HDC LGS Flashcards
1
Q
Distinguish between Immunogen and Toleragen and their immune responses
A
Immunogen - something you want the body to repsond to and lead to inflammation
Toleragen - something you don’t want to activate an immune response
2
Q
What is the failure of tolerance to self?
A
Autoimmunity
3
Q
Explain the pathogenesis of Autoimmune polyglandular syndrome (APS-1)/ APECED
A
AIRE gene mutation - Finn-major R257X mutation - nonsense mutation that results in premature stop codon and nonfuncational AIRE –> reduced expression of peripheral tissue antigens in the thymus –> defective elimination of self-reactive T cells –> T cells leave thymus and react with peripheral antigesn that weren’t properly presented
4
Q
Clinical features: generalized tonic-clonic seizures, recurrent oral ulcerations, dental problems, delayed growth, prolonged diarrhea, proptosis, pigmentation of lips and tongue, fingersnails yellow and mottled
A
Parahypothyroidism due to Autoimmune polyglandular syndrome (APS-1)/ APECED
5
Q
Explain the pathogenesis for Immune-dysregulation polyendocrinopathy, enteropathy, X-linked (IPEX)
A
FOXP3 mutation –> deficiency of T regulatory lymphocytes
6
Q
Clinical features: child with consanguinous parents, diarrhea, malnutrition, failure to thrive, hx of Celiac disease, failed to response to gluten free diet.
Height and weight < 5th percentile, hepatomegaly, eczematous dermatitis on trunk and extremities
Labs: increased liver enzymes (AST/ALT), increased glucose, anemia
Treg lymphocytes at 0.03% of all CD4+ T cells (normal = 4.4%)
A
Immune-dysregulation polyendocrinopathy, enteropathy, X-linked (IPEX) disorder
7
Q
How does the development of Central T cell tolerance differ from Central B cell tolerance?
A
T cell Central Tolerance - T cells undergo negative selection –> Medullary thymic cells present AIRE proteins (self-antigens) to T cells –> T cells with abnormal affinity undergo apoptosis (small percent become Tregs), T cells with normal affinity go on to become naive T cells
B cell Central Tolerance - Mature B cells presented with self-antigen in bone marrow –> Receptor editing - reexpression of RAG, resume light chain recombination of VJD, express new Ig light chain
8
Q
How does the development of Peripheral T cell tolerance differ from Peripheral B cell tolerance?
A
Peripheral T cell tolerance - mature T cell recognizes self-antigen –> Treg induces suppression of T cell
Peripheral B cell tolerance - mature B cell recognizes self-antigen –> deletion (apoptosis) or anergy (functionally unresponsive)
9
Q
What are some mechanisms by why infection may promote development of autoimmunity?
A
increase of PAMPS & DAMPS, or self-antigen mimicry
Activation of tissue APCs –> self-reactive lymphocytes bind and activate –> self-reactive lymphocytes present self-antigen to B cells –> formation of antibodies –> increase of inflammatory cytokines
10
Q
Explain how a genetic deficiency of complement proteins (C1q or C4) may lead to autoimmunity in the context of self-tolerance failure
A
Deficiencies in complement proteins –> no clearance of necrotic debri –> sustained exposure of debri to immune system –> allows opportunity for autoreactive lymphocytes to engage with antigens
11
Q
Describe the clinical manifestations of Sjogren syndrome.
A
Fatigue, arthralgia
Dry eyes - “feels like dirt/sand in eyes”
Dry skin
Dry mouth - may have difficulty swallowing, poor dentition
12
Q
Explain the pathogenesis of Sjorgen Syndrome and the laboratory tests used to confirm it
A
Autoreactive lymphocytes triggered by infection –> local cell death –> release of tissue self-antigens –> Increased activation of autoimmunity –> lymphocytic infiltration –> destruction of salivary and lacrimal glands
Non-specific tests: ANA, RF, ESR/CRP, Anti-Sm
Specific: Anti-Ro, Anti-La
13
Q
A patient diagnosed with Sjogren syndrome turns out to be pregnant. What are the possible complications?
A
Fetal fibrosis of the heart
Maternal Ro IgG antibodies cross placenta –> IgG inhibits physiologic clearance and binds to macrophages –> secretion of TGF-B and TNF and hypoxia induce myofibroblast formation of the heart
Unsure how much detail of this we need to know
14
Q
You and a friend are skiing in Colorado when you see their hands with well demarcated areas of lightening color, loss of vasular color to digits, and cyanosis.
What is the likely syndrome and what is it typically caused by?
A
Raynaud’s phenomenon - vasoplastic response to cold weather –> decreased blood flow to extremities –> ischemia
Can be idiopathic, but commonly associated with underlying diseases, medications or hyperviscocity
15
Q
Outline CREST syndrome
A
Calcinosis, Raynaud’s, Esophageal dysmotility, Sclerofactyly, Telangiectasia
16
Q
Systemic Sclerosis is a response from which three interrelated processes
A
Autoimmune response, vascular damage, collagen deposition
Autoimmunity - CD4+ T cells respond to unidentified antigen
Vascular damage - repeated yccles of endothelial injury follows by platelet aggregation –> release of factors that trigger endothelial proliferation
Collagen deposition - fibrosis
17
Q
How do you distinguish Systemic Sclerosis from other autoimmune disorders?
