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205 Cards in this Set
- Front
- Back
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What is immune tolerance?
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The active process of unresponsiveness in the presence of immunizing amounts of antigen
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What is immunity?
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Exemption from disease
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Are you exempt from disease/illness if you have an immune response?
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Not always
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What are cytokines?
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Chemical messengers released by one cell to act on another
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How do cytokines differ from hormones?
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Alway protein or peptides that REQUIRE a receptor on the cell membrane to act on the target cell.
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What is the function of increased body temperature (a immune response)?
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A fever:
1. Slows growth of viruses and bacteria 2. Allow a key anti-viral cytokine, INTERFERON, work better (optimise) |
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What is IL-1 and what is its function?
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Interleukin 1.
1. Increases body temperature by acting on the hypothalamus 2.Responsible for fatigue and muscle ache (when with the flu) |
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What are the two type of immunity?
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Innate Immunity and Adaptive Immunity
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What constitutes the Innate Immune system?
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1. Physical Barriers - Skin, Mucous, Stomach acid, Tears
2. Physiological Response a) Coughing, Fever, Sneezing, etc. b) Releasing soluble factors - Cytokines, vasoactive amines (histamine), Defensins (pore forming peptides) c.) Inflammatory Response |
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What is the function of Interferon?
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Interferon is released from infected cells and induces an anti-viral state in cell adjacent to the infected cells
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What are the function of defensins?
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These are pore forming peptides. The forming of pores trigger loss of cell integrity.
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What is the main form of an innate immune response?
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Inflammation
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What are the types of Inflammation response?
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Local and Systematic
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What does a local inflammation response involve?
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It involves the recruitment of effector cells in the local injury/infection through the use soluble factors
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What does a systematic inflammation response involve?
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System wide responses such as fever, aches, fatigue. Cold symptoms are due to this form of response
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Can a local response trigger a systematic response?
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Yes
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Describe the process that occurs upon an injury (local response)?
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1. Release and activation of kinnins (Bradykinnin) and complement from tissues
2. Vasodilation induced by cytokines, complement components, kinnin (Bradykinnin); also increase in vascular permeability 3. Rolling (white blood cells attaching adhesion molecules on endothelial cells, with higher affinity near site of injury due to more expression of adhesion on cells) 4. Increase activation of white blood cells and activation of chemokines produced in inflamed tissue 5. White blood cell enter inflamed area through opens to 'clean up' 6. Pus (by product) formation |
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What are the key pro-inflammatory cytokines involved in a local inflammatory response (to systematic response)?
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IL-1, IL-6, and TNFα (tumor neucrosis factor alpha)
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What is the vasculature change induced by a local response and what is the purpose of this change?
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Vasodilation.
Slowed blood flow, accumulation of cells and soluble factors at the site. Increased vascular permeability by opening of gaps between endothelial cells that line blood vessel - edema/swelling |
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What is ASSOCIATED with redness and heat at a site of injury/infection?
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Vasodilation
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What is ASSOCIATED with swelling and pain at a site of injury/infection?
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Vascular permeability
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What is another cause of pain at a site of injury/infection other than Vascular Permeability?
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Bradykinnin's action on pain receptors.
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What is extravasation?
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The process of vasodilation and vascular permeability increase to allow effort cell to access to the site of injury/infection. (also know as diapedesis)
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List the steps in Extravasation/Diapedesis
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1. Rolling (Selectin-mucin interactions; mucin on the killer cell)
2. Activation - Chemokines 3. Arrest/adhesion -Intergrin on kill cell interact with ICAMs(Inter Cellular Adhesion Molecule) |
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List the effector cells involved in a local inflammatory response and separate them into their mechanism for killing/activity
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Phagocytes: Macrophages, Dendritic cells, Neurophils
Extracellular Mechanism: Eosinophils and Natural Killer cells Recruiters: Mast cells and Basophils |
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Which effector cells are The Killers and which are the Histamine Releasers?
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The Killers: Macrophages, Dendritic cells, Neurophils, NK cells
The Histamine Releasers: Eosinophils, Basophils, Mast Cells |
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What are the three main class of cytokines?
