Immunology

Chapter 2 Innate Immunity: the immediate response: Disease is determined by what 4 factors?

1. Disease is determined by • species specificity Yur dog might get sick but u don't. u don't have the receptors for attachment. • infectious dose If you're exposed to too little of the infection that is needed, you won't get sick. • persistence outside the host Can't survive very long outside of the host, then they won't survive very long outside of host. EX: STD's • ability to spread in the body after invasion If they can go beyond local tissues, they will be more dangerous

Chapter 3 Innate Immunity: the Induced Response to viral infections: What are the two types of NK cells?

2 types of NK cells CD56 - A protein on NK cells that tells us if the cell has this protein it will be NK cell. Allows us to identify an NK cell. Two diff types on cell surface: CD56 Bright (a lot of protein on surface) - Good at making cytokines. The majority of NK cells that have migrated in to tissues are Bright. CD56 Dim (not as much protein on surface) The majority of NK's in the blood are dim. They're good at killing virus infected cells.

Chapter 2 Innate Immunity: the immediate response: Recovery from an infection is determined by:

2. Recovery from infection is determined by • killing the pathogen, so it can't replicate. • clearance If not cleared, the antigen will still warrant a response, and we will respond with inflammation etc. It is cleared with macrophages etc. • repair of damage

Chapter 3 Innate Immunity: the Induced Response: Define Lysosome:

A Lysosome is an organelle in the cytoplasm of eukaryotic cells containing degradative enzymes enclosed in a membrane. They fuse with phagosomes during Receptor-Mediated Endocytosis.

1-8 Immunoglobulins and T-cell receptors are the diverse lymphocyte receptors of adaptive immunity: Hematopoietic Cells: What is a Plasma Cell?

A fully differentiated form of B cell that secretes Antibodies.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Generation of immunoglobulin diversity before B cell encounter with antigen: Explain Gene rearrangement to generate antibody specificity:

A gene rearrangement is a structural alteration of a chromosome that causes a change in the order of its loci. (gene rearrangement gives us the many different Variable regions of the immunoglobulins) Made V D and J choice and brought them together. D and J choice brought together. V choice Is brought together. Only one choice from each. Book: V-region sequences are constructed from gene segments. Light-chain V-region genes are constructed from two segments (left panel). A variable (V) and a joining (J) gene segment in the genomic DNA are joined to form a complete light-chain V-region (VL) exon. After rearrangement, the light-chain gene consists of three exons, encoding the leader (L) peptide, the V region, and the C region, which are separated by introns. Heavy-chain V regions are constructed from three gene segments (right panels). First the diversity (D) and J gene segments join, then the V gene segment joins to the combined DJ sequence, forming a complete heavy-chain V-region (VH) exon. For simplicity, only the first of the heavy-chain genes, Cμ, is shown here. Each immunoglobulin domain is encoded by a separate exon, and two additional membrane-coding exons (MC, colored light blue) specify the hydrophobic sequence that will anchor the heavy chain to the B-cell membrane.

1-7 Cells of the immune system derive from hematopoietic cells: What are Leukocytes?

A leukocyte is a colorless cell that circulates in the blood and body fluids. They are involved in counteracting foreign substances and disease; a white (blood) cell. There are several types, all amoeboid cells with a nucleus: including lymphocytes granulocytes monocytes macrophages.

1-5 The adaptive immune response adds to an ongoing innate immune response: Define Lymphocyte, and give characteristics of Lymphocyte as it pertains to Adaptive Immunity:

A lymphocyte is one of the subtypes of white blood cell in a vertebrate's immune system. Lymphocytes include natural killer cells (NK cells) T cells and B cells. Every cell made, (B,T cells) have random specificity. Every B cell or T cell has a different receptor site. lymphocytes increase the power and focus of the immune response. Their contribution to defense is the adaptive immune response. lymphocytes recognize pathogens by using cell-surface receptors of just one molecular type. Lymphocytes travel through the Lymph nodes. There are many B and T cells available, but very few for a certain pathogen.

1-5 The adaptive immune response adds to an ongoing innate immune response: What is a Progenitor cell in regards to Adaptive Response?

A progenitor cell is a biological cell that, like a stem cell, has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its "target" cell. Which in the case of Adaptive immunity, the progenitor cell will differentiate in to Lymphocyte.

1-7 Cells of the immune system derive from hematopoietic cells: Define Stem cells: Define Hematopoietic Stem Cells:

A stem cell is: an undifferentiated cell of a multicellular organism that is capable of giving rise to indefinitely more cells of the same type, and from which certain other kinds of cell arise by differentiation. Hematopoietic stem cells (HSCs) are the stem cells that give rise to all the other blood cells through the process of hematopoiesis. They are derived from mesoderm and located in the red bone marrow, which is contained in the core of most bones. HSCs give rise to both the myeloid and lymphoid lineages of blood cells.

Chapter 3 Innate Immunity: the Induced Response to viral infections: mechanisms of innate immunity that cells use against viral infection: Explain type 1 interferons (Interferon)

A virus infects a cell and uses the cells own machinery to transcribe, translate, and replicate it's genome. Because of this, there are viral nucleic acids in the cytoplasm. our Cells have sensor proteins in the cytoplasm that detect viral nucleic acids and initiate a defensive response. This response results in the production of cytokines called type I interferons, or simply interferon, that interfere with the propagation of infection.

Chapter 3 Innate Immunity: the Induced Response: Define Acute-phase proteins:

Acute-phase proteins are a class of proteins whose plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the acute-phase reaction (also called acute-phase response). proteins in the liver that either increase or decrease their concentration by 25% or more are described as acute-phase proteins. The acute-phase response increases the supply of the recognition molecules of innate immunity. Acute-phase proteins are produced by liver cells in response to the cytokines released by phagocytes in the presence of bacteria. They include C-reactive protein, fibrinogen, and mannose-binding lectin. Both C-reactive protein and mannose-binding lectin bind to structural features of bacterial cell surfaces that are not on human cells. On binding to bacteria, they act as opsonins. They also activate complement, facilitating phagocytosis and direct lysis (dashed lines) of the bacteria by the terminal complement components (not shown).

1-5 The adaptive immune response adds to an ongoing innate immune response: Why does Adaptive Immunity have a slower response time than Innate Immunity? How is specificity for a certain pathogen improved?

Adaptive immunity has a slower response bc you need to expand the number of cells you have before you carry out the response to the pathogen. You don't have as many B,T cells as you do cells tht carry out innate immunity. Specificity can be improved after 1st use. Bc of proliferation step. Natural selection of the cells that bind the best to the pathogen, the body will make more of those

Chapter 3 Innate Immunity: the Induced Response: 3-8 Inflammatory cytokines recruit neutrophils from the blood to the infected tissue: Explain how 4 types of adhesion molecules help to adhere leukocytes(neutrophils) to vascular endothelium:

Adhesion of leukocytes to vascular endothelium involves interactions between adhesion molecules of four structurally different types. These are the vascular addressins, the selectins, the integrins, and proteins containing immunoglobulin-like domains.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Generation of immunoglobulin diversity before B cell encounter with antigen: What does allelic exclusion prevent:

Allelic exclusion prevents multiple specificities Each B cell has a unique specificity In a developing B cell, the process of immunoglobulin-gene rearrangement is tightly controlled so that only one heavy chain and one light chain are finally expressed, a phenomenon known as allelic exclusion. This ensures that each B cell produces IgM and IgD of a single antigen specificity. Although every B cell has two copies, or alleles, of the heavy-chain locus and two copies of each light-chain locus, only one heavy-chain locus and one light-chain locus are rearranged to produce functional genes.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Explain what a Multivalent Epitope is:

An antigen that contains more than one epitope (the part on the antigens surface that an antibody binds to), or more than one copy of the same epitope, is known as a: multivalent antigen Some antigens have different epitopes, but others can have the same type of epitope, so that an antibody can bind to two epitopes on the surface. Some antigens have different epitopes, but others can have the same type of epitope, so that an antibody can bind to two epitopes on the surface.

Define Antibody: What are the mechanisms by which antibodies combat infection?

Antibodies bind to pathogens and cause their inactivation or destruction The antibodies secreted by plasma cells circulate in the blood and can enter infected tissues. Immunity due to antibodies and their actions is often known as humoral immunity

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Before it encounters antigen, a mature B cell only expresses immunoglobulin in the membrane-bound form that serves as the cell's receptor for antigen. When antigen binds to this receptor, the B cell is stimulated to proliferate and to differentiate into plasma cells, which then secrete large amounts of antibodies with the same specificity as that of the membrane-bound immunoglobulin (Figure 4.1). This is an example of the principle of clonal selection

Antibody production is the single effector function of the B lymphocytes of the immune system

2-10 Antimicrobial peptides kill pathogens by perturbing their membranes Explain Defensins :

Antimicrobial peptides are soluble effector molecules of innate immunity that kill a wide range of pathogens. The major family of human antimicrobial peptides is the defensins

1-2 Pathogens are infectious organisms that cause disease: Define pathogen:

Any organism that has the potential to cause disease is known as a pathogen. They can be in the form of: Bacteria Viruses Fungi and Parasites

1-8 Immunoglobulins and T-cell receptors are the diverse lymphocyte receptors of adaptive immunity: Where are B and T cells made?

