BL Immunology Unit 1 Flashcards
innate immune system is necessary to activate what?
the adaptive immune system, T and B cells
how quicky is skin replaced?
every seven days
how quickly are the intestine cells replaced?
every 3 days
what can survive on skin and what is killed?
staphylococci can survive, but ecoli dies within minutes of landing on skin via toxic proteins
what proteins are made by epithelial cells to defend the skin?
defendins or cathelicidin families. Small proteins made by epithelial cells, or brought to them by white blood cells.
cathelicidin are ______ charged?
positive. (cathelicidin=CATatonic HELICal). Bind - charged pathogen membranes. Insert themselves into lethal pores
how many bacteria live on/in us?
10^4 bacteria in gut. 10^10 bacteria on skin.
innate immunity
one of our sense organs. Immune system is designed to detect intruders and arrange for inactivation, destruction, . Recognizes molecular motifs.
what are the 3 things innnate immunity recognizes:
- foreign molecular structures called pathogen-associated molecular patterns (PAMP).
- Stress or damage indicator molecules expressed by body cells, caused by damage associated mollecular patterns (DAMP).
- Absence of certain normal cell surface molecules, which would indicate a prroblem done by NK cells.
most cells have some ________ on surface or inner membrane.
PRR. Pattern recognition receptors. On surface/inner membrane.
what are TLR’s?
Toll like receptors. There are ten of them. Homologous to the toll gene of the fruit fly. Each one can recognize foreign molecular structures.
TLR4 binds what?
liposaccharides (part of cell wall of gram negative bacteria). TLR2 binds peptidoglycan (gram positive bacteria), TLR3 binds double stranded RNA.
what happens when TLR or a WBC passes by an infected wound?
bind the foreign pattern–>signal cascades activated–> expression factors cause/increase inflammation–>factors (cytokines/chemokines) are released
what is the point of inflammation?
inflammation is the increase in blood vessel diamater, stickiness, leakiness.
Increases efflux of fluid and phagocytic WBC into tissue to get defense and healing agents into damaged/invaded area
what is the net effect of TLR cascades?
activate the mother of all inflammatory transcripton factors: NF-kB.
All TLR except TLR3 use the IRaK pathwaywhich does this. Goes into the nucleus, permits transcription of pro-inflammatory genes. Designed to not be a linear cascade so that the body can tolerate things up to a threshold.
what happens when cells get damaged and stressed?
they release a certain amt. of their internal molecules (DAMPs) and then TLRs will bind them to increase local inflammation.
mediator cells such as chemokines are ________ for phagocytic WBCs that flow in from distant areas.
chemotactic
can the innate system adapt to new challnges?
no. it can only see established patterns
what happens if the innate system can’t handle a problem?
it activates the adaptive immune system. This is a slower but stronger and more capable system.
what is the connection between the innate and adaptive immune system responses?
special phagocytic cells interface btw the body and the world (skin, lung, mucosa)–>dendritic cells
what are dendritic cells?
highly branched cells that are the best phagocytes. At wound sites immature DCs get activated by cyto/chemokines and take up what they can. Then they leave and head to the lymph system to show what they ate to lymphocytes. This then is eventually recognized to initiate an immune response
what is recognized in lymph systems by B and T cells when dendritic cells present things?
antigens. (things recognzed by adaptive immunity)
can adaptive immune response develop in the periphery?
no.
what 2 cells divide the work of the immune system up?
lymphocytes and phagocytes
lymphocytes
specialized for recongition of foreignness. Have surface receptors that bind antigenic molecule with the best shape. All receptors on surface are identical.
phagocytes
specialized fore eating/digestion
how many parts of an antigenic molecule fit into a lymphocytes receptors?
10 to 20 amino acids. Called the antigenic determinant or epitope.
what happens to a lymphocyte after an antigen binds?
it is activated, it proliferates (makes clones) by doubling every 6-12 hours. Some cells differentiate and secrete proteins to activate the immune system. Once the clone is big enough and there are enough to fight infection, recovery starts
are lymphocytes short or long lived?
many are long lived. Contributes to immunologic memory. We have memory cells that can active quickly and respond to small amounts of antigen.
what are the 2 kinds of lymphocytes?
