Lecture 3 Barriers and Innate Immunity Flashcards

Question

How is the innate immune system stimulated?

Answer 1

PAMPs - pathogen associated molecular patterns - unique, conserved microbial components DAMPs - damage associated molecular patterns - signals of cell damage

Answer 2

When it binds to PRR -Pathogen Recognition Receptor Results in intracellular signal to gene expression to secretion of cytokines, chemokines, antimicrobials these innate cells can serve as link between type of pathogen and adaptive response - PRRs recognize different PAMPs - intracellular response will recruit lymphocytes - DCs will present antigens to activate T cells

Answer 3

Toll-Like Receptors -type of PRR Three domains 1. Ligand binding domain - made of extracellular Leucine Rich Receptors, LRR - These are exterior and dimerize to bind microbe 2. Transmembrane Domain - goes through membrane 3. TIR Domain - executes intracellular signalling

Answer 4

Intracellular vessicle which contains TLRs to recognize PAMPs within the cell

Answer 5

1. Ligand binding at cell membrane or endosomal TLR 2. Kinases phosphorylate transcription factors 3. Transcription factor proteins access nucleus to increase gene expression

Answer 6

1. Tissue damage and bacteria cause mast cells release inflamatory cytokines like histamine and chemokines 2. Permeable capillaries allow influx of exudate, fluid, and cells 3. Chemotaxis attracts neutrophils and other phagocytes 4. Phagocytes and antibacterial substances destroy bacteria

Answer 7

Vasodilation and increase vascular permeability - allows exudate containing antimicrobial proteins - recruit phagocytes like neutrophils

Answer 8

Defensins - attracted to prokaryote phospholipid bilayers and open up their membranes Lysozyme - digests bacterial cell walls Lactoferrin - sequester iron, important for microbial growth

Answer 9

Proteins called opsonins, like C3b, bind to and coat the microbial surface in a process call opsonization Phagocytes have receptors, like CR1, for opsonins that increase binding and ingestion of microbes Allows phagocytes to only need one receptor instead of multiple for different types of microbes

Answer 10

The DC TLR that is activated determines the type of T cell that is activated -like cytotoxic T cel or NK or

Answer 11

1. Initiation - complement binds to cell surface 2. Amplification - cascade 3. Termination - complement proteins impact microbial clearance

Answer 12

The first step of the complement cascade - Three ways to initiate - CLASSICAL, LECTIN, and ALTERNATIVE pathways CLASSICAL pathway - antibodies bind to antigens on microbial surface; C1q binds to antibodies; initiates the formation of C3 CONVERTASE (C4b2a) LECTIN pathway - MBL (mannose binding lectin) binds to carbohydrates on microbial surface; initiates the formation of C3 CONVERTASE (C4b2a) ALTERNATIVE pathway - spontaneous hydrolysis of C3 at microbial surface; initiates formation of ALTERNATIVE C3 CONVERTASE (C3bBb) All three pathways lead to the formation of the C3 CONVERTASE, an enzyme that hydrolyzes C3 into C3a and C3b

Answer 13

Complement proteins are activated by enzymes (also complement proteins that were previously activated by initiation) called CONVERTASES. -Positive feedback loop causes a rapid increase in complement activation and convertase formation. C3 CONVERTASE (C4b2a or C3bBb) hydrolyzes C3 into C3a and C3b C3b helps form the C3bBb alternative C3 CONVERTASE that help convert more C3 into C3a and C3b (positive feedback) C3b helps form the C5 CONVERTASE (C3bBbC3b) to hydrolyze C5 into C5a and C5b (important components of termination)

Answer 14

Where the final activated complement proteins act on the microbes directly or just help your immune system do its job better. C3a, C4a, and C5a (all the "a" products of convertases) are invovled in stimulating and enhancing INFLAMMATION (including chemotaxis of neutrophils) C3b is involved in OPSONIZATION of microbes to enhance adherence to PHAGOCYTES (neutrophils, macrophages, and DCs have receptors for C3b) C5b is involved in the formation of the MEMBRANE-ATTACK COMPLEX (MAC) - see figure 6-10 - that creates pores in the microbial membrane and leads to cellular LYSIS

Answer 15

(also known as interferon-alpha and beta, or IFN-α and IFN-β) are part of innate anti-viral response. When cell is infected with a virus, it expresses and secretes type I interferons which bind to IFN-receptors on nearby uninfected cells. Induces anti-viral response from these cells so when virus multiplies in first cell and tries to spread to the nearby cells, those cells will already be primed with the IFN response -degrade viral RNA and inhibit viral protein synthesis. This slows down viral multiplication and the spread of the virus to other host cells. -can trigger apoptosis in infected cells and help with the activation of immune cells. By themselves will not get rid of all virus from the host. But will help slow the virus enough to let NK cells, cytotoxic T cells, and antibodies do their job more effectively.