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34 Cards in this Set
- Front
- Back
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Cells of the innate response
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Mostly from myelopoiesis!
- Neutrophils, Monocytes are key! - Also Basophils, Eosinophils (parasites), Mast cells (from monocyte, allergies), dendritic cells (from monocyte), Natural killer cells, interferons |
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Monocyte overview
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2-10% of leukocytes
- Monocytes in circulation, differentiate in tissues (to macrophages) - Phagocytic - not as active as neutrophils (PMN's) - Roles in both innate and adaptive immune responses - Innate - recognize infection exists, migrate to site, recruit neutrophils, phagocytize some debris - Adaptive - pick up antigens from lysed cells, present them, activate lymphocytes |
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Neutrophil overview
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AKA PMN's = 40-60% of leukocytes (most abundant)
- Short 1/2-life = 1-2 days - Active phagocytes - 30-fold reserve in marrow - Major role of innate response - phagocytosis/destruction of bacteria |
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Elements of Innate Response
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Recognition, containment, amplification, elimination, control
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Innate response mechanism steps
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Monocyte makes way into CT, differentiates, hangs out waiting
- Recognizes surface elements unique to bacteria - distinct from "self" - Phagocytic receptors bind, internalize, degrade bacteria - Receptors for bacterial components induce production, release of cytokines - Cytokines induce release of neutrophils from marrow -> follow cytokine gradient to affected area - Cytokines also induce increase vascular permeability, easier access - Neutrophils enter tissue, phagocytize/destroy bacteria, then die - Macrophages engulf/degrade dead neutrophils - Continued cytokine production/release throughout response - increased production/release of neutrophils |
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Neutrophil phagolysosome mechanism
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Bacteria phagocytosed by neutrophil
- Phagosome (enclosing bacteria) fuses azurophilic/specific granules - pH of phagosome rises, antimicrobial response kills bacteria - Lysosomes fuse with phagosome, pH rises - Acid hydrolases degrade bacteria completely - Neutrophil apoptosis, phagocytosed by macrophage - Pus = dead neutrophils that took out bacteria |
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Cells of adaptive response
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Main players = Lymphocytes (T- and B- cells)
- Macrophages, dendritic cells - signal T-cells, help get things started |
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Lymphopoiesis
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Production of B- and T- cells
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B-cell production process
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Leave marrow almost mature
- Have ability to recognize antigens - Produce antibodies in response to antigens (pathogens) |
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T-cell production process
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Leave marrow as immature precursor cells
- Enter thymus, develop ability to recognize antigens - Leave thymus with specific functions |
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T-cell types
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TH-helper, CD4 (TH1, TH2)
- Tc-cytotoxic, CD8 - Treg - regulatory - TH17 |
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Organs of lymphoid system
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Primary and secondary
- Primary = site of development = marrow, thymus - Secondary = residence = spleen, lymph nodes, appendix, tonsils, Peyer's patches |
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Lymphatic circulation
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Lymphocytes = leave blood, enter nodes, efferent lymph vessels -> return to blood
- Pathogens = Transported to lymph nodes, activate immune response |
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Lymph node originating response
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Resident B-cells (germinal centers) interact with T-cells
- B-cells begin to divide, germinal center gets larger - B-cells enter circulation, release antibodies - Only specific B-cells activated, releaed - specific response! |
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Interface between innate and adaptive responses
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Dendritic cells pick up pathgens/particles, travel to lymph nodes (secondary tissue)
- Act as APC to T-cells, activate T-cells - T-cells follow cytokine gradient to affected area - T-cells also interact with, activate B-cells - Dendritic cells cannot dispose of bacteria/fragments, however! - Macrophages in the lymph nodes phagocytose bacteria/particles - Macrophages also act as APC's, activate T-cells |
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B- and T- cell receptors
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B-cells = Y-shaped antibodies (Ab) or Immunoglobulins (Ig) on surface
- Very specific to only certain antigen (Ag) - T-cells = column shaped receptor - also very specific to only certain Ag |
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Antigen types
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Can be any biomolecule - protein, lipid, carbohydrate, nucleic acids
- Haptens - molecules that are too small by themselves to generate immune response - Bind to carrier protein = seen as "foreign", elicit response - Penicillin - too small normally - binds to RBC proteins - becomes ID'able foreign entity - Any small chemical/medicine can become hapten, elicit immune response |
