Print Immunobio test 1 lecture 7 flashcards

Immunobio test 1 lecture 7

front 1 class 6, total lecture 7 Types of humoral immune responses and functional diversification of antibodies	back 1 2/08
front 2 antibody functional diversity by isotype class switch recombination	back 2 last class - isotype switching and mechanisms of how its done
front 3 Ig heavy chain class (isotype) switching	back 3 why we make diff isotype bc of their functions
front 4 antibody class: immunoglobulin M	back 4 IgM - first Ab on surface of a B cell (BCR) IgM secreted as a pentamer Ab IgM molecule w/ 5 antibodies held together by J chain present as pentameric form IgM is the main class without T cell help (T cell independent, TI) IgM is best in complement mediated killing of pathogens IgM always used as first antibody - doesn't matter if response is T dependent or independent have lower affinity bc have not undergone processes of B cell maturation to increase affinity IgM antibodies made have lower affinity bc has not undergone any processes to make binding site better in T cell independent immune response, where there is no germinal center reaction, the antibodies remain lower affinity bc those do not go through the same maturation for enhanced affinity IgM best in complement mediated killing antibodies act mostly as extracellular protective molecule typically, antibodies catch pathogens when they are not in cells thus, antibodies catch pathogens more as a whole, when this happens, IgM attaches to pathogens + recruits complement protein C31Q. Complement recruited to IgM molecule that is bound to molecule so this helps immune response earlier on, bc complement adds to it

front 5 antibody class: IgA	back 5 IgA is a monomer and a dimer serves as opsonin for neutrophils, eosinophils, and macrophages IgA dimer is the main Ig secreted at the mucosal surfaces (ex: lungs, intestines, etc.) How does structure affect function? IgM is BULKY - very limited to reach everywhere in body - drawback – its bulky size = less ability to go thru membranes Now IgA: - most protective antibody molecule in our mucosal membranes (areas exposed to world) - GI, lungs, genetalia, etc. - secreted + present in mucus
front 6 IgA dimer is transported through epithelial cells to be secreted at the mucosal surfaces	back 6 IgA is secreted through epithelial cells via poly-Ig receptor IgA is secreted in the mother's milk Mechanism for IgA - when produced, has ability to bind receptor on epithelial cells (lining of lung/gut), where there is polyIg receptor - IgA bind to receptor -> get internalized, pass thru cell, and IgA can pass thru the cell = transport protein (IgA) from 1 side to the other For IgA molecule to be present in all the palces it is, it binds to poly-Ig receptor to get secreted outside cell on the other side
front 7 antibody class: IgG	back 7 IgG is a monomer is most compact of Abs there are 4 subclasses of IgG (1-4) serves as an opsonin activates complement sensitizes NK cells + mediates antibody dependent cellular toxicity (ADCC) most abundant in the blood and at mucosal surfaces crosses placenta most versatile small + compact produced only after Ig class switching (during the germinal center reaction) during this time, there is also affinity maturation through somatic mutation thus, these IgGs always have higher affinity has most compact structure comes in subclasses functions examples: can serve as opsonin - target pathogen becomes more attractive for phagocytes can activate complement - IgG constant region can bind complement proteins + activate the complement system (which ultimately leads to formation of protein complex that pokes holes in biological membranes) complement leads to death of target pathogens recruits + activates NK cells - important for killing of infected cells important to protect fetus from infection, even after birth (give baby passive immunity from mother) multiple functions
front 8 antibody class: IgE	back 8 IgE is a monomer primarily induced by IL-4 (cytokine) triggers release on granular contents from mast cells, eosinophils, and basophils respond to non-pathogenic substances; pollen, peanut, etc -> allergies - to take care of large pathogens, like parasites - binds to certain types of innate cells (mast cells) - sensitizes mast cells and get them ready to be active vs target - molecule that first is on surfaces (skin, etc. bc where parasitic infections occur) in very small quantities - once pathogen, more IgG is made

