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66 Cards in this Set
- Front
- Back
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Mechanisms of Innate Immunity
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1. symbiotic or commensal bacteria limits attachment sites and nutrients
2. physical barrier, low pH 3. destructive enzymes (lysozymes) 4. muscocilliary escalator 5. antimicrobial peptides 6. complimentary proteins 7. ingestion by phagocytosis |
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5 Steps of Phagocytosis
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1. attachment
2. ingestion 3. fusion 4. digestion 5. release |
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3 Cellular Effectors of Innate Immunity
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1. Phagocytes (myeloid- monocytes/macrophage)
2. Mast Cells 3. Natural Killer (NK) cells |
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2 Triggers for Apoptosis
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1. Granzymes enter perforin pore
2. Fas ligand binds Fas receptor |
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Steps of Cellular Effector of Adaptive Immunity
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1. Naive lymphocyte
2. Encounter antigen 3. Proliferation 4a. Effector Cell- carry out immune functions 4b. Memory Lymphocyte- reenters and await the same antigen |
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2 Signals for B Cell activation
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Signal 1: binding of the T independent antigen to the mIg on the B cell
Signal 2: TH cell stimulated by antigenic fragment, T cell release factors that stimulate B |
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Cell:
-Circulate in blood -Differentiate into Macrophage -Migrate to site of inflammation/injury |
Monocyte
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Granulocyte:
-#1 in phagocytosis -granules: acid hydrolase, peroxidase, lysozyme -release defensins peptide -pro-inflammatory cytokines (TNFa, IL1, 6, and 8) |
Neutrophils
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Granulocyte:
-granule: histamine, neutral protease, heparin, and TNFa -IgE receptor -type I immediate hypersensity (allergy) -allergic inflammation cytokine |
Basophils
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Granulocyte:
-high affinity IgE Fc receptor -response to parasites; asthma -immediate hypersensitivity reactions -inflammatory response -express MHC class II molecules -differentiation factor cytokine |
Eosinophils
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Granulocytes:
-similar to Basophils (on mucousal surface) -granules contain tryptase -allergic inflammation cytokine |
Mast Cells
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Cells:
-most important APC -immature cell phagocytose antigens -migrate to draining lymph node w/ antigen -cell matures and processes antigen (MHC class II) -present T cell -can also present lipid, glycolipids using CD1 -produce cytokines: IL1b, TNFa, IL12 -regulation of TH1/TH2 balance |
Dendritic Cells
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Cells:
-present in follicles and germinal centers of lymphoid tissue -non-phagocytic -lack MHC class II proteins -extensive surface for binding Ag-Ab complexes -present antigen to B cells during antibody affinity maturation |
Follicular Dendritic Cells
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Cluster of Differentiation:
-T cell surface marker -65-70% -T helper cells -binds to MHC class II on APC and helps T cell recognize it -Fas/Fas ligand to induce apoptosis |
CD4
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Cluster of Differentiation:
-T cell surface marker -25-30% -cytotoxic T cell -binds to MHC class I molecules -produce IFN gamma activating macrophage -perforing and granzymes to induce apoptosis |
CD8
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-CD4+ T lymphocytes
-secrete IL-2, IFN gamma,TNF beta -differentiation inhibited by IL10 -IL12 secreted by macrophages, dendritic cells and neutrophils favor development -Intracellular Pathogens |
TH1
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-CD4+ T lymphocytes
-secrete IL4, IL5, IL6, IL9, IL10, IL13 -stimulate antibody production (B cell growth) -differentiation inhibited by IFN gamma -development stimulated by IL4 -mediate opsonization/destruction of extracellular pathogens |
TH2
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-Lymphocyte cells that lack TCR and BCR
-thymus independent -Part of innate immune system-rapid response -Have Fc receptors; can kill by ADCC -produce IFN gamma in the early response, directing T cell immune response away from TH2 |
Natural Killer Cells
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Organ:
-produce hematopoietic cells -mature leucocytes migrate out via the central vein -some stromal cells secrete cytokines |
Bone Marrow
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Organ:
-T lymphocytes complete their maturation -positive selection: capable of recognizing MHC-antigen complex -negative selection: binding to self antigen |
Thymus
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Organ:
