Exam 1 Flashcards
vaccination
severe disease is prevented by prior exposure to the infectious agent in a non-disease form
first vaccination
small pox in Asia a long time ago
Edward Jenner
cowpox as vaccination against smallpox in 1796
1979
smallpox officially eradicated
commensal organisms
500+ microbial species that live in a healthy human
flora
the community of microbial species that lives in a particular niche in the human body
Role of commensal organisms
digest food, vitamin synthesis, disease protection
colicin
antibacterial protein secreted by E. coli that help protect us from disease besides competition
Pathogenic Organisms
any organism with the potential to cause disease is a pathogen. can be common like influenza or opportunistic. evolve to invade host, replicate, transmit
Types of Pathogens
bacteria, viruses, fungi, parasites
First Line of Defense
skin and mucus secreted by epithelial which is continuous with the skin and the mucus connects it all
Mucus
contains proteins, peptidoglycans, and enzymes to protect from damage and infection
Epithelial Fatty Acids and Lactic Acids
inhibit cell growth
Epithelial Defensins
perturb membranes or bacteria, fungi, and bacteria
Epithelial Lysozyme
degrades cell walls of bacteria
Epithelial Acid
the lower pH of environment
pathogen recognition
involves soluble proteins and cell-surface receptors that bind to the pathogen or to human cells and serum proteins that are altered in the presence of pathogen
pathogen destruction
involves effector mechanisms that kill and eliminate the pathogen
effector mechanisms
provided by effector cells that engulf foreign entities and complement, which helps mark pathogens and can attack pathogens as well
Inducing Inflammation
1) cytokines induce local capillary dilation (warm red skin)
2) vasodilation introduces gaps in endothelium for increased plasma leakage (edema swelling pain)
3) cytokines change adhesive properties of vascular endothelium to recruit WBC
Adaptive Immunity
Highly specific lymphocytes that have unique receptors that are formed by genes being cut, spliced, and modified during lymphocyte development
Clonal Selection
during pathogen recognition, only the lymphocytes that recognize the pathogen are selected for to participate in the immune response
Clonal Expansion
the selected lymphocytes then proliferate to produce large numbers of effector cells
immunological memory
during clonal selection, some lymphocytes differentiate into memory cells to allow for eliciting of stronger faster immune responses upon subsequent exposure
pluripotent hematopoietic stem cells
cell that all blood cells differentiate from
hematopoiesis
process by which leukocytes are continuously generated
Lineage of Hematopoietic Stem Cells
self-renewal, erythroid, myeloid, lymphoid
Erythrocytes
red blood cells
Megakaryocytes
platelet producing cells
Myeloid Progenitors
granulocytes, monocytes, mast cells
granulocytes
polymonrphonuclear leukocytes which includes neutrophils, eosinophils, and basophils
monocytes
which are progenitors of dendritic cells and macrophages
mast cells
involved in inflammation
neutrophil
most abundant of all leukocytes and is phagocyte that can work under anaerobic conditions. short lived and die at infection making pus
phagocyte
specialized in capture, engulfment, and killing of microorganisms
eosinophil
granulocyte that defends against intestinal parasites
basophil
is implicated in regulating the immune response to parasites (because of low abundance, little is known about basophils)
macrophage
a scavenger and expert phagocyte, generally the first phagocyte to sense an invading microorganism that also makes cytokines
dendritic cells
act as cellular messengers to call up an adaptive response when necessary
Lymphoid Progenitors
gives rise to large granular lymphocytes and small lymphocytes
large granular lymphocytes
natural killer cells
small lymphocytes
B cells and T cells
Natural Killer Cells
important in viral infections as they kill virus-infected cells and secrete cytokines that block viral replication in infected cells
B Cells
utilize immunoglobulins as cell-surface receptors for pathogens. can further develop into plasma cells which secrete antibodies
antibodies
soluble immunoglobulins
T Cells
utilize T-Cell Receptors (TCR) as cell-surface receptors for pathogens. can further develop into cytotoxic t-cells or helper t-cells
Immunoglobulins
on B-cells and contain a heavy chain and light chain
T-Cell Receptors
have an alpha-chain and a beta-chain
antigen
any molecule recognized by immunoglobulin, antibody, or T-Cell receptor
variable region
specific for each antigen
constant region
binding sites for phagocytes, inflammatory cells, complement
