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Year of Variolation
1500
Year of Edward Jenenr producing Vaccinia Virus
1796
Year Louis Pasteur produced live, attenuated chicken cholera and anthrax vaccines
1880
Elie Metchnikoff Phagocytosis Year
1888
Emil Von Behring and Kitasato (Humoral Immunity)
1890
Emil Von Behring and Kitasato (Humoral Immunity)
1890
Emil Von Behring and Kitasato (Humoral Immunity)
1890
Emil Von Behring and Kitasato (Humoral Immunity)
Jules Bordet discovered complement
1894
Robert Kraus discovered precipitins
1897
Emil Von Behring serum antitoxins
1901
Karl Lansteiiner discovery of ABO
1901
Discovery of T-cell receptor
1984
Susumu Tonegawa for antibody diversity
1987
Acute phase proteins increase by __% after inflammation
25
Cytokines involved with APRs
IL-1 , IL-6, TNF-a
CRP was discovered by Tillet and Francis in ____
1930
Structure of CRP: __ identical subunits held by non-covalent bonds
5
CRP levels vs Cardiovascular Risk
Low
Average
High
Low: <1 mg/dL
Average: 1-3 mg/dL
High: >3 mg/dL
Major component of alpha band in electrophoresis
alpha-1-antitrypsin
Ceruloplasmin converts ___ iron to __ iron
ferrous to ferric
CRP
Response time (hours):
Increase:
Response time (hours): 4-6
Increase: 1000x
SAA
Response time (hours):
Increase:
Response time (hours): 24
Increase: 1000x
A1A
Response time (hours):
Increase:
Response time (hours): 24
Increase: 2-5x
Fibrinogen
Response time (hours):
Increase:
Response time (hours): 24
Increase: 2-5x
Haptoglobin
Response time (hours):
Increase:
Response time (hours): 24
Increase: 2-10x
Ceruloplasmin
Response time (hours):
Increase:
Response time (hours): 48-72
Increase: 2x
C3
Response time (hours):
Increase:
Response time (hours): 48-72
Increase: 2x
Normal neutrophil lobe
2-5
Type 1 granules of Monocytes has
peroxidase
ACP
arylsulfatase
Type 2 granules of monocytes has
Glucoronidase
lysozyme
lipase
Mast cell survive ___ than basophils
longer
Highest Toll-Like Receptors are seen in
Macro
Mono
Neutro
Cell surface TLRs
1,2,4,5,6
Endosomal TLRs
3,7,8,9,10
Interleukin important for NK cell development
IL-15
CD of NK cells
CD-16 (Fc gamma receptor)
CD56 (CAM)
Recall
NK Cell mediate what type of reaction
Graft-versus-leukemia (GVL) reaction
Aluminum salts preferentially stimulate
Th2 responses
Examples of oil-in-water emulsion
FCA, FIA, MF59, AS03, AS01B
Herd immunity is achieved through __% of population
70
T-cell receptor CD
CD3
B-cell coreceptors
CD19
CD21 - receptor for complement component C3d
T-cell
percentage:
lifespan:
T-helper percentage:
T-cytotoxic percentage:
T regulatory percentage:
percentage: 60-70%
lifespan: 4-10 years
T-helper percentage: 60%
T-cytotoxic percentage: 30%
T regulatory percentage: 10%
Type__ Helper T-cells produce IFN-gamma, TNF, IL-__
Type 1 Helper T-cells produce IFN-gamma, TNF, IL-2
Type __ Helper T-cells produce (6) interleukins
Type 2 Helper T-cells produce (6) interleukins
4,5,6,9,10,13
Type __ of Helper T-cells
17
CD marker of T cell-regulatory cells
CD4 and CD25
Critical for autoimmunity
POINT OF DIFFERENTIATION
Earliest T cell marker
Most specific T cell marker
Earliest T cell marker: CD2
Most specific T cell marker: CD3
B cell
Percentage in blood:
Markers:
Subset:
Percentage in blood: 10-20%
Markers: sIg (IgM, IgD), CD19, CD20, CD21, MHC-2
Subsets: B1, B2 (more common
Double negative thymocytes proliferate under____. Rearrangement of genes that code for ____
IL-17 ; TCR
Pro-B cell differentiaties to Pre-B cell once heavy chain rearrangement happens in chromosome __
14
Chromosome for kappa and lambda light chains
2, 22