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1. Chemokines
- conserved cysteine patterns - form a chemical gradient to recuit and/or activate mature effector cells 2. Interleukins (ILs) and interferons (IFNs) - act locally or systematically - induce differentiation and proliferation of immature cells - induce recuit and/or activation of mature cells 3. Colony Stimulating factors (CSFs) - act locally - induce differentiation and/or proliferation of immature cells |
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What are the two detector types?
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Soluble molecules and Cell-associated molecules
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Name the soluble detector molecules
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Complement (and its compenents)
Mannose binding protein (MBP) C-reactive protein |
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Name the main Cell associated detector
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Toll-like receptors (TLRs)
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On what principle do soluble and cell-associated function. (What does innate immunity need to detect)
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Pattern Recognition (binding of common structures found in or on bacteria, parasites, and viruses)
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What is the major soluble detection system?
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Complement
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What are the 3 pathways by which complement is activated/triggered?
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Alternative pathway
Lectin pathway Classical pathway |
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What do cell surface TLR's detect?
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Polysaccharides and Glycoproteins
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What do cytoplasm TLR's detect?
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Nucleic acids (important for detecting virus INSIDE the cell)
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What is 'arming?'
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The effector cell is able to detect specific structure through their surface Fc receptor. Each Fc receptor is specific for a particular antibody, thus the arm cell become specific
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Arming of a killer cell results in...
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Antibody Dependent Cell medicated Cytotoxicity (ADCC)
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Arming of a histamine releaser results in...
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an Anaphylotoxic response (through degradation - the emptying of histamine from granules)
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Fast, first, but no memory
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Innate Immunity
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What are PAMPs?
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Pathogen Associated Molecular Patterns. This is the pattern recognized in innate immunity.
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In ADCC, what determines that action that follows when antibody binds to the Fc recpetor?
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The effector cell (the type) that is armed determines the action
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What are the 4 cell types involved in ADCC?
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Neurophils - Lytic enzymes
Eosinophils - Lytic enzymes & perforin Macrophages - Lytic enzymes & TNF NK cells - Lytic, perforin, TNF, and Granzymes |
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Antibodies are part of ________ immunity.
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Adaptive
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How does adaptive immunity differ from innate immunity?
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Adaptive immunity:
- is more specific - has more diversity - has memory |
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Why do vaccines work?
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Because adaptive immunity is specific, has diversity, and has memory.
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Adaptive response can lead to or induce by innate immunity
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True
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What are the forms of adaptive response?
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Humoral (antibody response) and Cellular
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Innate responses are unlimited in specificity and this increases the the requirement for diversity
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False. Innate responses are LIMITED in specificity, but this REDUCES the need for diversity
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Adaptive responses are highly specific, but this requires diversity
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True
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Adaptive responses are antigen-specific
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True
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What does it mean to be antigen-specific?
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The cells that response to the infection have epitope specific receptors and respond only to that or a very similar epitope
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What is colonal selection?
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Any given cell in the adaptive response has a single specificity and the antigen “selects” the appropriate one(s), thereby selecting one or more cells that will then expand clonally, i.e., all of the daughter cells will have this same specificity
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What is an antibody?
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An immunoglobulin with known specificity (this also means the antigen is known)
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The Fab defines the isotype of an immunoglobulin
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False. The Fc defines the isotype of an immunoglobulin
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Antigen is to _________ as Immunogen is to ____________.
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recognition, response
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What is an epitope?
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A small chemical structure recognized by the immune system
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What is a hapten?
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A molecule that can bind to an antigen binding site but cannot induce an immune response
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What is Specificity?
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The ability to make fine discrimination between two similar entries.
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What is the process of breaking self tolerance?
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Immune response????
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What is Diversity?
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Millions of antigen specific receptors within the adaptive immune response
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What is immunologic memory?
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Allows for secondary response to be stronger and rapid
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What is an antigen?
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Anything the effectors of the adaptive system can recognize
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What is an immunogen?
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An antigen that actually triggers a response.
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What is an epitope?
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The portion of antigen recognized
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What is a hapten?
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A single epitope (that does not elicit a response, but bind and block receptors of responding cell or antibodies)
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Are haptens immunogens?