Antibody Action
soluble proteins secreted by plasma cells that can either be neutralizing or opsonizing
Neutralizing Antibodies
antibodies that bind to molecules and prevent them from functioning (typical targets are toxins and pathogen surfaces molecules needed for binding to target cells)
Opsonizing Antibodies
antibodies that bind to molecules to tag them for destruction by phagocytosis or attack using the complement system
Major Lymphoid Tissues
bone marrow, thymus, spleen, adenoids, tonsils, appendix, lymph nodes, Peyer’s patches
Primary/Central Lymphoid Tissue
where lymphocytes develop and mature (bone marrow and thymus - B cells develop and fully mature in bone marrow, T cells begin development in bone marrow but fully mature in Thymus)
Secondary/Peripheral Lymphoid Tissue
where mature lymphocytes become stimulated to respond to pathogens (all other lymphoid tissues)
Lymph Nodes
lie at the junction of the lymphatics, which collect plasma (fluid that leaks from blood vessels)
Lymph return
lymph is returned to the blood chiefly through the thoracic duct into the left subclavian vein in the neck
Mature B and T Cell Movement
through the body by both blood and lymph. once in capilaries close to node or 2nd tissue, lymphocytes can exit into node
B and T Cells in Lymph Nodes
1) lymphocyte encounters pathogen and remains in lymph node
2) lymphocyte can exit via the efferent lymph and eventually return to blood
Lymph Circulation with Infection
pathogens, pathogen components, and pathogen-infected dedritic cells are carried by the lymphatics to the lymph node (draining) leading to swollen glads
Lymph Node Filter
The lymph node filters pathogens and other foreign material so that it doesn’t reach the blood and can stay for activating lymphocytes
Draining Lymph Node
pathogens and pathogen-carrying dendritic cells enter the draining lymph node through the afferent lymphatics
Effector Cell genesis
in draining lymph node, pathogens are phagocytosed by MO or pathogens and their products are sensed by B and T cell receptors which causes the b cells and t cells to divide and differentiate into effector cells
Pathogens in blood
either blood-born or if not removed from draining nodes. the spleen can then filter and splenic MO and dendritic cells can take them up and stimulate b and t that arrive in spleen from blood
Spleen
removes damaged and senescent red blood cells and serves as a peripheral lymphoid tissue for blood-borne pathogens
Spleen Red Pulp
where red blood cells are monitored and removed
Spleen White Pulp
where white blood cells provide adaptive immunity
Asplenia
rare genetic disorder where there is no spleen - susceptible to infections with encapsulated bacteria but can be treated through vaccination with capsule
Respiratory and GI environments
harbor the largest and most diverse populations of microorganisms, making them vulnerable to infection and heavily invested with 2nd lymphoid tissue (mucosa-associated lymphoid tissue)
Gut-Associated Lymphoid Tissue
GALT - tonsils, adnoids, appendix, Peyer’s patches
Bronchial-Associated Lymphoid Tissue
BALT - line respiratory epithelium
M-Cells
specialized cells that directly deliver pathogens that arrive at the mucosa-associated lymphoid tissue across the mucosa
Movement of Lymphocytes in GALT and BALT
lymphocytes enter mucosa-associated lymphoid tissue from the blood and exit from the lymphatics
Pathogen Location
can be intracellular or extracellular and divided into more sub-groups which makes how the immune system responds different (extracellular needs soluble)
Complement
one of the first lines of defense in innate is a system of soluble proteins that are constitutionally made by the liver and transported in blood, lymph, and extracellular fluids. many components are proteases that circulate as zymogens. 30+ proteins
zymogens
inactive precursors
complement activation
series of protease cleavages triggered by infection
Complement component 3 (c3)
cleaves into C3a and C3b by C3 Convertase (protease). is a zymogen - happens because of exposure of high-energy thioester which can attach to proteins and carbohydrates on pathogen
C3a
chemoattractant for effector cells
C3b
attaches to pathogen - complement fixation for tagging pathogen for destruction
Complement Activation Pathways
Alternative Pathway, Lectin Pathway, Classical Pathway
Alternative Pathway
activated at the start of infection
Lectin Pathway
induced by infection and requires time to gain strength
Classical Pathway
part of both innate and adaptive immunity and requires binding of either antibody or C-reactive protein
Steps of Alternative Pathway
1) C3 secreted into plasma, confrontational change makes thioester bond available for hydrolysis