front 9 antibody classes are selectively distributed in the body	back 9 map for where they are in the body some antibodies recruit specific cells (like how IgE recruit mast cells + eosinophils)
front 10 Which antibody isotype can cross the placental barrier and is passed on to the fetus? Which antibody isotype is designed to be secreted via the epithelial cells at the mucous membranes?	back 10 pause for activity answer: IgG, IgA
front 11 effector mechanism of humoral immunity functions of antibody classes	back 11 no data
front 12 antibody functions	back 12 neutralization of microbes + toxins get pathogen before it enters opsonization and phagocytosis of microbes antibody dependent cellular cytotoxicity using NK cell Can bind bacteria directly and recruit complement (antibody molecules + complement together can form immune complexes) (big significance clinically bc the complexes can grow so big that cannot be filtered / can clog filtering system in kidneys that can lead to kidney dysfunction) lysis of microbes via complement phagocytosis of microbes opsonizes with complement fragments (ex: C3b) via complement inflammation via complement important inflammatory mechanism. Are often involved in autoimmune diseases

front 13 Ab blocks penetration of microbe through epithelial	back 13 without antibody: microbe get thru epithelial barrier cells with antibody: antibody blocks penetration of microbe thru epithelial barrier = antibodies protect from extracellular pathogens Microbes outside epithelial surfaces can bind to structures on microbes, which are used by microbes to attach to epithelial cells - ex: spike protein on covid causes covid 19 Bind to it, and prevent pathogen from causing harm and entering
front 14 which 2 antibody types work against microbes that try to penetrate epithelia?	back 14 IgG and IgA
front 15 Abs block microbes from infecting neighboring cells	back 15 IgG and IgA these antibodies block binding of microbe and infection of cells antibodies protect from extracellular pathogens IgA and IgG - generally protect vs extracellular pathogens - same concept. Neutralized
front 16 FcRs-mediate destruction of Ab-coated pathogens	back 16 Receptors on innate cells can be motivated/activated by antibodies to destroy pathogens Fc receptors Constant regions of antibodies – called Fc regions

front 17 Abs mediate phagocytosis of pathogens by opsonization	back 17 opsonization of microbe by IgG binding of opsonized microbe to phagocyte Fc receptors (FcyRI) Fc receptor signals activate phagocyte phagocytosis of micropbe killing of ingested microbe Phagocyte has receptors on surface 1st (Fc) receptor binds constant region on the antibody Fc receptor is specific for the constant region And binding site of antibody keeps microbe attached èGets phagocyte to internalize the pathogen that is attached to antibody This is not just physical action of antibody bindig – phagocyte grabbing - things changed in phagocyte
front 18 activation of phagocytes and phagocytosis of pathogens requires Fc receptors	back 18 free immunoglobulin does not cross link Fc receptors -> no activation of macrophage, no destruction of bacterium aggregation of immunoglobulin on bacterial surface allows cross linking of Fc receptors -> activation of macrophage, leading to phagocytosis and destruction of bacterium notes: Free floating antibodies do not bind well to phagocyte But when bound to pathogen, they bring Fc receptors together to activate the phagocyte – now bc has pathogen, it can bind well to phagocyte - cause intracellular signal transduction in the phagocyte and inside the phagocyte chemically changes -> phagocyte becomes activated -> phagocytosis
front 19 Ab dependent cellular cytotoxicity	back 19 the IgG receptor Fcy R can recruit NK cells to kill infected cells IgG bind to surface antigen of antigen -> go to NK cell which binds the antibodies -> lead to killing of the cell w/ surface antigens now bound to antigen on target cell that is infected when cells infection constant region recognized by NK cell -> forms holes and kills the infected cell
front 20 activation of NK cells requires Fc receptor cross-linking	back 20 Fc receptors on NK cells recognize bound antibody -> cross-linking of Fc receptors signals the NK cell to kill the target cell (via degranulation of NK cells) Bind foreign antigen on our own cells - recruit NK cells and activate them Process happens fast

front 21 Ab neutralize toxins by blocking toxin from binding cellular	back 21 pathologic effects of toxin antibody blocks binding of toxin to cellular receptor Another function of antibody - neutralize a toxin (poison, can be from anything) - toxins can be internalized by many cell types - cause intracellular biochemical processes to be disrupted and cause cells to be dysfunctional, etc. ex: toxins that cause paralysis of certain organs, etc. can bind to circulating molecule without immune cell participation (can do the job alone)
front 22 IgE binds to FcER1 and mediates degranulation of mast cells and eosinophils	back 22 Some cells express Fc receptors that bind only certain constant regions ex: mast cells and eosinophils express FcepsilonR1 which ONLY binds IgE -> bind thru Fc receptor - bound antibody targets allergen/pathogen - brings multiple Fc receptors together = Fc receptor cross linking Common thing in immune cell activation is clustering of receptors. Happens often. Just like the T cell indepndent IgM cross linking I think?
front 23 IgE binding to FcER1 and crosslinking mediates degranulation of mast cells	back 23 resting mast cell -> activated mast cell resting mast cell contains granules containing histamine and other inflammatory mediators -> multivalent antigen crosslinks bound IgE antibody, causing release of granule contents Antigen come, granules start secreting – doing degranulation - how mast cell look after degranulation
front 24 degranulation of mast cells and eosinophils results in the expulsion of parasites	back 24 mast cells/eosinophils attack parasites Mast cells bound to IgE specific to this parasite Mechanism of getting rid of huge parasites Releases histamine – mast cells