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No. Immunogens need at last two epitopes because a single epitope (a hapten), cannot induce a response.
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Adaptive can be T-helper regulated.
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True
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B cells make antibody
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False. B Cells make differentiate to plasma cells which make the antibody
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What are the two types of CD4+ cells?
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T-helper - help activate all other effectors
T- regulatory - limit effector activity |
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Which cells are controlled by CD4+ T cells?
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CD8+ T cell (AKA CTLs)
Innate effector cells Mediate killing of target cells either directly or indirectly |
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List 3 main properties of adaptive immunity that differ from innate immunity.
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Has memory, specificity, and diversity
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What properties allow vaccines to function?
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Antigen specificity
Cross reactivity/Shared epitopes Immunologic memory Herd Immunity |
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During an infection, ________ lymphocytes react the to _________ presented to the them proliferate, and differentiate into effector cells.
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naive, immunogens
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Plasma cells make Ig_, while CD8+ make ______.
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M, CTLs
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In an adaptive immune response, the initial antibody response is mostly T ___________.
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independent
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Why is secondary adaptive response faster and amplified?
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The presence of memory cells and there are more memory cells than naive cells
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What is herd immunity?
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The fact that if the majority of a population is immune, the few that are not will be very unlikely to contact an infected individual.
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How is diversity accomplished?
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Colonal selection
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What is colonal selection?
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Any given cell has a single specificity and the antigen "selects" the appropriate cell(s), thereby selecting one or more that will then expand clonally
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Secondary response is mostly T ___________.
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dependent (T helper)
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Ig_ is the dominate serum isotype because ____________ ____________ has taken place as part of the differentiation process.
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G, Ig switching
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Whether a secondary response is generated is a function of the immunogen's ability to drive memory cell development.
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True
(antigen must be able to activate T-helper cells b/c memory cells require T-helper cells) |
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What is the difference between primary and secondary tissues?
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Primary tissues are where immature develop. Secondary is where they stay as mature cells, and undergo expansion and maturation to effector cells (Note - all early development in bone marrow; T cell PROGENITORS migrate to thymus for complete development)
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The __ defines the isotype of an immunogloblin.
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Fc
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Immune surveillance is through these circulatory routes.
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Blood - Tissue and Spleen
Lymph - Tissue and Lymph node |
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The T-cell rich and B-cell rich areas in the Speen are ________ and ________ respectively.
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PALs (Para Arteriolar lymphoid sheath); 1(prime) lymphoid follicles
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What are germinal centers?
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Serve as the point for T-helpers cell, B-cells (various maturation stages) and dendritic cell interaction. Also is where they are activated by antigen. An area of rapid lymphocyte proliferation.
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The T-cell rich and B-cell rich areas in the MALT (or Peyer Patch) are ________ and ________ respectively.
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Lamina Propria; Submucosa
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The T-cell rich and B-cell rich areas in the Lymph Node are ________ and ________ respectively.
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Paracortex; Cortex
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MALT tissues select for/preferentially recuit B cells that express IgA on their cell surface. Why?
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IgA is essentially the only Ig that is secreted into the luminal spaces and in fluids (mucus).
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What is Hematopoiesis?
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Differentiation of the cells of the blood from stem cells
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What is the difference between a stem cell and progenitor cell?
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Progenitor cells have lost their ability to self-renewal and are committed to a particular cell lineage
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Stromal cells are nonhematopoietic cells that support the growth and differentiation of hematopoietic stem cells by providing Hematopoietic Inducing Micro-environment, which includes CSFs (colony stimulating factors)
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True
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This process involves transcription factors, cytokines, cell-cell contacts as well as cell contacts with extracellular matrix material (ECM), and survival factors; proliferation, differentiation, and programmed cell death.
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True
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All of the further subdivision of types of CD4+ T cells occurs after the CD4+ T in the thymus
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False
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B cells in mammals mature in the bone marrow.
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True
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The myeloid lineage is the lineage of innate immunity and cells in this lineage cannot be activated through adaptive immune responses and the cytokines that are produced in such responses
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False
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What are monocytes?
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The blood from of macrophages that give rise to macrophages and dendritic cells
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Which cell tpes are the most widely active in infection/inflammatory response?
