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216 Cards in this Set
- Front
- Back
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What are the primary functions of the immune system?
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Destroy potential pathogens (viruses, bacteria, protozoa, fungi, Multicellular parasites)
Attack cancer cells Eliminate toxins from the body left over from pathogens |
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What are pathogens?
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Organisms that cause disease
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List Intracellular and Extracellular pathogens
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Intra - Virus
Extra - Bacteria, Worms, Fungus |
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List the Major players in the immune response
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Macrophage
T Cells B Cells |
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What are Macrophages and what do they do?
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Big Eaters, ingest the pathogen and alert T cells
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What are T cells and what do they do?
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Interpret danger signals from macrophages and direct the response
Killer T-cells kill virus-infected cells |
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What are B cells and what do they do?
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When alerted by T cells, produce toxic antibodies
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What component of B cells secretes antibodies, and what should you remember them by?
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Plasma cells, they are like antibody factories
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Who first used the technique of variolation?
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Lady Montague, on her children she used crusts of smallpox to vaccinate her children
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What was Edward Jenner responsible for?
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vaccinated against cowpox by using cowpox crusts
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Who proposed the Germ theory of disease and when?
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1840, Henle, said that some diseases were spread by microorganisms
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Who developed the Rabies vaccine?
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Pasteur
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Who developed the idea of "antitoxins" in the serum, and what is the serum?
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Von Behring, the serum is the acellular part of the blood
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Who confirmed the identity of antibodies and adaptive immunity?
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Kabat
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What is Innate immunity responsible for?
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Immediate attack on pathogen using phagocytes
Recognition is by synthetic pathway differences (slightly different structure or conformation of Hydrogens or Oxygens) Innate Immune system predates adaptive, instructs it on what to do |
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What are some characteristics of the adaptive immune response?
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There is a 3-10 day wait period before proper antibodies can be synthesized, but thereafter the response is immediate
It has memory, so things it has encountered once can be recognized immediately the second time and third time. Only triggered when it is the initial exposure to the pathogen More specific and powerful than the innate immune response Uses the innate immune responses' strategy of production of antibodies and usage of T cells |
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What are two mechanisms of immune response?
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Recognition and Effector,
Recognition is phagocytes alerting T cells Effector is T cells telling B's plasma cells to produce antibodies |
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What are the primary functions of Innate immunity?
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Defend host from pathogens in the first minutes/hours of infection
Restrict the infection so that the host survives long enough for adaptive immune response to occur direct/modulate the adaptive response |
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Give examples of Innate immunity host defenses
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skin
mucous membranes body temperature low pH in blood chemical mediators (lysozymes) defensins complement system phagocytic cells natural killer cells |
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What are PRRs and what is their function?
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Pattern Recognition molecules/receptors
They recognize particular orientations of sugar residues or negative charges, as well as their spacing. Patterns that are recognized are only on pathogens, not host cells |
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what do lectins recognize?
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carbohydrates
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What are defense collagens?
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Blood soluble PRRs that bind to pathogen and link in to phagocytes
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What are PAMPs?
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Pathogen Associated Molecular Patterns (PAMPs)
Patterns in pathogens that are very hard for them to change. |
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What pattern does TLR2 recognize?
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Lipoproteins
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What pattern does TLR4 recognize?
*WILL PROBABLY BE ON TEST* |
LPS
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What pattern does TLR5 recognize?
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Flagellin
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What pattern does TLR9 recognize?
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CpG DNA
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What patterns does TLR3 recognize?
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RNA
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What are TLRs?
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Toll-like receptors, they are pattern recognition molecules that recognize many different pathogens' attributes
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What are the parts of the TLR Effector mechanisms?
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release of antimicrobial molecules
Expression of cytokines Alter the phagocyte surface to be able to stimulate the adaptive system - also called co-stimulation molecules - |
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What are cytokines?
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Proteins from cells that signal other cells to respond
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What are defensins and what do they do? What are they expressed by?
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Antimicrobial peptides that are cationic and so they can insert themselves into bacterial walls and disrupt the membrane, allowing other molecules to move in and destroy the pathogen.
Neutrophils and Epithelial Cells |
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What is the Complement System?
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A group of more than thirty interacting proteins located in plasma, extracellular fluids, and on cells that are activated by injury or infection
Often associated with inflammation, they tag dangerous intruders for destruction |
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What are the three pathways of the Complement system?