A
Striking cutaneous changes
Diffuse SS - initial widespread skin involvement with rapid progress, early visceral involvement
Limited SS - mild skin involvement, late involvement of viscera, CREST syndrome
18
Q
Why is it important to always rule out GAS when a viral or bacterial infection is suspected?
A
Group A Strep can cause Rheumatic Fever
19
Q
Outline the sequence of events in a typical Type I hypersensitivity reaction
A
Initial exposure - Allergen (Ag) recognized by APC –> APC binds to Ag –> APC binds MHC II receptor to CD4+ TCR and displays Ag –> T cell activation –> T cell binds to activated B cell receptor –> CD40L bind to CD40 for costimulation –> IL4 and IL13 released for IgM change to IgE antibodies –> FcE receptor of IgE antibodies bind to mast cell/basophils –> sensitized mast cell/basophils –> Fab portion open for future Ag binding
Re-exposure - Ag binds Fab portion of IgE antibody on sensitized mast cell/basophil –> crosslinking of IgE antibodies –> degranulation of mast cell –> histamine release –> bronchoconstriction, vasodilation, vascular permeability –> fluid leak into superficial dermis causing wheals and flares (urticaria)
20
Q
Food, medication, and insect sting allergies are what type of hypersensitivity
A
Type I
21
Q
Outline the pathophysiology of a Type II hypersensitivity
A
Antigen bind to cell-surface molecule –> antibody binds to antigen through Fab portion –> cell targeted as pathogen –> 4 different paths:
- Complement binds to Fc region of antibody –> MAC complex activation –> MAC breaks down cell wall –> cell lysis –> cell destroyed
- Complement binds to Fc region of antibody –> C3b actiation –> recruits phagocytic cells –> opsonization –> cell destroyed
- Complement binds to Fc portion of antibody –> C5a activation –> stimulation of neutrophil chemotaxis –> neutrophils release peroxidase –> cell destroyed
- Antibody binds to receptor on NK cell –> NK releases enzymes –> antibody-dependent cell mediated cytotoxicity (ADCC) –> cell destroyed
22
Q
What are some diseases that can be caused by Type II Hypersensitivity?
A
From RBC destruction:
Autoimmune hemolytic anemia, ITP, Acute hemolytic transfusion reaction, erythroblastosis fetalis
From inflammatory mediators:
Good pasture syndrome - targeting type IV collagen in lungs and kidneys
Rheumatic fever, Hyperacute transplant rejection
From issues with receptor binding:
Myasthenia Gravis - IgG antibodies binding to Ach receptors
Graves disease - IgG antibodies bind to and overstimulate TSH receptors on thyroid follicle causing overproduction of thyroid hormone
23
Q
Discuss how a Type III hypersensitivity can cause tissue injury and disease
A
Ag free floating in blood –> IgG antibody binding –> formation of Ag/Antibodies complexes –> deposited into endothelium, tissues, joints, kidneys –> extreme complement activation –> large amounts of C3a, C4a, C5a released –> vascular permeability, neutrophil chemotaxis –> edema, lysosomal destruction of tissue
Diseases:
Polyartheritis nodosa - deposition in vasculature
Post-strep golmerulonephritis - deposition in kidneys
Systemic Lupus - deposition in kidneys
IgA nephropahty
Hypersensitivity pnueumonitis - deposition in lungs
24
Q
What is Serum Sickness and what type of hypersensitivity is it?
A
Creating antibodies to an antitoxin or antivenom upon initial exposure –> re-exposure to antitoxin or antivenom –> systemic immune complex formation
Type III
25
List examples of disease caused by T cells and differentiate the CD4+ ones from CD8+ ones
Type IV hypersensitivity reactions -
**CD4+**
*Initial exposure* of Ag through epithelial cells --> Ag binds to protein --> APC presents Ag to naïve T cell --> CD4+ T cell binding MHC II --> release of IL-12 --> stimulation of Th1 differentiation --> Th1 release of IL-2 and IFN-y --> not as big a reaction
*Re-exposure* --> pre-formed T cells (memory response) --> increased release of IFN-y by Th1 --> macrophage activation --> larger inflammatory response
Disease: Allergic Dermatitis
**CD8+**
APC presents Ag on MHC I --> CD8+ T cell activation and proliferation --> CD+ T cells target cells expressing Ag --> release perforins and granzymes --> cell lysis --> cause of most inflammation and tissue damage on re-exposure
Diseases:
Multiple Sclerosis - CD8+ T cells target oligodendrocytes
IBD - targeting pancreatic cells
T1DM - targeting pancreatic cells
Hashimoto Thyroiditis - targeting thyroid tissue --> hypothyroidism
26
How do you distinguish between Type II and Type III hypersensitivies?
What is the primary target?
Is the antibody/antigen complex targeting a specific tissue, or is there just a predisposition for deposition?