Markers for Immature B-cell
IgM, CD21, CD40, MHC-2
Lymphocyte identification uses rosette assay since sheep RBC may have ____ receptor to lymphocytes
CD2
Ficoll-Hypaque specific gravity
1.077
Immunogens must be _____ MW
10,000 daltons
MHC gene
short arm of Chromose 6 band 21
MHC 1 is present in
All nucleated cells
lymphocytes and myeloid cells (highest)
MHC 2 present in
macro
mono
B cells
dendritic cells (HIGHEST)
APCs (immunocompetent cells)
MHC ____ are secreted proteins that have immune function
3
MHC class III consists of 5
C2
C4
Factor B
TNF
21-hydroxylase
MHC proteins inherited in parents
6 (3 from each parent in each allele as haplotypes)
Codominant
Structure of MHC 1
3 alpha chains
1 beta-2 microglobulin
HLA on RBC
Bennet Goodspeed antigen
HLA match to siblings
HLA match to parents
HLA match to siblings: 50%
HLA match to parents: 25%
HLA disease association
HLA-B27 (3)
Ankylosing spondylitis
Acute anterior uveitis
Reiter's syndrome
HLA B-27 Seronegative Arthropathies (4)
PAIR
psoriatic arthritis
ankylosing spondylitis
IBD-associated arthritis
reactive arthritis
HLA disease association
HLA-B8 (4)
Celia and Sjogren MaDe a BB
Dematitis herpeformis
Myasthenia gravis
Sjogren's syndrome
Celiac disease
HLA disease association
HLA-DR2 (2)
Multiple Sclerosis
Narcolepsy
HLA disease association
HLA-DR3 (5)
Hashi MaDe SLE3k Graves
Dermatitis herpeformis
Myasthenia gravis
Graves
Hashimotos
SLE
HLA disease association
HLA-DR4 (3)
Pemphigus vulgaris
RA
Type 1 DM
Basiliximab and Daclizumab bind to
CD25 receptor
Alemtuzumab bind to
CD52 receptor
Why cornea is the safest transplant
avascular
low MHC1
absent MHC2
Order of 3 most commonly transplanted organ
Kidney > Liver > Heart
Hyperacute
onset:
mechanism:
cause:
onset: minutes to hours
mechanism: humoral
cause: preformed ABO antibodies
Accelerated
onset:
mechanism:
cause:
onset: within 1 week
mechanism: cell-mediated
cause: previous sensitization to donor antigens
Acute (most common)
onset:
mechanism:
cause:
onset: within 1 month
mechanism: cell mediated
cause: allogeneic reaction
Chronic
onset:
mechanism:
cause:
onset: more than 3 months
mechanism: cell mediated
cause: disturbance of host-graft tolerance
GVHD
onset:
mechanism:
cause:
onset: varies/100 days or more
mechanism: cell-mediated
cause: donor competent T cells reject recipient T cells
Damage to new organs
onset:
mechanism:
cause:
onset: more than 3 months
mechanism: immune complex, complex with soluble antigens
cause:
Ratio of kappa: lambda light chains
2: 1
65%:35%
Variable region consists of the first ____ amino acids
110
Abundancy of Ab in blood
G A M D E
Abundancy of Ab in secretions
A G M D E
Complement bind to what Ig domain
CH2 (IgG) ; CH3 (IgM)
Antibody isotypes that contain additional CH domain
IgM IgE
Molecular weight of Ab order
M E D A G
Sedimentation coefficient
IgM - 19s
IgG, IgA, IgD - 7s
IgE - 8s
Longest half life
IgG (23 days)
Percentage of Ig
IgG : 70-75%
IgM: 10%
IgA: 10-15%
IgD: <1%
IgE: 0.02%
Heavy chain subclasses
IgG - 4
IgA - 2
Constant domains
IgM and IgE: 4
Others: 3
basis of differences between IgG subclasses
Disulfide bonds
IgG1: 2 / 67%
IgG2: 4 / 22%
IgG3: 15 / 7%
IgG4: 2 / 4%
Antigen binding sites of IgM
Monomers of IgM
10
5
Breaks disulfide of J chain to remove IgM and leave IgG intact
2-DTT, ME
Forms of IgA
serum: Type 1 (monomer)
secretions: Type 2 (dimer with J chain and secretory component)
Best indication of current infection is a _____________ rise in ab titer when comparing 2 serum samples from a patient during beginning and later stages of infection.
fourfold rise
Papain fragments
2 Fab and 1 Fc