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Classical Pathway, Lectin pathways, and the Alternative pathway
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Describe how the Alternative pathway works generally
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It coats the bacterial membrane with molecules that can be recognized by phagocytes and then eaten to destroy the bacteria
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What is the coating of the bacterial membrane with recognition molecules called?
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Opsonization
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Describe IN FULL DETAIL what happens in the Alternative Pathway
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C3 hydrolyzes spontaneously at a slow rate into C3a and C3b and when it does, C3b can covalently attach itself to a pathogen's membrane.
C3b then is bound by Factor B to make the C3bB complex. Then, factor D comes in and cleaves the factor B that is bound to the C3b, where it now becomes C3bBb and the Ba part is released. Now, the C3bBb complex is a C3 convertase, which cleaves C3 molecules directly into C3b so that they can attach to the pathogen's surface too. The C3bs on the membrane of the pathogen are signals to phagocytes to initiate ingestion and killing |
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What activates the CCP? What is CCP as an acronym?
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CCP is activated by microbial constituents like lipid A or antibodies bound to targets
CCP is the Classical Complement system |
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What is C3bBb3b?
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C5 convertase
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What two antibody types signal the complement system? How do they do this?
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IgM forms a pentamer bound to antigens on a bacterial surface, and it enters the staple form. Then C1q binds to bound Igm molecules
IgG moles bind to antigens on bacterial surface, then C1q binds to at least two IgG molecules |
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What are Masp-I and Masp-II and what do they do? Why is this important?
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Serine proteases from the Lectin pathway that cleave C4 and C2 into C4a and C4b and C2a and C2b.
This is important because C4b2b can make the C3 convertase |
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what is MBL?
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Mannan-binding lectin (MBL) specifically binds to mannose and fucose residues with correct spacing on pathogens. They MUST have the correct spacing
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What are the two C3 convertases and two C5 convertases? How do you know which one is alternative and which one is classical?
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C3 convertases are C3bBb from the alternative pathway and C4b2b from Lectin
C5 convertase is C3bBb3B, created after a C3 convertase (C3bBb) gets a 3B added to it AND C4b2b3b is one as well The ones with capital B in them are alternative |
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what is the recognition molecule of the CCP? (for molecules, not directly to pathogen). What does it bind to?
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C1, it binds to an IgM "stapled" pentamer or at least two IgG antibodies bound to antigen's surface
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what does C1s do? Which binds to microbial surface?
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cleaves C4 into C4a and C4b and also C2a and C2b. C4b binds to a microbial surface
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When C4b binds to microbial surface, what happens next? How many C3s can be cut?
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C4b is bound by 2b, which is a C3 convertase, and so then C3 is cleaved into C3a and C3b, where C3b can bind to the microbial surface OR attach to the C4b2b to make C4b2b3b complex, a C5 convertase
up to 1000 molecules of C3 can be cleaved |
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What is the Big MAC? In detail how is it formed?
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The Membrane Attack Complex, C5b binds C6 and C7, then C5b, 6, 7 complex binds to membrane by C7. C8 binds to complex and inserts into cell membrane, then C9 binds to the complex and polymerizes. 10-16 molecules of C9 bind to form a pore in the membrane
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What molecule's cleavage leads to the Big Mac's formation?
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C5's cleavage
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Which complement pathways are responsible for which surfaces?
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Lectin - Microbial surface, CARBOHYDRATES
CCP - antigens bound by antibodies Alternative - Only microbial surface |
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In brief molecular terms, which complement pathways do what?
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Lectin - MASP-2 cleaves C4
C4b attaches to cell surface C2b binds to C4b CCP - C1s cleaves C4 C4b attaches to cell curface C2b binds to C4b Alternative - B binds to bound C3b |
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In the CCP and lectin pathways what are some of the similarities and differences between them? How is C4 cleaved in each?
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They both cleave C4 first and then C4b attaches to cell surface and C2b binds to C4b
But, C4 is cleaved by C1s in the CCP while the Lectin pathway uses MASP-2 to cleave C4. Also, the CCP deals with antigen-antibody complexes while the Lectin Pathway deal with microbial surfaces and Carbohydrates |
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What starts the alternative pathway?
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spontaneously hydrolyzed C3
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In the CCP and lectin pathways what are some of the similarities and differences between them? How is C4 cleaved in each?
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They both cleave C4 first and then C4b attaches to cell surface and C2b binds to C4b
But, C4 is cleaved by C1s in the CCP while the Lectin pathway uses MASP-2 to cleave C4. Also, the CCP deals with antigen-antibody complexes while the Lectin Pathway deal with microbial surfaces and Carbohydrates |
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In the CCP and lectin pathways what are some of the similarities and differences between them? How is C4 cleaved in each?