2) hydrolysis of this bond on a subset of C3 forms iC3
3) iC3 can bind factor B making it susceptible to cleavage by factor d releasing small factor Ba while some stays bound forming iC3Bb
4) iC3Bb cleaves C3 into C3a and C3b
5) C3b can bind factor b, get cleaved by factor d, form C3bBb complex
iC3Bb
C3 convertase that cleaves C3 into C3a and C3b
C3bBb
the alternative C3 Convertase - can cleave much more C3 and produces positive feedback rapidly coating pathogen surface
Regulate C3b Deposition
Factor P prevents C3bBb degradation, factor H and I lower C3 convertase activity - factor H/sialic acid/pathogen evasion. P, H, and I are all soluble
complement control proteins
regulate complement reactions by mainly stabilizing or degrading C3b at cell surface
Properdin (factor P)
increases complement activation by preventing the degradation of C3bBb
Factor H
counters factor P by binding to C3b and facilitates its further cleavage to iC3b by factor I so iC3b cannot form an active C3 convertase
Prevent Complement on Human Cells
DAF and MCP
Lack of factor I
immunodeficient patients can lack factor I leading to depletion of C3 - more susceptible to ear infections and abscesses caused by encapsulated bacteria
Decay-Accelerating Factor
binds C3b of the alternative C3 convertase causing its activation to prevent activation
Membrane Co-Factor Protein
binds C3b of alternative C3 Convertase like DAF but also inactivates factor I
Macrophages and Complement
macrophages can be non-specific but have CR1 that can bind C3b, CR3 and CR4 bind iC3b on pathogen surface
Opsonization
coating of a pathogen with a protein to facilitate phagocytosis
Terminal Complement Proteins
C5b is the start and C9 is the end
C5b genesis
C3b can bind to alternative C3 convertase to produce a protease that acts on C5 forming alternative C5 convertase (Bb plus two C3b fragments = C3b2Bb)
Membrane Attack Complex
C5b bind in succession C6 and C7 and is inserted into the membrane, C8 binds C5b and inserts into lipid bilayer, C8 induces polymerization of C9, forming transmembrane pores
C9
the subunit of the membrane attack complex that forms transmembrane pores
Prevention of Lysis from MAC
1) Soluble proteins (S, clusterin, factor j) prevent C5b/C6/C7 binding to cell surface
2) at cell surface homolgous restriction factor (HRF) and CD59 prevent C9 recruitment
Paroxysmal nocturnal hemoglobinuria
complement mediated lysis of red blood cells caused by lack of CD59 due to loss of GPI anchor
C3a and C5a
aka anaphylatoxins -
physiologically active - increase local inflammation - can induce anaphylactic shock
Anaphylatoxins
induce smooth muscle contraction and degranulation of mast cells and basophils, histamine released, increased vascular permeability
coagulation system
plasma proteins that induce blood clots to prevent pathogen movement and reducing blood loss
platelets
major component of blood clots - also relase antimicrobial defense mediators like prostaglandins,hydrolytic enzmes, GF
kinin system
increases vasodilation
a-2-macroglobulin
protease inhibitor which lures in proteases (from pathogens) to covalently link the protease and envelop the protease
“Other Plasma Proteins”
coagulation system, platelets, kinin system, protease inhibitors (a-2-macroglobulin)
Defensins
major family of antimicrobial peptides (35-40 aa rich in Arginine w/ 3 intra-chain disulfides), two classes (alpha and beta), amphipathic (hydrophobic portion penetrates microbial membrane)
Pentraxins
act as bridging molecules that bind to surface molecule of a pathogen and escort to immune cells (has similar role in innate immune as antibodies in adaptive)
Innate Microbial Receptors
many are carbohydrates (recognized by lectin receptor (mannose receptor)) and lipids
CR3 and CR4
complement receptors/cell surface structures
scavenger receptors
bind to wide array of negatively charged molecules (sulfated polysaccharides, nucleic acids, lipoteichoic acid from Gram-positive cell walls)
Bacterial Lipopolysaccharide
LPS - gram-negative surface molecule is a binding partner for many receptors
Binding Initiates
either phagocytosis or secretion of cytokines
Phagocytosis
receptor-mediated endocytosis begins with pathogen binding to phagocyte, engulfed into vesicle called phagosome, phagosome fuses with lysosome makeing phagolysosome
Toll-Like Receptors
family of signaling receptors that are specific for a different set of microbial products. Humans have 10 TLR genes to recognize many microorganisms
TLR4
expressed by macrophages to detect bacterial LPS and related compounds outside of G- Bacteria. Binding causes gene activation of inflammatory cytokines. Also important to prime adaptive.
