Innate Immunity- Immediate Response Flashcards
What are the three major categories of innate defenses?
Pre-formed defenses, immediate responses, and inducible responses
What is included in the mechanical immediate innate defenses?
Epithelial cells of skin and mucosal surfaces are joined by tight junctions, peristalsis, mucociliary elevator, tears, nasal cilia
What is included in the chemical immediate innate defenses?
Fatty acids (sebum) on the skin, Low pH and antimicrobial enzymes of the gut, pulmonary surfactant, antimicrobial enzymes in tears and saliva, and antimicrobial peptides
How do commensals contribute to the immediate innate immune defense?
By forming a physical barrier, competition for nutrients, and by producing growth inhibitors
In what layer of mucosal surfaces do commensal bacteria reside? Why?
Most are restricted to the outer layer of mucous, because the inner mucus layer is very dense and contains high concentrations of anti-microbial
What is the immune function of lysozyme? Which bacteria are most affected by it?
Digests peptidoglycan in bacterial cell walls; Gram positive
What are defensins and how do they contribute to immune defense?
Peptides that penetrate and disrupt membranes of bacteria, fungi, and viruses by forming pores. The membrane loses integrity and the microbe is lysed
What is the first defense system to respond to a pathogen that breaches the physical barrier defense?
The alternative complement pathway
What are the outcomes of activating the alternative complement pathway?
Direct destruction of the pathogen, induction of local inflammation, or routing of the pathogen to local macrophages for phagocytotic destruction
How and where are complement system proteins synthesized? How are they activated?
Synthesized as zymogens by the liver and activated by cleavage
What is complement fixation?
The attachment of C3b to a pathogen surface
What is the consequence of a C3 deficiency?
Recurrent and severe infections by pyogenic (pus-forming bacteria)
What are the three complement pathways?
Classical, Lectin, and Alternative Pathways
What step converges all of the complement pathways?
Cleavage of C3 to C3a and C3b
Why does the alternative complement pathway act first?
There is always C3 in the plasma, and it is constantly undergoing a low level of hydrolysis in fluids
What is the C3 convertase of the alternative pathway? Classical pathway?
C3bBb; C4b2a
What cleaves factor B in the alternative pathway?
Factor D
What is the function of properdin?
Stabilization of the C3b and Bb complex
What is the C5 alternative convertase?
C3bC3bBb
Which complement fragment triggers formation of the membrane-attack complex?
C5b
How does the membrane-attack complex kill pathogens?
C6-C9 assemble into the MAC, which kills by creating a pore in the microbial membrane leading to lysis
What is the classical C3 convertase? Classical C5 convertase?
C4b2a; C4b2a3b
What is opsonization? For which microbes is this process most necessary?
The coating of a pathogen by C3b (or antibody) so it is more readily taken up by phagocytes; encapsulated bacteria
What is the function of C3a, C4a, and C5a?
They are anaphylatoxins, which can tirgger histamine release, stimulate muscle contraction and increase vascular permeability. Additionally, C5a is a chemoattractant for neutrophils and monocytes
What are the 3 essential roles of inflammation in combating infection?
Delivers addiitional affector molecules and cells, activates endothelial cells trigger the coagulation system’s kinin cascade, inducing local blood clotting, and it promotes repair of injured tissue
What cytokine is responsible for the heat associated with inflammation?
IL-6
How does activation of resident macrophages contribute to a local inflammatory repsonse
Production of proinflammatory cytokines (e.g., Il-1beta, TNF-alpha, IL-6
What are acute phase proteins? How are they made and what if their function?
Proinflammatory cytokines stimulate liver hepatocytes to produce c-rective protein, ficolins, and mannose-binding lectin which work to activate the classical and lectin complement pathways
What are lectins?
Cell surface receptors or soluble proteins that recognize carbohydrates
What is a MASP? Which are attached to MBL?
MBL-associated serine proteases; MASP-1 and MASP-2
How does Mannose binding lectin activate the lectin pathway?
The MBL-MASP complex binds to terminal mannose residues on pathogens, resulting in a conformational change that activates MASP-2, which cleaves C4 to C4a and C4b and C2 to C2a and C2b
How is the classical complement pathway activated?