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Macrophages and neutrophils
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What is the function of CD3?
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on thymocytes, T and NK (part of antigen binding complex)
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What is the function of CD11-18?
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Forms of LFA-1 (integrin) that binds to CD54 (ICAM-1) on endothelial cells
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What is the function of CD25?
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alpha chain of the IL-2 recpetor
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What is the function of CD28?
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Co-stimulatory molecule on T-cells that binds B7 on APCs
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What is the function of CD152?
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aka CTLA-4; binds B7 and limits T-cell activation (compete with CD28-B7 interaction)
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What is the function of CD154?
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aka CD40L; on the T-helper; reqiored for B cell Ig switching and memory cell development
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What is the function of CD16?
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Fc receptors of NK cells
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What is the function of CD31?
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Complement receptor
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What is the function of CD40?
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Required for Ig switching, binds to T-helper cells CD40L (CD154)
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What is the function of CD45R?
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earliest B cell marker (in B cell development)
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What is the function of CD79?
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Antigen binding co-receptor with mIg
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What are the characteristics of hematopoietic stem cells?
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Self-renewal: ability to retain all attributes of itself as well as proliferation (contd)
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What are the two type of herb immunity?
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Natural and Induced
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Vaccination is about protecting only the individual.
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False. Herb immunity is about protecting the individual and the population. It works because of herb immunity.
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List the primary and secondary organs in the immune system
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Primary (delivered via blood) - Bone marrow and thymus
Secondary (delivered via lymph) - Spleen, Lymph node, MALT |
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The phagocytic effectors are controlled by ___ cells while the histamine releasers are controlled by ____ cells.
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Th1; Th2
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Cytokines serve as positive and negative feedback loops in hematopoiesis.
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True
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What is the light chains main function?
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To add diversity of antigen binding recognition.
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What is the variable region?
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Contains the hypervariable sequences (made into Ig folds) that are responsible for the diversity and provide the actual contact sites with the epitope on the antigen. Also contains that framework sequences that provide structural stability for the CDR
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What is the function of CH1 and CL (constant regions of the Fab)?
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Extend antigen binding site away from the bottom end of Ig, allowing more flexibility.
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What is the hinge region and it function?
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It adds flexibility due to high concentration fo prolines and disulfide bridges(cysteines) which ties to the two Fab regions together to make it bivalent.
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What is the function of the CH2 region?
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Contains Carbohydrates to:
a) increase solubility b) thus giving accessibility to complement to bind |
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What is the function of the CH3(and CH4)?
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True Fc region; binds to Fc receptors. Determines which cells can bind the different isotypes of Ig (also for the classification of the Igs)
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What are the functions of disulfide bonds in the Ig structure?
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Holding the two Fab regions together in the hinge region. Also to form intra-chain bonds for the tertiary structure and stabilizes the Ig folds
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What are the difference between Ig M & E vs G, A, & D Ig structures?
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M & E have no hinge region and a CH4 which make it more ridge and the Fc longer respectively.
Purpose: M & E arm cells; M arm killers; E arm histamine releasers. Prevents interference with antigen binding by other cells surface structures and the ridgity force co-localization of of receptors for better cell activation |
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What is special about IgG 3 and 4?
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3 have a longer hinge, making the Ch2 more accessible to complement binding (classical pathway). 4 is tolerizing and competes with IgE for histamine releasers (allergies?)
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Which exon are used in light chain and high chains?
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Light chains - V, J, C
Heavy Chains - V, D, J, C |
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Describe the process of Ig formation
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Heavy chain first; light chain second.
Heavy Chain: a) RAG protein cause D-J random rearrange and joining b) V-DJ joining (Light chain don't have D so just V-J joining) C) RNA splicing to remove intron and bring VDJ and C region together |
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What are RSSs?
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Recombinant Signaling Sequences; for VDJ rearrangement. Made of high concentration of A and T nucleotides. To prevent inappropriate turns, One-turn RSS (one helix) align with only Two-turn RSS (two helix turns).
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True light chain rearrangement occurs when expression of mew heavy chain protein with a surrogate light chain (pre-BCR)
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True
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What are the source of diversity in Ig formation?