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They both cleave C4 first and then C4b attaches to cell surface and C2b binds to C4b
But, C4 is cleaved by C1s in the CCP while the Lectin pathway uses MASP-2 to cleave C4. Also, the CCP deals with antigen-antibody complexes while the Lectin Pathway deal with microbial surfaces and Carbohydrates |
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What starts the alternative pathway?
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spontaneously hydrolyzed C3
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What is CR1? What molecules does it recognize?
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Complement Receptor 1, it is a membrane receptor on phagocytes.
It recognizes opsonization fragments like C3b and C4b |
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What is complement effector function #1? which CRs bind what?
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Phagocytosis, C1q/MBL covalently bonds to the bacteria and then CR1 on the phagocyte binds to C3b and CR3 binds to iC3b
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What is complement effector function #2 and 3? How does this happen?
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#2 is recruitment,
#3 is Increased vascular permeability small complement cleavage products like C3a, C4a, and C5a act on blood vessels to increase permeability so that antibodies or macrophages and PMNs (polymorphonuclear leukocytes) and lymphocytes is increased. |
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What is complement effector function #4? What is the main player?
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Lysis of Pathogens, The Big MAC plays the role in forming a pore in the membrane
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How do we know the complement system is important?
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Lack of any of the complement factors or players causes severe disease
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Why do host cells not get lysed as well as pathogens? What are the molecules that do this (bind to C3b)? What is the last molecule that really renders it inactive?
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On host cells there are complement control proteins like...
CR1, H, MCP, and DAF, which bind to C3b Pathogens do not have the complement regulatory proteins like host cells factor I cleaves C3b (when bound by any one of the above molecules) to render it inactive |
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What factor can stabilize the binding of C3bBb complex?
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Factor P
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How can some pathogens survive opsonization (how can they disrupt it and render it useless?). What is one example?
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Some pathogens may have complement regulatory proteins just like host cells
Protectin (CD59) it inhibits C9 from polymerizing so that the big MAC can't make a pore in the membrane |
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What are two ways that microbes and viruses avoid complement attack? (molecularly)
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Recruitment of host factor H and recruitment of host C4bp that render the C3b and C4b inactive as iC3b and iC4b
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What are 3 kinds of phagocytes or Polymorphonuclear Leukocytes (PMN)
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Neutrophils
Eosinophils Basophils |
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What is a monocyte and what does it do?
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It is a white blood cell that differentiates into macrophages and dendritic cells when needed
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What is phagocyte effector Mechanism 1? 2?
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Phagocytosis and digestion, they engulf and digest bacteria that they bind
Effector Mechanism #2 is to release proteases and generate oxygen radicals that are toxic to kill microbes |
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Where are Lysosomes located? What is it called when lysosomes don't fuse with phagosomes? What happens?
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Inside of macrophages, they contain digestive enzymes.
Chediak Higashi Syndrome is when lysosomes don't fuse with phagosomes, this means less killing of bacteria |
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What are some non-oxidative killing mechanisms for phagocytes?
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Acidification (pH 3.5-4.0)
Antimicrobial peptides - Defensins and cationic proteins Enzymes - Lysozyme - Dissolves cell walls. Acid hydrolases further digest bacteria Competitors - Lactoferrin (binds Fe) and vitamin B12-binding protein |
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What are oxidative killing mechanisms for phagocytes?
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NADPH Oxidase
Superoxide O2-, hydrogen peroxide H2O2, singlet oxygen O2` hydroxyl radical OH INOS - Nitric Oxide, NO |
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What is Chronic Granulomatus Disease? What is the Respiratory Burst?
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CGD, Chronic Granulomatus Disease is when cells in the immune system cannot form the superoxide radical and other oxygen compounds to form a toxic environment for pathogens in phagocytes.
The respiratory burst is when NADPH oxidase generates toxic radicals by bringing in Oxygen and adding electrons |
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What is NADPH oxidase?
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generates the respiratory burst, it brings in oxygen and adds electrons to make it toxic for pathogens in the body.
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What is phagocyte effector mechanism 3?
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Release of Cytokines
When the phagocyte binds to a bacteria it releases cytokines that interact with other cells to promote protective responses (basically messenger function to notify other cells) |
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What are some effector mechanisms of the complement system and for which pathogens are they for?
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Lysis - Bacteria, Viruses
Phagocytosis - Bacteria Cell mediated Cytotoxicity - Viruses, Worms, parasites, Intracellular bacteria |
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What are some effector mechanisms of the complement system and for which pathogens are they for?