B and T cells are made in the bone marrow.

1-7 Cells of the immune system derive from hematopoietic cells: Why are B and T cells which are derived from lymphoid precursors, which were derived from hematopoietic stem cells, not always effector cells?

B and T cells don't become effectors until exposed to an antigen. They aren't always effectors bc it takes a lot of energy

2-6 Complement activation enhances phagocytosis (opsonization) Define Opsonization:

Bacteria coated with C3b are more efficiently phagocytosed by Macrophages than uncoated bacteria: The coating of a pathogen with a protein that facilitates phagocytosis (such as C3b) is called opsonization.

Chapter 3 Innate Immunity: the Induced Response: NOD Receptor activation of NFkB:

Book: NOD receptors are intracellular sensors of bacterial infections. Top panel: degradation of phagocytosed bacteria in the lysosomes of the macrophage leads to delivery of bacterial cell-wall components to the cytoplasm. Middle panel: on recognizing bacterial products, cytoplasmic NOD receptors dimerize and bind the kinase RIPK2. Bottom panel: RIPK2 phosphorylates the kinase TAK1, initiating reactions that lead to the activation of NFκB. This contributes to macrophage activation.

Chapter 3 Innate Immunity: the Induced Response: Define Cytokine:

Book: Cytokines are small soluble proteins used as a means of communication between cells. In response to an external stimulus such as infection, one type of cell secretes a cytokine that binds to a specific cytokine receptor on the surface of another type of cell. Binding of cytokine to the receptor induces intracellular signals that change the behavior of the second cell. In general, cytokines are short-lived molecules that exert their influence within a short distance from the cell that made them, and in some instances the cytokine-secreting cell makes direct contact with the cell it will influence. These properties of cytokines ensure that the immune response, which inevitably causes collateral damage to tissues, is restricted to where it is needed. Google: any of a number of substances, such as interferon, interleukin, and growth factors, that are secreted by certain cells of the immune system and have an effect on other cells.

2-5 Regulatory proteins determine the extent and site of C3b deposition: Control of complement activation: Explain the second category of complement control proteins that involve membrane proteins of human cells. Explain the membrane cofactor protein MCP

Bottom panel: when C3bBb is formed on a human cell surface, it is rapidly disrupted by the action of one of two membrane proteins: decay-accelerating factor (DAF) or membrane cofactor protein (MCP). In combination, these regulatory proteins ensure that much complement is fixed to pathogen surfaces and little is fixed to human cell surfaces.

Chapter 3 Innate Immunity: the Induced Response: Define C-reactive protein:

C-reactive protein (CRP) is one of the plasma proteins known as acute-phase proteins: proteins whose plasma concentrations increase (or decrease) by 25% or more during inflammatory disorders. CRP can rise as high as 1000-fold with inflammation.

Chapter 3 Innate Immunity: the Induced Response: At the start of infection, complement activation is mainly by the alternative pathway. As the inflammatory response develops and acute-phase proteins are produced, MBL and C-reactive protein provide increased activation of complement via the lectin and classical pathways, respectively. All three pathways contribute to innate immunity, and they work together to produce quantities of C3b fragments and C3 convertases at the pathogen surface.

C-reactive protein can initiate the classical pathway of complement activation. C-reactive protein bound to phosphorylcholine on bacterial cell surfaces binds complement component C1, resulting in the cleavage of C4 and opsonization of the bacterial surface with C4b.

Chapter 3 Innate Immunity: the Induced Response: Explain Chemokine:

CXCL8 (an inflammatory cytokine secreted from a macrophage) is a chemoattractant cytokine, or Chemokine, which attracts neutrophils away from the blood and in to infected area in which macrophages are secreting inflammatory cytokines to help fight the infection.

What is the roll of Cytokines in Innate Immunity?

Cells and proteins in the damaged tissue sense the presence of bacteria, and the cells send out soluble proteins called cytokines that interact with other cells to trigger the innate immune response. The overall effect of the innate immune response is to induce a state of inflammation in the infected tissue.

How does the body differentiate between it's own cells and cells of a foreign pathogen, so that it only initiates an immune response for pathogens?

Cells of the body contain unique membrane bound macromolecules on the membrane. Pathogens also have their own unique membrane bound macromolecules. These can be differentiated from our own. Any substance such as a macromolecule from a pathogen that initiates an immune response from the body is called a PATHOGEN.

1-5 The adaptive immune response adds to an ongoing innate immune response: Explain the Adaptive Response to pathogens:

Clonal selection guides the adaptive immune response. Clonal selection Finds the lymphocyte that binds best to the pathogen, and then it clones that one into many more because it is the best one.

Chapter 3 Innate Immunity: the Induced Response: Know the local and systemic effects of IL-1/IL-6/TNF-α (as a group)

Collectively, these cytokines are called inflammatory cytokines. their combined effect is to create a state of inflammation in the infected tissue. At the site of infection, resident microphages secrete inflammatory cytokines. They cause vasodilation, which allows for things to flow in to the cell from the blood. The inflammatory cytokines attract neutrophils from the blood in to the affected cell.

What does it mean to be a Commensal species? And how do they help humans?

Commensal means that the bacteria eat at the same table. There are over 1000 different types of microbial species in our gut microbiota. The commensal organisms in the human gut help us by processing our food, as well as producing vitamins etc. They also protect against disease, because their presence helps to prevent colonization by dangerous, disease-causing microorganisms.

Chapter 2 Innate Immunity: the immediate response: 2-3 Complement marks pathogens for destruction: Explain complement fixation:

Complement activation results in covalent attachment of C3b to a pathogen's surface. The key event in complement activation in response to a pathogen is the proteolytic cleavage of complement fragment C3. This cleavage produces a large C3b fragment and a small C3a fragment. C3b is chemically reactive and becomes covalently attached, or fixed, to the pathogen's surface, thereby marking the pathogen as dangerous. C3a recruits phagocytic cells to the site of infection. This attachment of C3b to pathogen surfaces is the essential function of the complement system; it is called complement fixation because C3b becomes firmly fixed to the pathogen.

Know the features, location and functions of the antibody isotypes: Know which antibody isotypes (don't worry about subtypes) are involved in: neutralization opsonization complement activation placental antibody transfer mast cell activation mucosal immunity:

Complement activation: IgM, IgG Opsonization: IgG Neutralization: IgG and IgA Placental antibody transfer: IgG Mast Cell activation: IgE Mucosal Immunity: Dimeric IgA Opsonization refers to the ability of the antibody itself to facilitate phagocytosis. Antibodies that activate the complement system indirectly cause opsonization via complement. Antibodies can clear pathogens from the body in various ways. Neutralizing antibodies directly inactivate a pathogen or a toxin and prevent it from interacting with human cells. Neutralizing antibodies against viruses, for example, bind to a site on the virus that is normally used to gain entry to cells. Another function of antibodies is opsonization, a term used to describe the coating of pathogens with a protein that facilitates its elimination. Monomeric IgA is made by plasma cells in lymph nodes, spleen, and bone marrow and is secreted into the bloodstream. IgA can also be made as a dimer, Dimeric IgA is made principally in the lymphoid tissues underlying mucosal surfaces and is the antibody secreted into the lumen of the gut; it is also the main antibody in other secretions, including milk, saliva, sweat, and tears. The IgE class of antibodies is highly specialized toward recruiting the effector functions of mast cells in epithelium, activated eosinophils present at mucosal surfaces, and basophils in blood. These cell types carry a high-affinity receptor that binds IgE in the absence of antigen. The presence of antigen, which binds to the IgE, triggers strong physical and inflammatory reactions that can expel and kill infecting parasites. In countries where parasite infections are rare, the major impact of the IgE response is from the allergies and asthma caused when IgE is made against otherwise harmless antigens. IgG is the most abundant antibody in the internal body fluids, including blood and lymph. Like IgM, it is made principally in the lymph nodes, spleen, and bone marrow and circulates in lymph and blood. IgG is smaller and more flexible than IgM, properties that give it easier access to antigens in the extracellular spaces of damaged and infected tissues. A key feature of the IgG molecule that contributes to its potency and versatility is conformational flexibility This allows the antigen-binding sites in the two Fabs and the effector-binding sites in the Fc to move in a partly independent manner and assume a wide range of different positions with respect to each other (Figure 4.32). This flexibility, due mainly to the hinge region, greatly improves the likelihood that an IgG molecule can simultaneously bind to two antigens on the surface of a pathogen and to effector molecules such as complement component C1 (see Section 3-12) and the Fc receptors of phagocytes, the cell-surface receptors that bind the Fc portions of antibodies. 4

