Week 1_b Flashcards
Innate Immunity
Innate Immunity- non-adaptive host defense against pathogens.
• Conserved- same as eukaryotes.
• Genes encoding are present in the germ line-do not undergo rearrangement or hypermutation
Physical barriers to infection
- Physical- Skin and other epithelial surfaces (mucosal surfaces- GI tract, respiratory tract, urogenital tract)
Skin- barrier for noxious insults such as infection (bacterial, fungal, or parasitic)- has multiple layers of keratinocytes.
To infect skin there must be direct tissue damage
Mucosal surfaces- are a primary site of infection (viral, bacterial. Fungal, parasistic)
For protection these surfaces can secrete a thick mucus layer that acts as a physical barrier to cell surface interaction by microbes.
Cilia movement of lung propels particulate matter and foreign material and prevents microorganisms for establishing infection
Mucosal surfaces also secrete antibodies.
Also contain IgA that offers protection
Chemical barriers to infection
Skin- low moisture content and high acidity of sweat. Lysosomes in tears and saliva which degrade the peptidoglycan layer of bacterial surfaces. Antimicrobial peptides (AMPS) secreted by epithelial cells and phagocytes (defensins, cathelicidins, histatins)- ALL mess up pathogen membranes.
Phagocytic myelod cells important for innate responses
macrophages, neutrophils, and dendritic cells
Why are kearatinocytes impiortant as an impasse to pathogen invasion
skin is thick, multilayered, low moisture and acidic
Which Ab does mucosal surfaces have
IgA- acts as a dimer when active
what are the professional cells of the innate immune system
phagocytes- 3 major: neutrophil, macrophages, dendritic cells
- Macrophages/Monocytes- long-lived widely distributed leukocytes, first to respond, mature circulating monocyte, increase in number at site of infection, secrete cytokines and chemokines for immune cell recruitment, are Antigen presenting cells for T cells.
- Neutrophils- Short-lived leukocytes, most abundant white cell in the circulation, RARELY found in normal tissue. Quickly recruited to site of injury or infection, Primarily BACTERIALCIDAL- kills invading microorganisms.
- Dendritic Cells- Found in most if not all tissue, have pattern recognition receptors, BROAD acting, APC, phagocytosis of pathogens. May be the most important cells of the immune system. They are the gateway to the adaptive immune response and determine the type of response to occur.
Describe Mediator Productiion- one of the main fucntions of phagocytes
When immune cells (especially macrophages) are activated and develop a response to a pathogen, they can produce cytokines, program cells for microbial combat, chemokines- chemical attractant molecules that recruit additional leukocytes, lipid mediators- prostaglandins that affect how cells behave, and hydrolytic enzymes and antimicrobial peptides that assist in the clearance of pathogens. This can act as a solely innate response or it can be amplified by the adaptive response.
Describe Pathogen Associated Molecular Pattern Recognition (PAMP)
MAny cells have highly conserved PAMP recognition receptors (PRRs) . PAMPS are present on most pathogens.- virus, bacteria, fungus, so PRRs can recognize these PAMPS to mount an immune response.
The PRR- TLR
Toll-like receptors are transmembrane receptors, and specifically recognize viral nuclei acids.
Also recognize bacteria, yeast, and fungi
The PRR-CLR
c-type lectin receptors- recognize sugar, mannose-conainigng structures. IT is transmembrane
The PRR- RIG-I-like
It is soluble and recognizes double stranded RNA and viruses.
What are Antimicrobial peptides (AMPS)
peptides made by epithelial cells and phagocytes that disrupt antigen membranes. The are small protein membranes that have electrostatic attractions that can insert into the membranes of microbes. (defensins, cathelicidins, histatins)
Major proinflammatory cytokines for fever, pain, and inflammation (local effects)
IL-1B, TNF-alpha (increases entry of IgG, complement, and cells and increased drainage of lymph nodes), IL6
PPR- NOD-like receptors
tracellular sensors of PAMPs that enter the cell via phagocytosis or pores an d DAMPs that are associated with cell stress. Soluble
Describe antigen presentation
DC and macrophages engulf microbes and display antigen via MHC clas I and II molecules
difference between MHC I and II
I- presents peptides in cells (cytostolic peptides) MHC II- presents exogenous antigens-
Describe Innate Lymphiod Cells
Broad acting, invariant cells that are similiar to lymphocytes.
Type 1- NK cells- produce IFN-gamma and activate dendritic cells
Type 2- produce IL4 and secre antimicrobial peptids to shut down extracellular microbes
Type 3- produce IL-17 for immunity to worms
Major ILC
natural killer cells. (type I)
Major inflammatory cytokines produced during a viral infection
INF-alpha and INF- beta
Key Pathogen Recognition Receptors
Activate in minutes
How to TLR recognize and respond to lipid antigen
TLR bind to lipid side chains and this leads to dimerization and an activation response that activates NFKB
How is IL-1B activated
PAMPS activate inflammasome which activates capase I which cleaves the precursor IL-1B for form the mature form.
Function of NFKB
Activates genes encoding proinflammatory cytokines
What is a secreted PRR
Mannose binding lectin- which activates the complement system
Role of complement system in bridging innate and adaptive immunity
Augment AB responses
lyse foreign cells
clear immune complexes and apoptotic cells
Can PRRs produce ROS
yes- neutrophils engulf bacteria, phagosome is produced and fuse with primary and secondary granules and a NADPH oxidase in the membrane and ROS is produced for microbial killing
Key events of inflammatory response
- Alteration of blood flow- vasodilation
- Increaed vascular permeability- endothelial cells contract to enlarge junctions for increased leakage of serum contents into tissue
- Infliltration of WBCs- Neutrophils, then macrophages (dilate blood vessels), then lymphocytes arrive- blood clotting occurs at site of microvessels
Major problem in systemic infection
Systemic coagulation and break down of endothelium, swelling, fluid loss and drop in blood pressure.
Ig classes and side chains
IgG - predominant Ab induced in secondary response (gamma)
● IgA - predominant Ig in external secretions (alpha)
● IgM - predominant Ab induced in primary response (mu)
● IgD - found mainly on surface of B cells (delta)
● IgE - involvement in allergic hypersensitivities (epsilon)
Domain
series of repeating, homologous units, about 110 AA, fold independently
regions of chain
1. Constant region - amino acid sequence in the Cterminal regions of the H and L chains is the same. 2. Variable region - amino acid sequence in the Nterminal regions of the H and L chains is different. This region provides antibodies with unique specificity. 3. Hyper-variable regions are regions within the variable regions (greater specificities). The hinge region is the area of the Ig where the arms of the Abs form a ‘Y’,it is a flexible region. Igs also have domains formed from folds of the globular region containing the intrachain disulphide bonds and they are VL and CL (light chain domains) and VH and CH (heavy chain domains), seen in the three dimensional images of the Ig