Immunology & Serology Flashcards
NPW for serum antitoxin/ therapy
Emil von Behring (1901)
NPW for cellular immunity in tuberculosis
Robert Koch (1905)
NPW for Phagocytosis
Elie Metchnikoff (1908)
NPW for immunity and side chain theory
Paul Ehrlich (1908)
NPW for anaphylaxis
Richet and Portier (1913)
NPW for complement
Jules Bordet (1919)
NPW for human blood group antigens
“ABO”
SSR (specificity of serologic reaction)
Karl Landsteiner (1930)
NPW for immunologic tolerance
Burnet and Medawar (1960)
NPW for structure of antibodies
Edelman and Porter (1972)
*Edelman: analytic ultracentrifuge, 7s
*Porter: papain, IgG
NPW for radioimmunoassay
Rosalyn Yalow (1977)
NPW for Major Histocompatibility complex
Benaceraf, Dausset, and Snell (1980)
NPW for Immunoregulation
Niels Jerne (1984)
NPW for Monoclonal antibody
Using hybridoma technique
Koehler and Milstein (1984)
NPW for Antibody diversity.
In 1978, he discovered the genetic principle underlying the generation of antibodies with different specificities.
Susumu Tonegawa (1987)
NPW for transplantation
Thomas and Murray (1991)
NPW for cytotoxic T cell recognition of virally infected cells
Doherty and Zinkernagel (1996)
NPW for HIV
Francoise Baree-Sinoussi and Luc Montagnier (2008)
NPW for antibody structure using pepsin
Alfred Nisonoff
Method of scratching the skin and applying pulverized powder from a smallpox scab.
Variolation
Cowpox virus
Vaccinia
Smallpox virus
Variola major
Alastrim
Variola minor
AKA Typhoid Mary. A cook and a carrier of Salmonella Typhi
Mary Mallon
Christopher Columbus.
Old World to New World
Smallpox
Christopher Columbus:
New world to old world
Syphilis
Demonstrated that protection from cowpox can be generated by the transfer of postural material from a cowpox lesion preventing formation of smallpox lesion. Vaccination
Edward Jenner (1798)
Father of Immunology
Edward Jenner
Father of Modern Microbiology
Louis Pasteur
Discovered therapeutic vaccination. Uses live “attenuated” vaccines for cholera, anthrax, rabies (CAR)
Louis Pasteur (1885)
Discovered that certain blood cells could ingest foreign material, now classified as phagocytes
Elie Metchnikoff (1888)
Discovered precipitins
Robert Kaus (1897)
Year of the discovery of T cell receptor genes
1984
1st recorded blood transfusion
Pope Innocent VII (1492)
Use of sodium phosphate / phosphate soda as blood preservative
Braxton Hicks (1869)
Use of sodium citrate as blood preservative (1% concentration)
Albert Hustin (1914)
Determined the minimum concentration of Citrate as anticoagulant (0.2%)
Richard Lewisohn (1915)
Acid Citrate Dextrose as preservative
*21 days
Loutit and Mollison (1943)
Citrate phosphate dextrose as blood preservative
Gibson (1957)
Carried vein-to-vein transfusion
Edward Lindemann
Discovered ABO blood group
Karl Landsteiner (1901)
Director of American Red Cross Blood Bank
Father of Modern Blood banking
Dr. Charles Drew (1941)
Invented Gel technology (standardization)
Yves Lapierre (1985)
AKA innate, inborn, non-adaptive immune system
Natural Immune System
Natural immune system has a __ immune response
Non specific
No memory cells formed
Natural immune system
Cleaves cell wall of certain bacteria (G+)
Lysozyme
Digest bacterial surface protein
Pepsin
Binds iron which is essential for bacterial growth
Lactoferrin
Acidity of the stomach
pH 1
pH of the skin
5.5 to 5.6
pH of the vagina
pH 5
Attacks virally infected cells and tumor cells by secreting perforins and granzymes.