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Lysis - Bacteria, Viruses
Phagocytosis - Bacteria Cell mediated Cytotoxicity - Viruses, Worms, parasites, Intracellular bacteria |
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What are 2 lipid mediators released during Phagocyte Effector mechanism 3? Name 3 Cytokines released as well
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Leukotrienes, PGE subscript 2,
IL-1, IL-6, TNF alpha |
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What happens after phagocyte effector mechanism 3 happens and the phagocyte sends out IL-6?
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IL-6 induces acute phase proteins to be synthesized,
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What are some acute-phase proteins? What do most of them do?
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Serum amyloid protein, fibrinogen, Mannan-binding lectin, C-reactive protein
Most of them act as opsonins, binding to bacterial surfaces and serving as signals for macrophages |
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What does release of Cytokines and lipid mediators do in terms of the body? (temp? blood cells?)
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Induces fever and more vascular permeability
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Which is better for survival, localized signaling or systemic signaling?
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localized, easier to control infection
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If a virus gets into a cell, what is then activated as cellular responses? (Two main ones, not interferons)
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Oligoadenylate Synthetase polymerizes ATP into 2'5' rather than 3'5', then activates an endo Rnase L which degrades viral RNA
PKR (P-1 kinase) is activated by dsRNA, which phosphorylates eIF2, which inhibits translation and inhibits viral synthesis |
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What do interferons do? How many are there and what is each secreted by? When are they needed?
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Interferons enhance MHC on neighboring non infected cells, which makes it so that those cells will not be killed by NK cells.
There are alpha and beta interferons that are secreted by infected cells, and then IFN-gamma goes from NK cells to macrophages They are needed when a virus has entered the cell and are used to notify other cells and protect them |
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What do NK cells use to recognize other cells? What are some activating NK receptors? What are some Inhibitory NK receptors? What are the pores used to activate?
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MHC
NKG2D, KIR2DS are activating NKG2A and 2DL are inhibitory |
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What are ITAM and ITIM domains? What have them?
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ITAM is when a protein that is both in and outside of the cell can interact with a protein outside the membrane and get phosphorylated to signal the inside to activate
ITIM does the opposite, it sends an inhibitory signal instead NK receptors have them |
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How do NK cells kill other cells? what molecule is delivered and through what?
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Cell-mediated Cytotoxicity,
granzyme B is delivered through perforing pores that activate apoptosis |
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If a cell loses its MHC class 1 or it is blocked or altered by bacteria, what happens when an NK cell comes into contact with it? Why does this happen?
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The NK cell will kill it, because it requires an MHC class 1 to give a negative signal so that it won't kill the cell, but without an MHC it cannot do that.
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What are TCRs? What is their structure like?
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T cell receptors, they are on the surface of T-cells since T-cells cannot bind to antigens, they are presented the antigen by MHC
Their structure: One alpha chain and one beta chain, each have 1 Constant and 1 Variable region |
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What does MHC stand for?What is it called in humans?
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Major Histocompatibility complex
HLA |
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what is another name for when a transplant tissue is accepted as "self?" What determines whether it is accepted as self or not?
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histocompatible
MHC |
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What is special about MHC class 1 as opposed to 2? (how many times is the membrane punctured?)
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MHC class 1 has only one transmembrane protein
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What is MHC class 1 expressed on? Does it bind from inside or outside the cell (endogenous or exogenous)?
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MHC class 1 is expressed on nearly all cells
It binds peptides from cytoplasm, endogenous |
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What is MHC class 2 expressed on? Does it bind from inside or outside the cell (endogenous or exogenous)?
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expressed on Antigen presenting cells (APC).
Bind peptide from extracellular proteins in endosomal-lysosomal system (EXOGENOUS) |
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MHC class 1 binds what size peptides? Do they fit in the groove?
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8-10 amino acid peptides
Yes they fit in the groove |
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MHC class 2 binds what size peptides? How do they fit in the groove?
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10-20 amino acid peptides
They extend beyond the groove |
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What are anchor residues?
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identical or similar set of peptides that bind with a high affinity to a particular MHC
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How many variants of classical MHC are there? What does this tell you?
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>500 variants, reflects selection for resistance to disease
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Where are most MHC polymorphisms? What does this give it?
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in the peptide binding groove
This gives MHC much more variability |
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Why does a child have more resistance to diseases than his parents?
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he can express all MHCs in both his father and his mother
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What is polymorphism?