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Germ line; Somatic; combinations of the heavy and light chain
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What are the source of diversity in Ig formation via the Germ line?
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Germ line
Multiple Germ line genes Combinatorial join of gern line genes Junction flexibility - variation in the actual join spot P & N region nucleotide addition |
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What are the source of diversity in Ig formation via Somatic?
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Hypermutation - nucleotide mutations that occur after B cell has fully developed. Expands antigen binding specificity and improves affinity of antibodies for antigen.
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How are sIgs and mIgs formed?
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Alternative splicing @heavy chain C region. C region contains hydrophilic then hydrophobic coding regions in that order with poly A excision site at the end of each. Cut at the first site results in hydrophilic (soluble) Ig; cut at second excision site make hydrophobic (membrane) Ig
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What are the steps involved with B-cell development?
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1. Pro B cells CD45R+ are, containing germ line genes, interact with stromal cell that release transcription factor and cytokine for B-cell survival and differentiation
2. Stromal cell release IL-7 causing IL7R+ increase and decrease adhesion molecules btw stromal and pro-B. H-chain rearrangement occurs also. Pre-B now has H-chain and surrogate on cell surface. 3.ITAMs (CD79) activate Btk which starts rearrange signal for light chain. 4. L chain rearrangement to make mIg M Now called late pre-B (immature B cell) |
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What are the positive and negative selection steps on B-cell development (in bone marrow)?
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1. Positive selection - The requirement of complete heavy chain and association of surrogate light chain
2. Positive Selection - mIg M on immature B cell (minimum threshold of antigen binding) 3. Central Negative selection - Cells with BCR (IgM already) recognizing self antigens on stromal cells can go through light chain editing (VJ rearrangements) or apoptosis if editing fails. |
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What are the positive and negative selection steps on B-cell development (in the periphery)?
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1. Positive Selection - requirement of Ig M and D(made through alternative splicing) to release
2. Negative selection - Those still with high affinity for self will bind haptens (monovalent), which decrease mIgM, causing anergy(unresponsiveness) leading to cell death |
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B cells and T cells both response to soluble and cell associated antigens.
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False. T cells can only react to a peptide bound to an MHC on a cell.
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All responses begin with ___________.
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Recognition
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What are the two key difference between T ans B cells?
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1. B cells recognize soluble and cell bound while T cell only those bound to a cell surface molecule (MHC or CD1)
2. B cells recognize non-protein containing antigens while T-cells do not |
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What characteristics affect immunogenicity?
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1. Chemical composition - higher number of epitopes leads to activation of B or T cells clone with different specificities
2. Size - B cell epitope can be sequential or non sequential amino acids while T cell only sequential. T-cells only recognize small proteins so can recognize conformational (secondary and tertiary structure) 3. Foreigness - How different from me are you 4. Ability to be processed - Needed for T helper dependent response |
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Arrange the carbohydrates, glycoprotein, lipids, nuclei acids, and polysaccharides in order of immunogenicity.
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Proteins and glycoproteins> polysaccharides>> lipids and nuclei acids
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What are the steps for B cell signal transduction?
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1. Antigen binding componen (BCR) that must be associated with ITAM (CD79).
2. The BCR must bebevalent to allow receptor aggregation, allowing for neighboring ITAM to get phosphorylated, promoting signal tranduction 2. |
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What is a TI antigen?
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Antigens that can activate B cell in the absence of T-helper cells. These are usually lipopolydaccharides and proteins with repeating structures
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What is TI-1?
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Truly T independent antigens. Example include the lipopolysaccharides of bacteria cell walls.
They are mitogenic (nonspecific inducers) Bind B cell and TLR(these recognize non-protein structures remember) |
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What is TI-2?
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TI-2 antigen are highly repetitious molecules which allow high levels of BCR cross-linking. They require T-helper cytokines to activate B cells.
Tend to be soluble proteins |
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3 main differences between TI-1 and TI-2?
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1. TI-2 are not mitogen, thus dont act a polyclonal activators.
2. TI-1 activate both immature and mature B cells while TI-2 activate only mature B cells (and inactivate immature) *3. TI-2 require the T-helper cell cytokines to activate B-cells while TI-1 is truly T independent |
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What is TD?