T and B. recognize and remove foreign substances.
what do B cells do?
protect extracellular spaces of body (tissue, fluids, secretions). Release antibody into fluids
What do T cells do?
survey the surfaces of body cells (look for ones that ingested antigens, parasites, changed/mutated)
how do T cells recognize antigens?
via surface receptors. When it sees antigens in a DC, it activates, proliferates, and daughters go to invasion site. There they release family of short-range mediators (lymphokines) that call up an augmented inflammitory respone. Moncytes, macrophages attracted.
lymphokines
cytokines made by a lymphocyte
how do B cells work?
arrange for phagocytosis/destruction foreign moecule. Recognize antigens on surface receptors, are activated, proliferate. Then release soluble receptors (antibodies) to do the work.
T lymphocites are also called_________.
T cells
where do T cells develop and mature
develop in bone marrow, mature in thymus
what are the 2 main classes of T cells
helper and killer
Type 1 helper T cells, Th1
recognize antigens and make lymphokine that attracts macrophages to area where antigen has been recongnized. Can wipe out infection/kidney
Th17 helper T cells
similar to Th1, but cause focused inflammation. More powerful than Th1. resist tough infections/organisms. Implicated in autoimmunity
Type 2 helper T cells, Th2
stimulate macrophages to alternatively activate. Wall off pathogens and promote healing after Th1 response. Important parasite immunity
Follicular helper T cells, Tfh
migrate from T cell are to B cell foicles, help activate B cells to make IgM, IgG, IgE, IgA antibodies
regulatory T cells, Treg
make lymphokines that suppres activation and function of T helper cells so they keep immune response in check
Cytotoxic/killer T cells, CTL
detroy body cells they identify as bearing foreign/abnormal antigens
Th1, Th2, Th17, Tfh, Treg all have molecular marker_______
CD4 on surface. Increases antigen affinity, helps activate, tags for identification.
CTL have molecular marker_______
CD8
list steps of T cell mediated immunity:
virus enters body and makes infection–> innate immune response stimulated–>dendritic cells activated–>peptides are loaded into special antigen preserving molecules (MHC Class 2) and recycled to cell surface–> dendritic cell travels to lymphatic node/spleen–>presents to T cells till find one that recognizes–> T cells activated, divide, make 1000’s of daughter cells–>travel through body to find antigen–>inflammation and healing
Cytotoxic T cells are looking for fragments of ________
MHC Class 1. on all cells. Clonse of CTL gene are expanded and daughters circulate through body. When a daughter CTL binds a cell with the same peptide, it signals target cell to commit suicide via apoptosis. Then killer T cell can kill other infected cells.
immunity to antigen means that?
a person has had a previous encounter with it.
B cells
receptors see antigen alone, don’t need to be stimulated by MHC molecule presentation like T cells. Binds antigen, becomes activated to proliferate/differentiate.
what is a fully differented B cell?
plasma cell. Protein production factory that releases soluble versions of its receptors (antibodies)
what do antibodies do?
they bind to the corresponding antigens and neutralize a toxin, preventing from organisms binding target cells
list the 5 classes of antibodies (immunoglobulins):
IgG, IgM, IgD, IgA, IgE. “IG GAMED”
IgG, Immunoglobulin G
most abundant antibody. Two adjacent molecules bind antigen, then cooperate to activate a complement. Only antibody that passes from mother to fetus. 2 light chains, 2 gamma. MW=150,000. appears after IgM after primary immunization. Plasma half life is ~3 weeks. Phagocytic cells have receptors for Fc of bound IgG (opsonizing). 2 IgG’s must be close together to activate first component of complement.
“IgG has the Greatest amount!”
1000 mg/dL of blood
what is complement?
important to disease resistance. Some can burst bacterium via holes in membrane, others attract phagocytotic cells.