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Explain the Constant region of an Antibody:

Constant region maintains structure and function. It stays the same. It is the antibodies Isotype. The remaining parts of the light chain (that don't make up the variable region) and the heavy chain have limited variation in amino acid sequence between different antibodies and are therefore known as the constant regions or C regions. Antibody fragments are derived artificially. VH and VL heavy and light chain (Fab)'2 = two Fab regions connected Fab = Fragment antigen binding. Fc = fragment that's crystallizeable

1-4 The innate immune response causes inflammation:

Cytokines induce the local dilation of blood capillaries, which by increasing the blood flow causes the skin to warm and redden (vasodilation) Vascular dilation (vasodilation) introduces gaps between the cells of the endothelium, the thin layer of specialized epithelium that lines the interior of blood vessels. This makes the endothelium permeable and increases the leakage of blood plasma into the connective tissue Expansion of the local fluid volume causes edema or swelling, putting pressure on nerve endings and causing PAIN. The effector cell is the macrophage. Anywhere apoptosis is happening,there are macrophages to clean up those dead cells. Macrophages recognize the peptidoglycan on the bacteria cell wall etc. that's how they distinguish between bacterial cell and our own cells. Cytokines are communication proteins. They're the signal to the nutriphiles. You get vasodilation of the blood vessels. You get increased permeability of endo layer. Gaps between the endothelial cells. Endothelial cells express adhesion molecules. (neutrophils bind) Macrophages are he regulaters of the whole response. They don't perform apoptosis. Redness heat from vasodilation Swelling is from permeability change Pain bc edema is hitting receptors for pain. Innate immunity is categorical, they recognize the same types of things. EX: peptidoglycan. Everyone has innate immunity. Their response is always the same no matter how many exposures you've had to the specific pathogen.

How do Defensins Work:

Defensins disrupt microbial membranes. The structure of human β1-defensin is shown in the top panel. It is composed of a short segment of α helix (yellow) resting against three strands of antiparallel β sheet (green), generating an amphipathic peptide with separate regions having charged or hydrophobic residues. This feature allows defensins to interact with the charged surface of the cell membrane and then insert into the lipid bilayer (middle panel). This leads to the formation of pores and a loss of membrane integrity (bottom panel).

Chapter 3 Innate Immunity: the Induced Response: Explain Diapedesis:

Diapedesis is the passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation. Under the guidance of these chemokines, the neutrophil squeezes between the endothelial cells and penetrates the connective tissue (diapedesis). Extravasation - leave the blood vessel. Diapedesis - walking across

Chapter 3 Innate Immunity: the Induced Response:

Different Toll-like receptors sense bacterial infection outside the cell and viral infection inside the cell. The TLR4 homodimer and the TLR1:TLR2 heterodimer at the cell surface sense bacterial infection. The homodimer of TLR3 in an endosomal vesicle detects viral infection. In previous sections we saw how TLR4 recognizes bacterial products, and how it signals macrophages to respond to bacterial infection. Complementing this function of TLR4, other members of the family of Toll-like receptors recognize the presence of viral, fungal, and parasitic infections (Figure 3.29). The Tolllike receptors form two distinctive groups in terms of their function. Receptors in the first group, which includes TLR4, are located on the plasma membrane and recognize carbohydrate, lipid, and protein structures on the outer surfaces of pathogens. By contrast, receptors in the second group are located inside the cell and in the membranes of endosomes, and recognize features that distinguish the nucleic acids of pathogens from the nucleic acids of human C1q For example, TLR3 recognizes double-stranded RNA, which characterizes many viral infections, and TLR9 detects the unmethylated CpG nucleotide motifs that are abundant in bacterial and viral genomes but not in human genomic DNA (Figure 3.30). Uptake of pathogen-derived nucleic acids from the extracellular environment delivers them to endosomes for recognition by these Toll-like receptors.

1-5 The adaptive immune response adds to an ongoing innate immune response:

During infection, only those lymphocytes bearing receptors that recognize the infecting pathogen are selected to participate in the adaptive response. They then proliferate and differentiate to produce large numbers of effector cells which are specific specific for that pathogen. These processes, which select the small subset of pathogen-specific lymphocytes for proliferation and differentiation into effector lymphocytes, are called: clonal selection and clonal expansion. Because these processes take time, the benefit of an adaptive immune response only begins to be felt about a week after the infection has started.

Know when gene rearrangement and isotype switching occur during B cell development or maturation. Do these events require exposure to antigen?

During the development of B cells, the arrays of V, D, and J segments are cut and re-spliced by DNA recombination. This process is called somatic recombination and it brings together a single gene segment of each type to form a DNA sequence encoding the V region of an immunoglobulin chain Gene rearrangement happens after exposure to antigen. Somatic hypermutation occurs at this time as well creating more variability. Isotype switching, like somatic hypermutation, occurs only in B cells proliferating in response to antigen.

1-4 The innate immune response causes inflammation: Define Endothelium:

Endothelium is the thin layer of specialized epithelium that lines the interior of blood vessels.

Define Epithelial Cells:

Epithelium is composed of one or more layers of densely packed cells. In vertebrates, it lines the outer layer of the skin (epidermis), the surface of most body cavities, and the lumen of fluid-filled organs, such as the gut or intestine. All epithelial surfaces secrete antimicrobial substances.

Chapter 3 Innate Immunity: the Induced Response: Explain extravasation:

Extravasation is when the neutrophil leaves the blood by squeezing through gaps between neighboring endothelial cells. Under the guidance of these chemokines, the neutrophil squeezes between the endothelial cells and penetrates the connective tissue (diapedesis). Extravasation - leave the blood vessel. Diapedesis - walking across

The structure of the human immunoglobulin classes:

Figure 4.5 The structures of the human immunoglobulin classes. In particular, note the differences in length of the heavy-chain C regions, the locations of the disulfide bonds linking the chains, and the presence of a hinge region in IgG, IgA, and IgD, but not in IgM and IgE. The heavy-chain isotype in each antibody is indicated by the Greek letter. The isotypes also differ in the distribution of N-linked carbohydrate groups (turquoise). All these immunoglobulins occur as monomers in their membrane-bound form. In their soluble, secreted form, IgD, IgE, and IgG are always monomers, IgA forms monomers and dimers, and IgM forms only pentamers.

1-8 Immunoglobulins and T-cell receptors are the diverse lymphocyte receptors of adaptive immunity: What are the differences in cell surface receptors between B lymphocytes (B cells) and T Lymphocytes? (T cells) Define Them

For B cells, the cell-surface receptors for pathogens are immunoglobulins aka Antibodies(soluble forms). Effector B cells, called plasma cells, secrete soluble forms of immunoglobulins, which are known as antibodies. The Cell-surface receptors for T cells are just called T-cell receptors each B cell expresses a single type of immunoglobulin. Each T cell expresses a single type of T-cell receptor. Receptor diversity: Many millions of different immunoglobulins and T-cell receptors are represented within the population of small lymphocytes in one human being. Receptor specificity: T cell receptors are always on T cells. Only one binding site. T cells have to be physically present. They don't go all over the body like B cells do.

Chapter 2 Innate Immunity: the immediate response: Describe the Initial steps of complement activation in the alternative pathway when the initial C3b hasn't been generated yet when there is no convertase around to do so:

Formation and action of the soluble C3 convertase that initiates the alternative pathway of complement activation. In the plasma close to a microbial surface the thioester bond of C3 spontaneously hydrolyzes at low frequency. This activates the C3, which then binds factor B. Cleavage of B by the serine protease factor D produces a soluble C3 convertase, called iC3Bb, which then activates C3 molecules by cleavage into C3b and C3a. Some of the C3b fragments become covalently attached to the microbial surface.

1-7 Cells of the immune system derive from hematopoietic cells: Where does hematopoiesis occur during different stages of fetal development in to adulthood?

Hematopoiesis (cells of the immune system are generated) from conception in the yolk sac. From 1 - 7 months they're generated in the fetal liver and spleen of the fetus. By Birth, hematopoiesis occurs in the Bone Marrow.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Photo of the Hypervariable regions: What makes up the antigen binding site on an immunoglobulin?

Hypervariable regions make up the antigen binding site. Red regions where most variable regions where binding occurs. Hypervariability. 3 CDR loops on variable region of light chain. 3 CDR loops on variable region of heavy chain. So made up of 6 CDR's. They make up antigen binding site

Chapter 4: Antibody Structure and Generation of B Cell Diversity: What are the 5 different isotypes of Immunoglobulin?

IgG IgM IgD IgA IgE

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Generation of immunoglobulin diversity before B cell encounter with antigen: How is it possible to have simultaneous expression of IgM and IgD?

