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118 Cards in this Set
- Front
- Back
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Pathogens contain what on their cell surfaces that are recognized by Macrophages?
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PAMPS or DAMPS which activate Macrophages
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What do macrophages have on their cell surface to recognize PAMPs?
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TLR bound with CD14 and LPS
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The binding of mannose results in what?
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Phagocytosis of the microbe into the phagosome which results in death
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What does the binding of TLR-4 result in when bound to a microbe?
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Phagocytosis
NOS and ROS Cytokine release (IL-12 & TNF) Fibrinogen |
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How do macrophages phagocytose?
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NADPH oxidase
Myeloperoxidase or Lysosomal Contents |
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Chronic Granulomatous Disease?
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The loss of NADPH oxidase.
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Cytokines stimulate what?
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Inflammation
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Chemokines stimulate what?
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movement of leukocyte from blood to tissue
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What are the endogenous Pyrogens?
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IL-1
IL-6 TNF alpha |
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What does IL-6 stimulate?
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An acute phase response by the generation of Mannose Binding lectin, Cq protein, and fibrinogin
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Explain how neutrophiles get to the site of infection and get into the tissue?
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Once a foreign microbe is in the body macrophages secrete IL-1 and TNF alpha which stimulate the upregulation of selectin on the endothelial surface. This allows for rolling of the neutrophile. Then the neutrophile contains ligand on its cell surface that recognizes Ligand receptor stimulated by IL-8. Diapedisis results
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Leukocyte Adhesion Deficiency?
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Lack CD18 so no extravasation occurs. there will be no pus formation due to no neutrophile diapedisis into the tissue. Bacterial infections are reccurent
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NK-cells are activated by what?
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IL-12
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What are NK cells best at fighting off?
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Intracellular infections such as viruses and Cancer
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How do NK cells fight intracellular infections?
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By use of Granzymes and Perforins
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What activates Complement?
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IgM and IgG
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What are our anaphylotoxins?
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C3a/ C4a/ C5a
These induce an immune response by increasing capillary permeability |
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What inhibits the complement cascade?
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C1 inhibitor
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What is the primary inactivator of C3b and C4b?
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Factor I can bind to:
C4b-BP CR1 MCP DAF |
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What is the common receptor that causes the Epstein Barr Virus?
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CD 21
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What prevents MAC formation?
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CD 59
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Hereditary Angioedema?
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Lacks C1 inhibitor which causes spontaneous complement activation leading to severe inflammatory responses
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What does C3b contribute to?
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Opsonization or the contribution to form C5 Convertase
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How does the innate immune response innitiate the addaptive immune response?
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By:
Proccessing and presenting the peptide to the T-Cell Generation of surface molecules that function as co-stimulatory signals with antigen to activate B and T lymphocytes |
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Where is the central lymphoid tissue?
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Bone Marrow and Thymus
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Where is the Peripheral lymphoid tissue?
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Lymph nodes
Spleen Tonsils MALT This is where the adaptive immune response is initiated |
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How do B and T cells migrate into the Lymph node?
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High endothelial venule
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What is contained in the paracortex of the lymph node?
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Macrophages, T-Lymphocytes, and dendritic cells
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What is contained within the Follicle of the Lymph node?
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The follicle is also known as b cell zone and contains the B cells
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What is located in the PALS of the spleen?
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Dendritic cells and T-lymphocytes which surround the central arteriole
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What is found in the follicle of the spleen?
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B-Cells
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What is both the PALS and the Follicle of the spleen known as?
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the White Pulp
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Where are macrophages found in the spleen?
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Red Pulp
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Where are MHC I found?
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All nucleated cells
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Where are MHC II found?
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Professional APC
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How many binding sites are available on a B-cell?
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2 binding Sites
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What allows intracellular signaling of the B-Cell Receptor?
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Ig alpha and Ig beta
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Each site of the variable region of an immunoglobbulin contains what?
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1 variable region light chain and 1 variable region heavy chain
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What enables variability in a constant framework in BCR?
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Having 3 hypervariable regions with 4 framework regions. The Hypervariable regions are 3 loops that are furthest away from the constant region.
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What are Isotypes determined by?
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Isotypes are determined by the constant region of the heavy chain
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What are the Allotypes determined by?
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The constant region of the light and heavy chains
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What is the idiotype determined by?
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Determined by the antigen binding sites. the hypervariable region is distinct and unique to the specific antigen.
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How many antigen binding sites are present on the TCR?
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There is only 1 single antigen binding site
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What are the co-stimulatory factors for a TCR?
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1 alpha and 1 beta chain
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What does TCR form a complex with in order for signal transduction to occur?
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CD3
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CD4 is found on what and what do they bind to?
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Helper T cells and they bind to MHC II cells which are only found on APC
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CD8 is found on what and what do they bind to?
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CTL and they bind to MHC I which are found on all nucleated cells
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Explain the proccess of peptide loading for MHC I?