IgM
large polymeric immunoglobulin. Better at activating complements than IgG (very good at this). FIRST antibody to appear in blood after a new antigen exposure. only antibody that the fetus makes. Pentamer of basic unit, 2 light and 2 mu chains, extra CHmu4 domain. Linked by s-s bonds and closed by J chain. MW=900,000. unlikely to bind more than 2 of the 10 sites.
“IgM has the Most sites!”
Remember-too much makes blood viscous, so you have to bring in IgG to keep that from happening.
IgD
inserted into B cells membranes as antigen receptor. 2 light, 2 delta chains. Extra long hinge region. MW=180,000. Important as a B cell receptor, so even if found in plasma doesn’t do anything but receptor role.
IgA
most important antibody in secretions (saliva, tears, genitourinary, intestinal fluids, milk). Associated with secretory component (makes it resistant to digestive enzymes). First line of defense against microorganisms trying to get through mucosus membranes. Secreted as a dimer. 2 light and 2 alpha chains. Joined by J chain. So 5 chains total! Wrapped in secretory component. MW=400,000. preferentially made by plasma cells in lymph tissues near mucosal membranes. 2 are made into a dimer by a J chain addition in the plasma cell, then they are secreted into the interstitial space. Secretory component protects it from digestion in the gut
IgE
attach to mast cells. When it encounters antigen, causes them to make prostoglandins, leukotrienes, cytokines and release granules with inducers of inflammation (histamine). Mediators replicate allergy. Resistant to parasites (worms). 2 light and 2 epsillon chains. Extra constant domain. CHepsillon4 and lots of sugars. MW=190,000. Fc end binds to corresponding receptor on mast cells/basophils to trigger them. Cause of hypersenistivity/allergy (or as Dr. Cohen said-it’s your body getting bored and then freaking out about pollen).
“IgE is Extra crazy about Every Allergen!”
antibody is important for extracellular pathogens like_________________ (4 things)
Staph, Strep, Nisseria, Hemophilus. Also impt. In neutralizing toxins (tetauns), blocking spread of virus in blood
where do you encounter the different Ig immunoglobulins?
in the nearby lymph tissues to antigen entrance: T B cells, IgA, IgE. (BATE= Bcell/igA/Tcell/igE)
Draining lymph nodes/spleen: IgM, IgG
where is type 1 immunopathology (immediate hypersensitivity) seen?
in patients who make too much IgE to environmental antigen. Food, allergies, etc.
what is Type 2 immunopathology?
autoimmunity. Due to antibodies that react against yourself.
when can type 3 immunopathology occur?
when someone makes antibody against soluble antigens. If antigena and antibodies are trapped or are too small, they activate compliment and the nearby cells are affected/are casualties.
What is type 4 immunopahtolgy mediated by?
T cells. It can be autoimmune or innocent bystander injury. (forms cavities of lungs in tuberculosis, liver destruction in hepatitis). Damage done by t cells not by bacterium
what is chronic frustrated immune response?
conditions where antigen is not “self” but isn’t something you can get rid of. Eg: your gut bacteria (IBS, celiac), or unless you stop eating it
HIV/Aids basics
infects Th cells since has glycoprotein envelope (gp120) that binds CD4 molecules. Reverse transcriptase used to make DNA inserted into the cell. Activated when this T cell is activated. Progressively lose Th cells.
erythrocytes
red blood cells (5x10^6/uL or 5x10^12/L of blood)
platelets
fragments of megakaryocytes. Used for clotting. 150-400,000/uL
leukocytes
nucleated cells of blood, wbc. Sediment on top of rbc’s when centrifuged to form buffy coat
mononuclear cells
leukocytes whose nucleus has smooth outline includes monocytes, lymphocytes
monocytes
immature, becoming mature macrophages or dendritic cells in the tissue. Sometimes in tissue sections hard to distinguish btw. These two, so they are referred to as mononuclear infiltrate T cells and macro)
polymorphic nuclear cells
cells w/ lobulated nucleus. Aka: granulocytes (have prominent cytoplasmic granules). Contain: eosinophils, basophils, neutrophils)
basophils are closely related to _________
mast cells
how long do neutrophils live?
a few hours in tissue
basophils like _______
basic things. Have histamine. Equivalent of mast cell. Used in inflammation
how many WBC’s exist per unit of blood in an adult?