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TD antigen requires T helper.
They induce memory. Only few BCR bound. Tend to be proteins glycoproteins. |
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Explain the TD interaction
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Antigen and receptor internalized, degraded, and presented by Class II MHC on B cells. TCR on T-helper then interacts wit antigen on MHC. B cell also have CD40 which interacts with Th's CD40L to simulate release of cytokines for Th and cytokine receptor expression on B.
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Rank the effect of TI 1, TI 2, and TD on Ig switching
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TD>>TI-2>>TI-1
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What are the steps that occur in the Germinal center and what is the overall outcome of the entire process?
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1. Somatic hypermutation - mutations in the VJ region
2. Positive selection and affinity maturation - B cells with higher affinity to antigen on APC dendritic cells survive. 3.Ig switching - 4 Memory cell development (Overall this process creates more B cells of higher affinity) |
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Difference between Naive B cell and Memory cell.
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Naive cells have short lofe span compared to memory cells.
Through affinity maturation, memory have higher affinity for antigen Memory have higher affinity for ICAM which T-cells can bind to. Therefore, competes to drive plasma development through better antigen capturing and better interactions with T-helper cells. |
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Explain the dark zone and the light zone of affinity maturation of B cells.
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Dark zone is clonal expansion thought hypermutation and interacting with follicular APCs
Light zone - Selection of higher affinity BCRs through binding APC dendritic. Cell go through Ig switching. High affinity become plasma cells and medium affinity become memory cells. |
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Talk about Ig switching
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Its the making of isotypes other than M and D.
Requires CD40(B cell) and CD40L (Th) to make needed cytokines and signal B cell to make AID (cytodine deaminase). AID allows DNA recombination by switch sites and DNA looping |
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Ig switching involves gene excision at the RNA level
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False. At the DNA level
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Why are IgM (the D) allows the first isotypes produced?
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They are the first genes in the C region of germ line. Produced together because there is not stop codon or switch site between them.
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Membrane bound forms of Ig are never monomers.
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False. Always monomers
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_________ differences among isotype confer difference in ________.
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Structural differences; function
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That allows IgA and IgM to form multimers?
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The J-chain added to them by the plasma cell
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How is IgA secreted?
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The J-chain is recognized by the poly Ig receptor on the epithelial cell and transported across to the lumen. The J-chain is cleaved leave a secretory piece attached to the IgA.
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Why is IgM best a complement activation?
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Due to it pentameric structure, it brings the CH2 domain closers together. Since complement has 6 binding domains, more Fc CH2 present leads to stronger activation.
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What is complement?
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A set of heat liable proteins, that when activated, cause the cell to lysis.
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What are the differences among the complement pathways?
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- Neither alternative or lectin require antibody
- The alternative process does not require any host protein involvement |
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What are anaphylotoxins?
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Agents that induce basophil, eosinophil, and a mast cell degranulation which releases histamine. C3a, C5a, and C4a in complement pathways do this.
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What is an opson and what is opsionization?
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An opson is than molecule that targets antigen to induce an immune response; ***binding enhancers for phagocytosis. Opsonization is the process of coating and binding of the antigen to promote phagocytosis. (C3b and C4b)
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What are the activities of complement?
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Cell lysis - via the MAC (C5b6789)
Opsonization - ehanced phagocytosis (C3b and C4b) Immune complex clearance - C3b Anaphylotoxins - degranulation (C3a, C4a, C5a) Chemotaxis - C3a, C5a, C5b67 |
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What is immune complex clearance?
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CR 1 (upregulated by C5a) binds C3b promoting bindind to immune complexes which allow macrophages to phagocytosis them.