IgM cuts out D domains, IgD cuts out M domains. Specificity in red is done and permanent. Then it figures out what type. IgM IgD etc. Manipulation of constant region to get diff types of B cells. Coexpression of IgD and IgM is regulated by RNA processing. In mature B cells, transcription initiated at the VH promoter extends through both the Cμ and Cδ genes. For simplicity we have not shown all the individual C-gene exons but only those of relevance to the production of IgM and IgD. The long primary transcript is then processed by cleavage, polyadenylation, and splicing. Cleavage and polyadenylation at the μ site (pAμm; the 'm' denotes that this site produces membrane-bound IgM) and splicing between Cμ exons yields an mRNA encoding the μ heavy chain (left panel). Cleavage and polyadenylation at the δ site (pAδm) and a different pattern of splicing that removes the Cμ exons yields mRNA encoding the δ heavy chain (right panel). AAA designates the poly(A) tail. MC, exons that encode the transmembrane region of the heavy chain.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: 4-2 Immunoglobulin chains are folded into compact and stable protein domains:

Immunoglobulin isotypes vary in the number of domains, glycosylation, hinge location, disulfide bond location

2-9 Plasma proteins limit the spread of infection: Explain the Kinin System

In addition to complement, several other types of plasma protein impede the invasion and colonization of human tissues by microorganisms Further mediators, including the vasoactive peptide bradykinin, are produced by the kinin system, a second enzymatic cascade of plasma proteins that is triggered by tissue damage. By causing vasodilation, bradykinin increases the supply of the soluble and cellular materials of innate immunity to the infected site.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: 4-1 Antibodies have variable and constant regions: What are antibodies?

In an adaptive immune response, the body is cleared of extracellular pathogens and their toxins by means of antibodies, the secreted form of the B-cell receptor for antigen. Antibodies are produced by the effector B lymphocytes, or plasma cells, of the immune system in response to infection. They circulate as a major component of the plasma in blood and lymph and are always present at mucosal surfaces. Antibodies can recognize all types of biological macromolecule, but in practice, proteins and carbohydrates are the antigens most commonly encountered. Binding of antibody to a bacterium or virus particle can disable the pathogen and also render it susceptible to destruction by other components of the immune system. Antibodies are the best source of protective immunity, and the most successful vaccines protect through stimulating the production of high-quality antibodies.

What are the benefits of having Innate AND Adaptive Immunity?

In normal individuals, a primary infection is cleared from the body by the combined effects of innate and adaptive immunity (yellow line). In a person who lacks innate immunity, uncontrolled infection occurs because the adaptive immune response cannot be deployed without the preceding innate response (red line). In a person who lacks adaptive immune responses, the infection is initially contained by innate immunity but cannot be cleared from the body (green line).

Chapter 3 Innate Immunity: the Induced Response: Recruitment of neutrophils to the infected tissues: Explain the weak selectin mediated adhesion of neutrophils:

Inflammatory Cytokines induce the expression of selectin on vascular endothelium, enabling it to bind leukocytes. The upper panel shows the rolling interaction of a neutrophil with vascular endothelium as a result of transient interactions between selectin on the endothelium and sialylLewisx (s-Lex) on the leukocyte.

Chapter 3 Innate Immunity: the Induced Response: 3-3 LPS (ligand) binding to TLR4 (receptor on macrophage surface) activates macrophages to induce inflammation: Explain how because of binding of LPS from bacterial cells to the TLR complex, a Kinase cascade is initiated and inflammatory Cytokines are activated:

Inflammatory cytokines (IL-1, IL-6, TNF-α) via the transcription factor NFκB Once TLR4 is bound and activated, it starts a kinase phosphorylation cascade, which ultimately activates NFkB, which enters the nucleus of the macrophage, and activates transcription of genes for inflammatory cytokines, which mediate inflammation response.

What are the two different types of Immunity that comprise the Immune system? How long do they take to initiate?

Innate Immunity: An immediate response to a foreign pathogen. Responds right away. Consists of 2 parts Acquired Immunity: Takes several days to respond to a foreign pathogen.

Chapter 3 Innate Immunity: the Induced Response: Define Integrin:

Integrins contribute to adhesive interaction between cells. They allow cells of the immune system to interact with each other.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Generation of immunoglobulin diversity before B cell encounter with antigen: Define Junctional Diversity: Define TdT - terminal deoxynucleotidyl transferase

Junctional diversity describes the DNA sequence variations introduced by the improper joining of gene segments during the process of V(D)J recombination. • TdT - terminal deoxynucleotidyl transferase: the enzyme terminal deoxynucleotidyl transferase (TdT), which randomly adds nucleotides during recombination, generating further diversity.

Chapter 3 Innate Immunity: the Induced Response: 3-9 Neutrophils kill pathogens and then die: What are the 3 steps in Neutrophil Phagocytosis? (how it kills bacterium and then dies)

Killing of bacteria by neutrophils involves the fusion of two types of granule and lysosomes with the phagosome. After phagocytosis (first panel), the bacterium is held in a phagosome inside the neutrophil. The neutrophil's azurophilic granules and specific granules fuse with the phagosome, releasing their contents of antimicrobial proteins and peptides (second panel). NAPDH oxidase components contributed by the specific granules enable the respiratory burst to occur, which raises the pH of the phagosome (third panel). Antimicrobial proteins and peptides are activated, and the bacterium is damaged and killed. A subsequent decrease in pH and the fusion of the phagosome with lysosomes containing acid hydrolases results in complete degradation of the bacterium (fourth panel). The neutrophil dies and is phagocytosed by a macrophage (fifth panel).

Chapter 3 Innate Immunity: the Induced Response: Define Lectins:

Lectins are cell-surface receptors and plasma proteins that recognize carbohydrates of invading bacteria etc.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Explain what a linear epitope is: Explain what a discontinuous epitope is:

Linear epitopes, the protein sequence is just one after the other. Discontinuous epitopes, the protein sequence isn't one after another. (on right) If protein is denatured, the antibody won't be able to bind, because the epitope won't work in the binding site of the antibody.

Exlain how B and T cells use Primary and Secondary lymphoid tissues:

Lymphoid tissues. B cells do all of the development in the bonemarrow. Primary, where cells begin. Where they go thru their development. No antigen exposure. T cells when they leave the thymus they're ready to respond. B cells when they leave the bonemarrow. Secondary where B and T cells engage with Antigens. In secondary lymphoid tissue. Lymph vessels drain fluid? Check. Eventually u have lymph nodes. They remove all of the stuff that's in the lymph you're draining with the lymph cells. When u have an infection they clean up that fluid before it gets back to the bloodstream, so the infection doesn't circulate. The first lymph node u come to with the fluid from the site of infection traps 99.9 % of the infection. Good trapping system. B and T cells in blood regularly go in to lymph nodes to see if an antigen has bound a receptor, if yes they stay, if not they move on and keep looking.

2-6 Complement activation enhances phagocytosis (opsonization) Define Macrophage

Macrophages are the mature forms of circulating monocytes that have left the blood and taken up residence in the tissues. They are prevalent in the connective tissues, the linings of the gastrointestinal and respiratory tracts, the alveoli of the lungs, and in the liver Macrophages are long-lived phagocytic cells that participate in both innate and adaptive immunity.

1-7 Cells of the immune system derive from hematopoietic cells: Where are macrophages found?

Macrophages stay in tissue their whole life. Monocytes are at the ready in case u need more macrophages, they'll move in to the tissues to become a macrophage.

1-7 Cells of the immune system derive from hematopoietic cells: Where are Neutrophils, Eosinophils, and Basophils found?

Made from the Granulocyte (macrophage progenitor) Neutrophils eosinophils and basophils hangout in the blood.

Chapter 2 Innate Immunity: the immediate response: 2-3 Complement marks pathogens for destruction: Explain some general information about the complement system:

Made up of 30 proteins. Made in the Liver. Many of them are enzymes. Many made as proenzymes. (zymogen) Needs to have a cleavage event to activate enzyme activity. Once activated they have a very short half-life. On a very short leash so they don't overdo it and cause problems w their enzyme activity. A cascade of events once the process is started. Domino effect. One event leads to the next. Nomenclature, made in order of discovery, not in order of how they work. C1 - C9 we will cover. As well as B and D When there is a cleavage event, we end up with an A fragment goes away, and a B fragment binds. proteins made constitutively by the liver and present in the blood, lymph, and extracellular fluids.

Chapter 3 Innate Immunity: the Induced Response to viral infections: Simpler diagram explaining the interferon response to a viral infection:

Major functions of the type I interferons. Interferon-α and interferon-β (IFN-α and IFN-β) have three major functions. First, they prevent viral replication by activating host genes that destroy viral mRNA and inhibit translation of viral proteins. Second, they increase the expression of ligands for NK-cell receptors. Third, they activate NK cells to kill virus-infected cells. NK cells need to be activated. IFN's are doing the marking of infected cells and the activating of NK cells so that they can do their killing of those infected cells.

