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Title: Immunology Notes
Description: These notes include general, introductory information about the immune system. Topics outlined include the innate immune system, the adaptive immune system, cells/organs of the immune system, and antigens + antibodies.
Description: These notes include general, introductory information about the immune system. Topics outlined include the innate immune system, the adaptive immune system, cells/organs of the immune system, and antigens + antibodies.
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Thursday, January 21, 2016
Immunology- Myths about the immune system
✴ The common cold and the flu are viruses
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Antibiotics work by inhibiting synthesis of outer membrane of bacteria
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viruses lack machinery that antibiotics affect
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viruses have evolved to be less deadly
•
anti-viral drugs (ex
...
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measles, mumps, whooping cough, rubella have been making comebacks because of unvaccinated children
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subunit vaccines designed against a particular protein on a virus
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live attenuated vaccines give lifetime immunity
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Cell-mediated immune response = T-cells
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Humoral immune response = B-cells
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Innate Immune System is first line of defense, recognizes patterns in major classes of
pathogens
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responds instantly, strong response but take days to work
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first step is signal reception (need receptor that recognizes a signal)
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second step is transduction (signaling cascade)
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Adaptive Immune System recognizes exact 3D structures of pathogens
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B-cells
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Y-shaped, 4 molecule structure
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2 types 1) bound to membrane of B-cell 2) soluble
wait for something to bind to antibody
T-cells
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T-helper CD4+= MHC class II
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T-cytotoxic CD8+ = MHC class I
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need antigen presentation
T- cells activate B-cells which then produce antibodies
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Thursday, January 21, 2016
Chapter 2: Innate Immunity
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cells and organs of the immune system located diffusely throughout the body
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Hematopoietic cells*
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Myeloid progenitor cells —> INNATE
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dendritic cells* (main connecting branch between innate and adaptive immune systems; antigen-presentation) OR
progenitors for other cell types
Lymphoid progenitor cells —> ADAPTIVE (think lymphocytes)
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most immature lymphocytes are killed because body tries to eliminate cells that recognize “normal” things (allergies)
Apoptosis: programmed cell death, destroys cell from inside and packages components to
be reabsorbed into the body
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webbed appendages
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bcl family of genes regulates apoptosis
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Necrosis: from injury, inflammatory response occurs when cell’s contents explode out into
surroundings
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Experiment: hematopoietic stem cells in mice left after injecting radiation
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Leukocytes
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Lymphocytes 20-40% (B/T/NK-cells)
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Monocytes (macrophages + dendritic cells)
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Eosinophils
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Neutrophils 50-70%
Basophils (non-specific, release histamine)
B-cell maturation
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B-cell lymphoblast
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plasma cell: rough ER produces antibodies (most lymphoblasts become this)
memory cell
Monocytes become macrophages
•
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has lysosomes, phagolysosomes, etc
...
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lymph nodes: swelling=pumping out of B-cells, filters lymph
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spleen: filters blood, can live without it because does same function as lymph
nodes
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GALT gut-associated lymphoid tissue
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MALT mucosa-associated lymphoid tissue
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mucosa moves antigens into pockets with T-cells which then activates
B-cells
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populated by lymphocytes, plasma cells, macrophages
Chapter 3: Cells + Organs of the Immune System
Innate Immunity reacts almost immediately, broad specificity
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limited number of receptors
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no memory
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perfect self/non-self discrimination
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First line of defense
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skin, mouth, stomach, small intestine, large intestine, airway + lungs
ex: skin has Psoriasin which kills E
...
interactions between selectins and mucins—>break which
slows neutrophil
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6
is it important to slow down neutrophils (leukocytes in general) because
blood moves quickly
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Thursday, January 21, 2016
Chapter 4: Antigens + Antibodies
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Antibody-antigen binding site
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specificity of antibody recognition is exact; bond may as well be covalent
receptor for B-cell is antibody (immunoglobulin)
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B-cells can recognize soluble antigens (T-cells cannot)
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B-cells mostly recognize protein, one antibody only recognize a single epitope
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receptor for T-cell is T-cell receptor (need MHC)
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Epitope: structure on antigen that is recognized by antibody; has many turns, B-cell favors
carboxy domain (T-cell favors amino domain)
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outside is hydrophilic
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protein must be in a specific orientation to be recognized
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Immunogenecity: ability to induce an immune response (B-cells + T-cells)
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Antigenicity: ability to combine with final products of an immune response
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Experiment: Hen egg lysosome
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make synthetic loop peptide, don’t allow disulfide bond in open loop so antibody will not recognize it
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antibodies have to encounter those regions in tact to recognize epitope
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B-cells initially carry IgM and IgD, but will class switch if activated by a cytokine
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IgM = primary immune responses
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IgG = secondary immune responses
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Thursday, January 21, 2016
Antibodies
IgG, IgM, IgA, IgE, IgD
The variable regions of antibodies get shuffled which allows for variability/rearrangement; this
is where the antigen binds
...