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Few (additional) notes on Complement Receptors
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Complement Receptors (CRs) on Effector Cells:
C3a/C4aR, C5aR induce degranulation of mast cells, basophils CR1 expression increased by C5a - binds C3b, C4b - blocks C3 convertase formation - promotes immune complex internalization CR3 expression increased by C5a - binds iC3b - promotes neutrophil extravasation |
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Describe the classical pathway
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By formation of an antigen-antibody complex involving IgM or IgG (same two that arm macrophages)
the initial C4 convertase is comprised of C1q:C1r:C1s |
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Describe the lectin pathway
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By high mannose containing structures on specific pathogens
requiring presence of a high mannose containing molecule which binds mannose binding ligand (MBL) and MASP1 and 2 to form the initial C4 convertase |
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Describe the alternative pathway
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By certain bacterial structures
Directly induce cleavage of C3 to C3a and C3b, skips the C4 convertase and starts with the formation of the next convertase, C3 convertase |
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The terminal event for all three is formation of __________, then the ____________.
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C5 convertase; MAC complex C5b:C678:6C9
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How do T cell and B cells differ?
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T cells are monovalent in have weaker binding compared to BCR
The use additional interactions to improve binding T cell only recignize antigen that are presented as a small molecule on a cell surface. |
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Alpha beta TCR respond to _________ or ___________ presented by _____________ or ___________ ACPs, which are ________(3).
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protein; glycoprotein
Class I MHC; Class II MHC Dendritic cells, macrophages, and (endothelial cells?) |
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T cells with gamma delta (g,d) TCRs (AKA gd T cells) respond to ________, _______ presented by _______ molecules
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lipids; glycolipids; CD-1
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What are the differences between Class I MHC and Class II MHC?
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Class 1 bind shorter peptides than.
Class 1 have specific terminal anchor resides whose interaction with peptides determine affinity. Bound by resides at the ends so form a convex (bugling out) shape (closed ends) Class 2 bind longer peptides that tend to be hydrophobic in the middle. Affinity in class 2 is driven by the h-bonding occurring in the middle. Bound in the center of the cleft so peptides form a conave shape (open ends) |
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Name and describe the four classes of APCs
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Class 1 MHC - present on almost all cells (CTLs & immune surveillance), CD8+, endogenous antigen peptides
Class 2 - present on professional APCs (dendritic, macrophages?), CD4+, exogenous antigen peptides CD1 - present non (B-cells) and professional APCs, (gb) T-cells & NKT respond, Glyco and phoholipids MIC - present on stressed cells, NK cells respond, carbohydrate antigens |
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What is gene polymorphism?
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Individuals having several copies and types of a gene (alleles), giving the population a very large range of antigen binding specificities.
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How does gene polymorphism influence herd immunity?
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MHC polymorphism allows for diversity of antigen recognition in the population so that at least some individuals should be immune to a particular pathogen
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What are the properties of DCs?
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They present antigen through endocytosis and phagocytosis
Constitutive expression of B7 and Class II MHC (which is why they are best APCs), and the activate naive T cells, effectors, and memory cells. |
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What are the properties of Macrophages?
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Antigen presenting through phagocytosis, induced expression of Class II MHC and B7 from little
Activate effector and memory (no naive because they require cytikines to fully activated) |
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What are the properties of B cell (as APCs)?
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Antigen presentation through Receptor mediated endocytosis
Constitutive Class II MHC and inducible B7 Can activate Naive, effector and, Memory T cells |
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Why is it important for class I to present endogenous antigens?
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Class I is expressed on almost all cells. Endogenous antigens include: defective cell proteins; tumor protein antigens; virally encoded proteins. So this represents immune surveillance.
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What is the relationship between what cells express class I vs. class II and immune responses?
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Class I is on most cells provides for immune surveillance.
Class II is normally restricted to antigen presenting cells which limits T helper cell activation and this is important because T helpers can activate essentially all of the other cells involved in immune responses. |
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What are the two antigen processing pathways and their differences?
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Endogenous Antigens = Class 1 =Cytosolic (CD 8)
Require TAP protein to transport antigen to binding cleft Only one chain plus B2 microgobulin interacts with the protein Protein degraded and added to MHC Exogenous antigen = Class II = Endocytic MHC formed first, then protein endocytosis and degradation. Invaritant chain block binding cleft till degrade to CLIP, which is later displaced by antigen |
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What are the similarities between BCR and TCRs?
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Both have:
Ig domains Variable and constant regions Disulfide bonds (inter and intra) TCR = Fab Membrane bound Both have coreceptors Both heteordimers Genes rearrange and organized similarly |
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What are the differences between BCRs and TCRs?
