ISBB Flashcards
Elie Metchnikoff
Phagocytosis
Jules Bordet
Complement
Karl Landsteiner
Human Blood Group Ag
- book: SSR
Gerald Eldelman
Immunologic tolerance
Rosalyn Yallow
Radioimmunoassay
Susumu Tonegawa
Ab diversity
Francoise Barre-Sinoussi
HIV
Poxvididae pathological manifestations
Vaccinia virus: cowpox
Variola major: small pox
Variola minor: alastrim
Chinese process for “immunization”
Variolation - inhale powder
Year of discovery of T Cell Receptor
1984
Year of Discovery of ACD
1943
Year of discovery of CPD
1957
Edward Jenner vs Louis Pasteur
Jenner: cross immunization (cowpox –> small pox)
Pasteur: attenuated vaccine; Father of Immunology
First recipient of blood transfusion
Pope Innocent
3 young people - all died
Father of Pathology
Virchow
Father of Microbiology
Leewenhoek
Gel Tech
By Yves LaPierre
Adv: standardization
Disadv: specific instruments
Charles Drew
Blood preservation
Transfusion tech
From American Red Cross
Called the Private Ag
Low Incidence Ag
<1% of the population
Natural vs Acquired
Natural
- present at birth
- std response for all Ag
- no cell memory
- first and second line of defense
Acquired
- “adaptive”
- diverse response for each Ag
- 2nd exposure has a greater response than 1st
- with cell memory – B and T cells
- 3rd line of defense
First Line of defense
Skin and mucous membrane
Secrete lysozyme to attact bacterial CW
Acidity of GIT and vagina
Second line of defense
Phagocytosis – neutrocyte, monocyte, macrophage
Infammation and fever
Antimicrobial substances – complement, properdin, INF, TNF, betalysin
Third line of defense
Specialized lymphocyte – B and T cel
Abs
Cellular components of Natural Immune System
Phagocytes
Basophilic mast cells
Eosinophil
3rd population lymphocyte – null lymphocyte, NK cell (5-10%; CD 16 and CD 56)
Humoral Components of the Natural Immune System
Complement Major INF Lysozyme Antimicrobial Lymphokine-activated Killer Cells
Cellular component of Adaptive System
T and B cells
Humoral components of adaptive system
Lymphokines
Abs
“Steps” in Phagocytosis
Initiation
Chemotaxis
Engulfment
Digestion
Describe the initiation of Phagocytosis
Initiated due to tissue damage – result of trauma or microorganism multiplication
Activated phagocyte has increased surface receptors for adherence – CD3; laminin receptor; larcyl-formyl-methionylphenylalanin receptor
First to migrate due to initiated phagocytosis
Neutrocyte
Role of monocyte during initiation of phagocytosis
Second to migrate
Complement component that acts as a chemotaxin
C5a
Job’s syndrome of chemotaxis
Normal random act
Abnormal directional/chemo activity
Lazy Leukocyte syndrome
Abnormal random and chemo activity
Test: Boyden Chamber Assay
What initiates engulfment
Large capsules
Opsonins
Interact with surface bacteria to render them acceptable to the phagocyte
- specfic Abs
- complement C3b
Complement that acts as an opsonins
C3b
Process of Digesting jn Phagocytosis
Lysozyme approaches phagosome – fuse – rupture – discharge hydrolitic enzymes and peroxidase
Cells become granulated as foreign materials
Destruction of the Antigen
- formation of phagolysosome leads to release of lysosomal contents
- activated macrophages produce nitric oxide
- activation of NADPH oxidase from phagosome membrane leading to ROXs
Disease with impaired NADPH oxidase
Chronic Granulomatous Disease
Cardinal signs of Inflammation
Rubor: redness Calor: heat Tumor: swell Dulor: pain Fundio laesa: loss of function
Vascular response during infamm
Vasodilation –> increase blood flow and cell permeability –> redness and heat
Cellular response during inflamm
Activation of neutrophils and macrophages –> fever
Interleukin responsible for fever
IL-2
Interferes with viral replicaton
Interferon
INF produced by virus-induced leukocyte
INF alpha
Major producer of INF alpha
Null lymphocyte
Produced by double stranded RNA fibroblast cell
IFN beta
Major producer of IFN beta
Fibroblasts and epith cells
Reactant/s that increase 1000x during inflamm
CRP and Serum Amyloid A
Type 2 IFN
Gamma
IFN produced by immunologically stimulated lympho
IFN gamma
Major producer of IFN gamma
T cell
IFN primarily produced as a component of the specific immune response to viral and other pathogens
IFN gamma
Cytotoxic against tumor cells and virally infected cells
TNF
TNF produced by macrophages
TNF alpha aka CACHETIN
TNF produced by CD 4+ and CD8+
TNF beta aka LYMPHOTOXIN
Series of protein whose overall fxn is to mediate inflamm
Complement
Serum protein thay exerts bactericidal and viricdal effects in the presence of C3 abd Mg++
Properdin
Heat stable cationic substance with bactericidal activity
Betalysin
Ab production is done by the body
Active immunity
Type of immunity: vaccination
Artificial active
Type of immunity: infection
Natural active
Type of immunity: administration of immune serum
Artificial passive
Type of immunity: transfer in vivo
Natural passive
Type of immunity: colustrom
Natural passive
Primary lymphoid organs
Thymus and BM
Secondary Lymphoid organd
Spleen, lymph nodes, peyer’s patches, tonsils, appendix, adenoids, MALT, etc
Cells involved in Cell-mediated immunity
T cell
Cell involved in humoral immunity
B cells
Where do T cells develop?