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Immunogenicity
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Not all proteins equally good at producing immune response
- Certain portions more likely to generate response, others not very likely |
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Elements of Adaptive Response
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Recognition, containment, amplification, elimination, control (pathogen & turning off response), MEMORY
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B-cell antigen recognition
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Ab on B-cell surface recognize native (unprocessed by APC) antigens on pathogen surface
- When activated, produces same Ab as the one that matched native Ag |
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B-cell response
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Ag-specific receptors (membrane Ig) on B-cells
- IgM and IgD = surface Ig's of naive resting B-cell - Binds antigen, internalizes, B-cell activated - Produces, releases lots of IgM corresponding to Ag - IgM = has no memory - like innate response! - Digestion event - allows B-cell to interact with Helper-T-cell - Helper T-cell releases cytokines - induces B-cells to change isotypes - IgE = parasites, IgA = mucosal regions, etc. - T-cell interaction also signals differentiation of B-cells -> antibody factories or memory cells |
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B-cell T-cell interaction
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Process essential for Isotype switching, making memory B-cells
- B-cell surface Ig binds bacteria/fragment - B-cell engulfs, degrades bacteria into peptides - Peptides bound to MHC class II in vesicles - Bound peptides/MHC class II complex travels to B-cell surface - Helper T-Cell recognizes MHC class II/peptide antigen complex, activates that B-cell |
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Antibody-mediated defense
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Opsonization - "preparing to eat" - like putting ketchup on french fries
- Antibodies from B-cells bind to bacteria they recognize - Macrophages will phagocytose those bacteria because they are bearing the antibodies |
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Complement system
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Original innate response
- Bacteria get coated with C3B molecule - C3B is opsonin - marks the bacteria as something to "eat" - Macrophages with CR1 receptor recognize C3B, phagocytose bacteria |
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Response against toxins
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Ab to bacterial toxins produced by B-cells, float around
- Toxin bound up by Ab, complexes recognized, phagocytosed |
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T-cell Ag recognition
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T-cells don't recognize "native" Ag
- Only recognize things when presented in the MHC protein |
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T-cell response mechanism
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MHC restriction - T-cell learns in thymus to only recognize things within the MHC complex
- MHC = major histocompatability antiges - Class II - only professional APC's - Class I - present on every nucleated cell in body - any infected cell presents antigens via class I - Some pathogens (viruses) block MHC class I - try to evade immune response |
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T-lymphocyte role education
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Enter thymus with no surface receptors
- Interact with MHC class I and II in thymus - determine stronger affinity for one - Affinity helps determines T-cell fate |
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Types of antigens
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All processed, presented by APC's
- Exogenous = Extracellular, intracellular - Extracellular - pathogen derived, plant derived, artificial, etc. - Intracellular - pathogen Ag inside phagocyte - Endogenous = Synthesized by host cell machinery = viral products |
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Professional APC's
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Macrophage, Dendritic cell, B-cell
- Interact with T-cells via MHC class II |
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MHC class I response
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Fragments of viral protein bind to MHC class I in ER
- Shipped to cell surface - cytotoxic T-cell recognizes MHC class I complex, kills cell - Binding of cytotoxic T-cell tells cell to undergo apoptosis - Also releases granules of proteases, pore-forming proteins to kill cell |
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MHC class II response
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Macrophage engulfs/degrades pathogen or dead neutrophil
- Bacterial peptides bind to MHC class II in vesicles, go to surface - Helper T-cell recognizes MHC class II - Dendritic cells also present via MHC class II |
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MHC importance reasons
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Influences development of lymphocytes, T-cell repertoire, adaptive responses
- Plays key role (when things go wrong) with organ transplants, autoimmune diseases |
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Clonal selection hypothesis
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- All lymphocytes that recognize "self" are eliminated early to prevent auto-immune problems
- Each lymphocyte bears single receptor with unique specificity - Interactions with pathogens only activate small fraction of cells recognizing specific Ag - When activated, T-cells and B-cells multiply to make clones responding to same Ag - Clones all bear identical receptor to parent cells |