27
What is the immediate treatment for anaphylaxis and it's MOA?
Epinephrine injected into lateral thigh
Agonist for adrenergic alpha receptors --> causes vasoconstriction
Agonist of adrenergic beta receptors of the lungs --> bronchodilation
28
What is the criteria for anaphyalxis?
1. Skin reaction + respiratory involvement or hypotension
2. Any two organ systems involved
3. Hypotension alone is exposure to allergen is known
29
A patient presents to urgent care three days after starting TMP-SMX for a UTI. They have an widespread erythematous rash you believe to be exanthematous drug eruption. What is the likely cause?
Delayed hypersensitivity reaction due to the Sulfa in TMP-SMX
30
Why should patients always be tapered off of long-term glucocorticoids?
To reduce risk of adrenal insufficiency
31
What is the MOA of glucocorticoids?
Anti-inflammatory - decreases proinflammatory gene transcription and inhibit PLA2
Immunosuppressive - cytotoxic to leukocytes
32
What is the MOA of antihistamines?
Inverse agonist - competes with active site and gets the opposite effect
33
What is the biggest difference between the first and second generation of antihistamines?
Which generation should be given to children?
First generation crosses the BBB --> can lead to sedative effect (Benadryl)
Second generation
34
A patient presents to the clinic with fever, bullae and peeling skin over < 30% of their body. They have a positive Nkolski sign and mentioned they recently switched their seizure medication.
What is the likely cause and how do you treat it?
Likely cause: Type IV hypersensitivity to drugs
**SATAN** drugs most common
**S**ulfa, **A**llopurinol,**T**etracyclines, **A**nticonvulsants, **N**SAIDS
Treat with: infeciton contraol, skin grafting, pain management, steroids
| Disease is Steven Johnson Syndrome
35
What are the classic clinical findings of seasonal allergies, and what type of hypersensitivity are they?
Mildly erythemetous conjunctiva
Boddy pale to bluish nasal turbinates
Postnasal drainage
Mild tenderness of frontal and maxillary sinuses
Type I hypersensitivity
36
What type of medication do you avoid giving to someone with Karposi Sarcoma?
Corticosteroids - increases the replcation of the virus
37
What are some of the PREP and PEP access issues?
Cost barriers
Provider Reluctance (lack of training, time restraints)
HIV stigma
Legal challenges
38
Drug interactions with amphotericin B
Chemotherapy drugs, vancomycin, aminoglycosides
Anti-HTN drugs (lowers BP)
39
Adverse effects of amphotericin B
Acute: Rigors syndrome, electrolyte abnormalities, hypotension
Seizures if given intrathecally
Delayed: Nephrotoxicity
40
Which fungi forms a spherule with endospores?
Coccidioides immitis
41
Label the fungi for each geographic location
Orange - coccidioimycosis
Blue - Histoplasmosis
Green - blastomycosis
42
Which fungi is often associated with bat/bird droppings?
Histoplasma Capsulatum
43
What class of medications can cause hepatotoxicity due to its interactions with CP450?
Azoles
44
What medication is typically used for aspergillis and candidiasis, and what's the MOA?
Echinocandins - blocks B-1,3-glucan synthase --> stops formation of B-1,3-glucan --> prevents cell wall formation
45
What fungi is the exception to the "mold in the cold, yeast in the heat" rule?
Candida - yeast at 25, mold at 37
46
Which disease has a characteristic rash described as "Sea of Red with Islands of White"?
Dengue fever
47
What is the case definition of Dengue fever?
2 or more in febrile person who traveled to or lives in endemic area:
N/V
Rash
Aches/pains
positive tourniquet test
leukopenia
48
What is the case definition of severe Dengue?
Any of the following symptoms:
Severe plasma leakage --> shock or fluid accumulation
Severe bleeding
Severe organ impairment
impaired consciousness
heart impairment
49
Explain the difference between Jungle, Urban and Intermediate transmission styles for Yellow fever
Jungle: mosquito --> primate --> mosquito --> primate
Urban: human --> mosquito --> human --> mosquito
Intermediate: human --> mosquito --> primate --> mosquito
50
What are the four Zika transmission routes?
1. Mosquito to human
2. Human to mosquito
3. Mother to baby in utero
4. Sexual transmission
51
What a mosquito infected with West Nile bites a human or other mammal, what are they called?
Dead end hosts - cannot be passed on to other mosquitos
52
What is the most significant variable that determines the severity of a parasitic infection?
Parasite burden
53
Outline the different forms of the life cycle of the malaria species
Ring (thin rings inside RBC) --> Trophozoite (variable shape) --> Schizont (cell filled with replicants, mini parasites) --> Gametocyte
54
Which malarial parasite replicates in young RBC?
P. vivax
55
Which malarial parasite replicates in old RBC?
P. malariae
56
Which malarial parasites causes the RBC to become enlarged?
P. ovale
57
How does Cloroquine treat malaria?
Induces breakdown of heme --> parasite needs heme to form hemazoan
58
How does Ato-Pro treat malaria?