Thymus
End product of activation of T cells
Cytokines
Antigens for T cells
CD2, CD3, CD4, CD8
Forms rosette formation with sRBCs
T cells
Region of lymph nodes where T cells are located
Paracortical
Organ for development of B cells
Bone marrow
End product of B cells
Antibody
Antigens for B cells
CD19, CD20, CD21, CD40, MHC Class II
Identified by surface immunoglobulins
B cells
Region of lymph nodes for B cells
Cortical region
Helper-inducer T cell
CD4+
Suppressor-cytotoxic T cell
CD8+
Ratio of CD4+ : CD8+
2:1
CD4+ : CD8+ ratio of HIV
1:2
Stage of T cell dev that lacks both CD4 and CD8
Double-negative thymocytes
Stage of T cell dev where CD4 and CD8 are both expessed
Double-positive thumocyte
After selection, T cells migrate to…
Medulla
Percent of peripheral T cells expressing CD4
2/3 = 65%
Life span of resting T cells in peripheral organs
Several years
T helper cells 1 (Th1) produce
IFN-y and TNF-B which protect cells against intracellular pathogens
T helper cells 2 (Th2) produce
Variety of interleukins
Essential role of Th2 cells
Help B cells produce antibodies against extracellular pathogens
Receptor of activated T cells for IL-2
CD 25
Secreted by sensitized T cells
Cytokines
Immune response by sensitized T cells
Cell-mediated immunity
Precursor cells in antibody production
B cells
Distinctive markers of this stage of B cells include CD19, CD45
Pro-B cells
Pro-B cells have intracellular proteins for the gene rearrangement of chromosome…
Chromosome 14 – codes for the heavy chain of Ab molecule
First synthesized heavy chains in Pre-B cells
mu chains – IgM
Kappa light chain chromosome
Chromosome 2
Lambda light chain chromosome
Chromosome 22
Stage of B cell distinguished by the appearance of complete IgM
Immature B cells
Other surface proteins on immature B cell
CD 21, CD 40, MHC Class II
Target cell of EBV
CD 21
In addition to IgM, this stage of B cells also exhibit IgD
Mature B cells
Unless contact with Ag occurs, what is the life span of mature B cells
Few days
Upon stimulation of B cells to an Ag, it undergoes transformation into a _____
Blast stage –> forms memory cells and Ab-secreting plasma cells
Name of the process wherein B cells transform into Blast stage
Ag-dependent phase of B cell development
Site for Ag-dependent activation of B cells
Primary follicles of peripheral lymphoid organ
B cell characterized by abundant cytoplasmic Ig with little to no surface Ig
Plasma cell
Most fully differentiated lymphocyte
Plasma cell
Main function of plasma cell
Ab production
CD2
Cell type and function?
- Thymocytes, T cells, NK cells
- T cell activation
CD3
Cell type and function?
- Thymocytes, T cells
- Assoc. with T cell antigen receptor; TCR transduction
CD10 aka Calla Ag
Cell type and function?
- B and T cell precursors, bone marrow stromal cells
- Common acute lymphocyte – leukocyte Ag
CD16
Cell type and function?
- Macrophage, NK cells, neutrophils
- Phagocytosis and ADCC
CD34
Cell type?
- Hematopoietic stell cell
CD56
Cell type and function?