4500-10500 per uL of blood.
how many neutrophils are there within the WBC content per unit of blood (percent)?
40-60%
how many eosinophils are there within the WBC content per unit of blood (percent)?
1-4%
how many basophils are there within the WBC content per unit of blood (percent)?
.5-1%
how many monocytes are there within the WBC content per unit of blood (percent)?
2-8%
how many lymphocytes are there within the WBC content per unit of blood (percent)?
20-40%
young children have more ________ than neutrophils, so their percentages are reversed.
lymphocytes
what makes up 70% of lymphocytes?
T cells
what makes up 20 % of lymphocytes?
B cells
how many grams of lymphocytes do you have in ~5L of blood?
12g
why do people in developing countries have a higher eosinophil count?
parasites!
what 2 categories is the lymphoid system divided into?
central and peripheral
central lymph organs
where lymphocytes develop: bone marrow, thymus
peripheral lymph organs
mature cells are organized to trap/repsond to foreign invaders (arriving from body surfaces via lymphatics). Lymph nodes, spleen, peyers patches, mesenteric nodes (gut, tonsils, adenoids)
arterioles enter at the _______ of the lymph node and split into capillaries that drain into venules.
hilum
veins exit at the ________ of the lymph node.
hilum
lymph channels enter at the ______ of the node.
periphery.
where does lymph flow into in the the node and where does it exit from?
flows into subscapular sinus–>percolates thorugh substance of node–>leaves through efferent lymphatics in hilum
what is the outer region of a lymph node called?
cortex
what is the cortex full of?
tightly packed but motile lymphocites arranged in follicles
what are germinal centers?
crowded areas in a lymph node cortex where many of dividing cells can be seen. They represent evidence of immune response
is the deep/paracortex more or less dense than a germinal center?
less dense. Still has large #’s of lymphocytes.
where do dendritic cells arriving from afferent lymph tend to gather?
at the interface btw. The cortex (mostly B cells arising from marrow) and paracortex (mostly T cells arising from thymus)
____________ T cells (Tfh) migrate from deep cortex into follicles to help activate B cells.
Follicular helper T cells
describe the pattern of lymphocyte recirculation:
lymphocyte in blood encounters special cells lining poscapillary venules in peripherial lymphoid (esp. nodes)–> these cuboidal cells allow them to bind and pass thorugh into the node–>they may stay or move to the lymph draining from the node to migrate to the next one–> eventually they work to the largest lymph channels, thoracic duct, then venous blood–>cycle starts again
what are the 2 lymphocyte circulations?
blood and lymphatic. Lymphocytes cross from blood to lymph at nodes, from lymph back to blood at heart
where do leukocytes preferentially leave blood?
postcapillary venules. Ones in lymph nodes are specialized for high-turnover recirculation
what is the red pulp of the spleen?
corresponds to medulla in lymph node: many phagocytic cells, can make RBC. Makes the spleen the best filterer of particulates (bacteria, damaged platelets).
what is the white pulp of the spleen?
islands of cells. Sheath surrounding arteriole is T cells, diffuse collection further out is B cells.
where is the largest collection of secondary lymphoid tissue located?
in the gut due to its large permeable surface. Secondary lymph is called GALT or MALT (gut/mucosa-associated lymphoid tissue)
peyer patches
specialized mucosa M cells (gatekeepers) ingest proteins and particles (eg: virus) and transport them to albuminal side. There, dendritic cells acquire antigens and carry tme to B and T zones of the patch. Patches drain to mesenteric lymph nodes.
antigen
substance that can be recognized by the immune system
immunogen
also an antigen in form that causes an immune response (can immunize).
tolerogen
antigen delivered in a form/by a route which doesn’t cause an immune response. Prevents immune response to subsequently administered immunogen with same antigenic determinants
each lymphocyte has thousands of ___________ for antigen.
receptors. All are identical, so each cell is specific.
