Innate and Acquired Immunity Flashcards
1
Q
What are defensins?
A
- An array of antimicrobial peptides that protect almost every part of our bodies from a wide range of pathogens; ubiquitous, and produced by many cell types
- At a minimum, their production increases the minimum infectious dose of microorganisms
1. The higher inoculum that is needed to cause a disease, the less likely an organism is to cause symptomatic infection
2
Q
Describe the shape of the defensins. How does this shape determine their MOA?
A
- Amphipathic, alpha-helical structure (hydrophobic AA
side chains on one side and hydrophilic AA side chains on other side): rich in + charged AA (ARG and LYS) - Multiple copies can multimerize via hydrophobic interaction, and overall + charge causes them to insert across (-) charged outer bacterial envelope (more effective in G- bugs)
- Once inserted, the hydrophobic faces of each peptide monomer interact w/the hydrophobic lipids of the outer
envelope, while the hydrophilic faces come together to form a pore in the surface of the pathogen (bactericidal)
3
Q
What is the primary source of defensins in the gut?
A
Paneth cells
4
Q
What are cathelicidins?
A
- A type of antimicrobial peptide (distinct from defensins) that is produced in lysosomes of macrophages, neutrophils, and epithelial cells
- Secondary structure of alpha helical and beta sheet motifs
5
Q
Is the MAC more effective against G- or G+ bacteria?
A
- Much more effective as a defense against G- (compared with G+) bacteria because of the differences in their outer envelop construction
6
Q
Explain macrophage-mediated initiation of inflammation.
A
- Injury to the skin w/bacterial pathogen in tissue
- Resident macrophage recognizes the bacterium via
PRRs and produces inflammatory cytokines to activate vascular endothelium, resulting in movement of fluid/inflammatory cells into tissue - Newly recruited phagocytes take up bacteria they encounter and produce more inflammatory cytokines (IL-1, IL-6, and TNF-alpha)
- Mvmt of fluid into tissues results in flow of fluid via the lymphatics toward the draining lymph nodes where APCs can present antigen to naïve T cells
- In many cases, innate phagocyte-mediated response can completely clear bacterial infection before symptoms
- If not, an amplified innate response will be produced to hold infection down until acquired response primed
7
Q
What is NETosis?
A
- A type of cell death that neutrophils can undergo that results in what is essentially the opposite of apoptosis
- Instead of the genome being digested (like in apoptosis), it is expelled from the cell in undigested form, allowing it to create a web or net of chromatin material that can entrap pathogens, preventing their dissemination
- Also results in expulsion of cytoplasmic contents, including digestive enzymes, anti-microbial peptides, etc.
8
Q
What are endocytic PRRs?
A
- Promote phagocytosis of microorganisms by phagocytes without relaying an IC signal
1. Primarily recognize carbohydrates, i.e., mannose, glucan, and scavenger receptors
9
Q
What are signaling receptors? Briefly describe the two types.
A
- Toll-like receptors (TLRs): recognize microbial constituents (LPS, flagellin, peptidoglycans, etc.), and mediate signaling that initiates cytokine production
- NOD-like receptors: cytoplasmic proteins that have affinity for microbial products; initiate signaling that results in production of inflammatory cytokines
10
Q
Identify four specific TLRs, and their primary functions.
A
- TLR2/6: heterodimers that recognize lipoteichoic acid (G+ bacteria) and zymosan (fungi)
- TLR3: bind to double-stranded viral RNA
- TLR4: heterodimers serve as receptor for LPS (G- bacteria)
- TLR7/8: recognize single-stranded viral RNA
11
Q
What are secreted PRRs? Provide at least 2 examples.
A
- PRRs secreted from host cells (e.g., complement receptors, serum amyloid, c-reactive protein, mannose-binding protein)
1. MBL: secreted PRR and acute phase reactant involved in initiation of the Lectin Complement Pathway
2. C-reactive protein: binds to phosphocholine residues to initiate the Classical Complement Pathway (also an acute phase reactant)
12
Q
List 5 of the cytokines released by macrophages in the innate response, and briefly describe their functions.
A
- IL-6: fever, acute-phase reactant production by liver
- TNF-alpha: activates vascular endothelium and increases vascular permeability locally, and also induces fever, mobilization of metabolites, and shock systemically
- IL-1beta: activates vascular endothelium and lymphocytes locally, and induces fever and produces IL-6 systemically
- CXCL8: chemotactic factor for neutro/basophils
- IL-12: activates NK cells
13
Q
How do IL-1, IL-6, and TNF-alpha released by macrophages work synergistically to initiate the innate immune response?
A
- Initiation of the acute phase response: stimulate the production of C-reactive protein and MBL
- Initiate neutrophil mobilization by acting on bone marrow endothelium, resulting in increased phagocytosis and killing of the pathogen.
- Act on both the hypothalamus and on fat and muscle to increase body temperature
14
Q
What is fibrinogen?
A
A critical acute phase protein important for the clotting cascade
15
Q
How does TNF-alpha localize inflammation and help limit the infection?
A
- Activates vascular endothelium, causing leakage of fluids into the tissues, increasing diapedesis of phagocytes from the circulation into the tissues and platelet
adhesion to the walls of small blood vessels - This results in occlusion of the blood vessels and prevents the bacteria form disseminating via the
blood, allowing time for local phagocytes to engulf and kill the organisms