Ato - disrupts electron transport in plasmodium
Pro - dihydrofolate reductase inhibitor
59
What medication is contraindicated for G6P deficient patients and why?
Primaquine/tafenoquine
Pts can't neutralize free radicals
60
Small eye, larger than RBC = T. [ ]
Brucei
61
Large eye, smaller than RBC = T. [ ]
cruzi
62
What are the treatments for West African Trypanosomiasis
Early - Pentamidine
Late - Eflomithine
63
What are the treatments for East African Trypanosomiasis
Early - Suramin
Late - Melarsoprol
64
What disease is it common not to have acute symptoms?
Chagas (T. cruzi - American Trypanosomiasis)
65
What is Romana sign and what disease is it associated with?
Elastic edema of the upper and lower eyelids, chmosis of th econjunctiva, and enlargement of the ipsilateral lymph nodes
Pathogneumonic for T. cruzi
66
What type of hypersensitivity reaction is Romana sign?
Type II - antibody and antigen - lysis of cells holding the organism
67
What parasite only replicated in cells of infected tissues?
T. cruzi
68
What parasite shows tetrad figures in RBC?
Babesia
69
Name the hosts, vectors and reservoirs of Babesia
Primary reservoir - field mouse
Vector - Ixodes tick
Host - human
Incompetent host - Deer - host of where tick grows
70
How do you calculate sensitivity and specificity?
Sensitivity = A/(A+C)
Specificity = D/(B+D)
71
How do you calculate PPV and NPV?
PPV = A/(A+B)
NPV = D/((C+D)
72
How do you calculate Case Fatality Rate?
(Death/cases) * 100
73
How do you calculate Attack Rate?
(cases/number of people exposed) * 100
74
What does normal staph flora release to rid bad staph from the body? How does it work?
Lysostaphin
Degrades the crossbridge of the cell wall
75
Explain the difference between simple stain and negative stain
Simple stain - stains bacteria with basic dye
Negative stain - stains background with acidic dye
76
What is the Schaeffer-Fulton method?
Endospore stain
77
Differentiate between selective, differential and enriched media
Selective - testing for specific properties
Differential - determining which bacteria can/can't do something
Enriched - enriching media to help specific bacteria grow
78
What antibiotic interferes with CP450 enzymes, and thus can't be used with medication that need CP450 metabolism?
Macrolides - Erythromycin and Clarythromycin
79
What is the role of the innate immune response to the pathogen?
Recognize PAMPs and recruit phagocytic cells
First line of defense against pathogens
80
High nitrate levels in a dipstick urinalysis is indicative of
gram negative bacteria
81
PTX3 is detected in concentrations very early in innate immunity because
it's released by epithelial cells as soon as they are in contact with the pathogen
82
Where are TLRs located?
On the surface of the cell and within endosomes
83
In mild COVID19, what roles do TLR3/7 play? What roles do TLR2/4 play?
TLR 3/7 are antiviral and release Type I/III IFN - covid virus supresses TLR 7
TLR 2/4 are proinflammatory and release IL6, IL8, TNFa
84
Whats a major difference from mild COVID that leads to severe COVID?
Mild - rapid IFN response
Severe - Delayed or poor IFN response --> increase of viral replication and auto-IFN antibodies
85
What are the roles of NK cells?
1. Killing of virus infected cells - binding activating receptor to activating ligand
2. Killing of phagocytosed microbes - macrophage releases IL12 onto NK cells --> NK cell realeases IFN-y onto macrophage
86
Explain how the inhibitory receptor of an NK cell works?
How does it work with viral infected cells?
When NK cell binds to normal cell --> normal cell expresses MHC I self peptide complex --> NK cell binds and recognizes self peptide --> not activated
With viral infected cells --> virus inhibits MHC I expression --> NK cell doesn't detect MHC I receptor --> NK cell activated --> kills cell
87
Where are NOD, Mannose, and DNA/RNA receptors found?
NOD - cytosol
Mannone - plasma membrane
DNA/RNA - cytosol
88
Which complement pathway is activated by antibodies?
Classical
89
Which complement pathway is activated by the microbial cell surface?
Alternative
90
What are the role of C3a and C3b in the complement pathway?
C3a - inflammation
C3b - opsonization and phagozytosis
91
What pathogen bind factor H to its surface and induces C3bBb dissociation?
What does this lead to?
Borrelia Burgdorferi - Lyme disease
No C3bBb of the alternative pathway --> no formation of C5 convertase --> no MAC complex
92
What are the components of innate immunity?
Epithelial barriers, Mast cells, phagocytes, dendritic cells, complement, NK cells
93
What are the components of adaptive immunity?
T cells, B cells, antibodies
94
What is the action of T helper cells?