T cells are composed of?
alpha and beta chains.
B cell receptors are _______ of antibodies cells will eventually secrete.
samples
what is the part of an antigen that fits into the receptor?
antigenic determinant or epitope.
what must happen to activate a T or B cell?
fit of receptor and antigen must be good–>nearby receptors must be simultaneously bound by antigen–> other surface molecules must be involved (costimulation)–> cell correctly activated–>proliferation
how quickly can lymphocytes divide?
every 6 hours. They also differentiate into effectors that do the job and memory cells that recirculate to be triggered by another exposure to antigen.
when a T cell becomes large and differentiated, it is called a __________.
lymphoblast. Differentiated descendents of T cells. B cells also become lymphoblasts and go further to become plasma cells
what do plasma cells do?
they make antibodies at a rapid pace. They have a large rough ER and work themselves to death in a few days (unles they slow to become long-term memory cells)
antibody
when animals/humans exposed to bacterial toxoid, could neutralize the toxins so no longer harmful, and yield a precipitate when mixed with toxoid or toxin.
what is electrophoresis?
separates proteins on the basis of net electrical charge. (proteins have net - charge at pH of 8.2, migrate towards anode)
what does serum separate into when it undergoes electrophoresis?
albumin and globulin bands. Antibody activity is in the gamma globulin zones, some in beta region–>resulted in term immunoglobulin.
describe the antibody’s basic structure.
2 heavy and 2 light chains joined by disulfide bonds. Fab components are the upper regions (where the 4 are) and then the Fc regions are the 2 lower legs that form one unit. When some disulfide bonds reduced you get the 3 components of 2 Fab and 1 Fc unit.
what is the molecular weight of the light chain?
25000
what is the molecular weight of the heavy chain?
50000
what happens if you adjust antibody digestion with proteolytic enzymes?
you can get 2 Fab fragments or you can get 1 fragment of all the Fabs called F(ab2). Fab is univalent (binds 1 antigen), F(ab2) is divalent
chains of an antibody are composed of _________.
domains. Compact areas held together by intrachain s-s bonds
light chains have what 2 domains?
a variable domain (VL) and one constant (CL)
Heavy chains have how many domains?
one variable domain (VH), and 3-4 constant (CH1-4)
each antibody molecule is made up foa basic unit of ______ chains, ___ heavy and ___ light.
4, 2, 2
_______ is a dimer of these 2 basic antibody units that is wrapped in Secretory Component.
Secreted IgA
___________ is a pentamater of these basic antibody units.
IgM
Basic units in _____________ (2 things) are held together by J chains.
IgA, IgM
The 5 kinds of H chains define what about the antibody?
the class of the antibody to which the molecule belongs, and it’s biological properties
what are the 2 varieties of L chains?
kappa and lambda. Even though the cell can make either, each antibody will be only one of these. A cell may switch from making IgM to IgA, but the L chain stays the same even if the heavy chain switches.
what is the constant region?
a region in antibody sequence that is identical in many antibodies no matter what the antibody specificity. Made of 1-4 “C” domains. Each has an N terminal domain that varies in sequence btw different species
what is the variable region in the N domain of antibodies called?
variable domain
what is the combining site that binds antigen made up of?
parts of the V domain of H and L chains
complementarity-determining regions (CDR)
where there is most of the amino acid variablity in the 3 areas of the V domain.
what are the subclasses of IgA’s H chain C regions?
IgA 1-2
what are the subclasses of IgM’s H chain C regions?
IgM 1-2
what are the subclasses of IgD’s H chain C regions?
IgD
what are the subclasses of IgE’s H chain C regions?
IgE
what are the subclasses of IgG’s H chain C regions?