-Filtration of pathogens and old/damaged cells from blood -"white pulp"- dendritic cells, lymphocytes -Phagocytosis of damaged RBCs, senescent granulocytes -Platelet storage |
Spleen
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Organ:
-encapsulated -drain specified body regions -lymphocytes enter Peyer's patches through post-capillary venules -During antigenic stimulation, entry rates increases resulting in lymphadenopathy -FDCs capture antigen in immune complexes complexes for presentation to B cells -Naive antigen-specific T and B lymphocytes |
Lymph Nodes
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Organ:
-To protect against microbial invasion and internalize exogenous antigen for priming immune cells -Composed of: mucosal barrier, organized lymphoid tissue along GI tract, dispersed lymphoid cells within epithelium -Follicles with germinal centers and B lymphocytes -Interfollicular T lymphocyte regions -Produce IgA |
Mucosa Associated Lymphoid Tissue
(MALT) |
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Cells:
-intestinal epithelial cells -transport antigens and microbes to MALT |
M cells
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Antigen specific T cells become activated, proliferate and differentiate to recognize antigenic fragments derived from products made by the intracellular organism presented on MHC molecules
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Cell Mediated Immunity
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4 Phases of Delayed-type Hypersensitivity (DTH)
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1. Induction
2. Inflammatory 3. Effector 4. Chronic |
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-Selective elimination of infected cells
-CD8+ cytolytic T cells (Killer Cells) -ADCC |
Cell Mediated Cytotoxicity
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-a family of proteins and proteolytic fragments
-react with foreign bodies and label it for destruction -regulatory proteins on membranes of host cells or in serum that protect the host's cells from accidental self-inflicted damage -cell surface receptors that bind to products of complement activation and leads to host cell participation in inflammatory/immune response |
Complement
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Pathway:
-activation by Ag-Ab complex -C1 binds multiple Fc regions simultaneously -activation of C3 or C4 near activator's surface or Ag-Ab complex and leads to covalent binding of C3b or C4b to the surface proteins/carbohydrates |
Classical Pathway
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Pathway:
-activation in the absence of antibody -spontaneous activation of fluid-phase C3 on biologic membrane 1. near appropriate surface C3(H2O) binds covalently to surface 2. stabilized by Properdin 3. destabilized by Factor II (sialic acid prevents further cascade after C3(H2O) is produced |
Alternative
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Pathway:
-Binding of Mannon-binding-lectin (MBL) -Mannose or N-acetylglucosamine on microbes to initiate complement cascase |
Lectin Pathway
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Organs:
-secondary follicle -site of B cell differentiation 1. immunoglobin isotype switching 2. clonal expansion 3. affinity maturation |
Germinal Center
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Complement Receptor:
-on myeloid cells during inflammation -chemotaxis of myeloid cells to site of production -increase adhesiveness of myeloid cells to endothelium -activate respiratory burst (superoxidem NO, etc.) -increase vascular permeability -hemorrhagic necroses of tissue (w/ TNF) |
C5aR (CD88)
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Complement Receptor:
-promotes cellular uptake of complement containing immune complexes -clears immune complexes (Ag-Ab) from the circulation |
CR1
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Complement:
-Virus Neutralization -Antibody forms immune complexes -Complex C3 sterically blocks virus cell binding site -Opsonizes virus for phagocytic killing -Complement mediated lysis of infected cells -Viruses with lipid envelope susceptible to disruption |
C5b-9
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Complements:
-Anaphylatoxins -Diffusible fragments -Trigger de-granulation of mast cells -Smooth muscles: contract or relax (dose dependent) -Vasodilation (increase blood flow) -increase capillary permeability -increase CR1 and CR3 expression by neutrophils, thus increase opsonization activity |
C3a, C4a, C5a
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Antibody:
-5 to 10% of total serum immunoglobin -first isotype secreted in the immune response -expressed on primary B cells -low affinity/high avidity -strong activator of complement cascade -does not bind to FcR on phagocytic cells unless involved in antigen-antibody-complement reaction -does not pass the placenta -does not pass the blood-brain barrier |
IgM
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Antibody:
-80% of total serum antibody -directly inactive viruses -neutralize bacterial toxins -activate complement -binds to FCR -able to cross placenta -able to cross blood-brain barrier |
IgG
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Antibody:
-10% to 15% of total serum -dominant in secretions: tears, saliva, GI tract -secreted from plasma cells in the submucosa and transported onto mucosal surface by poly-Ig receptor (pIgR) |