IL12 stimualtes **Th1 helper** - releases IFN-y --> **macrophage** activation against intracellular pathogens --> plays role in chronic inflammation, granuloma formation
IL4 stimualtes **Th2 helper** - releases IL4, IL5, IL13 --> **eosinophil** and **mast cell** activation --> plays role in allergic reactions
**Th17** - releases IL17, IL22 - **neutrophil** recruitment and activation against extracellular bacteria/fungi --> plays role in autoimmunity
**Tfh** - release IL21, IFN-y, IL4 --> **B cell activation** leading to antibody production - plays role in autoimmunity
95
Explain Cytotoxic T cells activation
Nucleated cells present Ag via MHC I --> CD8+ cells bind to MHC I and recognizes intracellualr pathogen --> CD8+ T cell releases perforin and granzyme B --> perforation of cell membrane --> cell death
96
What is the role of Tregs and how are they
TGF-B stimulates **Tregs** - effective against autoimmunity - releases TGF-B, IL10 - decreased immune response
97
What mechanism provides the most diversity to Ig and TCR?
Junctional diversity - addition or removal of nucleotide base pairs after VDJ recombination
98
What is the role of PD-1 expression by CD4+ T cells?
PD-1 is a regulatory molecule --> has suppressive effect on CD4+ --> diminsihed adaptive immune response
99
Discuss the significance of higher concentratops of IL-6 and TNF-a in blood panel
IL6 and TNF-a levels indicate acute phase reactants
100
Discuss the significance of decreased HLA-DR4 expression by monocytes
HLA-DR4 encodes for MHC II receptors --> less receptors --> less CD4+ activity --> decreased adaptive immune response
101
Explain the roles of the following surface molecules:
TCR
CD4
CD8
CD3
CD28
CTLA-4
PD-1
LFA-1
TCR - antigen recognizition of any MHC-peptide
CD4 - signal transduction of APC
CD8 - signal transduction of all nucleated cells
CD3 - initial stimulation
CD28 - costimulation of APC B7 - cytokine production
CTLA-4 - regulatory protein w/ higher affinity for B7 - target for cancer therapeutics
PD-1 - negative regulation of APC, tissue cell or tumor cell PD-L1 - inhibits initial stimulation
LFA-1 - adhesion to APC or endothelium ICAM-1
102
What activates expression of B7 on MHC-II cells?
PAMPs
103
Explain the role that CD4+ and CD8+ T cells play in the adative immune response to viral infections
Virus inside endosome in cell --> CD4+ recognition of MHC-II --> release of IFN-y --> disruption of translation of viral protein
Viral microbe in cytosol --> CD8+ recognition of MHC-I --> release of perforins and granzymes --> perforins facilitate entry of granzymes into cytosol --> granzymes activate apoptosis --> cell death
104
Explain the process of T cell maturation
RAG (Recombinase Activating Gene) creates precursor T cell --> Adds CD4/8/3 (double positive stage) --> positive selection --> negative selection --> naive T cell
105
Explain the process of T cell Positive selection
Thymic epithelial cells present either MHC-I or MHC-II to double positive T cells --> weak binding of one or the other leads to CD4+ or CD8+, no binding or too strong binding leads to apoptosis
106
Explain the process of T cell negative selection
Positively selected T cells transported to thymic medulla --> medullary thymic cells present self-antigen (AIRE protein) --> if T cell binds it undergoes apoptosis, cells that don't bind become naive mature cells
107
What HLAs encode for MHC-I receptors? MHC-II receptors?
MHC-I - HLA-A/B/C
(MHC-1 = 1 letter)
MHC-II - HLA-DP/DQ/DR
(MHC-2 = 2 letters)
108
What is the purpose of the costimulatory signal B7/CD28
Activates T cell --> proliferation, cytokine production and release
109
What section of the antibody contains light chain?
Fab portion - antigen binding
110
What part of the antibody changes to determine the isotope?
Heavy chains
111
What is the site of complement binding? Site of phagocyte binding?
Complement - CH2
Phagocyte - CH3
112
Differentiate the role of naive B cells, activated B cells, memory B cells, and plasma cells
Naive B cells - B cell that hasn't come into contact with antigen - only IgM/IgD
Activated B cells - B cell that has come interacted with antigen, ingone class switching, and can proliferate/differentiate
Memory B cells - B cells that have been produced by activated B cells can contain antibodies for specific antigens
Plasma cells - produce and release antibodies for specific antigen
113
Distinguish T cell independent activation from T cell dependent activation
T cell dependent:
Antigen presentation on B cell MHC-II binds to T cell --> Th cell activates B cell --> isotype switching --> B cell proliferation and differentiation to memory/plasma cells
Two signals required: B7/CD28 - stimualtion of t cell cytokine production; CD40/CD40L - Isotype class switching
T cell independent:
B cell antibodies bind to peptide --> B cell Ig receptors crosslink --> intracellular signalling --> B cell activation --> maturation to plasma cells --> generation of IgM antibodies but no class switching or memory B cells formed
114
# ```
Describe the varied functions of the Ig subclasses
IgG - neutralization of microbes, opsotionzation fo antigens, activation of classical pathway, antibody dependent cellular cytotoxicity, neonatal immunity, feedback inhibition of B cell activation
IgM - activation of classical pathway
IgA - mucosal immunity, neutralization of microbes
IgE - eosinophil and mast cell mediated defense against helminths (response to allergens)
115
Discuss the antibody response to bacteria on initial and subsequent exposure
Initial - IgM formation and eventually IgG
Subsequent - More rapid neutralizing effect of IgG expression of antibodies
116
Discuss the role IgG plays in facilitating phagocytosis of microbes
Neutralization of microbes/toxins
Opsonization and phagocytosis
Antibody-dependent cellular cytotoxicity
Complement activation --> lysis of microbes, phagocytosis of microbes with C3b receptor, inflammation
117
What is B cell inhibition?