- NK cells, subsets of T cells
- Not known
Lab identification for Lymphocytes
- Cell Flow Cytometry
- Forward: Cell size
- Side: Cell granulation - Fluorescence microscopy
- Rosette Test
Genes that control expression of a large group of proteins
Major Histocompatibility Complex
Chromosome for gene coding of MHC in humans
Short arm of Chromosome 6
Genetic loci of MHC Class I
HLA - A, B, C
Genetic loci for MHC Class II
HLA - DP, DQ, DR
Chain structure of MHC Class I
Alpha chain + beta2 microglobulin
Chain structure of MHC Class II
Alpha chain + beta chain
Cell distribution of MHC Class I
All nucleated cells
Cell distribution of MHC Class II
B cells, APCs (Antigen Presenting Cells)
Antigen presentation of MHC Class I
To CD8+ –> TNF-Beta OR lymphotoxin
Antigen presentation of MHC Class II
To CD4+ –> Plasma cells for antibody proloferation
Substance that is capable of inducing an immune response and antibody production
Immunogen
Antigenic determinant
Epitope
Parts of an antigen
- Carrier
- protein nature = high MW
- immunogenic - Hapten
- non-protein = low MW
- antigenic
Importance of HLA typing
- Tissue/Organ transplant
- Disease association
- Paternity Testing
Factors affecting immunogenecity
- Foreignness
- Size
- Chemical composition and complexity
- Rouse, dosage, and timing
- Adjuvants
Autograph/autoantigen
From same individual
Allogen/isograft
From different individual but same species
Heteroantigen/Heterograft
From different species
Most immunogenic transplant tissue
Bone marrow
Least immunogenic transplant tissue
Cornea
Potent Antigen size
MW >= 10 000 daltons
Size of a “Good immunogen”
MW >= 40k daltons
Size of an “Excellent immunogen”
MW >= 1M daltons
Function of adjuvants
To enhance immune responce
General functions of immunoglobulins
- Neutralize toxic substances
- Facilitates phagocytosis
- Combine with antigens on cellular surfaces to destroy cells
Theory of antibody diversity stating that prior to contact, cells already have receptors and the antigen then binds to specific/proper receptors to break them off and enter the circulation as antibody molecules
Ehrlich’s Side-Chain Theory
Theory of antibody diversity stating that cells produce “general” template of antibodies and antigens would act as a mold
Template theory
- by Felix Haurowitz
Theory of antibody diversity stating that lymphocytes produce specific Ig
Clonal selection
- by Niels Jerne and Macfarlane Burdet
Structure of IgG
Monomer
Structure of IgM
Pentamer
Structure of IgA
Serum: monomer
Secretion: dimer
Structure of IgD
Monomer
Structure of IgE
Monomer
Concentration % of Igs
G > A > M > D > E
“Heaviest” Ig and with the highest sedimentation coefficient
IgM
Ig with the longest half life
IgG (23 days)
Complement fixation of Igs
IgG: Classical
IgM: Best!; multiple binding
IgA: Alternative
Only Ig that is able to cross the placenta
IgG
Heavy chain of IgA
Alpha
Heavy chain of IgD
Delta
Heavy chain of IgE
Epsilon
Heavy chain of IgG
Gamma
Heavy chain of IgM
Mu
Light chain kappa:lambda ratio
2:1 or 65%:35%
Bond between HC and LC
Disulfide bonds
Flexible region of an Ig
Hinge region
- proline determines flexibility
Number of domains in a light chain
2 (VL and CL)
Number of domains in a heavy chain
4 (VH and 3CH)
Ig with extra CH4 –> HC with 5 domains
IgM and IgE
Papain cleavage of monomer
- Cleaves above hinge
- Results to 3 fragments = 2 Fab and Fc
Pepsin cleavage of monomer
- Cleaves below hinge
- Results to 2 fragments = F (ab)2 and FC’
Major/general functions of IgG (5)
- Provide immunity for newborn
- Fixation of complement
- Opsonization
- Neutralization of toxins and viruses
- Agglutination and precipitation reactions
IgG subclasses cross placenta except
IgG2
Best IgG subclass for the fixation of complement
IgG3
All IgG subclasses fix complement except
IgG4
Functions of IgM
- Complement fixation
- most efficient - Agglutination
- best! - Opsonization
- Neutralization of toxins
Subclass of IgA found in serum
IgA1
Subclass of IgA found in secretions
IgA2
What produces the secretory component of IgA
Epithelial cells
Function of IgD
- Immunoregulation
- Postulated to be anti-idiotypic antibody –> feedback mechanism of B cells
Secondary Ig to appear on B cells
IgD
- primary is IgM
Ig that mediates hypersensitivity reactions, allergies, and anaphylaxis
IgE
Ig generally responsible for immunity against parasites
IgE
IgE molecule is unique because it binds strongly to ______ to release histamines and heparin