NK cells
Inhibitory receptors of NK cells
Killer Cell Immunoglobulin-like receptor (KIR)
CDs expressed by NK cells
CD 16 and CD 56
NK cells are also called ___ when exposed to IL-2 and IFN-y
Lymphokine Activated Killer Cells/ LAKs
Engulfment and destruction of microorganisms or damaged cells
Phagocytosis
Stages of phagocytosis
- Initiation
- Chemotaxis
- Engulfment
- Digestion
Chemotaxis is a process by which cells tend to move in a certain direction under the stimulation of a chemical substance known as ___
Chemotaxin
3 classic examples of chemotaxins
Antibodies, CRP, C5a
Test for chemotaxis
Boyden Chamber
Migration toward the site
Positive chemotaxis
Migration away from the site
Negative chemotaxis
Adhesion-Receptors of the innate immune system recognized by PPR through ___
PAMPS (Pathogen Associated Molecular Pattern)
Toll from drosophilia fly or fruit fly
Toll like receptor
TLR1
For mycobacteria
TLR2
For targeting the teichoic acid
TLR4
For targeting LPS
Speeds up phagocytosis
Opsonins
Respiratory burst – NADPH oxidase enzyme activity leads to the formation of reactive oxygen species
Oxygen-dependent pathway
Leads to the production of hypochlorite
Myeloperoxidase system
Cleave cell membrane
Defensins
Proteases that cleaves proteins in the cell
Cathepsin G
Produced by activated macrophage
Nitric oxide
Body’s overall reaction to injury or invasion by an infectious agent
Inflammation
Redness or erythema
Rubor
Heat
Calor
Pain
Dolor
Swelling or edema
Tumor
Loss of function
Function Laesa
Originally thought to be an antibody to the C-polysaccharide of the pneumococci.
-Best indicator or most widely used indicator of acute inflammation
C-Reactive Protein
Half-life of C-Reactive Protein
19 hours
Associated with HDL cholesterol;
-activates monocytes and macrophages
-found to be increased significantly more in bacterial infections than in viral infections
Serum Amyloid A
Polypeptide products of activated cells that control or regulate various cellular responses thereby regulated immune response
Cytokines
A group of cytokines discovered in virally infected cultured cells that interfere with viral replication, virus nonspecific but host specific
Interferons
Other name of TNF-a
Cachectin
Other name of TNF-b
Lymphotoxin
Cytokines that stimulate transendothelial leukocyte movement from the blood to the tissue and regulate the migration of PMNs and mononuclear leukocytes within tissues
Chemokines
AKA acquired, specific immune system
Adaptive Immune System
Anamnestic immune response, formation of memory cells
Adaptive Immune System
They modulate inflammation and immunity by regulating growth, mobility, and differentiation of lymphoid cells. Interact with leukocytes but do not bind to the antigen
Interleukins
Cytokine secreted by monocytes, macrophage, dendritic cells
-inflammation, fever, acute phase response
IL-1
Cytokine secreted by T cells
-growth and proliferation of T and B cells
IL-2
Cytokine secreted by activated T cells
-hematopoiesis
IL-3
Cytokine produced by Th2 , mast cells
-AKA B cell growth factor I
-promotion of Th2 differentiation
-stimulation of B cells to switch to IgE production (isotype switching)
IL-4
Cytokine produced by Th2
-AKA B cell growth factor II
-eosinophil generation and activation
-T cell and B cell growth and differentiation
IL-5
Secreted by monocyte, macrophage
-initiation of acute phase response
IL-6
Cytokine secreted by stromal cells
-stimulates proliferation of lymphoid progenitors
IL-7
Cytokine secreted by macrophage and endothelial cells
-potent stimulator of neutrophils
-activates respiratory burst and release specific and azurophilic granule contents
IL-8
Cytokine secreted by Th cells
-proliferation of T cells, thymocytes, and mast cells
IL-9
Cytokine secreted by Th2, macrophage
-suppression of Th2 cells, inhibition of antigen presentation, inhibition of interferon-gamma
IL-10
Cytokine secreted by T cells, macrophages, other cells
-inhibition of both T and B cell proliferation
-induction of IgA
-inhibition of macrophages
TGF-B
Proinflammatory cytokines
IL-1
IL-6
IL-8
IL-15
IL-18
TNF-a
IFN-y
Anti-inflammatory cytokines
IL-10
TGF-B
IL-35
Traps antigen entering from subcutaneous
Lymph nodes
Traps antigen entering from blood (blood borne pathogens)
Spleen
Pan marker
CD 19
Ion channel
CD 20
C3D receptor, EBV receptor
CD 21
Activated cell marker, IL-2 receptor
CD 25
Isotype switching, memory cell formation
CD 40
Classical marker
CD 2
Complexed with T cell receptor
CD 3
MHC II receptor, HIV receptor
CD 4
MHC I receptor, cytotoxic T cell
CD 8
Mitogens in B cells
LPS, SPA, Pokeweed mitogen
Mitogens in T cells
Pokeweed mitogen, PHA, concanavalin A
Gold standard in laboratory identification of Adaptive immune response.