IgG 1-4
allotypes
minor allelic differences in sequence of immunoglobulins btw. Individuals. The allotype you express is determined by your parents.
idiotypes
each antibody has a unique combining region of CDR aa’s of L and H chains. This structure is the idotype.
anti-idiotype
antibodies can be made to recognize the unique idiotype combining site, and no other
antigen-antibody binding interaction
when IgG or IgM bind antigen with one of their multiple binding sites, the angle btw. Fab and Fc changes. Allosteric effect transmits through the hinge, causing a bulge at the Fc part so that biologic activities are initiated
what biologic activities are initiated by antigen-antibody binding?
- bind phagocytic cells
2. C1q binds Fc ends of 2 adjacent IgG’s to become activated
list the basic steps of antigen-antibody interactions:
binding, antibody can do something else (cross link, activate complement, bind phagocyte)
antibody mediated immunity is often referred to as _______.
humoral. T cell mediate immunity is cellular.
not all of protein antigen binds to an antibody. The part that interacts is called the ________ and is ____ to _____ amino acids long.
epitope; 10-20 aa’s long. Typical proteins have several epitopes.
when is an antibody divalent?
when it is rotationally symmetrical (2H and 2L chains), and therefore can bind 2 identical antigen agtigenic determinants. A complete IgM molecule would be DECAVALENT
soluble isolated antigenic determinants are ________.
haptens.
when are antigens (and immunogens) multivalent?
when they are bigger than haptens and have multiple, different antigenic determinants or epitopes (the case with most anigens and all immunogens). Can often cross link 2 antigens to build a lattice/immune complex
what is a precipitation?
large IMMUNE COMPLEX formed at/near equivalence. They fall out of solution/suspension. When it’s a molecule it’s precipitation. When it’s a cell/cell sized particle its agglutination.
which is more readily detected-precipitation or agglutination?
agglutination
how do you perform a quantitative precipitin test?
you mix antigen and antibody in different ratios to see how much precipitate is obtained. In relative antigen/antibody excess, the total amount of precipitate diminishes b/c the complexes are smaller and not all molecules get bound. where there is antibody or antigen excess, not as much precipitate. there is a point of optimal equivalence (e.g.: 0.5 of antigen and protein=1 g of precipitate–>all out of the solution)
precipitation in gels–immunodiffusion
layer of agar gel, cut 2 holes in it, put antibody in 1 antigen in the other, watch the diffusion of these 2 outward. Area btw. The 2 wells you will see equivalence reached, and a line of precipitation btw the wells. curved due to mass of antibody.
opsonizing
vital for clearance of extracellular bacteria. can “flow” around and grab complement “handles” on bacteria in order to engulf it. Floating “a”s are chemotactically attractive to poly.
eosinophil chemotactic factor
triggered for release by IgE
complement
main inflammatory mediator of humoral immune system. Large number of proteins similar to clotting system that when activated, follows a cascade to kill invaders (there are 3 different paths it follows)
classical path of complement
activated by IgG or IgM antibodies with antigen (main way IgG and M deal with bacterial invaders). Fc portions change after antigen interaction–>C1q binds and activates–>C1q interacts with 2 Fc’s simultaneously.
C1 esterase inhibitor
inhibitor of complement activity to prevent constant C activation
alternative path of complement
activated by cell wall structures of microorganisms (dextrans, levans, zymosan, endotoxin). Bacteria can activate without antibody (part of innate immune system). C3 always breaking down into C3a and b; if C3b stabilized C5 activates:
cell wall structure provides proper binding surface–> anchor for C3b assembly, factor B, factor D–> C3bDbC3b complex forms–>C5 activates
lectin path of complement
innate immunity. Mediated by mannose binding protein (MBP/MBL-a lectin). Similar to classical complement path
lectin
proteins that bind (usually foreign) carbs. MBP binds mannose-containing structures in bacterial carbs
membrane attack (lytic) complex (MAC)
C5 is activated very strongly–>C6-9 are activated–>C8 and 9 form lesions on target cell membranes (holes)–>cell cannot regulate osmotic pressure, pops!
cross reactivity
tendency of one antibody to react with more than one antigen (has to do with affinity). Two cross reacting species may have similar aa sequences. (eg cowpox and smallpox)
how many phases are involved in activating a B cell?