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TCR monovalent which Ig are divalent
TCR don't have a soluble form TCR transmembrane region is positively charged More complex coreceptors TCR require MHC, BCR don't Little to no hypermutation in TCR TCRs (of αβ T cells) only recognize peptides while BCRs can bind non-protein structures • TCRs bind to peptide antigen in association with MHC on a cell only while BCRs can bind soluble antigens • BCRs and Igs in general undergo isotype switching but TCRs do not |
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Comparing TCR and BCR gene organization, ________ and ________ plus the __________ and __________in the TCR are equivalent to _________ __________ in the BCR respectively.
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Beta chain; alpha chain
delta chain; gamma chain Heavy chain; light chain |
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TCRs genes, unlike BCR gene, undergo somatic hypermutation.
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False. TCR gene do not; while BCR gene do.
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Notch lymphoid progentiors become _____ cells and notchless become ________ cells.
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T,B
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CD__ is expressed on both resting and activated T cells and binds to __ on the APC (hence the need for high expression of it).
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CD28, B7
CD28: expressed on resting and activated T cells; binding to B7 is co-stimulatory |
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How is T cell activation regulated?
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CD28 must bind B7 on the APC to activate the T-cell. CTLA-4 binds with a higher affinity to B7 though there are more CD28 receptors. Binding of CTLA-4 inhibits T-cell activation. This competition limits response.
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What is the function of CTLA-4?
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CTLA-4: expressed only on activated T cells; binding to B7 is inhibitory
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What is the relationship between CD28 and CTLA-4?
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CD28 found on both resting and activated T cells while CTLA-4 is only on activated T cells
CD28:B7 engagement required for T cell activation and lack of it leads to T cell anergy CTLA-4:B7 engagement inhibits continued T cell activation so it triggers anergy and limits response |
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Compare B to T cell development
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• Both have an early requirement for stromal cell contact although mediated by different cell surface receptors and development of both involves losing this requirement.
• Both start with the antigen binding receptor genes in a germ line configuration that will undergo a stepwise set of recombinations to generate the two mRNAs needed for the two distinct peptides in each antigen binding receptor structure. • Both can utilize combinatorial joining of the variable region gene segments, junctional flexibility of joining between these segments, and nucleotide addition to expand the diversity of antigen specificity. • Both rearrange the genes for the more complex variable region first, that is, the one VDJ vs VJ. The joining of this to the constant region for each cell type is a critical step of positive selection; failure to do so after trying both mu heavy chain alleles will trigger cell death in B cells but failure to rearrange the beta chain will trigger rearrangement of the delta chain and generatio |
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Naive T-cell require CD 28 and B7 for co-simulation action while memory/effector T cells do not required for activation.
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True. But this interaction is needed for optimal cytokine production in memory/effector T cells.
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What is necessary to prevent runaway T cell proliferation?
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The upregulation of CTLA-4 which competes with CD28 for B7 binding.
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What determines the type of T cell developed in T cell activation?
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Dependent on thet antigen that starts the process.
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What is an effector cell?
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Any cell that when activated performs functions on another cell
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What is necessary for T-cell activation? Without these what will T-cell experience?
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T-cell activation requires antigen binding (CD3 to Class II MHC presenting antigen) and CD28 binding to B7.
Without this co simulation, the cell will experience a failure to respond aka anergy |
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Effector T cells need(and express) high cell adhesion molecules. These are ______ and ______.
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LFA 1 and CD2
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What is licensing?
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Binding of the Th cells to APC, activating the Th cell to produce IL-2 that is needed for proliferation in the Naive CTL-P.
Memory CTL-P can produce their own IL-2 when binding APC through binding TLR. Thus for them, no licensing (T independent) |
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Perfornin is _____ dependent while C9 is _____ dependent. However, there is much resemblance between the two.
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Ca2+, Zn2+
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What are the method by which CTLs kill?
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FasL engagement of Fas, TNFa bind to TNFR, perfornin-granzyme.
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What are the killing mechanisms used by NK?
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TNF to TNFR, perform - granzyme
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NK cells can produce INFg to upregulate Th1, this activating CTLs
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True
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