Chapter 3 Innate Immunity: the Induced Response: 3-11 Lectin pathway of complement activation: Define Mannose-Binding Lectin:

Mannose-Structure of mannose-binding lectin. It resembles a bunch of flowers, with each flower composed of three identical polypeptides. The stalks are rigid triple helices like collagen, with a single bend; each flower comprises three carbohydrate-binding domains. Associated with the mannose-binding lectin (blue) are the mannose-binding lectin associated serine proteases (MASP) 1 and 2. binding lectin (MBL) is a C-type lectin that binds to mannose-containing carbohydrates of bacteria, fungi, protozoa, and viruses. it is also an acute-phase protein

Innate Effector Mechanism:

Many families of receptor proteins contribute to the recognition of pathogens in the innate immune response. They are of several different structural types and bind to chemically diverse ligands: peptides, proteins, glycoproteins, proteoglycans, peptidoglycan, carbohydrates, glycolipids, phospholipids, and nucleic acids.

Chapter 3 Innate Immunity: the Induced Response: Explain Receptor-Mediated Endocytosis by a macrophage of the innate immune response:

Many of the ligands (specific lipids, carbohydrates on bacterial cell's surface) densely populate the bacterium's surface, enabling many receptors on the marcrophage's surface to bind their ligands in a cooperative fashion. This creates an irreversible bond, which initiates a process of engulfment of the bacterium by the macrophage called Receptor-Mediated Endocytosis. receptor-mediated endocytosis, in which the receptor-bound pathogen is surrounded by the macrophage membrane and internalized into a membrane-bound vesicle called an endosome or a phagosome.

Chapter 3 Innate Immunity: the Induced Response: Define Inflammatory mediators

Molecules that are released by immune cells during times when harmful agents invade our body.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Explain Monoclonal Antibodies:

Monoclonal Antibodies are antibodies that are cloned, so they are all identical. The antibodies made by a hybridoma cell line are all identical and are therefore called monoclonal antibodies Book: Lymphocytes from a mouse immunized with the antigen are fused with myeloma cells by using polyethyleneglycol. The cells are then grown in the presence of drugs that kill myeloma cells but permit the growth of hybridoma cells. Unfused lymphocytes also die. Individual cultures of hybridomas are tested to determine whether they make the desired antibody. The cells are then cloned to produce a homogeneous culture of cells making a monoclonal antibody. Myelomas are tumors of plasma cells; those used to make hybridomas were selected not to express heavy and light chains. Thus, hybridomas only express the antibody made by the B-cell partner.

Chapter 3 Innate Immunity: the Induced Response: How do the body's receptors, (macrophages, NK cells etc.) distinguish non self from self?

NK cells and Macrophages etc. use receptors on their surface to bind to carbohydrates (only bacteria or viruses have) on the bacterial surface, do differentiate between a healthy human cell, or one that's infected. Book: In the left-hand panel, the surface receptors of a macrophage are shown binding to cell-surface carbohydrates that abound on bacterial surfaces but are not on human cell surfaces. In the right-hand panel, the surface receptors of a natural killer (NK) cell, a type of lymphocyte that mediates innate immunity, are shown interacting with molecules that are present on the surface of virus-infected cells but not on uninfected cells. NK-cell receptors are able to detect the features that distinguish virus-infected cells from healthy uninfected cells. Phagocytic receptors bind to bacterial lipids and carbohydrates to trigger phagocytosis

Chapter 3 Innate Immunity: the Induced Response to viral infections: What are Natural Killer Cells? (NK Cells)

NK cells are large and active lymphocytes that are more speedily induced to respond to infection, cancer, or other form of stress. NK cells have two distinctive functions in the innate immune response to viral infection. The first is to kill cells infected with virus. This sacrifice of cells hosting the virus impedes virus replication and thus its spread to neighboring cells. The second function of NK cells is to maintain, and even increase, the state of inflammation in the infected tissue. This is achieved by their secretion of inflammatory cytokines that act mainly on the resident macrophages and increase their capacity to secrete inflammatory cytokines and to phagocytose viral particles and microorganisms in the extracellular environment. NK cells thus contribute to defense against both intracellular and extracellular pathogens.

Chapter 3 Innate Immunity: the Induced Response to viral infections: How do NK cells provide an early response to Viral infection while Killer T cells are developing?

NK cells provide an early response to virus infection. The kinetics of the immune response to an experimental virus infection of mice are shown. As a result of infection, a burst of cytokines is secreted, including IFN-α, IFN-β, TNF-α, and IL-12 (green curve). These induce the proliferation and activation of NK cells (blue curve), which are seen as a wave emerging after cytokine production. NK cells control virus replication and the spread of infection while effector killer T cells (red curve) are developing. The level of virus (the virus titer) is given by the curve described by the yellow shading.

Chapter 3 Innate Immunity: the Induced Response: Explain how NOD receptors activate NFkB:

NOD receptors are floating in a macrophage's cytoplasm, (unlike TLR which are transmembrane proteins on macrophage's surface) They respond to pathogen's degradation products (products of the pathogen trying to degrade cell wall for entry) The NOD receptors bind the degration product ligands which triggers them to dimerize. This activates a kinase phosphorylation cascade activating NFkB, which enters the macrophage nucleus and begins trancription of inflammatory cytokines which give signals to other cells to start the inflammatory process. Book: NOD receptors are intracellular sensors of bacterial infections. Top panel: degradation of phagocytosed bacteria in the lysosomes of the macrophage leads to delivery of bacterial cell-wall components to the cytoplasm. Middle panel: on recognizing bacterial products, cytoplasmic NOD receptors dimerize and bind the kinase RIPK2. Bottom panel: RIPK2 phosphorylates the kinase TAK1, initiating reactions that lead to the activation of NFκB. This contributes to macrophage activation.

Chapter 3 Innate Immunity: the Induced Response: Define Neutrophils, and their job in the immune response:

Neutrophils are dedicated phagocytes and the first effector cells recruited to sites of infection. Neutrophils, in contrast, are short-lived dedicated killers that circulate in the blood, awaiting a call from a macrophage to enter infected tissue. Thus neutrophils are the first population of effector cells to be recruited to an infected tissue. Neutrophils are a type of granulocyte the most abundant white blood cells, a healthy adult having some 50 billion (5 × 1010) in circulation at any time. Mature neutrophils are kept in the bone marrow for about 5 days before being released into the circulation. the cells of the immune system have some limited access to healthy tissue, but for neutrophils—the destructive phagocytes that do the hardest work in clearing infection—all access is denied. A major task of the inflammatory cytokines (Cytokines secreted from macrophages to induce inflammation response) is to reverse this situation. They cause vasodilation, which allows for things to flow in to the cell from the blood. The inflammatory cytokines attract neutrophils (as well as monocytes and NK cells) from the blood in to the affected cell. Neutrophils are excluded from healthy tissue, but at infected sites the release of inflammatory mediators attracts neutrophils to leave the blood and enter the infected area in large numbers, where they soon become the dominant phagocytic cell.

Chapter 3 Innate Immunity: the Induced Response:

Neutrophils are directed to sites of infection through interactions between adhesion molecules

Chapter 3 Innate Immunity: the Induced Response: 3-9 Neutrophils kill pathogens and then die: Neutrophils have phagocytic receptors but not TLR's How do Neutrophils kill bacteria?

Neutrophils bind bacteria with their phagocytic receptors. They engulf the bacteria, then destroy them with toxic contents of the neutrophil granules.

1-9 On encountering their specific antigen, B cells and T cells differentiate into effector cells

On encountering the antigen recognized by their antigen receptors, B cells differentiate into antibody-producing plasma cells, and this is their only effector function (discussed in Chapter 9). Antigen-activated effector T cells, however, undertake a variety of functions within the immune response (discussed in Chapter 8). Effector T cells are subdivided into two main kinds, called cytotoxic T cells and helper T cells. Cytotoxic T cells kill cells that are infected with viruses or with certain bacteria that live inside human cells. NK cells and cytotoxic T cells have similar effector functions, the former providing these functions during the innate immune response, the latter during the adaptive immune response. Helper T cells secrete cytokines that help other cells of the immune system become fully activated effector cells. For example, one subset of helper T cells helps macrophages become more functionally active in phagocytosis, whereas another subset helps activate B cells to become antibody-secreting plasma cells. A third subset of helper T cells comprises the regulatory T cells that control the activities of the cytotoxic and other types of T cell, thereby preventing unnecessary tissue damage and stopping the immune response once the pathogen has been defeated.

Chapter 3 Innate Immunity: the Induced Response: 3-12 C-reactive protein triggers the classical pathway of complement activation: What is the Structure and function of C-reactive protein?

Once C-reactive protein has bound to a bacterium it can also interact with C1, the first component of the classical pathway of complement activation. At the start of infection, complement activation is mainly by the alternative pathway. As the inflammatory response develops and acute-phase proteins are produced, MBL and C-reactive protein provide increased activation of complement via the lectin and classical pathways, respectively. All three pathways contribute to innate immunity, and they work together to produce quantities of C3b fragments and C3 convertases at the pathogen surface.

