Module 2 Lectures and Chapter 2 Flashcards
What are the four kinds of anatomic barriers?
- Structural
- Mechanical
- Chemical
- Microbiological
What are the five symptoms of inflammation?
- Redness
- swelling
- heat
- pain
- loss of function.
What are the five categories of innate immunity?
- Anatomic barriers
- inflammation
- phagocytosis
- compliment system
- cell mediated toxicity.
Why does inflammation cause pain?
The sensitization of local nerve endings.
What causes the redness and heat of inflammation?
Mast cells and macrophages that stimulate capillary endothelial cells to dilate the blood vessels and increase blood flow.
What are four benefits of acute inflammation?
- Delivery of O2 and clotting factors that heal wounds
- Infiltration of phagocytes that destroy pathogens
- Sensitization of the nervous system that alerts host to the infection
- Initiation of the adaptive response
What are two consequences of acute inflammation?
Pain and loss of function
What are four risks of acute inflammation?
- Permanent tissue damage
- Widespread inflammation leading to death
- Hypersensitivity induced pathology
- Autoimmunity and allergies
What is phagocytosis?
The process by which microorganisms and debri are engulfed in phagocytosis vesicles, fuse with lysosomes and are degraded.
What are the four leukocytes that are also phagocytic?
Neutrophils, monocytes, macrophages and dendritic cells
Which leukocyte is the most prolific of the phagocytes?
Neutrophils
How many circulating protein sets make up the compliment system?
30
What are the three activation pathways of the complement system?
Alternative, lectin and classical
What are the three key effector functions of the complement system?
Cytolysis of target cells
Enhanced phagocytosis
Induction of inflammation
What is cytolysis of target cells?
Membrane attack complex (MAC) forms pores on target cell causing them to burst.
What is enhanced phagocytosis?
Opsonization, where products of the complement system coat the pathogen surface.
How is inflammation induced?
Anaphylatoxins induce the response
What is cell mediated cytotoxicity?
When cells kill other cells
What is the difference between direct and indirect cell mediated cytotoxicity?
Direct destruction of a pathogen vs self induced death through apoptosis
How do the cells of the innate immune response recognize pathogens?
By carrying a fixed set of non variable receptors that recognize the general structure of microorganisms.
What are PAMPs?
Pathogen associated molecular patterns that alert immune cells to destroy the pathogen.
What are PRRs?
Pathogen recognition receptors that are used by the innate immune cells to detect bacteria and viruses.
What three classes of pathogen recognition receptors (PRRs)?
- Toll like receptors (TLRs)
- RIG I like receptors (RLRs)
- NOD like receptors (NLRs)
What are DAMPs?
Danger associated molecular patterns that are released by damaged or dying self cells and activate the innate immune response.
How was the Toll gene originally discovered?
A fruit fly in a German lab studying fruit fly development
What does the Toll gene do?
Recognizes fungal pathogens
How are Toll Like Receptors (TLRs), expressed?
Through the plasma membrane where they can detect microbial surface molecules or endosomal receptors where they can detect microbial DNA or RNA.
How many Toll Like Receptors (TLRs) are there in humans?
At least 10
How is the specificity and diversity of antigen specific receptors developed in the adaptive immune system?
Gene rearrangement during B and T cell development
Where do antibodies come from?
They are secreted B cell receptors (BCR) that come from B cells
What are antibodies made up of?
Four polypeptide chains, two heavy and two light, with two identical antigen binding sites at the end of each light chain.
What are the two steps of Ag (antigen) recognition for TCRs (T cell receptors)?
- Antigen processed into small pieces that serve as peptide antigens
- Peptide antigens presented in MHC molecules on antigen presenting cells active T cells
What are the two types of Major Histocompatibility complex (MHC) molecule?
MHC class 1: presents antigens to cytotoxic T cells MHC class 2: presents antigens to helper T cells
What are the two premises that underlie global selection?
- Each B and T cell is unique to Ag
2. Specificity is determined before contact with Ag
What is the process of clonal selection?
A large number of lymphocytes are made and circulated. Most remain silent and die. Those that interact with an antigen proliferate and make memory cells.
What happens during primary response activation in the adaptive immune system?