Toll-interleukin receptor and Leucine Rich Region
TIR - transmembrane proteins with an extracellular domain for recognizing pathogens (leucine-rich region (LRR)) and a cytoplasmic domain for conveying information
Recognition of LPS by TLR4 Components
Needs CD14(co-receptor), MD2, TLR4, LPS
TLR4 Activation
1) LPS recognized by MD2, CD14, TLR4
2) binding of ligand recruits MyD88 to the intracellular side of TLR4
3) MyD88 activates IRAK4 which phosphorylates TRAF6
4) TRAF6 activates kinase cascade activating inhibitor kappaB kinase (IKK)
5) IKK phosphorylates IkB which is degraded releasing txf nuclear factor kappaB (NFkB),
6) NFkB translocates to nucleus and transcription of cytokines (IL-1b, TNF-a, IL-6, CXCL8, IL-12 from MO)
IL-6
induces fever through increased metabolism
TNF-a and IL-1b
induces changes in endothelial cell walls to allow effector cells to enter infection area
CXCL8
a chemoattractant cytokine (chemokine) that recruits neutrophils - acts through G protein linked receptors
IL-12
activates NK lymphocytes (viral infection)
TNF-a The Good
local action causes vascular endothelial cells to make platelet-activating factor triggering blood clotting and blockage of local blood vessels thus preventing pathogens from entering blood and causing systemic infection
TNF-a The Bad
sepsis (infection of blood) can cause widespread TNF-a released by liver, spleen, and other sights causeing massive dialtion of blood vessles/leakage of fluid to tissues = septic shock
Septic Shock
widespread blood lotting and failure of vital organs (kidneys, liver, heart, lungs)
NOD-Like Receptors
intracellular sensor that detects presence of bacteria in the cytoplasm - aka nucleotide-binding oligomerization domain proteins
muramyl peptides
cell wall component that NOD recognizes
RIPK2
kinase activated by the binding of NOD. then activates NF-kB like in TLR4 signaling causing synthesis of cytokines, chemokines, defensins
NOD Problems
NOD genes linked to IBD/Crohn’s
The Inflammasome Function
increase local concentration of procaspase 1 to promote autoproteolysis and activation. More caspase 1 = more inflammation
The Inflammasome Steps
1) IL-1b secreted by MO bind to IL-1 receptors of the MO to increase proIL-1b production (pathway like TLR4)
2) ProlL-1b activated to IL-1b by protease called caspase 1
3) potassium ions released by MO due to other signals
4) ionic change supports assembly of inflammasome
Inflammasome Structure
complex of a NOD-like protein NLRP3, and adaptor protein and procaspase 1
Neutrophils
professional phagocyte aka polymorphonuclear leukocytes, most abundant WBC, 50billion circulting, leave blood when signaled by inflammatory mediators, work under anaerobic conditions, form pus when dead
pyogenic bacteria
are extracellular bacteria that are pus-forming due to their attack by neutrophils (like S. aureus)
Adhesion Molecules
needed to move neutrophils from blood to tissue - selectins, vascular addressins, integrins, immunoglobulin-like molecules
Neutrophil Inflammatory Mediators
CXCL8, C5a, bacterial chemoattractants, induce expression of lignads on endothelial cells of blood vessels to allow for neutrophil binding
Extravasation
neutrophil migration from blood to tissue
Extravasation Steps
1: Rolling adhesion
2: Tight Binding
3: Diapedesis
4: Migration
Rolling Adhesion
selectins on the endothelium bind to Sialyl-Lewis* (carbohydrate on neutropil surface)
Tight Binding
LFA-1 on neutrophil binds TCAM-1 on endothelium
Diapedesis
Neutrophil crosses blood vessel wall (adhesion helps)
Migration
CXCL8 gradient helps
Neutrophil Phagocytosis
Similar to MO but can recognize wider range or materials but have potent antimicrobial weapons.