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variation at a single genetic locus (like on MHC)
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What are some functions of MHC?
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It allows CD8 killer T-cells to recognize virus infected cells and kill them
It allows helper T-cells to release cytokines and activate macrophages MHC also allows helper T-cells to induce B-cell antibody release |
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What is MHC restriction?
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A given TCR (T-cell Receptor) is specific to both the peptide that is bound AND the particular MHC molecule
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What does the proteosome do to help MHC bind to peptide?
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it chops up the proteins to certain sizes for MHC class 1 and 2. Then it pumps the peptide into the ER from the cytoplasm using TAP proteins
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What do pH levels in the cell activate when talking about MHC class 2 and exogenous presenting?
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activate caspases and cathepsins
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What happens with exogenous proteins?
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Internalized by phagocytosis, then acidic vesicles like caspases and cathepsins are activated, then the peptide meets MHC II on cell surface
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What does the proteosome do to help MHC bind to peptide?
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it chops up the proteins to certain sizes for MHC class 1 and 2. Then it pumps the peptide into the ER from the cytoplasm using TAP proteins
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What do pH levels in the cell activate when talking about MHC class 2 and exogenous presenting?
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activate caspases and cathepsins
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What happens with exogenous proteins?
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Internalized by phagocytosis, then acidic vesicles like caspases and cathepsins are activated, then the peptide meets MHC II on cell surface
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What does class 1 presentation lead to? Class 2 presentation? (MHC)
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Class 1 leads to target cell killing
Class 2 presentation leads to T cells providing help |
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Where does isotype switching occur? What is it triggered by?
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heavy chain, induced by cytokines
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What are two membrane associated regulators of C3b?
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CR1 and MCP or DAF
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During DNA recombination a V segment of the heavy chain cannot join directly with J segment of a heavy chain because of...
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12-23 rule
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What molecules are critical links between the adaptive and innate immune response?
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dendritic cells and cytokines, also macrophages or ARC
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What are some primary lymphoid organs? Secondary lymphoid organs?
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thymus and bone marrow
Lymph nodes, spleen, peyer's patch, BALT/MALT |
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Which lymphocytes are considered parts of the innate immune system and adaptive immune system?
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NK cells are considered to be innate immune system
T cells and B cells are considered to be part of the adaptive immune system |
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What is an example of a pattern recognition receptor? What about examples of PAMPs?
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Pattern recognition receptors -TLR, scavenger receptor,
PAMPs--- Clq, MBL, MMP |
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What are defensins expressed by?
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neutrophils or epithelial cells
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What is classical C5 convertase? Alternative C5 convertase?
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Classical - C4bC2bC3b
Alternative - C3bBb3b |
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What components does the Big Mac have?
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C5-C9
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What prevents the big mac from polymerizing?
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CD59 or protectin
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What are some components of the B cell receptor?
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Ig, Ig alpha, Ig Beta
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What does antigen-bound C3d do in B-cell activation?
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binds to CD21 and lowers the threshold of antigen crosslinking needed for B-cell activation
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What are the two signals needed for B cell activation?
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antigen cross-linking
T-cell help (cytokines) |
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What type interferons are synthesized by cells in response to virus infection? What do they do?
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type 1
upregulate MHC class I in surrounding/nearby cells |
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MHC class 1 molecules are complex of what? Which part of it doesn't contain a transmembrane domain?
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3 alpha domains and 1 beta2- domain
Beta subscript 2 - microglobulin does not contain a transmembrane domain |
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What is the CDR? Where is it?
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complementarity determining region, responsible for antigen recognition.
It is located on the LOOPS of antibodies (immunoglobulin) AND on T-cell receptors |
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two of the intermolecular antibody-antigen interactions are...
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ionic and hydrogen bonding
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What is clonal selection? What does this ultimately result in?
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it is when daughter cells which express surface immunoglobulin and are altered in their antigen binding capacity by somatic hypermutation are selected to proliferate
affinity maturation |
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how are the two chains of the T-cell Receptor (TCR) held together?
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disulfide bonds
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What does CDR1 on the TCR mostly bind? What does CDR3 on the TCR mostly bind?
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CDR1 binds MHC
CDR3 mostly binds peptides |
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Where are pre-T cells born and where do they migrate?
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They are born in the bone marrow and they migrate to the thymus
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What does positive selection look for in TCRs?
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it looks for TCRs that have any/some affinitiy for MHC
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What does negative selection look for in TCRs?