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An intracellular pathogen is ubiqunated and sent to the protesome to be chopped up. Once chopped up in the cytosol it is transported through the TAP protein into the ER where it is placed on the MHC I and shipped to the Golgi. From there it is exocytosed to the surface of CTL's
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Explain the proccess of peptide loading for MHC II?
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A pathogen is phagocytosed into the cell and broken down in the lysosome. At the same time the MHC II is being formed in the ER and stuck with an Invarient Chain and shipped to the golgi where it is then shipped to fuse with the phagosome. In the Phagosome HLA-DM degrades the invarient chain and places the peptide into the MHC II. It then is exocytosed to the cell surface to be expressed to T helper cells
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Bare Lymphocyte Syndrome?
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Where the TAP protein is missing so no transport of peptide from Cytosol to ER to be loaded onto class I MHC. Or it can be a defect in CIITA for MHC class II
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MHC I Isotypes?
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HLA-A
HLA-B HLA-C |
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MHC II Isotypes?
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HLA-DQ
HLA-DR (Most Variable) HLA-DM |
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What increases diversity for MHC's?
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Polymorphism and Polygeny
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What occurs in the Early Pro B Cell?
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The Rearrangement of the DJ region of the heavy chain
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What occurs in the Late Pro B cell?
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The rearrangement of the V with the DJ heavy chain.
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What occurs in the Pre B cell?
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The Light chain rearranges. There are 4 chances to get it right
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What happens with the Immature b cell?
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the appearance of IgM and IgD are present on the cell surface
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What is essential to express for B cell survival?
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IL-7
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T-Cell maturation occurs in what direction in the thymus?
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It matures from the Cortex to the Medulla
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What is the first to rearrange in the T-Cell receptor?
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The Beta chain is the first to rearange and then the alpha chain
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What is a double negative T-lymphocyte?
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When neither CD4 or CD8 is expressed on the cell surface
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What is a double positive T-lymphocyte?
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When the T-lymphocyte expresses CD4, CD8, and CD3 on its cell surface along with a surrogate chain.
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How do we move past the pre-TCR phase?
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The T-cell tries out the Pre-TCR to see if it works and if it does then it rearranges the alpha chain.
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What is a single Positive T-lymphocyte?
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When it expresses only CD4 or CD8 along with CD3
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What is B-cell tolerance?
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In a nut shell if the B-cell recognizes self as antigen it is detained in the bone marrow. if it does not it will then move to the blood to express IgM and IgD.
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Soluble antigen?
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This is when the recognition of self antigen has occured but the b-cell migrates out into the peripheral without IgM and only expression of IgD
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T-Cell Positve Selction?
T-Cell negative selection? |
Positive- needs to recognize self MHC
Negative-needs to not be activated by self antigen |
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What happens to T-cells that recognize self antigen?
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They will migrate to the periphery and become regulatory T-cells
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What are the 2 signals that must occur in order for T-cell activation?
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MHC with peptide
B7(APC) binding to CD28 (T-cell) |
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Upon infection what do dendritic cells upregulate on their cell surface?
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B7
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What does the APC secrete to increase affinity of binding when it has an antigen peptide to present?
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It presents a chemokine
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What do APC secrete to stimulate formation of TH-1 cells? To increase proliferation?
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They secrete IL-12 to stimulate formation of TH1 and IL-2 to stimulate the increase of proliferation
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What is the "On Switch" for proliferation and differentiation?
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The phosphorylation of ITAMS by kinases. This will enable the interaction between CD4 and MHC II
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Effector T-cells do not need what at the site of infection in order to perform their function?
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They do not need CD28 and B7 binding
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What is the autocrine secretor of T-cells?
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IL-2
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What are the 2 functions of CD4+ T-cells?
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Go to tissues to activate macrophages and activate B-cells to secrete plasma cells so they can secrete Immunoglobbulin
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T helper 1 secrete what for what purpose?
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INF gamma to inhance macrophage killing and to increase B-cell secretion of IgG to increase opsonization and phagocytosis. These fight Intracellular Microbes
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T helper 2 secretes what for what purpose?
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IL-4 to increase secretion of IgG and IgE to kill Helminth worms
IL-4 and IL-13 to cause Macrophage tissue repair IL-5 Eosinophile activation |
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T helper 17 secretes what for what purpose?
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IL-17 and IL-22 to secrete antimicrobial peptides and mobilization of neutrophiles to the infected site. Good for bacterial and fungal infections
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APC secrete what to increase T helper 1 cell proliferation?
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INF gamma and IL-12
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APC secrete what to increase T helper 2 cell proliferation?
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IL-4
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APC secrete what to increase T helper 17 cell proliferation?
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TGF-beta
IL-6 IL-23 |
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How do Naiive T helper cells get in secondary lymph tissue?
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They have a high amount of L selectin being expressed which binds to L selectin ligand on the high endothelial venule in the lymph node
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How do effector t-cells excape the secondary lymph tissue to travel to the site of infection?