IgA
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Antibody:
-bound by high affinity -FceR1 present on tissue based mast cells and basophils -function in immune response to parasitic worms |
IgE
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Antibody:
-No known function |
IgD
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Definition:
Non-response to self antigens |
Tolerance
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Definition:
-antigenic determinants -small portion of the antigen that binds specifically to the antibodies and TCR |
Epitope
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Definition:
-small single antigenic epitopes that bind specifically to antibodies -"incomplete antigens" -must be conjugated to a carrier to be immunogenic |
Haptens
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3 Factors affecting immunogenicity
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1. Molecular size
2. T cell interactions 3. Dose/ route of administration |
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Definitions:
-function as polyclonal stimulators of T cell subsets -exogenous: exotoxins produced by gram+ bacteria; some viruses |
Superantigens
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Definition:
area of interaction between an APC and a T cell where ligands and MHC-antigen interact |
Immune Synapse
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-cytokine produced by platelets, lymphocytes, activated monocytes/macrophages, granulocytes
-fast acting -mediate inflammation -induce phagocytes to produce toxic oxygen intermediates -chemo-attraction: regulate movement of leukocytes -alter cell morphology |
Chemokines
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Definition:
-coordinate the innate and acquired immune response -soluble proteins -secretion is brief and limited |
Cytokines
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Definition:
Have different biological activities when bound to different cell types |
Pleiotropism
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Definition:
different cytokines may produce similar effects |
Redundant
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Definition:
influence production and action of other cytokines |
Antagonistic, Additive, and Synergistic
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Definition:
induce or inhibit the production of other cytokines |
Regulatory networks
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Definition:
act on the cell which secreted them |
Autocrine
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Definition:
act on a nearby cell |
Paracrine
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circulate in blood and have a systemic effect (e.g., IL-1, TNFa)
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Endocrine
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Interferon:
-secreted by macrophages and virus-infected cells -inhibit viral replication, increase MHC Class I -Inhibit protein synthesis |
Interferon type 1: alpha and beta
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Interferon:
-secreted by T cell and NK cells -effector of immune response, activate other cells |
Interferon type 2: gamma
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7 steps to nterferon type 1 signaling
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1. dimerization of receptor on contact with the cytokine
2. activation of JAK (kinase) and phosphorylation of receptor "tail" 3. STAT dimerization 5. tranlocation to Nucleus 6. Changes in Gene expression 7. SOCS gene activate and SOCS binds to JAK and turns off the signal |
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Receptors:
-component of the innate immune system -recognition pathogen-associated molecular pattern (PAMPs) -Structurally-related to the IL1 receptor |
Toll-like Receoptors
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characteristics of pathogens
-dsRNA -LPS (Lipo-polysaccharide) -flagellin |
Pathogen-Associated Molecular Patterns (PAMPs)
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Interleukin:
-required for T cell activation |
IL-2
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Cytokines:
-secreted by TH1 which promotes cell mediated immunity |
IFN gamma, TNF, IL-2
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Cytokines:
-secreted by TH2 to activate humoral immunity |
IL-4, IL-5, IL-10
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Gene transcription is activated based upon the sequence-specific binding of a transcription factor to the promoter, located upstream of the gene. This protein recruits _________ to assemble the transcription complex (~15-20 proteins)
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Accessory Proteins
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Gene transcription is repressed based upon the sequence-specific binding of a transcription factor to the promoter, located upstream of the gene. This protein recruits additional _____________ which physically block access to the DNA and prevent transcription.
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Co-repressor Proteins
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