The C1q subunit of C1 binds to c-reactive protein on a pathogen yielding a conformational change that activates C1r and C1s subunits
How is the classical C3 convertase formed in the classical pathway?
C1s, activated by C1q binding to CRP, cleaves C4 and C2 to form C4b2a
What membrane molecule is required for binding of c-reactive protein?
Phosphorylchlorine
How do antibodies contribute to the complement system?
IgM and IgG (not 4) have C1q binding sites- so antibodies bind to pathogen and then attract complement
What is an immune complex?
Antigen bound to antibody
How does the classical pathway contribute to the elimination of soluble immune complexes?
BInding of C1 to IgG:antigen complex activates the classical pathway, resulting in the deposition of C3b on the complex. RBCs express C3b receptors and bind to complex and deliver it to Kupffer macrophages in the liver
What type of cell normally removes immune complexes in kidney glomeruli?
Mesangial cells
What results from classical complement component deficiencies?
Sustained formation of immune complexes that causes aggregation and precipitation at the basement membrane of blood vessels of renal glomeruli or synovial tissue of joints, can lead to vasculitis
What is subacute bacterial endocarditis?
A prolonged bacterial infection on the heart valves and induced inflammation damage valves results in a stong antibacterial IgG response that results in the formation of immune complexes that become trapped in the renal glomeruli and cause glomerulonephritis
What is mixed essential cryoglobulinemia?
Rheumatoid factor IgG complexes or IgG complexes produced in response to chronic infections (Hep C) that induce formation of immune complexes that get trapped in glomeruli, and small blood vessels of the skin, nerves, and other tissues causing inflammation and vasculitis
What is the precipitating factor in systemic lupus erythematus?
Autoantibodies (often to DNA)
What is associated with C5-C9 or Properdin deficiency?
Associated with increased susceptibility to Neisseria species,which cause gonorrhea and bacterial meningitis. that results in recurrent meningococcal meningitis
What is a CH50 assay?
Complement activity in plasma is measured by testing the ability of the patient’s serum to lyse antibody-coated sheep RBC
What is the CH50 level of a patient with a defective complement component relative to a normal patient?
Less than normal- zero if absent
Why don’t C5-9, Properdin deficiencies more significantly weaken the defense?
Some C3 cleavage still occurs in the absence of properdin, and the action of C1-C4 are more important than the MAC
True or False: All complement components are spontaneously activated at a low rate in plasma and sometimes bind to protein on host cell surfaces?
True
What are the safeguards against unnecessary and prolonged complement activation?
Released complement fragments usually only bind to nearby cells and complement components are rapidly inactivated by hydrolysis unless they bind to a surface
What are the soluble plasma proteins that control complement and their function?
C1 inhibitor limits activation of C1, Factor H and Factor I prevent C3 convertase from forming
What are the important complement control proteins on human cell membranes and their function?
Decay accelerating factor and membrane cofactor protein disrupt C3 convertases, CD59 and vitronectin prevent formation of MAC
What are the consequences of no C1-INH or dysfunction?
Chronic activation of classical and lectin complement pathways, leading to overproduction of C2 kinin and bradykin which causes extensive swelling and angioedema
What are the two types of hereditary angioedema? Which is more common?
Type I (decreased plasma level of C1-INH) and Type II (normal levels, but defective protein)
How does hereditary angioedema present?
Characterized by painful recurring attacks of swelling in the hands, feet, face, throat, abdomen, or genital areas
How do Factor H and I work together?
Factor H binds to C3b allowing Factor I to cleave C3b into an inactive form
What is the result of a Factor I deficiency?
C3 depletion, reduced complement fixation-> reduced bacterial clearance, increased susceptibility to infections by encapsulated bacteria
How do DAF and MCP function?
DAF binds to C3b, causing its dissociation; MCP binds to C3b, making it susceptible to cleavage and inactivation by Factor I
What is the cause of paroxysmal nocturnal hemaglobulinuria? How is it characterized and what causes this?
CD59 and DAF deficiency; Characterized by very dark urine in the morning due to contration of red blood cells lysed by MAC
True or False: Soluble innate effectors are effective against pathogens that present both extracellularly and intracellularly.
False