IgG turns down B cell response after infection
T dependent B cell activation --> formation of B cells that secrete IgG --> IgG binds to pathogen and fomrs complex --> Fc receptors on B cell bind to IgG/pathogen complex --> B cell turned off
118
Define variolation
practice of taking a lancet to a ripe pistule of an infected person and introducing the infectious material to a non-infected person
119
Why was small pox able to be eradicated?
Humans were the only host, no animal reservior
Only one serotype = only one vaccine needed
No carrier state = disease is shown fast and pt can be quarantined to prevent spread
120
What are the sources of passive immunity?
Blood tranfusions
Homologous human antibody (IgG) - PEP for hep a, measles
Homologous human hyperimmune globulin (specific antibodies) - PEP for hep B, rabies, tetanus, varicella
Hereologous hyperimmune serum (from animals) - antitoxin, antivenom
121
What are the live, nonattentuated vaccines?
Adenovirus
122
What are the live, attenuated vaccines?
VZV, MMR, Influenza, rotavirus, BCG (TB), Dengue, Ebola, Yellow fever, Typhoid, Herpes zoster
123
What are the inactive, whole cell vaccines?
Hep A, Rabies, Influenza (IM), Pertussis
124
What are the inactive, Fractional vaccines and the types?
Subunit: HepB, Influenza (IM), Pertussis, HPV, HZ, Anthrax, Pneumococcus, Meningococcus, SARS-CoV-2
Toxoid: diphtheria, tetanus
Conjugate: HiB, Pneumococcus, Miningococcus, Malaria
Nucleic Acid: SARS-CoV-2
125
How are the different types of fractional vaccines made?
Subunit - using a protein from the virus
Toxoid - using a toxin from the virus
Conjugate - using a protein connected to a toxoid
Nucleic Acid - using viral dna/rna
126
Which vaccines induce a humoral response only?
Live attenuated bacteria - Pertussis, BCG
Killed viruses - Hep A, polio, rabies
Recombinant protein subunit vaccines - HPV, Hep B
Modified protein vaccines - Tetanus toxoid, diphtheria toxoid
127
Which vaccines induce a T cell mediated and antibody response?
Live attenuated viruses - MMR, Rabies, influenza A
Conjugate vaccines - HiB, strep pneumoniae
mRNA vaccines - SRAS-CoV-2
Hybrid viral vaccines - SARS-CoV-2, Ebola
DNA vaccines
128
Justify the use of the following ingredients in vaccines:
Preservatives
Adjuvants
Stabilizers
Cell culture materials
Inactivating ingredients
Antibiotics
Preservatives - help prevent contamination
Adjuvants - help stimulate stronger immune response
Stabilizers - help vaccines maintain potency during transport and storage
Cell culture materials - vaccines are grown in cultures and hard to eliminate
Inactivating ingredients - used to kill the vaccine or inactivate toxins
Antibiotics - helps with prevention of contamination
129
All DNA viruses are double stranded except
Parvovirus
130
What is the difference between negative and positive sense RNA
negative sense RNA must come with extra components to be able to be transcribed into positive sense and hist host machinery
131
Nonenveloped, dsDNA viruses
Adenoviruses - common cold, meningitis
Papillomaviruses - warts, cervical cancer
132
Enveloped, dsDNA viruses
Smallpox
Herpesviruses
Hep B
133
Noneveloped, ssDNA viruses
Parvoviruses
134
dsRNA viruses
Reoviruses
135
nonenveloped, +ssRNA viruses
Polio, Hep A, Common cold
Gastroenteritis
136
enveloped, +ssRNA viruses
Togaviruses
Flaviviruses
Coraonaviruses
Retroviruses
137
enveloped, -ssRNA viruses
Filorviruses
Orthomyxoviruses
Paramyxoviruses
Rhabdoviruses
138
What vaccines are given at birth?
HepB, RSV
139
What vaccines are given at 2m, 4m, 6m?
Rotavirus, DTaP, HiB, Pneumococcal conjugate, Inactivated polio
140
When are the MMR, Varicella, and Hep A vaccines given?
1 year, earlier for at risk groups
141
By 13, what vaccines should be completed?
RSV
HepB
Rotavirus
DTaP
HiB
Pneumococcal conjugate
Influenza
COVID
MMR
Varicella
HepA
1st dose of Tdap, HPV, Meningococcal
142
How would you differentiate between AML and CML on a CBC w/ differential?