The response is delayed and weak. Clonal proliferation happens, B cells are activated, antibodies will be secreted and live for a few weeks. Memory cells made that live for years.
What happens during a secondary innate immune response?
Memory cells that are made from primary response become activated, differentiate and the response is rapid and more intense.
What are the three regions of epithelial tissues that serve as physical barriers against pathogens?
Digestive, respiratory and urogenital tracts
Which serves as a larger/richer habitat for microbes. The mucosal surface or skin?
Mucosal surface
What is a pathogen?
A collection of organisms that exploit the human body.
How are extracellular infections addressed by the immune system?
They are attacked by the solvable secreted molecules of the immune system between cells.
How are intracellular infections addressed?
The immune system kills the host cells and exposes the pathogen to the soluble secreted molecules.
Where are the soluble proteins of the complement system made?
The liver
Where is the complement system present?
Blood, lymph and extracellular fluids
What does complement do?
Coats the surface of pathogens for easy phagocytosis
What kinds of pathogens are most resistant to phagocytosis?
Bacteria with thick polysaccharide capsules
What are zymogens?
Functionally inactive complement components
What family of enzymes do the complement system belong to?
Serine proteases, which includes digestive enzymes chymotrypsin and trypsin
Which of the 30 complement proteins is most important?
C3, without it host suffers successive severe infections
What kind of bond is stabilized in the hydrophobic interior of C3?
High-energy thioester bond
What do all three complement pathways have in common?
All trigger C3 to cleave into C3a and C3b, and C3b to bind to the pathogen’s surface for phagocytosis and effector recruitment
What order were the complement pathways discovered in?
Classical
Alternative
Lectin
What order do the complement pathways work in?
Alternative
Lectin
Classical
Where are the soluble proteins of the complement system made?
The liver
Where is the complement system present?
Blood, lymph and extracellular fluids
What does complement do?
Coats the surface of pathogens for easy phagocytosis
What kinds of pathogens are most resistant to phagocytosis?
Bacteria with thick polysaccharide capsules
What are zymogens?
Functionally inactive complement components
What family of enzymes do the complement system belong to?
Serine proteases, which includes digestive enzymes chymotrypsin and trypsin
Which of the 30 complement proteins is most important?
C3, without it host suffers successive severe infections
What kind of bond is stabilized in the hydrophobic interior of C3?
High-energy thioester bond
What do all three complement pathways have in common?
All trigger C3 to cleave into C3a and C3b, and C3b to bind to the pathogen’s surface for phagocytosis and effector recruitment
What order were the complement pathways discovered in?
Classical
Alternative
Lectin
What order do the complement pathways work in?
Alternative
Lectin
Classical
How do the two classes of complement control proteins regulate C3d deposition?
One class compounded plasma proteins that interact with C3b attached to cell surfaces
The other includes membrane proteins on human cells that prevent fixation
What does Pepperdine (factor P) do?
Increases speed/power of complement activation by binding C3 convertase C3bBb on pathogen surface and prevents degradation by proteases
How does factor H counter the effect of properdin?
It decreases C3 by binding to C3b and causing plasma serine protease factor I to cleave and form iC3b which cannot assemble a C3 convertase
How does decay-accelerating factor (DAF) regulate complement?
DAF binds to C3b part of alternative C3 convertase casting dissociation and inactivation
How does membrane cofactors protein (MCP) regulate complement?
MCP functions similar to DAF and factor H but binds to C3b and causes cleavage and inactivation by factor I
How do some bacteria hide from complement?
By covering themselves in suspicion acid to mimic human cells - when C3b is deposited it is inactivated by factor H binding to the bacterial suspicion acid
What are made of complement control protein (CCP) modules?
DAF, MCP and Factor H, all in varying numbers of CCP modules
What is a complement control protein (CCP) module made up of?
60 amino acids folded into a sandwich made of two slices of beta-pleated sheets stabilized with two conserved disulfide bonds
What are regulators of complement activation (RCA)?
DAF, MCP and Factor H, all proteins made of CCP modules
What is the result of regulatory proteins determining C3b deposition?
Distinguishing self from non-self by ensuring deposition on pathogens and not human cells.