- An automated system for identifying cells based on scattering of light as cells flow in single file through a laser beam
Flow cytometry
Use of labeled monoclonal antibodies against specific surface Ag
Fluorescence microscopy
Use of sheep RBCs to detect T cells by binding to the CD2 marker
(+) if there are at least 3 sRBCs that attaches to a T cell
Rosette test
Lymphocyte separation
-has a SG of 1.077 – 1.114
-Sample: defibrinated or heparinized/ACD
Ficoll Hypaque
Layers of Ficoll Hypaque from top to bottom
Plasma > Mononuclear cells > granulocytes and RBCs
Normal CD4 : CD8 ratio
2:1
Normal CD4 count is:
500 to 1200/uL
Ratio during HIV
0.5:1 or 1: 2
CD4 during AIDS
< 200/uL
Destroy virally infected cells, tumor cells, and allografts through secretion of perforin and granzymes. Also activate macrophage through secretion of cytokines (IFN-y)
CD8
Tc (20-25%)
Activate macrophage, enhance cytotoxic T cell response by secretion of cytokines (IL-2) , activate B cells into plasma cells
CD 4
Th (50-60%)
Limit immune response
CD8 (Ts)
CD3, 4, 25 (Treg)
Circulating immunosurveillance and anamnestic response
CD 4 & CD8 ™
CD markers in Pro B-cell
CD 19 and CD45R
CD markers in Naïve or immature B cell
CD 19, 20 , 21, 35
CD markers in activated B cells
CD 25
Virally infected cell is recognized by ___ through ___
T cytotoxic CD8 +; MHC Class I
Tc is activated by __ produced by Th cell
IL-2
Activated Tc kills virally infected cell by secreting: (2)
Perforins
Granzymes
APC presents antigenic fragments through ___ to ____
MHC II; T helper CD4 + cell
Stimulates activated Th cell to become Th1
IL-12
Stimulates activated Th cell to Th2
IL-4
Th1 cells produce __ which activates phagocytes to kill ingested microbes.
IFN-y
Th2 cells produce IL-4 which stimulates the production of ___ (isotype switching)
IgE and IgG4
Th2 cell produce __ which activates eosinophil
IL-5
AKA Human leukocyte antigen (HLA) system in human
Major Histocompatibility Complex (MHC)
Genes coding for MHC are found ____
Chromosome 6 short arm
HLA association of Myasthenia gravis, Addison’s disease, Grave’s disease
HLA B8
HLA association of ankylosing spondylitis / bamboo spine disease
HLA B27
HLA association of Celiac disease, DM I
HLA DQ2
HLA association of DMI, Celiac disease
HLA DQ8
HLA association of SLE, DM I, Grave’s disease
HLA DR3
HLA association of RA, DM I
HLA DR4
HLA class found in all nucleated cells
Class I
HLA class I presents antigens that attack the inside of a cell (endogenous cytosolic pathway) to ___ triggering cytotoxic response
CD8+ T cell
HLA Class I is important against ___
Viral infection, tumor and graft rejection
HLA Class found in APCs and composed of A chains and B chain
Class II
HLA Class II present antigens found outside the cell (exogenous/ endocytic pathway) to ___ cells triggering antibody production
CD4+
HLA Class where C2, C4, Factor B, TNF are found
Class III
In vitro test that mimics the in vivo condition of transplantation
Mixed lymphocyte reaction
AKA Complement Dependent Cytotoxicity (CDC)
Complement Mediated Microlymphocytotoxicity (Antigen-Level Typing/Phenotyping)
In CDC, the accepted sample is
ACD or heparinized blood (1-2 ml)
Dye used to visualize the cells in CDC
Eosin Red and Trypan Blue
Positive result in CDC
Flattened, large, dark, non refractile
Substances that react with antibodies sensitized T cells but may not evoke immune response
Antigens
Substances that provoke an immune response
Immunogen
Antigen but non-immunogenic. AKA incomplete antigen.