-these locations secrete huge amounts (5-15
grams a day)
- constant regions require interaction between J-chain and secretory component (signals
the movement of Ig to where it should be)
- IgE
• mast cells (which histamine and other substances during inflammatory/allergic reactions;
binding of 2 antibodies to particular antigen is needed
- IgD: FUNCTION NOT KNOWN
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Thursday, January 21, 2016
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Thursday, January 21, 2016
Chapter 5: Organization + Expression of Antibody Genes
Germ-line theory: genome contributed by the germ cells (egg and sperm), contains large
repertoire of antibody genes — no antibody diversity
Somatic-variation theory: genome contains small number of antibody specificities which are
generated in somatic cells by mutation/recombination
•
neither theory could account for constant region and variable region
Experiment- showed that there is rearrangement within antibody genes
• germ line vs rearranged segments
• restriction enzymes added to cut around J-region—>
• then probe bound to J-region, blip on Southern blot in germ-line was same size as Jregion
• in rearranged, was larger because had rearranged and combined with a variable region
• Light chains have VJC segments
• VJC-joining is mostly “random”, but some regions used more than others
• Heavy chains have VCJC segments (starts at DNA level)
• DJ joining
• then V-DJ joining
• transcribed to RNA
• Polyadenylation RNA splicing (splice out introns)
• translate to protein
• each V-segment has a L (leader) at 5’ end that guides the chain through the ER + Golgi apparatus
• chromosomal locations of heavy and light chains are in different locations
• many J-regions, few C-regions
• a functional transcript is possible by recombination at the genome level (lymphocytes do
this) DNA—>RNA—>Protein
• RSS (Recombination Signal Sequences)
• sequences that flank each germ-line V,D,J segments—function as signals for the
recombo process that rearranges genes
• each tontine conserved palindromic heptameter and conserved AT-rich sequence
• 1 turn and 2 turn RSS
• 1 turn=12 bp long
• 2 turn=23 bp long
• 12/23 Rule
• VDJ Recombinase: enzyme that catalyzes VDJ recombination (which takes place between
RSSs)
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Thursday, January 21, 2016
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RAG-1 and RAG-2: recombination-activating genes
• mediate recombination
• enzymes in V-J or V-DJ joining
• take out = no recombination (which is essential!)
• only lymphoid-specific gene products that are involved w/ VDJ rearrangement
• Steps:
• recognition of RSS
• cleavage of DNA strands by RAG-1 and RAG-2 at junctures of RSSs
• RAG-1/RAG-2 catalyzes reaction to create hairpin loop
• hairpin cut and P-addition occurs at those sits
• then N-addition can occur at cut ends of V,D,J sequences
•
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Productive rearrangement: resulting VJ/VDJ unit can be translated to a function antibody
Nonproductive rearrangement: resulting VJ/VDJ unit has premature stop codons (no successful translation of antibody)
Allelic exclusion: ensure that functional B-cells never contain more than one VDJ and one
VJ unit
• one from mom and one from dad, but B-cell expresses only 1 chromosome from
heavy chain and light chain
• if nonproductive from both parents, gene is cut out completely
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Junctional flexibility
• Improper joining of genes during VDJ combination causing variation
Somatic hypermutation
• occurs in germinal center during B-cell maturation
• rapid single base-pair changes in variable regions
• changes affinity in antibody for antigen
• leukocytes mutate most in mammals compared to all other cell types
Class switching
• occurs in germinal center during B-cell maturation
• switch in antibody class
• only affects heavy chain
• activated by cytokines
Title: Immunology Notes
Description: These notes include general, introductory information about the immune system. Topics outlined include the innate immune system, the adaptive immune system, cells/organs of the immune system, and antigens + antibodies.
Description: These notes include general, introductory information about the immune system. Topics outlined include the innate immune system, the adaptive immune system, cells/organs of the immune system, and antigens + antibodies.