2
B cell activation:
binding of B cell receptors occurs w/ particular Ka–>activation takes place
what if an antigen binds a B cell with low affinity?
may never activate the cell. Furthermore, if another antigen comes along, binds, and activates the cell, secreted antibody may bind the low affinity antigen enough to make things inconvenient
clonal selection theory
each cell of the immune syste is programmed to make only 1 antibody (including T cells), the choice of which antibody the cell make is random, and the entire population of potential antibody-making cells preexists in normal people.
what is the basic principle of clonal selection theory?
that the best fitting clones are selected by antigen
describe how the antibody structure allows for us to get so many varieties of antibodies:
combining site is made of the V (variable region) domains of H and L chains. If the H and L chains are under separate genetic control, and any two can associate randomly, then with 1000L and 1000H, you make 1 million antiboies. The actual system is even better
what are the 3 gene families that live on different chromosomes that are part of the antibody?
lambda, kappa, and H chain gene families
do you make copies of the genes from each parent or only one?
one, just like X inactivation–>allotypic exclusion
What happens in developing B cells to bring different V’s with the correct C so that the unit can be made into mRNA?
Dna rearranges–>recobination
V domains are broken up into smaller sets of ________.
minigenes
the variable domain region of heavy chain genes is made of multiple______, _____, and ______ gene segments
V, D, J. described as V (D) J. the cell chooses one v, one D, and one J to make a VH domain region
how do you make a heavy chain?
domain is coded by V, D, J segments–>b cell brings a random D close to a J–>DNA is cut–>ends are joined–>a V segment is brought up to the recombined DJ and repeats the cut/join process–>entire region from VDJ unit is trancribed into nuclear RNA–>primary RNA transcripts are processed via splicing via VDJ-mu and then later both mu and delta messages
how do you make light chains?
similarly to heavy chains. Instead they have only V and J, so no D and only one C domain, Kappa, or lambda depending on what the cell wants. Cannot change throughout a B cell’s life!
what are RAG recombinases?
enzymes that recombine antibody and T cell recptor DNA (RAG 1 and 2)
what happens if RAG is knocked out?
you don’t make B or T cells
what are the randomizing mechanisms used for VD and DJ joinings?
exonucleases chew away some nt’s after DNA is cut prior to joining–>TdT (terminal deoxynucleotidyl transferase) randomly adds some nt’s
what is the sequence at a joining area called?
the N region
how many times are frame-shift mutations caused when randomization occurs in joining?
2/3 times. In these times a nonsense is created which will terminate transcription
what happens when a frame shift mutation, abortive rearrangement, and nonsense codons are created during randomization?
the cell first tries to fix the error with the other allele, if it works, Yay! B cell! If it does not work, the cell commits suicide.
receptor editing
when a rearrangement is detected as faulty, as long as RAG is around, it can try again.
another source of diversity in the receptors is due to the fact that V(D)J units are ______.
hypermutable. Each time a daughter divides after antigenic stimulation there is a chance that the daughter will make a slightly different antibody. Allows for gradual increase of affinity during immune response
how does hypermutation work?
AID (activation induced cytitidine deaminase) converts cytosine in CDR gene region to uracil. Uracil is removed and polymerase fills in the gap. Single base mutations.
class switching
a mature B cell can make IgM an IgD, but it may switch later to IgG, IgE, IgA. V domain stays the same but C region of H chain changes. Common in antibody responses. Removes the mu and delta regions and gets rid of them so no going back!
does lymphoid or immune system development increase, remain the same, or decrease with age?
decrease
the ________ stem cell, HSC, is restricted and generates RBC, WBC, and their derivatives
hematopoeitic
what are the 2 differentiated daughters of the HSC?
common lymphocyte progenitor (CLP) and common myeloid progenitor (CMP)
CLP gives rise to???