Hapten
Immunogenic, carrier molecule. When coupled to a hapten will confer new antigenic specificities
Schlepper Molecule
Antigenic determinant or antigen binding site
Epitope
The greater the difference between the substance and the host, the more potent it is as an antigen
Foreignness
Size of a strong immunogen
> 6kD
At least ___ daltons is needed to be immunogenic
10,000
Have the highest molecular weight and are the best immunogens
Protein
Substances that can be mixed with antigens to enhance and accelerate immune response by protecting immunogen from degradation allowing longer response
Adjuvants
Enhances phagocytosis by increasing the size and prevents rapid escape from the tissue
Alum precipitate
AKA MSDA, derived from shark’s oil. Used for HIV vaccines that are being developed.
Squalene
Water in oil emulsion of killed Mycobacterium tuberculosis or Bordetella pertussis
Freund’s complete adjuvant
Antigen from the host
Autoantigen
Antigen from other individuals but the same genome. Identical twins
Syngeneic antigens
Antigen from other individuals but within the same species.
-Other name: homologous/allogeneic antigen/ isoantigen
Alloantigen
Antigen from different species
-Other name: xenogeneic/heterologous / heterogeneic antigens
Heteroantigens
Antigen that exists in unrelated plants or animals nut either identical or closely related, so that antibody to one will cross react with antibody to the other.
-Ex: Weil-Felix
Heterophile antigens
Autologous antigen that does not come in contact with antibody producing cells
Eg. Lens of eye, spermatozoa
Sequestered antigen
Antigen unique to a specific organ.
Eg. MBP in nerves, PSA
Tissue Specific Antigen
Transfer of tissue within the same individual
Autograft
Transfer of cells or tissues to a genetically identical individual
Isograft/ Syngraft
Transfer of cells or tissues to a genetically non-identical member of the same species
Allograft
Transfer of cells or tissues to a member of a different species
E.g. transplant of a pig valve
Heterograft or Xenograft
Specific glycoproteins produced in response to an antigen stimulation referred to as immoglobulins
Antibody
Theory of antibody diversity wherein cells have surface receptors that were present before contact with antigen. Antigen selects the cell with receptors specific for it then would break off and enter the circulation as antibody molecules. New receptors would form on the surface of the cell
Ehrlich’s Side Chain Theory
Theory of antibody diversity wherein lymphocytes are genetically preprogrammed to produce one type of antibody, and that a specific antigen finds or selects those particular cells capable of responding to it, causing it to proliferate.
Clonal selection
Determines the Ig class. Either alpha, delta, epsilon, gamma, or mu. Encoded by chromosome 14
Heavy chain
Either kappa or lambda but can never be present both in a single antibody
-Kappa encoded by chromosome 2, lambda encoded by chromosome 22
Light Chain
Links H-H chain and H-L chain but not L-L chain.
Disulfide bonds
L-L chain is only found on ___
Bence Jones Protein
Provide flexibility of the antibody due to the presence of amino acid ___
Proline
Contains the Fab region (antigen binding site) / Paratope where the antigen binds
Variable region
Determines the specificity of the antibody
Hypervariable region
Contains the Fc region or fragment crystallizable
Constant region
Composed of 1 variable and 1 constant domain
Light chain
Composed of 1 variable and either 3 or 4 constant domain depending on class
Heavy chain
Used by Rodney Porter to describe Ab structure
-Yields 2 Fab portion and 1 Fc portion
Papain
Used by Alfred and Nisonoff
-Yield 1 F(ab’)2 and 1 Fc’ portion
Pepsin
AKA incomplete immunoglobulin
IgG
Most abundant immunoglobulin in serum
-Longest half-life.