CML would show more differentiated WBCs - higher neutrophils/eosinophils/basophils/monocytes, or metalyelocytes/myelocytes
AML would should a left shift of immature cells - less differentiated, more blasts
143
What would you see on a PBS in the case of CML?
adbundant mature leukocytes - nothing more immature than myelocytes
144
What would you see on a PBS with AML?
Blasts
AURE rods
145
What is the pathogenesis of CML?
t(9:22) BCR-ABL
BCR-ABL fusion --> ABL is a kinase, BCR keeps signaling turned on --> proliferation and survival of pluripotent hemopoietic stem cell w/ preferential differentiation into neutrophils
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What are the three phases of CML?
Chronic phase - often no symptoms, most of life spent in this phase - leukocytosis of all granulocytes --> possible splenomegaly (N/V, fullness), thrombocytosis; < 10% blasts
Accelerated phase - more proliferation leads to more mutations earlier on --> neutrophil differentiation becomes progressively impaired - more blasts cells (10-19%) decrease space in bone marrow --> anemia, thrombocytopenia; high basophils --> increase histamine --> pruritis
Blast crisis - high mortality - transition to AML - >20% blast cells - anemia, thrombocytopenia, leukocytopenia, increased blasts --> infections; leukostasis, TLS
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What is the treatment for CML?
Tyrosine kinase inhibitors
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What is the etiology of Essential Thrombocytosis that is absent in CML?
JAK2 mutation
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Explain the natural history of Primary Myelofibrosis
Early on looks similar to others - same pathogenesis - high platelet count, high WBC
Later on - bone marrow replaced with scar tissue - pancytopenia
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What is the definitive test used to determine AML?
Bone marrow aspirate confirming 20% or more blasts (w/ or w/out AURE rods) present
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What role can flow cytometry play for determining myeloid neoplasms?
Can tell us the difference between acute and chronic by the markers on the cell surface
CD34 on immature stem cells, CD63 on mature myeloids
Determine if T-ALL (CD2-8) or B-ALL (CD10)
Determine if B-ALL (CD10) or B-CLL (CD5)
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What is the pathogeneis of Acute Promyelocytic Myelocytic Leukemia?
t(15:17) - disfunctional retinoic acid receptors
AMP-RAR
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What is the treatment for APML?
ATRA - All Trans Retinoic Acid Receptors
dysfunctional retinoic acid receptors --> poor differentiation --> stuck in intermediate phase/stuck at blasts --> ATRA allows for maturation --> short term allows cells to mature to neutrophils
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What is the most significant risk of APML?
Disseminated Intravascular Coagulation
High cell turnover --> granule release --> myleoperoxidase --> spontaneous coagulation
Tissue factor release --> coag cascade --> DIC
No platelets --> prolonged bleeding
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What immunochemistry can differentiate between AML and ALL?
myloperoxidase (+) - AML
Tdt (+) - ALL
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What is the treatment for AML?
Chemotherapy
Stages: Induction --> Consolidation --> Maintainence
Meds: Cytarabine, Ida/Daunarubicin
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What are the three common genetic disorders that lead to ALL?
Down Syndrome
t(12:21) - most common - seen more in children
t(9:22) - seen more in adults
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What is the relationship between Human T Lymphotrophic Virus infection and ALL?
While other ALL is primarily B cell lines being effected, HTLV ALL only effects T cells
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Hepatosplenomegaly and meningeal Leukemia are complications of
ALL
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What are the complications are specific to T-ALL?
Thymic enlargement:
Compression of the trachea - dypsnea, stridor
Compression of the esophagus - dysphagia
Compression of the SVC - SVC syndrome - enlargement of head/neck/UE veins, cyanosis
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Splenomegaly in CML is caused by
Deposition of leukocytes
Extramedullary hematopoiesis - Luekocytosis can cause the spleen to start producing RBC to help the bone marrow
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What can CLL turn into if lymphocytes begin to deposit in the lymph nodes and create a tumor?
Diffuse Large B-cell Lymphoma
(Richter Transformation)
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What is Evans Syndrome?
In CLL when plasma cells are over proliferating and not maturing correctly, they can release autoantibodies that attack the RBC and platelets.
The ensuing Autoimmune Hemolytic Anemia + Immune Thrombocytopenic Purpura = Evans Syndrome
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Smudge cells on a PBS are indicative of which disease?
Chronic Lymphocytic Leukemia
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How do you classify CLL?
RAI Classification
RAI 0 - Lymphocytosis
RAI 1 - RAI 0 + LAN
RAI 2 - RAI 1 + Hepatosplenomegaly
RAI 3 - RAI 2 + Anemia (not AIHA)
RAI 4 - RAI 3 + Thrombocytopenia (not ITP)
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What is the treatment for CLL classes?
Asymptomatic RAI 0, 1, 2 - no treatment, observation only
Symptomatic RAI 1, 2 - chemotherapy
RAI 3, 4 - chemotherapy
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Which types of non-Hodgkin's Lymphoma occur due to decreased cell apoptosis?
Are they slow or aggressive?
Follicular Cell (14:18) BCL2
Marginal Zone lymphoma - BCL10
Slow
| Both lymphomas that happen *after* Centroblast maturation
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What types of non-Hodgkin's lymphoma occur due to increased cell proliferation?