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negative selection looks for TCRs that have a high affinity for MHC
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do T cells and Bells recognize whole proteins or peptides?
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No
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Why can B-cells act as APC? What molecule do they up regulate when activated?
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B-cells constitutively express MHC II, and they express B7 when activated
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What does positive selection look for in TCRs?
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it looks for TCRs that have any/some affinitiy for MHC
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What does negative selection look for in TCRs?
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negative selection looks for TCRs that have a high affinity for MHC
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do T cells and Bells recognize whole proteins or peptides?
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No
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Why can B-cells act as APC? What molecule do they up regulate when activated?
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B-cells constitutively express MHC II, and they express B7 when activated
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What are the main recognition components of each complement pathway? What is the basis for activation of each pathway?
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Classical: C1
Antibody complexes or Fc of antibody in complex with antigen Lectin MBL (or MBL-MASP complex) mannan on the top of antigens Alternative C3 (or C3b) Thioester binding to permissive surface (thioester bond is open because of spontaneous hydrolysis) |
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What are the 4 mechanisms that contribute to the generation of diversity of the immunoglobulin recognition regions?
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Combinatorial Diversity
DNA recombination Junctional Diversity Somatic Hypermutation |
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At what stage of B cell development do each of these generators of diversity occur?
Combinatorial Diversity DNA recombination Junctional Diversity Somatic Hypermutation |
Combinatorial Diversity - pre B cell or immature B-cell
DNA recombination - Pro and Pre B cell Junctional Diversity - Pro and Pre B-cell Somatic Hypermutation - After activation of mature B cell by antigen |
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What are three characteristics of the innate immune system that differ from the adaptive?
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Specificity is encoded in the genome with innate, but adaptive specificity is in gene segments
Innate recognizes broad classes of pathogens but adaptive has a specific molecule for each pathogen. Innate has rapid response in hours, but adaptive has response in days to weeks |
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How many CDRs are there per immunoglobulin or T cell receptor?
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6, there are three on each heavy or light chain in the immunoglobulin, and 3 on each alpha and beta chain in the TCR (CDR1 CDR2 and CDR3)
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When talking about CDR, how is the alpha chain generated? How is the beta chain generated?
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VJ recombination
VDJ recombination |
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What do V, D, J, and C stand for in terms of the encoding of CDRs?
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V is variable
D is called |
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How many constant regions does a heavy chain have?
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3 Constant regions, and 1 Variable region
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How many different V regions are there for alpha encoding in genes? J? C?
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50 V
70 J 1 C |
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How many different V, D, J, and C regions are there for beta encoding in genes?
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57 V
2 D 13 J 2 C |
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What do RAG 1 and 2 do? What does it stand for? What diversity does this create?
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Recombination Activation Gene,
RAG 1 and 2 cut DNA and put it back together, but they also add one nucleotide >10^13 |
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Why doesn't RAG introduction of nucleotides and reorganization of the gene work sometimes?
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the protein made is sometimes non-functional
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What are alleles? What is allelic exclusion?
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Copies of genes (like one from each parent)
BOTTOM LINE IS ALLELIC EXCLUSION RESULTS IN ONE SINGLE SPECIFICITY FOR EACH T cell receptor/antibody Allelic exclusion is when rearrangement occurs by RAG proteins and only one of the alleles is used while the other is shut down. This results in only one single specificity for each T cell and B cell |
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What does CD4 do? What does CD8 do?
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CD4 makes sure helper T-cells can bind to class 2 Antigen presenting cells
CD8 allows Killer T-cells to bind to class 1 MHC |
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What other two structures help a killer T-cell bind to target cells (class 1 MHC)? Another molecule that helps this interaction?
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LFA-1 and iCAM-1
CD2 |
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Which cells do APCs and target cells bind to?
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APCs bind to helper T-cells and target cells bind to killer T-cells
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What is a cell adhesion molecule expressed on APCs?
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CD58
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What is the signaling pathway for TCR when it interacts with an APC?
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TCR --> PKA --> AP-1
TCR --> Ca2+ --> NFAT CD28 --> NFkB |
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how does the TCR, when interacting with an APC cell release Ca2+?
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calcineurin is activated
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Describe this signaling pathway
TCR --> Ca2+ --> NFAT |
TCR activates calcineurin, which activates transcription factors that open up a part of the gene to express NFAT
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Describe this signaling pathway
TCR --> PKA --> AP-1 |
TCR interacts with APC, ZAP70 is released and activates PKC, which then activates the transcription factor AP-1
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Can B cells take up antigens? Can B cells be activated by antigens?