Chapter 3 Innate Immunity: the Induced Response to viral infections: Define Autocrine and Paracrine

Once IFN-β is secreted, it acts both in an autocrine fashion, by binding to receptors on the cell that made it, and a paracrine fashion, by binding to receptors on uninfected cells nearby

Chapter 3 Innate Immunity: the Induced Response: 3-10 Inflammatory cytokines induce the acute phase response: Know the local and systemic effects of IL-1/IL-6/TNF-α (as a group)

One systemic effect of the inflammatory cytokines IL-1β, IL-6, and TNF-α is to raise the body temperature, causing fever. The cytokines act on temperature-control sites in the hypothalamus, and on muscle and fat cells, altering energy mobilization to generate heat

What are the body's physical barriers against infection?

Skin: Our skin creates a physical barrier that prevents pathogens from entering. The skin is the human body's first defense against infection. It forms a tough, impenetrable barrier of epithelium. The skin can be breached by physical damage, such as wounds, burns, or surgical procedures Mucosal Surfaces: Respiratory: Our air passageways contain mucous that traps pathogens that enter with the air we breathe in. they are continually bathed in the mucus they secrete. This thick fluid layer contains glycoproteins, proteoglycans, and enzymes that protect the epithelial cells from damage and help to limit infection. Gastrointestinal: Stomach secretes HCl that kills off pathogens entering with food. Urogenital: pH kills pathogens etc. (look more up)

1-7 Cells of the immune system derive from hematopoietic cells: What regulates production of hematopoietic cells?

Stromal cells = nurse cells - Stromal cytokines. They help white blood cells develop. Responsible for giving baseline number of white blood cells. Cytokine is a small protein excreted by a cell. Very local like by inflammation response. Inflammatory Cytokines. They are the ones that travel in the blood to distant locations

Which lymphoid organs are primary and which are secondary lymphoid organs?

The Bone Marrow and Thymus are primary lymphoid tissues. The adenoid

Chapter 3 Innate Immunity: the Induced Response: 3-10 Inflammatory cytokines induce the acute phase response: Define Pyrogenes:

The Inflammatory cytokines and other molecules that induce fever are called pyrogens.

Which immune response causes inflammatioin?

The Innate Immune response causes inflammation.

1-7 Cells of the immune system derive from hematopoietic cells: What are Granulocytes? What are Polymorphonuclear leukocytes (PMN) What are Myeloid Cells?

The Myeloid progenitor gives rise to the Myeloid lineage. One group of myeloid cells consists of the granulocytes. Granulocytes have prominent cytoplasmic granules containing reactive substances that kill microorganisms and enhance inflammation. Because granulocytes have irregularly shaped nuclei with two to five lobes, they are also called polymorphonuclear leukocytes. (PMN) In hematopoiesis, myeloid cells are blood cells that arise from a progenitor cell for granulocytes, monocytes, erythrocytes, or platelets

Do anaphylatoxins increase blood flow in blood vessels, or decrease blood flow?

The anaphylatoxins induce the contraction of smooth muscle and the degranulation of mast cells and basophils, with the consequent release of histamine and other vasoactive substances that increase capillary permeability. They also have direct vasoactive effects on local blood vessels, increasing blood flow and vascular permeability. These changes make it easier for plasma proteins and cells to pass out of the blood into the site of an infection

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Define Immunoglobulins:

The cell-surface B-cell antigen receptors and the secreted anibodies are known more generally as immunoglobulins. any of a class of proteins in the cells of the immune system, that function as antibodies.

1-7 Cells of the immune system derive from hematopoietic cells: What is Hematopoiesis?

The cells of the immune system are principally the white blood cells or leukocytes. The cells of the Immune System are continually being generated by the body in the developmental process known as hematopoiesis.

The innate immune response causes inflammation: Step 1: Explain how the innate immune response recognizes pathogens:

The first step of the innate immune response is recognition that a pathogen is present. This involves soluble PROTEINS and CELL-SURFACE RECEPTORS that bind either to the pathogen and its products or to human cells and serum proteins that become altered in the presence of the pathogen

1-5 The adaptive immune response adds to an ongoing innate immune response: Explain a Primary Immune Response:

The first time that an adaptive immune response is made to a given pathogen it is called the primary immune response. There is a lag phase bc they have to get to the area of Infection, as well as proliferate. Which takes some time. Primary response, it's safe to say you will get sick, but the whole point is to make memory B cells, so next time hopefully u won't

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Explain the Fab and Fc parts of an Antibody:

The fragments corresponding to the arms are called Fab (Fragment antigen binding) because they bind antigen. The fragment corresponding to the stem, called Fc (Fragment crystallizable) because it readily crystallizes, mediates the effector functions of the antibody molecule by binding to serum proteins and cell-surface receptors. The stem of a complete antibody molecule is therefore often known as the Fc region or Fc piece, and the arms as Fab. The hinge of the IgG molecule allows the two Fabs to adopt many different spatial orientations with respect to each other. This flexibility enables antigens spaced at different distances apart on the surfaces of pathogens to be bound tightly by both Fab arms of an IgG molecule.

2-7 The membrane attack complex (MAC) lyses pathogens : What are the pieces that make up the Membrane Attack Complex? (MAC) And what is the Membrane Attack Complex?

The function of C5b(which is made from C5, unlike C3 in normal complement processes) is to initiate the formation of a membrane-attack complex, which can make holes in the membranes of bacterial pathogens and eukaryotic cells.

Chapter 3 Innate Immunity: the Induced Response: Explain the second part of innate immunity:

The human immune response to an invading pathogen can consist of one, two, or three phases, depending upon the severity of the infection. This later phase of innate immunity involves soluble and cellular receptors that detect the presence of infecting organisms and then recruit leukocytes to do something about it. The integrity of blood vessels is deliberately damaged by inflammation so that a vast army of destructive cells can freely enter the infected tissue to confront the infecting pathogen.

Chapter 3 Innate Immunity: the Induced Response to viral infections: What are the immediate effects of type 1 interferon?

The immediate effects of type I interferon are to interfere with viral replication by the infected cell, and to signal to neighboring uninfected cells that they, too, should prepare to resist a viral infection. Further effects of type I interferon are to alert cells of the immune system that an infection is about, and to make virus-infected cells more vulnerable to attack by killer lymphocytes. As all types of human cell are susceptible to viral infections, they are all equipped to make type I interferons and their receptors. The receptor is always present on cell surfaces, ready to bind interferon newly made in response to infection. Although type I interferon is barely detectable in the blood of healthy people, upon infection it becomes abundant.

Chapter 3 Innate Immunity: the Induced Response: Inflammatory cytokines trigger liver production of acute phase proteins.

The kinetics of acute-phase proteins in the blood. The left panel shows representative examples, and their functions, of the different types of plasma protein that increase during the acute-phase response. The graph on the right shows the change in concentration of five proteins in blood plasma after the initiation of an inflammatory response. C-reactive protein and serum amyloid A are massively increased acute-phase proteins, whereas C3 and fibrinogen are moderately increased. Serum albumin, the most abundant plasma protein, is reduced in concentration during the acute phase.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: What are the two Isotypes of the light chain?

The light chain has only two isotypes or classes—kappa (κ) and lambda (λ). No functional difference between antibodies carrying κ light chains and those carrying λ light chains has been found; light chains of both isotypes pair with all the heavy-chain isotypes. Each antibody, however, contains either κ or λ light chains, not both

Chapter 3 Innate Immunity: the Induced Response: Recruitment of neutrophils to the infected tissues: Explain how the neutrophils get to the region of infected tissue after the weak selectin mediated adhesion of neutrophils:

The lower panel shows the conversion of rolling adhesion into tight binding and subsequent migration of the leukocyte into the infected tissue. The four stages of extravasation are shown: Rolling adhesion is converted into tight binding by interactions between integrins on the leukocyte (LFA-1 is shown here) and adhesion moleules on the endothelium (ICAM-1). Expression of these adhesion molecules is also induced by cytokines. A strong interaction is induced by the presence of chemoattractant cytokines (the chemokine CXCL8 is shown here) that have their source at the site of infection. They are held on proteoglycans of the extracellular matrix and cell surface to form a gradient along which the leukocyte can travel. Under the guidance of these chemokines, the neutrophil squeezes between the endothelial cells and penetrates the connective tissue (diapedesis). It then migrates to the center of infection along the CXCL8 gradient.

Chapter 3 Innate Immunity: the Induced Response: Define and explain the two ways in which a neutrophil dies:

The mature neutrophil cannot replenish its granule contents; once they are used up, the neutrophil dies. Some neutrophils die by apoptosis and are then phagocytosed by a macrophage. A second way in which neutrophils die is by a process called netosis, which produces neutrophil extracellular traps (NETs) Nucleus with swell up and burst. Acts as a net to trap bacteria. Traps negatively charged bacteria with a positively charged DNA web.