Neutrophil Phagosomes
Fuse with two neutrophil granules Azurophilic (primary) and Specific (secondary) before binding with lysosome
Azurophilic granules
contain proteins and peptides that disrupt and digest microbes (lysozyme, defensins, proteases)
Specific Granules
contain lactoferrine (iron and copper sequestration), lysozyme, and NADPH Oxidase
NADPH Oxidase
produces superoxide radicals which are converted into hydrogen peroxide by superoxide dismutase. Raises pH of phagosome to activate molecules of granules
Respiratory Burst
consumes oxygen to make two potent cell killers, superoxide radicals and hydrogen peroxide
Lack of Respiratory Burst
leads to chronic intracellular infections of neutrophils and macrophages that are contained in localized nodules called granulomas
Granulomas
imprison macrophages that have eaten too many neutrophils
Cytokines for Fever
IL-1, IL-6, TNF-a act on hypothalamus, muscle and fat cells to generate heat
Fever
slows bacterial and viral growth and also increases potency of adaptive immunity
Acute-Phase Response
induced by inflammatory cytokines - liver cells secrete the plasma proteins C-reactive protein and mannose-binding lectin
Mannose-Binding Lectin
opsonin - binds to carbohydrates on bacteria, fungi, protozoans, and viruses, triggers the lectin pathway of complement activation, doesn’t bind tightly to human
C-Reactive Protein
opsonin- binds to phosphocholine component of LPS on bacteria and fungi but doesn’t bind to human phosphocholine.
The Lectin Pathway of Complement Activation
mannose-binding protein opsonization is first leading to cleavage of C4 by serine protease associated with mannose-binding protein, cleavage of C2 by same serine protease, associate of C4b with C2a - classical C3 Concertase
Nonfunctional Mannose-binding Lectin
alleles common (>10%), two nonfunctional alleles susceptibility to meningitis
The Classical Pathway of Compliment Activation
c-reactive protein opsonization is first step, the association with C1 (protease), cleavage of C4 by C1, cleavage of C2 by C1, associatio of C4b and C2a
Sensing Viruses
normally intracellular, recognition of cytoplasmic or endosomal nucleic acids, detected by receptors like TLR3, TLR7, or RLR leading signal cascade and txf for type 1 interferones (alpha beta)
Type 1 Interferons do
block viral repication, signal neighbors about virus, alert immune system cells, promote destruction of virus infected cells by killer lymphocytes
Interferon Response
changes expression in human genes and increase NK ligands on infected cells and activate NK cells
oligoadenylate synthesis
blocks viral genome replication
protein kinase R
inhibits initiation factor elF2 and blocks viral protein synthesis
transcription factors
activates expression of more interferon
NK Cells
5-25% of blood lymphocytes, effector functions: cell killing, secretion of cytokines, activated by INF-a, INF-b, IL-12, TNF-a
NK Cell Action
distunguish between healthy and infected cells based on receptor action and balance of signals from inhibitory and activating receptors
Cytotoxic Effector Cells
differentiated from NK cells in response to type 1 interferons - release cytotoxic granules to induce apoptosis
NK Cells and MO
MO recruit NK with IL-12, CXCL8, can then bind in a synapse to form conjugate pair, promotes proliferation and activation of NK cells to secrete cytokine INF-b which induces action of macrophages
Dendritic Cells Bridge
phagocyte similar to MO, specialize in presenting foreign antigens to adaptive, can be infected by intracellular pathogens and viruses at site of infection
NK and Denritic
Can form a synapse under viral infections
Weird things with NK and Dendritic
when more NK than dendritic, NK kill them (maybe limit adaptive response) and when less Nk than dendritic, NK activate the dendritic (induce adaptive maybe)
Role of B Cells
make antibodies - activation of B cells leads to proliferation and differentiation into effector cells called plasma cells
Antibodies Can…
prevent pathogen infection, target pathogen for destruction, recognize native macromolecules on the outside of pathogens
antibody repertoir
variablility in antibodies in an individual can be 10^9 different antibodies
B Cells and CD4 Helper T Cells
naive B cells come into contact with pathogens in draining lymph node, B cell with right immunoglobulin receptor binds pathogen and engulfs, pathogen peptides presented on MHC class II molecules, CD4 Helper T cells recognize and activate the B Cell
Antibody Structure
glycoproteins made of four polypeptide chains (2 heavy, 2 light) - disulfide bonds link each light chain to a heavy chain and the heavy chains together
Antigen Binding Site
formed by the variable regions of heavy and light chains
Hinge Region
flexible connection of the two antibody fragments Fab and Fc. flexibility allows for Fab fragments to adopt many differnt orientation allowing antibodies to recognize antigens at different distances
Fab
fragment antigen binding - binds antigen
Fc
fragment crystallizable (constant) stem region
IgM
