Kaposi sarcoma and malignant melanoma
255
How do we use IFN-B clinically?
for the treatment of MS
256
How do we used IFN-y clinically?
for the treatment of chronic granulomatous disease
257
What is oprelvekin and how is it used clinically?
it is recombinant IL-11 used to treat thrombocytopenia
258
What is romiplostim and how is it used clinically?
a recombinant thrombopoietin receptor agonist used to treat thrombocytopenia
259
What is eltrombopag and how is it used clinically?
a recombinant thrombopoietin receptor agonist used to treat thrombocytopenia
260
What is the target of alemtuzumab and how do we used it clinically?
targets CD52 for the treatment of CLL and MS
261
What is the target of bevacizumab and how do we used it clinically?
targets VEGF for the treatment of colorectal cancer, renal cell carcinoma, and neovascular age-related macular degeneration
262
What is the target of cetuximab and how do we used it clinically?
targets EGFR for the treatment of colorectal, head, and neck cancer
263
What is the target of rituximab and how do we used it clinically?
targets CD20 to treat non-Hodgkin lymphoma, CLL, RA, and ITP
264
What is the target of trastuzumab and how do we used it clinically?
targets HER2/neu for the treatment of breast cancer
265
What is the target of adalimumab and how do we used it clinically?
targets TNF-a for the treatment of IBD, RA, ankylosing spondylitis, and psoriasis
266
What is the target of certolizumab and how do we used it clinically?
targets TNF-a for the treatment of IBD, RA, ankylosing spondylitis, and psoriasis
267
What is the target of infliximab and how do we used it clinically?
targets TNF-a for the treatment of IBD, RA, ankylosing spondylitis, and psoriasis
268
What is entercept and how do we used it clinically?
a decoy TNF-a receptor used to treat IBD, RA, ankylosing spondylitis, and psoriasis
269
What is the target of eculizumab and how do we used it clinically?
targets C5 for the treatment of paroxysmal nocturnal hemoglobinuria
270
What is the target of natalizumab and how do we used it clinically?
targets a4-integrin for the treatment of MS and Crohn disease
271
What is the target of abciximab and how do we used it clinically?
targets platelet glycoproteins GP IIb-IIIa to prevent ischemic complications in patients undergoing percutaneous coronary intervention
272
What is the target of denosumab and how do we used it clinically?
targets RANKL in those with osteoporosis to inhibit osteoclast maturation
273
What is the target of omalizumab and how do we used it clinically?
targets IgE to treat those with allergic asthma
274
What is the target of palivizumab and how do we used it clinically?
targets the RSV F protein to prevent RSV infection in high-risk infants
275
What is the target of ranibizumab and how do we used it clinically?
targets VEGF for the treatment of neovascular age-related macular degeneration