front 25 Fc receptors signal and the activation of innate immune cells	back 25 there are Fc receptors specific for each Ab class
front 26 How do diff antibody isotypes enhance their functional diversity?	back 26 pause for activity
front 27 Ab neutralize toxins by blocking toxin from binding cellular	back 27 Carried out by antibody protein molecules by themselves Cannot do this if have specific antibodies
front 28 binding of C1q to Ab initiates activation of the classical complement pathway	back 28 pentameric IgM molecules bind to antigens on the bacterial surface and adopt the "staple" form -> C1q binds to one bound IgM molecule -> binding of C1q to Ig activates C1r, which cleaves + activates the serine protease C1s IgG molecules bind to antigens on the bacterial surface -> C1q binds to at least 2 IgG molecules -> binding of C1q to Ig activates C1r, which cleaves + activates the serine protease C1s Antibodies can bind to targets that have multiple binding sites -> recruit binding + activation of complement Important: IgM (despite poor affinity) overcomes the deficit by having multiple binding sites -> create complex that is good for activating complement Same thing achieved by IgG. HE WILL ASK ABOUT ON TEST: 2 functions of antbodies that are independent of other cells answer: 1.Neutralize toxins 2.Activate complement

front 29 which 2 Ab functions can be performed without the help of other immune cells?	back 29 pause for activity * EXAM QUESTION * 1- Toxin neutralization 2. Complement fixation (activation)
front 30 inhibition of BCR and FcR signaling	back 30 Immune system response can be destructive Don’t want it to go on for longer than needed, would cause more disease than pathogen would - excessive/prolonged immune response is BAD and cause many problems Then how do u calm active immune response? - mechanisms to turn off response – we will discuss this in terms of B cells
front 31 FcRs activate innate cells	back 31 ITAM, immunoreceptor tyrosine based activation motif Fc receptord activcate innate cells bc they have ITAM In their cytoplasm - very potent
front 32 B cells express FcR that inhibit B cell activation	back 32 ITAM, Immunoreceptor Tyrosine Based Activation Motif ITI(?)M, Immunoreceptor Tyrosine Based Inhibition Motif Antibody bound to target Specific clone of B cell also has same specificity So these floating complexes w/ Fc come back and bind Fc receptor on B cell Antibody bring antigen to bind to original B cell receptor, and antibody is bound to Fc receptor - Fc receptor carries inhibitory motif (ITAM) usually tyrosine kinase is necessary for activation in the cells by phosphorylation, initiating signaling cascade to activate B cell ITIM motif has activity to recruit phosphatase – disrupts the process of activation and phosphorylation is STOPPED Presence of Fc gamma receptor on B cells bind to antibodies the B cell made(??? Idk what he was saying), When they find B cells, they attenuate process of activation - temper/reduce b cell actvation and can no longer be activated

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FcR mediate Ab feedback inhibition of B cell activation

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BCR activated motifs

FCR has inhibitory motifs?

Idk

How prevent excessive inflammation

Excessive inflammation causes most of damage

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distribution and functions of immunoglobulin classes

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Antibodies of different classes operate in distinct places and have distinct effector functions.
Transport proteins that bind to the Fc regions of antibodies carry particular isotypes across epithelial barriers.
High-affinity IgG and IgA antibodies can neutralize bacterial toxins.
High-affinity IgG and IgA antibodies can inhibit the infectivity of viruses.
Antibodies can block the adherence of bacteria to host cells.
Antibody:antigen complexes activate the classical pathway of complement by binding to Complement.
Antibodies inhibit BCR activation signaling through inhibitory Fc receptors

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Immunobio test 1 lecture 7