B and T cell progenitors.
CMP descendants are????
progenitors of erythrocytes, megakaryocytes, eosinophils, mast cells/basophils, common granulocyte/monocyte progenitor (neutrophils, macrophages, dendritic dells come from this)
What in birds gave the name to B cells?
Bursa of Fabricus. In Humans- Bone marrow cells
when can B cells be identified?
when they begin to synthesized immunoglobulin components. First is mu in cytoplasm then complete cytoplasmic IgM (cIgM).
which chain do B cells rearrange first?
heavy. Pro-B cell divides–>then one of light chian rearranges to make IgM.
what is a pre-b cell?
a cell with cytoplasmic IgM but not surface IgM.
list the steps of b cell growth:
pro B cell, pre B cell, immature B cell, mature B cell
what is an immature B cell?
a cell where surface IgM has appeared (IgM monomer with extra membrane embedded extension at Fc).
what is present in a mature B cell?
IgM and IgD are found on cell surface. Immature has only sIgM, mature has sIgM and D
when a B cell is exposed to a correct antigen,the receptors do what?
they are gathered and brought inside, antigen is partially digested, and if conditions are right it goes on to differentiate into antibody secretor.
what happens if immature B cell is exposed to an antigen?
the signal causes the receptor to try out editing, if this fails then the cell kills itself. (clonal deletion)
clonal deletion
whay we don’t make antibody to ourselves. Happens due to random chance
what happens with B cells during intial exposure and response to antigen?
IgM secrted–>helper T cells get in the mix–> switch to IgG (or A or E)–>helper T cells drive M to A in gut/lung
in response to secondary immunizations the IgM response is __________ as primary, but IgG response is _________ and more prolonged
about the same, faster
can the fetus make IgG before birth?
no it cannot make IgG until 3-6 months postnatally. It CAN make IgM before birth
what crosses the placenta to protect babies??
IgG. Half life is around 3 weeks, so in 7 half lives, is only about 1% of maternal IgG left.
When does production of IgA start in babies?
around the same time as IgG
what induces T cell differentiation in the thymus?
Notch ligands. They rearrange receptor genes (V(D)J and another set of genes), and select them for response to self+antigen.
T cells can only see antigen where?
on the surface of another cell (antigen presenting cell)
list steps of T cell maturation:
arrive and divide like crazy–>try to make T cell receptors (TCR)–>once they make TCR, they become CD4+/8+ (double positive)–>filter through cortex to medulla–>undergo selection–>become either CD4+ OR 8+ cytotoxic T cells.
how many thymocytes survive selection?
1%
how old are you when you stop reconstituting your T cell numbers?
after 40. diversity becomes limited, more cells are memory phenotype, clones are larger and fewer.
what is the valence of a secreted IgA be?
4
what is the valence of an IgM?
10
what is that number he wanted us to know in relation to how many parts make up an IgA?
10! 4 heavy, 4 light, 1 J, 1 Secretory
light chains are shared between what Ig antibodies?
ALL OF THEM ;)
classical path of complement
there is an antibody, when it binds and antigen, a conformational change in FC end occurs. This is transmitted down the molecule. First component of complement, C1q, can bind 2 adjacent ends of FC to start eh cascade (need 2 adjacent IgG). Then activates 1, 4, 2, 3, 5, 6, 7, 8, 9 cascade. When 4 activated, it splits into 4b and a. A components diffuse away, B components stick to the molecule. One molecule of IgM can activate this whole chain of complement (0 order Kinetics). Takes 2 IgGs close together (500x’s as much needed to equal 1 IgM)
alternative pathway doesn’t need antibody, is it innate immune response?
no!
lectin binding pathway
starts with mannose binding pathway, similar to classical.
6789 is what?
the attack complex of complement. 9 creates a hole through the plasma membrane once activated. Complement is lytic (problems caused if you can’t get up to C9)