-Main antibody for secondary immune response
IgG
Best IgG crossing placenta
IgG1
Short hinge, cannot cross placenta
IgG2
Largest number of disulfide bonds. Most efficient IgG in complement fixation
IgG3
IgG type that cannot fix complement
IgG4
Provide immunity in newborn, fix complement, enhance phagocytosis, and neutralized toxins and viruses through (ADCC)
-Precipitates in agglutination but best in precipitation
-Respond best against protein antigens
IgG
AKA macroglobulin/ complete immunoglobulin
-main antibody in primary / early immune response and usually indicates acute infection
-Effective in agglutination and cytolytic reaction
-Most primitive and last to leave in senescence
-most often formed in response to gram-negative, endotoxin neutralization
-best respond to carbohydrate antigens
-complement fixation, opsonization, toxic neutralization and agglutination
IgM
-monomer on serum, dimer on secretions
-predominant antibody in secretions
-protect surface mucosa, by inhibiting of microorganism
-binds to a secretory component produced by epithelial cells which prevents enzymatic degradation
IgA
-present in the mature B cell surface
-plays as role in B cell maturation, differentitation and immunoregulation
IgD
-AKA Reagin
-Binds to mast cells and triggers immediate hypersensitivity, allergic, and anaphylactic response
-also plays a role in defense mechanisms to parasites
-heat labile antibody
IgE
Determines the immunoglobulin class
Heavy chain
Variation of allotype is seen in ___
Constant region
Difference of idiotype is seen in __
Variable region
Purified antibodies which are capable of reacting to a specific antigen and are derived from a single parent antibody-producing cell
Monoclonal antibody
Fused B cells and myeloma cells capable of secreting antibodies indefinitely
Hybridoma
Cancerous plasma cell
Myeloma cell
Surfactant and fusing agent
PEG
Used for DNA production
Thymidine and Hypoxanthine
Blocks production of new nucleotides
Aminopterin
Use of monoclonal antibodies
For diagnosis and treatment of diseases
Series of more than 30 proteins that play a role in amplifying inflammatory response to destroy and clear foreign antigens
-cascade phenomenon were the product of one reaction is the enzymatic catalyst of the next
Complement system
The classical pathway is triggered by ___
Immune complex
Immunoglobulins triggering the classical pathway
IgM > IgG3 > IgG1 > IgG2
In C1- trimolecular composed of C1q, r, s stabilized by ___
Calcium
In Classical pathway, IgG binds to ___ region
CH2
In classical pathway, IgM binds to ___ region
CH4
Cleaves C1s
C1r
Cleaves C4 and C2
C1s
AKA Properdin pathway
Alternative pathway
Alternative pathway is triggered by ___
IgA aggregates, bacterial cell wall (LPS), fungal cell walls (zymosan), virus, parasite and cobra venom
Stabilizes C3 convertase
Properdin
Latest and newest discovered pathway but classified as the most ancient pathway
MBL pathway
Where all of the pathways converge; most pivotal/ important
C3
Dissociates C1r and C1s from C1q. Inactivates MASP-2
C1 inhibitor
Cleaves C3b and C4b
Factor I
Cofactor with factor I to inactivate C4b, binds C3b and prevents binding of Factor B
Factor H
Acts as cofactor to factor I to inactivate C4b
C4 binding protein
Prevents attachment of the C5b67 complex to call membranes
S protein (vitronectin)
AKA Membrane Inhibitor of Reactive Lysis, Blocks assembly of MAC by binding C8 and C9
CD59/ MIRL
AKA Homologous Restriction Factor. Binds to C8 therefore prevents formation of MAC
HRF
AKA Decay Accelerating Factor. Prevents assembly of C3 convertase by dissociating C2a and Bb in the membrane
CD55/ DAF
Deficiency of complement. Lupus-like syndrome
C1 (q, r, s)
Lupus-like syndrome, recurrent infection, atherosclerosis (deficiency of complement)
C2 (most common)
Severe recurrent infection, glomerulonephritis (deficiency of complement)
C3 (most severe)
Lupus-like syndrome (deficiency of complement)
C4
Recurrent infection with Neisseria sp (deficiency of complement)
C5, 6, 7, 8
Properdin
No known disease association
C9
Recurrent pyogenic infection
Factor H and I
Pneumococcal infection, sepsis, and Neisseria infection
MBL
Pneumococcal infections
MASP-2
Paroxysmal Nocturnal Hemoglobinuria (PNH)
DAF, MIRL/CD 59, HRF
Hereditary Angioneurotic edema (HANE), edema is due to accumulation of C2b
C1 INH
Uses agarose gel with incorporated specific antibodies then measures the radius of the circle that will be formed. Requires 24 hours before the result is available
Radial immunodiffusion (RID)
Measures concentration according to the amount of light scattered by a solution containing a reagent antibody and measured patient sample
Nephelometry
Measures the amount of patient serum required to lyse 50% of a standardized concentration of antibody sensitized sheep erythrocytes.