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Yes, they can take up antigens
No, they need a helper T cell to become activated |
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When a helper T-cell receptor is triggered, what happens?
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Activates cytokines - IL-2 IL-4 and IFN-2
Proliferates releases CD40 to help B-cells and macrophages get activated |
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when a T cell is getting activated, what two domains play a crucial role? Which cells are they on?
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CD 28 and CD80,
CD28 is on the T cell CD80 is on APC |
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What is another name for CD80? What is it usually found on? what cells up regulate it when activated?
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B7, it's found on APCs
B Cells upregulate it when activated and thus can function as APCs |
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What do unactivated B-cells do?
When a TCR comes along what happens? |
take up and process antigens
present on MHC class 2 and act as an APC TCR will recognize MHC class 2 presented antigen T cell becomes activated and makes IL-4, IL-8, and CD40 |
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What does CD40 do?
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Helps B-cells produce antibodies, helps induce class-switching
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What does IL-4 do and when is it released?
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It helps stimulate B cells to make antibodies and proliferate T cells
Released after TCR recognizes MHC class 2 presented antigen (after T cell activation) |
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What does IL-8 do and when is it released?
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IL-8 helps macrophages, stimulates antibody production in B-cells
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How do Helper T-cells detect antigens? Can they see free floating antigens?
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They need APCs like B cells to present antigens to them, they cannot see free, floating antigens
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What are the structures of Immunoglobulins and TCRs?
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Immunoglobulins have 2 light chains and 2 heavy chains, heavy chains have 3 constant regions and 1 variable region. Light chains have 1 constant and 1 variable region. 3 CDRs
TCR receptors have alpha and beta chains, 1 constant and 1 variable alpha regions, 1 constant and 1 variable beta regions with 3 CDRs. |
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What is the Fab region of an immunoglobulin molecule? What about Fc?
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there are two Fab regions where the antibody branches off, the two top parts with each made of 2 variable and 2 constant regions
Fc is the bottom part of the immunoglobulin, (composed of 6 constant regions) |
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MHC class 2's structure is what?
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2 transmembrane chains, beta1 and beta2 connected to each other and alpha1 and alpha2
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What is an epitope? What are the two types of Epitopes?
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The specific site on an antigen that an antibody binds to
There are linear and discontinuous epitopes linear is when the binding is straight on, discontinuous is when the protein is folded like a hairpin |
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How big is the immunoglobulin fold? (just like the peptide grooves in MHC)
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110 amino acids
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How many CDRs does an antibody have?
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12, 6 per Fab, 3 for each chain, 2 light chains 2 heavy chains
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How much does each part of the antibody weigh?
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light chain is 25 kDa
Heavy chain is 50 kDa |
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What does cleavage of the antibody by papain do?
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completely cuts the antibody into three parts, Fab, Fc, and Fab
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What does Pepsin do to the antibody when used to cleave it?
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you are left with F(ab')2 or two Fabs connected
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Which receptors on Phagocytic cells recognize antibodies or antibody complexes and opsonization fragments??
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Fc receptors recognize antibodies
CR1 recognizes C3b and C4b CR3 recognizes iC3b |
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What are 2 Antibody neutralization mechanisms?
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Block bacterial adhesins by binding to them
Block toxicity - bind to toxins and do not allow them to go to receptors Antibodies |
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When antibodies bind to mast cells with antigens on them what happens?
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mast cells release granules containing histamine to kill extracellular parasites
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When antibodies are bound to antigens on a bacterial surface and an NK or macrophage comes along, what happens?
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The NK or macrophage cross links its Fc receptors and becomes activated and kills the cell
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What is combinatorial diversity?
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Any Heavy chain can combine with Any light chain
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How does DNA rearrangement happen for antibody heavy chain genes?
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First the part between D and J is cut out and J is moved closer to D, then the part between V and D is cut out so you have VDJ
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How does DNA rearrangement happen for antibody light chain genes?
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The section of the gene between V and J is cut out and so you have VJ right after another
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Where is IgE found?
Where is IgD found? Where is IgG found? Where is IgM found? Where is IgA found? |
IgE is found in mast cells
IgD is found in B cells IgG is found in Blood cells IgM is found in the blood IgA is found in the mucosa |
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Do NK cells need to contact MHC if there are antibodies on an antigen?
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no, it can go ahead and get activated via its Fc receptors and cross linking
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How did Tonegawa know that DNA rearrangement occured?