1-7 Cells of the immune system derive from hematopoietic cells: Explain Phagocyte and Explain Neutrophils:

The most abundant granulocyte of all white blood cells, is the neutrophil Neutrophil's are specialized in the capture, engulfment and killing of microorganisms. Cells with this function are called phagocytes, of which neutrophils are the most numerous and most lethal. Neutrophils are effector cells of innate immunity that are rapidly mobilized to enter sites of infection and can work in the anaerobic conditions that often prevail in damaged tissue.

1-7 Cells of the immune system derive from hematopoietic cells: What is the difference between hematopoietic stem cells and progenitor cells? and what cell types come from each?

The most important difference between stem cells and progenitor cells is that: stem cells can replicate indefinitely, progenitor cells can divide only a limited number of times. Progenitor cells come from myeloid cells, which are used in innate immunity. They have effector cells available to respond to an infection right away. Hematopoietic stem cells make myeloid and lymphoid precursers. Which lymphoid precursers are used in Adaptive immunity. They make B and T cells, which when exposed to antigens become effector T cells and plasma cells.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Explain what an Antigenic Determinant or EPITOPE is:

The part of an antigen (on it's surface) to which an antibody binds is called an antigenic determinant or epitope. In nature, these structures are usually either carbohydrate or protein.

2-11 Pentraxins are plasma proteins of innate immunity that bind microorganisms and target them to phagocytes Define Pentatraxins:

The pentraxins are a family of cyclic multimeric proteins that circulate in the blood and lymph and bind to the surfaces of various pathogens and target them for destruction.

2-5 Regulatory proteins determine the extent and site of C3b deposition: Control of complement activation: Define and explain the role of plasma protein Properdin (Factor P)

The plasma protein properdin (factor P) increases the speed and power of complement activation by binding to the C3 convertase C3bBb on microbial surfaces and preventing its degradation by proteases

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Explain the Variable region of an Antibody:

The polypeptide chains of different antibodies vary greatly in amino acid sequence, and the sequence differences are concentrated in the amino-terminal region of each type of chain; this is known as the variable region or V region. This variability is the basis for the great diversity of antigen-binding specificities that antibodies have. The Antigen binding site is composed of a pair of variable regions. A heavy chain and a light chain. • Variable region forms the antigen binding site Heavy chain - bigger chain. Goes all the way thru. Light chain - smaller chain Two heavy chains are linked via disulphide bonds. Heavy and light connected via disulphide bonds as well.

Define Primary and Secondary Lymphoid tissues:

The primary lymphoid tissue is the marrow, the site where all lymphocyte progenitor cells reside and initially differentiate. No

Chapter 3 Innate Immunity: the Induced Response: What is a Respiratory Burst in regards to neutrophils? What is the purpose of the respiratory burst in neutrophils?

The respiratory burst is an intracellular attack by the neutrophils on the pathogen it has phagosized, by increasing oxygen consumption, with which radical forms of oxygen are released. The respiratory burst kills both Gram-positive and Gram-negative bacteria and also fungi with those radical forms of oxygen. Respiratory burst (sometimes called oxidative burst) is the rapid release of reactive oxygen species (superoxide radical and hydrogen peroxide) from different types of cells.

1-5 The adaptive immune response adds to an ongoing innate immune response: Explain Secondary Immune Response:

The second and subsequent times that an adaptive immune response is made, and when immunological memory applies, it is called a secondary immune response. The purpose of vaccination is to induce immunological memory to a pathogen so that subsequent infection with the pathogen elicits a strong, fast-acting adaptive response.

2-5 Regulatory proteins determine the extent and site of C3b deposition: Control of complement activation: Explain the second category of complement control proteins that involve membrane proteins of human cells. Explain Decay-accelerating Factor (DAF)

The second category of complement-control proteins comprises membrane proteins of human cells that interfere with complement activation at human cell surfaces. Decay-accelerating factor (DAF) binds to the C3b component of the alternative C3 convertase, causing its dissociation and inactivation

2-8 Small complement fragments (C3a, C4a, C5a) induce inflammation Explain how they induce inflammation as well as in some cases cause anaphylactic shock. What are they called when they do this?

The smaller soluble C3a and C5a fragments are also physiologically active, increasing inflammation at the site of complement activation through binding to receptors on several cell types. Inflammation is a major consequence of the innate immune response to infection. In some circumstances, the C3a and C5a fragments induce anaphylactic shock, an acute inflammatory reaction that occurs simultaneously in tissues throughout the body; they are therefore referred to as anaphylatoxins Phagocytes, endothelial cells, and mast cells have specific receptors for C5a and C3a. a fragment (C3a, C4a, or C5a) that is produced during the pathways of the complement system. Along with other mechanisms, it mediates changes in mast cells leading to the release of histamine and other immunoreactive or inflammatory reactive substances.

Chapter 3 Innate Immunity: the Induced Response: What are the two types of C3 convertase?

The two types of C3 convertase have similar structures and functions. In the C3 convertase produced by the classical pathway, C4bC2a, the activated protease C2a cleaves C3 to C3b and C3a (not shown). In the analogous C3 convertase of the alternative pathway, C3bBb, the activated protease Bb carries out exactly the same reaction.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Generation of immunoglobulin diversity before B cell encounter with antigen: The Variable region is made up of gene segments. Explain the layout of this in regards to heavy chain(VH), and light chain (VL)

The upper row shows the λ light-chain locus, which has about 30 functional Vλ gene segments and four pairs of functional Jλ gene segments and Cλ gene segments. The κ locus (center row) is organized in a similar way, with about 35 functional Vκ gene segments accompanied by a cluster of five Jκ gene segments but with a single Cκ gene segment. In approximately half of the human population, the entire cluster of Vκ gene segments is duplicated (not shown, for simplicity). The heavychain locus (bottom row) has about 40 functional VH gene segments, a cluster of about 23 D segments and 6 JH gene segments. For simplicity, a single CH gene (CH1-9) is shown in this diagram to represent the nine C genes. The diagram is not to scale: the total length of the heavy-chain locus is more than 2 megabases (2 million bases), whereas some of the D segments are only six bases long. L, leader sequence.

Explain what happens to B Cells once they are exposed to an antigen:

The whole point of getting a vaccination is to have memory B cells generated, which will lower lag time and heighten response time, so that hopefully you can stop the antigen (pathogen) without getting sick.

Innate Immunity:

The word 'innate' refers to qualities a person is born with, and innate immunity comprises a genetically programmed set of responses that can be mobilized immediately an infection occurs.

1-8 Immunoglobulins and T-cell receptors are the diverse lymphocyte receptors of adaptive immunity: How do the receptors of Adaptive immunity distinguish cells that are their own, from foreign cells of pathogens? How do they Remember after being exposed to a certain pathogen?

There is a mechanism that deletes cells from recognizing "self" so they only recognize foreign pathogens. Memory: Expand the number of useful cells, and keep them on hand after the infection is gone to circulate for years in case we get the same type of pathogen (sickness) again.

Chapter 2 Innate Immunity: the immediate response: 2-3 Complement marks pathogens for destruction: More in depth look at complement fixation, and exposing the thioester:

This attachment of C3b to pathogen surfaces is the essential function of the complement system; it is called complement fixation because C3b becomes firmly fixed to the pathogen.

Chapter 3 Innate Immunity: the Induced Response to viral infections: Explain the Interferon Response to a viral infection:

Type 1 IFN - IFN alpha, and beta 2IFN - 8IFN IRF 3 is activated by virus. 3 transcription factors need to be activated before IFN beta is produced. Autocrine, cell makes product and acts on itself Paracrine, one cell makes product and works on another cell Endocrine one cell in one place in the body is going through the blood cell to act on another IFN alpha recruits cells needed to kill infected cell Point is to kill infected cell so neighboring cells are saved. Natural killer cells are apart of innate immunity. They're lymphosytes Book: Virus-infected cells produce type I interferons. The cell on the left is infected with a virus that triggers signals that lead to the phosphorylation, dimerization, and passage to the nucleus of the transcription factor interferon-response factor 3 (IRF3). Transcription factors NFκB and AP-1 are mobilized and coordinate with IRF3 to turn on transcription of the interferon (IFN)-β gene. These events are depicted in the upper half of the cell. Secreted IFN-β binds to the interferon receptor on the infected cell surface, acting in an autocrine fashion to mobilize other interferon-response factors and change patterns of gene expression to give the interferon response. These events are depicted in the lower half of the cell, being exemplified by IRF7 turning on transcription of the IFN-α gene, which it does without the need for AP-1 or NFκB. Secreted IFN-β will also bind to the interferon receptor expressed by nearby cells (top right) that are not infected by the virus, acting in a paracrine fashion to induce the interferon response that helps these cells to resist infection.