Mast cells and basophils
RIST for IgE
Test for Total IgE
Radioallergosorbent Test for IgE
Measures specific IgE
Factor ___ claves C3b and C4b
Factor I
Cofactor of I to inactivate C3b and prevents binding of B to C3b
Factor H
Function of Decay Accelerating Factor
Dissociates C3 convertase
C2 deficiency
- Lupuslike syndrome
- Recurrent infections
- Atherosclerosis
Complement component/s deficiency that is/are associated with lupuslike syndrome
C1, C2, C4
C3 deficiency
- Severe recurrent infections
- Glomerulonephritis
Complement component/s deficiency that is/are associated with Neisseria infections
C5-C8(C9)
Complement component/s deficiency that is/are associated with hereditary angioedema
C1INH
Complement component/s deficiency that is/are associated with paroxysmal nocturnal hemoglobinuria
DAF, MIRL
Most common complement component deficiency
C2
Most severe and most recurrent complement component deficiency
C3
Recognition unit for the complement system
C1
Anaphylatoxin-associated complement component/s
C4a, C3a, C5a
Chemotoxin-associated complement component
C5a
Opsonin-associated complement component/s
C3a
C3 convertase classical cascade
C4b2a OR C4b2b
C3 convertase alternative cascade
C3bBb
C5 convertase classical cascade
C4b2a3b OR C4b2b3b
C5 convertase alternative cascade
C3bBb3b
Ions associated with the complement system
Ca++ and Mg++
Autoimmune disease associated with HLA-DR3
- SLE Class 2
- Scleroderma (weak association)
- Sjogren’s syndrome
Autoimmune disease associated with HLA-DR4
Rheumatoid arthritis
Autoimmune disease associated with Complex Age dependent
Myasthenia Gravis
Antibodies associated with Grave’s disease
Anti-TSH receptor antidobies –> hyperthyroidm
Antibodies associated with pernicious anemia
Anti-parietal cell antibodies and anti-intrinsic factor antibodies
Antibodies associated with Goodpasteur’s syndrome
Anti-glomerular basement membrane
Antibodies associated with Primary Billary Cirrhosis
Anti-microbial antibody
Antibodies associated with Chronic Active Hepatitis
Anti-Smooth Muscle antibody –> hypothyroidism
Antibodies associated with Hashimoto’s thyroiditis
Antimicrosomal antibody
Initial force of attraction that exists between a single Fab site on Ab and a single epitope/determinant on Ag
Affinity
- Ionic bond
- H-bond
- Hydrophobic
- Vander waals forces
Sum of all attractive forces between a multivalent Ag and a multivalent Ab
Avidity
Smooth curve in Ouchterlony Double Diffusion
Serological identity
Crossed lines in Ouchterlony Double Diffusion
Non-identity
Spur formation in Ouchterlony Double Diffusion
Partial identity
Chromosome coding for ABO Blood Group
Chromosome 9
Chromosome coding for Rh
Chromosome 1
Chromosome coding for MNS
Chromosome 4
Chromosome coding for Kell
Chromosome 7
CChromosome coding for Kidd
Chromosome 18
Chromosome coding for H, Lewis, Lutheran
Chromosome 19
Genes for the ABH antigens code for:
a. enzyme
b. sugar
Enzyme
H gene codes for what enzyme?
L-fucosyltransferase
A gene codes for what enzyme?
N-acetylegalactosaminyltransferase
B gene codes for what enzyme?
D-galactosyltransferase
L-fucosyltransferase attaches to what sugar?
L-fucose
N-acetylegalactosaminyltransferase attaches to what sugar?
N-acetyl-D-galactosamine
D-galactosyltransferase attaches to what sugar?
D-galactose
Individuals who did not inherit the H antigen and are mistaken to be Group 0
Bombay individuals
Amount of H Antigen in ABH phenotypes
o > A2 > B > A2B > A1 > A1B
Acquired A antigen is associated with infections caused by __________
Proteus mirabilis
Acquired B antigen is associated with infections caused by __________
Proteus vulgaris and E. coli O86
Acquired B antigen : EPIC
E. coli O86
Proteus vulgaris
Intestinal obstruction
Carcinoma of colon / rectum
Predominant Ig of antibodies produced by Blood Group A and B
IgM
- naturally occuring
- react at room temp
Predominant Ig of antibodies produced by Blood Group O
IgG
- immune antibodies
- react at 37C
Rh Blood Factor of D
Rho
Rh Blood Factor of d
None
Rh Blood Factor of C
rh’
Rh Blood Factor of c
hr’
Rh Blood Factor of E
rh”
Rh Blood Factor of e
hr”
Mechanism wherein D antigens expressed appear to be complete but are few in number
Genetic Weak D
Mechanism wherein the allele carrying D is trans to the allele carrying C
C Trans
Mechanism wherein one or more parts of the D antigen is missing
D Mosaic or Partial D
Rh with the highest D antigen
Rh deleted
RBC morphology of Rh null individuals
Stomatocyte