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used restriction enzymes to cut a germline DNA and B cell DNA, but when he cut the germline DNA the V and C regions were on different strands while on the B cell the C and V were on the same strand.
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What is the 12/23 rule?
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In order for there to be viable gene products after recombination, 23 base pairs are conserved between V and D, and 12 base pairs are conserved between D and J, thus the 23/12 rule
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How do RAG1 and RAG2 cut the DNA during rearrangement?
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They first get it into a loop and then cut it at two parts so you basically cut out a piece that looks like a plasmid
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What is the syndrome when someone has limited junctional diversity?
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Omenn Syndrome
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What is Junctional Diversity?
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The Addition of nucleotides during the junction or linkage of fragments (like V closer to D or D closer to J) creates diversity since when it is translated it alters the CDR
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What are the four mechanisms that contribute to the GOD of CDRs?
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Combinatorial Diversity
DNA recombination Junctional Diversity Somatic Hypermutation |
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Which antibodies are used for:
Opsonization? degranulation? ADCC (cell mediated lysis)? Antigen Neutralization? |
Complement Activation: IgM and IgG
Opsonization: IgG degranulation: Mast Cells, basophils -IgE ADCC - FcR on NK cells - IgG Antigen Neutralization - Any Ig |
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What are the 5 effector mechanisms of Antibodies?
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Complement activation
Opsonization Neutralization Degranulation of mast cells ADCC |
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How does opsonization occur with antibodies?
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IgM and IgG are bound to bacteria along with C3b, phagocyte comes in with CR1 to recognize C3b and Fc receptors bind the antibodies and help phagocytosis
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What is the path from stem to mature b cell?
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stem cell - Early pro B cell - Late Pro B cell - Large Pre-B-cell - small pre-B cell - Immature B Cell - Mature B-cell
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Which Igs do B cells express on their surface? What stage do they first express them?
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IgD and IgM
Immature B cell is when they express IgM on surface |
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When does D-J heavy chain rearrangement occur during B cell development?
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Early pro B-cell
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When does V-DJ heavy chain rearrangment occur during B cell development?
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Late Pro-B cell
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When does VJ light chain rearrangement occur in B-cells?
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Small Pre-B cell
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What did Lderberg and Nossal find out?
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One B cell secretes only one type of antibody.
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How does a B cell secrete only one type of antibody if there are 2 chromosomes and 2 genes for each Ig chain?
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allelic exclusion
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When do Combinatorial Diversity, DNA Recombination, somatic hypermutation, and Junctional Diversity occur in terms of stages of B-cell development?
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Combinatorial Diversity - Pre B cell --> Immature
DNA recombination - Pro and Pre B cell Junctional Diversity - Pro and Pre B cell Somatic Hypermutation - During proliferation after activation of B cell |
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How is the B cell activated? What does it require?
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Antigen receptor cross linking
cytokines from T-cell after presentation on MHC II |
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When B cells are activated and begin proliferating, Describe Somatic Hypermutation and how it leads to Affinity maturation
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When a B-cell is activated, it proliferates and while it proliferates there are antibody gene mutations that create many lymphocytes with different binding capacities. Then those interact with the antigen, and only the B cells who can interact with it will proliferate, which results in clonal selection, so Somatic Hypermutation and clonal selection are characteristics of affinity maturation, where the b cells keeps proliferating and maturing toward a specific antigen
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What are the differences between V region recombination and Isotype switch recombination?
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All isotype switches are productive (because they occur in introns)
Different recombination signals and enzymes Switch recombination occurs after antigen stimulation and not during B-cell development Switch recombination is regulated by T cell (cytokines) |
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What is special about IgM and IgD? What level of processing does this occur at?
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They are co-expressed
Controlled at the level of RNA processing |
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What is the antibody not secreted by plasma cells?
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IgD
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do monovalent antigens activate B-cells? Why not?
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No
Antigens must be multivalent so they can cross link with B cell surface antibodies |
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what is BcR made up of?
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Ig alpha, Ig Beta, and Ig
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Why are Ig alpha and Ig beta significant?
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They are what signals the B cell for activation since they are ITAMs.
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What interacts with the Ig alpha and beta ITAMs and phosphorylates them?
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Src kinases
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What family of kinases binds after the ITAMs on Ig beta have been phosphorylated?
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Syk
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What does CR2 (CD21) do in terms of B-cell activation?
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They help lower the threshold for crosslinking and B-cell activation
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What does C3d come from? What does it do again?
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iC3b, it is a cleavage fragment that helps lower the threshold for antigen needed for B cell activation
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