Chapter 3 Innate Immunity: the Induced Response to viral infections: What induces NK Proliferation, Differentiation, and killing of virus infected cells?

Type I interferon induces NK proliferation, differentiation, killing. Once activated, NK cells scan infected tissues that need to be killed. They engage and kill one cell at a time. They induce apoptosis.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Define Hypervariable regions and what they do:

Variable domains = hypervariable region + framework region Hypervariable regions form the antigen-binding site Antigen binding site is made up of 6 CDRs White is variable region of heavy chain. Other colors are light chain. Book: Comparison of the V domains of heavy and light chains from different antibody molecules shows that the differences in amino acid sequence are concentrated within particular regions called hypervariable regions (HV),

Chapter 3 Innate Immunity: the Induced Response: Define Toll-Like Receptors: (TLR) What do they induce?

Well-studied signaling receptors are the family of Toll-like receptors (TLRs), which recognize a variety of microbial ligands and are expressed by different types of innate immune cell. Of the Toll-like receptors, TLR4 is expressed by macrophages and associates with CD14 to recognize LPS. In the next section, TLR4 is used to exemplify the structure and function of Toll-like receptors. They induce inflammation.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Generation of immunoglobulin diversity before B cell encounter with antigen: 4-7 The V region is made up of gene segments: Antibody = Immunoglobulin:

When B cells leave the bone marrow, they have their certain specificities in their variable regions.

Chapter 3 Innate Immunity: the Induced Response: 3-11 Lectin pathway of complement activation: Explain the Lectin pathway of complement activation:

When bound to the surface of a pathogen, mannose-binding lectin triggers the lectin pathway of complement activation. Book: The activated MBL complex cleaves C4 and C2 to produce C4b and C2a, which associate to form the classical C3 convertase. First panel: a complex of MBL and MASP-1 and MASP-2 binds to the pathogen surface. This activates MASP-2, which binds and cleaves C4 to reveal the thioester bond of the C4b fragment. C4b becomes covalently bound to the microbial surface. Second panel: C2 binds to the MBL complex and is cleaved by activated MASP-2. Third panel: the C2a fragment binds to C4b to form the classical C3 convertase, C4bC2a. Fourth panel: C3 is bound and cleaved by C4bC2a. The thioester bond of the C3b fragment is exposed, and C3b becomes covalently bound to the microbial surface.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: What is the Antibody Repertoire?

antibodies are diverse in their antigen-binding specificities; the total number of different specific antibodies that can be made by an individual is known as the antibody repertoire and it might be as high as 10^16.

Define Lipoprotein and their role in Immunity:

any of a group of soluble proteins that combine with and transport fat or other lipids in the blood plasma.

2-9 Plasma proteins limit the spread of infection: Explain the Coagulation system:

coagulation system, a cascade of plasma enzymes that forms blood clots. Microorganisms are immobilized in the clots, which prevent them from entering the blood and lymph, as well as decreasing the loss of blood and fluid. Platelets are a major component of blood clots, and during clot formation they release a variety of highly active substances from their storage granules. These include prostaglandins, hydrolytic enzymes, growth factors, and other mediators that stimulate various cell types to contribute to antimicrobial defense, wound healing, and inflammation

Chapter 3 Innate Immunity: the Induced Response: Define Phagosome:

during receptor-mediated endocytosis, the receptor-bound pathogen is surrounded by the macrophage membrane and internalized into a membrane-bound vesicle called an endosome or a phagosome.

2-5 Regulatory proteins determine the extent and site of C3b deposition: Control of complement activation: Explain the role of Factor H and Factor I in C3b inactivation:

factor H binds C3b and changes its conformation to one susceptible to cleavage by factor I. The product of this cleavage is the iC3b fragment of C3, which remains attached to the pathogen surface but cannot form a C3 convertase.

2-9 Plasma proteins limit the spread of infection: Explain what a protease inhibitor is, and why protease inhibitors in the blood are so important for defense against pathogens:

many pathogens make cell-surface or secreted proteases as a part of their invasive mechanism. These enzymes break down human tissues and can also inactivate antimicrobial proteins. In response, human secretions and plasma contain protease inhibitors, which constitute about 10% of serum proteins If there were no protease inhibitors in the blood, pathogens would be able to break through membranes and in to tissues far easier.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Explain Avidity vs. Affinity in regards to Naive B cells:

several different antibodies may recognize the same epitope, but the small differences in the shapes and chemical properties of the binding sites give these antibodies different binding strengths, or affinities, for the epitope. Avidity: the overall strength of binding between an antibody and an antigen. the accumulated strength of multiple affinities. IgM as a secreted antibody has 10 binding sites. Naïve B cells have less affinity, but to make up for that, they have more avidity. Once they have experienced a pathogen, they take on the two binding site conformation, bc their affinity is higher so they don't need as much avidity.

Chapter 2 Innate Immunity: the immediate response: Describe the steps of complement activation in the alternative pathway once C3b is covalently bonded to a pathogen's surface:

the alternative pathway of complement activation, is one of the first responses of the innate immune system. Formation and action of the C3 convertase C3bBb of the alternative pathway at a microbial surface. Through the action of iC3Bb, the soluble C3 convertase, C3b fragments are bound to the microbial surface (see Figure 2.6). These bind factor B, which is then cleaved by factor D to produce C3bBb, the surface-bound convertase of the alternative pathway. This enzyme cleaves C3 to produce further C3b fragments bound to the microbe and small soluble C3a fragments. The C3b fragments can be used either to make more C3 convertase, which amplifies the activation of C3, or to provide ligands for the receptors of phagocytic cells. The small, soluble C3a fragments attract phagocytes to sites of complement fixation. C3b needs to cover pathogen's surface to be most effective. Goal: generate a C3 convertase (= C3bBb )

Explain the innate immune response. What are the two parts?

the innate immune system refers to nonspecific defense mechanisms that come into play immediately or within hours of an antigen's (pathogen) appearance in the body. These mechanisms include physical barriers such as skin, chemicals in the blood, and immune system cells that attack foreign cells in the body. The first part is recognition that a pathogen is present.

2-7 The terminal complement proteins lyse pathogens by forming membrane pores: Explain the alternative C5 Convertase:

the most important product of complement activation is C3b bonded to pathogen surfaces. However, the cascade of complement reactions does extends beyond this stage, involving five additional complement components. C3b binds to the alternative C3 convertase to produce an enzyme that acts on the C5 component of complement and is called the alternative C5 convertase; it consists of Bb plus two C3b fragments and is designated C3b2Bb (Figure 2.12). Complement component C5 is cleaved by C5 convertase to give a soluble active C5b fragment. The C5 convertase of the alternative pathway (C3b2Bb) consists of two molecules of C3b and one of Bb. C5 binds to the C3b component of the convertase and is cleaved into fragments C5a and C5b, of which C5b initiates the assembly of the terminal complement components to form the membrane-attack complex.

The innate immune response causes inflammation: Step 2: Explain how the innate immune response destroys pathogens:

the second part of the response involves the recruitment of compliments, that tag the pathogens, to be recognized by an effector cell through effector mechanisms. The effector cell itself is what kills the pathogens. Although compliments do some of the killing as well. effector cells of various types: engulf bacteria kill virus-infected cells or attack protozoan parasites proteins called complement that help the effector cells by marking pathogens with molecular flags. They also attack pathogens themselves. Compliment attaches to the bacterium, and then the macrophage recognizes the complement tag which covalently bonds, and the macrophage eats it. Phagocytes do phagocytosis.

Chapter 2 Innate Immunity: the immediate response: Explain how a different response is required by intracellular pathogens vs. the response required for extracellular pathogens:

• extracellular - Outside cells. Not in cytoplasm of cell. Most bacteria are extracellular. Can kill via phagocytosis. • intracellular Have to have mechanisms to kill infected cells to save the healthy. To shut down replication. Natural killer cells identify infected cells and kills them. Extracellular pathogens are accessible to soluble, secreted molecules of the immune system, whereas intracellular pathogens are not. The strategy used to attack intracellular pathogens is to kill the human cells in which the pathogens are living. This sacrifice interferes with the pathogen's life cycle and exposes any pathogens released from the dead cells to the soluble molecules of the immune system.

Chapter 4: Antibody Structure and Generation of B Cell Diversity: Generation of immunoglobulin diversity before B cell encounter with antigen: Explain the purpose of RAG enzymes, and their role in development of specificity of antibody's variable regions that bind to the epitope regions of antigens:

•Recombination activating genes (RAG-1/RAG-2) are required •Intervening sequences are permanently removed Enzyme RAG removes choices not chosen and combines the chosen sections. Brings together two choices then cleaves the rest and combines two choices. What would happen if a person would not make rag enzyme? If recombination can't be made, cell will die. Person will have no B cells. Severe combined Immune deficiency, they will have no adaptive immunity. To keep other cells from creating variable regions that bind to antigens, they shut off the gene that codes for RAG enzyme. RAG important for development of specificity.