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They dowm regulate their L Selectin and upregulate their E or P selectin which allows them to leave and then bind to the E or P selectin ligand at the site of infection
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What are the two things that are needed at the site of infection that will lead to macrophage activation by t-cell?
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CD40 on the macrophage must bind to CD40 ligand on the t-cell which will increase INF gamma receptor on macrophage. We must also have IFN gamma from our t-cells
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What forces naiive CD4 t-cells in the lymph nodes to differentiate into T helper cells to go to the site of infection to help?
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IL-12 will do this so the t helper response at the site of infection will increase
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IL-12 and INF gamma ar inducers of what?
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An inflammatory response!!!
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CTL's produce what to increase MHC I expression on infected cells?
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IFN alpha and IFN beta
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What do memory cells have to express in order to survive?
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IL-15
IL-7 |
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What is the difference between TD antigen and TI antigen?
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TD antigen- the first signal comes through the BCR and the second comes through the binding of a T-helper cell
TI antigen- antigen and costimulatory signal are provided WITHOUT T-helper cells |
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What do follicular B-cells (TD) recognize? What do they secrete?
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They rocognize Protein antigen + Hellper T-cells
They secrete IgG, IgA, IgE |
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What do marginal B cells (TI) recognize? What do they secrete?
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They recognize polysachrides and lipids
They secrete ONLY IgM |
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What makes up the B-cell co receptor complex?
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CD-19, CR2, and CD 81
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How does the Co receptor complex bind to the BCR?
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Through cross linking of complement with CR-2 (CD-21)
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What does the co receptor complex binding to the BCR initiate?
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This will lead to signal transduction by the cleaving of the CD19 by Tyrosine Kinase
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In TI-1, LPS or carbohydrates bind to the BCR to induce what?
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High levels--> Poly clonal b-cell activation
Low levels-->IgM production |
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In TI-2, what initiates the first signal? What about the second signal?
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First Signal-generated by the BCR binding of the epitope on pathogen
Second signal-generated through C3d binding with CR2 (CD21). This causes massive amounts of cross-linking |
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Primary signal for B cell activation is?
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Epitope
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Secondary signal for B-cell activation is?
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T helper cells via CD40:CD40 L
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Explain how B-cells interact with T-cells in the lymph nodes to become activated?
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The antigen flows through the lymph and is taken up and presented by the dendritic cell to T-cells causing a formation of T helper cells to form. Some B-cells interact with T helper cells causing proliferation of B-Cell with the same affinity for that antigen
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2 signals needed to activate B-Cells?
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Antigen binding to BCR
Interaction between CD40 on B cell with CD40 L on the Th cell |
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Explain the process of B-Cell affinity?
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A B-lymphoblast interacts with a T helper cell to become a centeroblast in the dark zone. This is where hypermutation occurs to increase affinity. The centeroblast leaves the dark zone to enter the light zone to become CENTROCYTES. The Centrocytes interact with the FDC. When this happens they move to the outer region to engage T-cells for activation
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How does Isotype switching occur?
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B-cells originally express IgM and IgD without ever being exposed to antigen. Once they have been exposed they can undergo isotype switching causing the secretion of IgA, IgE, and IgG.
THIS REQUIRES CD40:CD40L |
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After CD40:CD40L what is secreted to initiate IgG?
IgE? IgA? |
IFN-gamma-->IgG-->tons
IL-4-->IgE-->helminths TGFB-->IgA-->Mucosal |
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What is first wave?
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B-cells are activated by T-cells and then move to the medulla of lymph node to create plasma cells to secrete IgM
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What is second wave?
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Some of the B-cells migrate to a follicle to form germinal centers where hypermutation occurs. The ones with great affinity are secreted to the bone marrow to create the second wave of defense.
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Upon secretion of IL-10 from Th cells what occurs?
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Centrocytes differentiate into plasma cells
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Upon secretion of IL-4 from the T helper cell what occurs?
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Centrocyte differentiates into memory cells.
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Antibodies are only effective against what?
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Extracellular pathogens
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What are the 2 purposes of Fc region on antibody?
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Deliver antibody to inaccesable sites
Links the bound antigen to the destructive cells |
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Anitbodies are responsible for what? (4 things)
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Neutralization
Opsonization with phagocytosis Cytotoxicity Complement activation |
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Free antibody binds to FcR with what kind of affinity? What about Ab-Ag?
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Low affinity
High Affinity |
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IgG coats pathogens and binds to what on phagocytes in order to be phagocytosed?
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Binds to Fc gamma
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NK cells can kill without?
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Signal transduction
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How does IgG get form the blood to tissue?
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By binding to the Brumbell receptor and then trancytosis
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How does IgA get to the luminal side of the cell?
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By being trancytosed with a Poly-Ig receptor
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How does the IgA stay bound to the luminal surface after transcytosis?
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By being bound to the secretory piece
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Maternal Ig?
Breast milk Ig? Ig produced at birth? Present 6-12 months post birth? |
IgG
IgA IgM IgG and IgA |