Hemolytic Titration (CH50) Assay
Based on the lysis of liposomes that release an enzyme when lyzed. More accurate than traditional CH50 testing.
Liposome lysis
Sensitized rabbit RBCs are implanted in an agarose gel. Patient serum is then added in the punched wells. Clear zones indicate lysis and the diameter of the circle is related to the concentration
Radial hemolysis
Solid phase IgM is attached in a microtiter plate and is used to initiate complement activation.
ELISA
Performed in the same manner as CH50, however magnesium chloride and ethylene glycol (EGTA) is added to the buffer which chelates calcium. Rabbit RBCs is used as indicator
AH50 Assay
Test can detect C3bBbP or C3bP. Microtiter wells are coated with bacterial polysaccharide to trigger activation of alternative pathway
ELISA
Antigen associated with thyroid cancer
Thyroglobulin
Antigen associated with multiple myeloma
Bence Jones Proteins
Antigen associated with lymphoma
Beta-2-microglobulin
Antigen associated with neuroendocrine tumors, melanoma, neuroblastoma
S-100
Antigen associated with sarcomata, hemotopoietic origin
Cytokeratins
Antigen associated with urinary bladder cancer
Bard’s BTA and Nuclear Matrix Protein (NMP-22)
Antigen associated with lung and breast cancer
CYFRA 21-1
Oncofetal antigen associated with colorectal, breast, and lung cancer
CEA
Oncofetal antigen associated with nonseminomatous testicular cancer, primary hepatoma
AFP
Carbohydrate antigen associated with ovarian adenocarcinoma
CA 125
Carbohydrate antigen associated with breast cancer, pancreatic, colorectal, lung, ovarian, liver cancer
CA 15-3
Tumor marker associated with pancreatic cancer
CA 19-9
Tumor marker associated with prostate cancer
PSA
Tumor marker associated with small cell cancers of the lung, endocrine tumors
Neuron-specific enolase
Tumor marker (enzyme) associated with lymphoma
Lactate dehydrogenase
Hormone associated with hydatidiform mole, chrociocarcinoma, germ cell trophoblastic cancer (nonseminomatous testicular cancer)
HCG
Hormone associated with familial medullary thyroid carcinoma
Calcitonin
Hormone associated with parathyroid carcinoma
Parathyroid hormone
Cell markers for T cell leukemia
IL-2 receptor (CD25)
Cell marker for hematopoietic malignancies
CD45
Cell marker for lymphoma
CD20
Cell marker for breast adenocarcinoma
Her2/neu
To identify in asymptomatic individuals in a population detection of cancer at an early stage
Screening
To identify cancer in a particular patient. Help distinguish between diseases with clinical manifestation
Diagnosis
TO predict the clinical outcome of cancer patients and aid in therapeutic decision making. Used to identify the level and type of therapy that is best for a particular patient
Prognosis
To observe the response of a cancer patient to treatment, and to monitor effectiveness of treatment. Elevations can indicate tumor recurrence before other signs become evident
Monitoring
Immune response against self-antigen due to loss of self-tolerance. Ability to recognize self from nonself-antigen
Autoimmunity
All autoimmune diseases involve antigen-antibody complexes (immune complexes). Associated most commonly with MHC Class ___
II
Autoantibodies associated with SLE
ANA
Anti-dsDNA, Anti-DNP
Anti-ENA, Anti-Sm
Antiphospholipid antibodies
Systemic and multi-organ. Immune complex is formed in the serum and deposits to organs
SLE
HLA associated with SLE
HLA DR2 and HLA DR3
Autoantibodies associated with Scleroderma
Anti-centromere Ab
ANA
Target are connective tissues leading CREST form:
C- calcinosis
R – Raynaud’s phenomenon
E – esophageal dysmotility
S – sclerodactyly
T – telangiectasias
Scleroderma
HLA associated with scleroderma
HLA DR3
Autoantibodies associated with Sjogren’s syndromes
Anti salivary duct Ab
Anti lacrimal gland Ab
Antinuclear Ab
RA factor
Mainly affects the exocrine glands (lacrimal and salivary glands)
Sjogren’s syndrome
HLA associated with Sjogren’s syndrome
HLA DR3
Chronic systemic inflammatory disorder in which joint cartilage, ligaments and tendons are destroyed
Rheumatoid arthritis