always the isotype used as immunoglobulin receptor on a naive B cell and is the first antibody isotype secreted
Improve antibody effectiveness during clonal expansion of b cells
1) Somatic Hypermutation
2) Isotype Switching
Somatic Hypermutation
nucleotide changes in the variable region to allow tighter binding
Isotype Switching
the isotype is determined by the constant region, B Cells can rearrange the gene to bring a new constant region together with the variable region
Antibody Isotypes
difference in the heavey chain C region define the five isotopes IgG, IgM, IgD, IgA, IgE (heavy chain is corresponding greek leter) and the light chains have kappa and lambda with no functional differences but abundance changes with organism
Immunoglobulin Domain
repeating domain found in heavy and light chains
Variable Domain
Vh and Vl, the amino terminal end of each chain (one domain)
Constant Domain
light chains have 1, heavy either 3 or 4 depending on isotype
Hypervariable Region
concentrated area of amino acid differences in the variable regions - three in each variable region surrounded by framework regions - antigen binding is the clustering of hypervariable regions from light and heavy chains
Epitope
part of the antigen the antibody binds to - mostly carbohydrates and protein components but sometimes DNA and small molecules
Multivalent Antigen
any antigen that contains more than one epitope or more than one copy of the same epitope
linear epitopes
are adjacent sugars or amino acids
discontinuous epitopes
far apart in linear sequence but are close together in three-dimensional structure
antigen-antibody interactions
noncovalent interactions - hydrophobic, van der Waals forces, electrostatic)
Monoclonal Antibodies
fusion of B Cells with a tumor cells to form a hybridoma that produces antibodies indefinitely, separation of hybridomas, selection of hybridomas
Traditional Antibody Production
injection of animal with an antigen and removal of antisera from blood
Flow Cytometry
lasers see cells surfaces tagged with fluorescent antibodies and get a histogram or dot plot
First Monoclonal Antibody
mouse antibody that recognized CD3 I cells to prevent rejection after kidney transplant but human body rejects it
Chimeric Monoclonal Antibody
combine mouse V regions and human C regions (rituximb non-hodgkin B cell lymphoma)
Humanize Monoclonal Antibody
produced by genetic engineering - only move hyper-variable region of mouse antibodies into human antibodies (omalizumab asthma)
Variable Gene Segments
Heavy chains and TCRb have V, D, J, light chains have V, J
Antibody Diversity?
primarily from numerous combos of V, D, and J segments, splicing is imprecise and leads to diversity, also arises from different combos of heavy and light chain and TCRa and TCRb proteins
Not B-Cell Immunoglobulins
genes are fragmented in gene segments (inherited germline configurations)
B Cell Immunoglobulins
rearrangement of gene segments allows for production of immunoglobulins, C regions are ready to be made but V regions are encoded by two (Vl) or three (Vh) gene segments that must rearrange to produce and exon
V, J, and D stand for
variable, joining, diversity
Recombination Signal Sequences
RSSs - flank the 3’ side of the V segment, both sides of the D segment, and the 5’ side of the J segment - provide recognition sites for the enzymes that cut and rejoin DNA and ensure that gene segments are joined in the correct order
V(D)J recombinase
set of enzymes responsible for recombining V, D, and J
Recombination-Activating Genes
RAG-1 and RAG-2 are two proteins of V(D)J recombinase that are specific to lymphocytes
Other Recombination components
DNA ligase IV, DNA-dependent protein kinase, Artemis (nuclease), and Ku protein
RAGs-RSSs
RAG complexes interact to align the RSSs and cleave the DNA (forming hairpins) and repair the broken ends of DNA to form the coding joint
Junctional Diversity
enzymes that open the hairpins and form the coding joint introduce diversity into the third hypervariable region of heavy and light chains
1) nick opens hairpin to create a sequence that would be palindromic in double-stranded DNA (generates P nucleotides)
2) opened hairpins can be shortened by exonucleases or lengthened by terminal deoxynucleotidyl trasferase (TdT) (addition of N nucleotides)
3) base pairing occurs and gaps are filled
- -enzyme definiciencies affect T and B development and cause most sever combined immunodefincienceis.
Junctional Diversity Effect
increase overall diversity by 3 x 10^7
IgM and IgD in Developing Naive B Cells
isotype determined by heavy chain but only heavy chain in B cells before they encournter antigen u and deltat – Naive B Cells express both IgM and IgD on surface because of alternative splicing
IgM and IgD Alt Splicing
transcription produces a transcropt that contains exons for both u and delta heavy chains but not the other isotype genes - splicing removes either u or delta exons
Allelic Exclusion
only one heavy chain and one light chain are expressed in a developing B cell (single antigen specificity