What are macrophages?
Mature forms of circulating monocytes that have moved from the blood to tissue. Phagocytes that are a part of innate and adaptive immunity.
What are Kupffer cells?
Phagocytic macrophage cells found in the liver to help in processing red blood cells.
What is opsonization?
Improved phagocytosis through the process of costing the pathogen with proteins.
What does complement receptor 1 (CR1) do?
Some protect the cell by distrusting C3 convertase by making C3b susceptible to factor I and the rest engage C3b fragments on the pathogen to facilitate opsonization.
What do complement receptor 3 (CR3) and complement receptor 4 (CR4) do?
They serve as ligands for CR3 and CR4 to facilitate phagocytosis by binding to iC3b fragments on microbial surface.
How do complement receptors work best?
CR1, CR3 and CR4 work best together rather than individually at inducing phagocytosis.
What is the most important product of complement activation?
C3b bonded to pathogen surfaces
What are the terminal complement components that make up the membrane attack complex (MAC)?
C5, C6, C7, C8 and C9
What is the function of MAC protein C5?
On activation, soluble C5b fragment initiates assembly of MAC
What is the function of MAC protein C6?
Binds and stabilizes C5b forming the binding site for C7
What is the function of MAC protein C7?
Binds to C5b6 and exposes hydrophobic region that attaches to cell membrane
What is the function of MAC protein C8?
Binds to C5b67 and exposes hydrophobic region that inserts into cell membrane
What is the function of MAC protein C9?
Polymerization on the C5b678 complex to form membrane-spanning channel that disrupts cell integrity and results in cell death
How do S protein, cluster in and factor J regulate terminal complement components in human cell interactions?
These soluble proteins prevent C5b with C6 and C7 proteins from attaching to human cell membranes
How do homologous restriction factors (HRF) and CD59 (protectin) regulate terminal complement component interaction with human cells?
These human cell surface proteins prevent C9 recruitment by complexes of C5b, C6, C7 and C8
When C3 and C5 are cleaved into larger C3b/C5b and smaller C3a/C5a, what is the function of the smaller fragments?
C3a and C5a are anaphylatoxins that
- Can cause anaphylactic shock
- smooth muscles contract
- degranulate mast cells and basophils
- release histamines
- Increase capillary permeability
How does C5a protein work on neutrophils and monocytes?
- Increases adherence to blood vessel walls
- Chemoattractant directs migration towards complement fixation sites
- Raises expression of CR1 and CR3 on pathogen surfaces for increased phagocytic potential
What are antimicrobial peptides?
Soluble effector molecules of the innate immune system
What are defensins
A major family of human antimicrobial peptides
What are defensins made up of?
35-40 amino acids rich in arginine residues with three intra-chain disulfide bonds
What are alpha defensins?
Defensins secreted by Panera cells of the small intestine. There are six types coded for with 2-14 alpha-defensin gene copies.
What are beta-defensins?
Defensins produced by epithelial cells, respiratory tract and urogenital tract. There are four types of beta-defensins codes for by 2-12 gene copies.
What determines the amount of defensin proteins a person makes?
The number of gene copies. 2-14 for alpha defensins and 2-12 for beta defensins.
What does it mean that defensin molecular dare amphipathic?
That they have both hydrophobic and hydrophilic regions on its surface that help it penetrate pathogen’s membranes.
What are the plasma proteins of innate immunity that bind and target microorganisms for phagocytes?
Pentraxins circulating in the blood and lymph
What is the primary mechanism of pentraxins?
They serve as a bridging molecule that connects pathogens to human cell surface receptors
What binds to the same phagocytic surface receptors as antibodies?
Pentraxins
What are short pentraxins?
They are made by hepatocytes in the liver and represented by serum amyloid P component (SAP)
What are long pentraxins?
They are made by myeloid, endothelial and epithelial cells and represented by PTX3
What provides the larger surface are for commensal microorganisms?
The skin
What is the inactive form of an enzyme that participated in complement activation?
Zymogen
What is the primary role of the complement control protein that operates in the early stage of complement activation?
It ensures that C3b is deposited on the correct surfaces
Where do Panera cells reside?
The crypts of the intestinal tract