Are they slow or aggressive?
Mantle cell (11:14) Cyclin D
Burkitt's Lymphoma (8:14) c-myc
Diffuse Large B cell - BCL6
Aggressive
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What is the pathogenesis of Follicular lymphoma?
t(14:18)
Increased expression of BLC2 - inhibits apoptosis
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What is the pathogenesis of Marginal Zone Lymphoma?
Increased expression of BCL10 --> increased NK-kB --> decreased apoptosis
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What is the pathogenesis of Mantle cell lymphoma?
t(11:14)
Increases expression of Cyclin-D --> pushes cells into S phase --> increases cell proliferation
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Mutations of the Centroblast can cause what types of cancers, and how are they different?
Burkitt's Lymphoma - t(8:14) - increased c-myc expression --> massive cellular proliferation
-- triggered by EBV/HIV
Diffuse large B cell lymphoma - increased expression of BCL6 on chromosome 3 --> increased cell proliferation
**-- most common type of NHL**
High association with EBV/HIV
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What is a key clinical feature that differentiates Hodgkin's from Non-Hodgkin's lymphoma?
Hodgkin's Lymphoma has continguous LAD
NHL is noncontiguous LAD
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Alcohol-induced Lymphadenopathy pain is associated with
Hodgkin's Lymphoma
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Explain how Marginal Zone Lymphoma can be caused by chronic infection
Chronic infections such as H. pylori, Hashimoto, Sjogren's - chronic inflammation can lead to mutation and increased expression of BCL10 gene
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Explain why patients with NHL present with hypercalcemia
Large deposits in the kidneys can stimulate expression of 1-a-hydroxylase enzyme --> increases Vit D --> increases calcium absorption
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What is the treatment for NHL?
R-CHOP
Rituximab (only for CD20+ B cells) - complement mediated lysis of B cells - eliminate mature B cells
Cyclophosphamide
Hydroxydaunarubicin
Onvolin (Vincristine)
Prednisone (Steroids)
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What type of hypersensitivity reaction is Steven Johnson Syndrome?
Type IV delayed hypersensitivity
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What type of hypersensitivty reaction are season allergies?
Type I
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What is a positive Nkolski sign?
Sloughing of the epidermis - seen in Steven Johnson Syndrome as a result of reaction to medication
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Describe Good Pasture Syndrome
Glomerulanephritis as a result of type II hypersensitivity - antibodies specific for glomerular basement membrane of the kidney
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Describe Sjogren syndrome
Chronic disease resulting from Ig mediated destruction of lacrimal and salivary glands - can be triggered by viral infection
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Describe Systemic Sclerosis
Three interrelated processes:
Autoimmunity - CD4+ T cells response to unidentified antigen
Vascular damage - repeated cycles of endothelial injury follwoed by platelet aggregation lead to release of factors that trigger proliferation and fibrosis
Fibrosis
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Why is Rituximab associated with an increased risk of death by infection?
Elimination of all B cells leave opportunity for serious infection without having an immune response to fight back
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Describe CART therapy used in Diffuse Large B cell Lymphoma
Chimeric Antigen Receptor Therapy
Newly bioengineered protein that enables T cell to engage malignancy without costimulation with CD28
Small chain receptor is directed at CD19
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What antibodies titers are seen in Sjogren syndrome?
SS-A, SS-B, Anti-Ro, Anti-La
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ANA testing determines what
ANtibodies directed at nuclear antigens - just identifies autoimmune antibodies
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Rheumatic fever caused by Strep is considered what type of hypersensitivity
Type II
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What HIV medication is contraindicated for HLA-B5701 positive patients?
Abacavir
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What HIV medication can result in lipodystrophy?
Indinavir - protease inhibitor
191
What is the primary receptor for EBV?
CD21 on B cells (C3d complement receptor)
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What are the three potential outcomes of EBV?
1. Replcate in B cells or epithelial cells permissive for EBV replication and produce and spread virus
2. Cause latent infection of memory B cells in presence of competent T cells
3. Stimulate grown and immortalize B cells
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What are the three key clincal presentation of EBV and relate to pathophysiology
Pharyngitis - virus adheres to epithelium, , atypical Downey cells reactive to antigen
LAD - signs that antigen is being filtered through lymph nodes --> T cells become activated --> fight between B and T cells in small space --> swelling
Malaise - Physically draining process until EBV force dinto latency --> length of time depends on immune system
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What bugs grow on chocolate agar?
Moraxella catarrhalis
HiB
Tularemia
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What ILs do macrophages secrete?
IL1, IL6, IL8, IL12 (NK cell activation), TNF-a
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What ILs do Th1 cells secrete?
IL2 - growth of T cells
IL3 - eosinophil survival
IFN-y - macrophage recruitment, NK activaiton
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What ILs do Th2 cells secrete?
IL2
IL3
IL4 - enhances class switching to IgG and IgE
IL5 - stimualtes eosinophil growth/differentiation
IL6
IL10
IL13
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