52-Granulocytes and Protein Components Flashcards
Overactive granulocyte activation
Allergic symptoms
Overactive pathogen sensing receptors
Autoimmune disorders
Defects in protein components
Increased risk of infection
granulocytes
eosinophils, basophils, mast cells
Contains large granules that are released non specifically upon activation
What do granulocytes protect
Epithelial and mucosal surfaces from multicellular parasites and mucosal pathogens
Role of mast cells
Sentinels
Recruit eosinophils and basophils
Activation of mast cells
Production of IgE antibodies from antibody producing B cells after encountering pathogen
IgE antibodies bind Fc epsilon receptor to release histamine
Activation of eosinophiles
Priming with cytokines, soluble Its, or pattern recognition receptor ligans
Activation with immobilized Its, microbial produces, interim engagement, cytokine mediators
Function of inflammatory mediators
Create hostile environment for pathogens that are too big to eat
Directly kill pathogen
Further activate immune response
Function of histamine
Alter smooth muscle contraction, vascular permeability, and neuron function
Inflammatory mediators
Histamine Protease and antimicrobial peptides-kill pathogens Lipid mediators Cytokines-alter function of immune cells chemokines-recruit other cells
Inappropriate granulocyte function
Linked to human disease
What causes allergies and asthma
eosinophils and mast cells
Drugs that inhibit granulocyte function
Antihistamines
anticytokine drugs
NSAIDS
croticosteroids
Type 1 interferon release
Antiviral response
Detected by toll like and RIG-I receptors
Induction of genes encoding type 1 IFNs
Release of IFN into environment and binding to receptor
What happens after IFN bind receptor
Activation of downstream signaling pathways JAK/STAT
Induction of IFN stimulated genes (ISGs)
What drives the transcription of type 1 INF
IRF3, IRF7, NF-kB, and MAP kinase pathways
Function of IFN
Upregulated ISG
Stimulate antigen presenting cells
Enhance functions of NK, T, and B cells
What does up regulation of ISG do
Suppress viral function by blocking replication cycle
What does stimulation of antigen presenting cells do
produce inflammatory cytokines and enhance presenting function
What do NK, T and B cells do
NK and T-target and kill
B-produce antibodies
defensins
Small antimicrobial agents
Positively charged
Bind to negative pathogen membrane
Form pore to destroy pathogen
cathelicidins
Small antimicrobial agents
Positively charged
Bind to negative pathogen membrane
Form pore to destroy pathogen
Where are defensins and cathelicidins found
Neutrophils, macrophages, mast cells
paneth cells
keratinocytes
Defensins and cathelicidin in neut, mac, and mast
In primary and secondary granules
Defensins and cathelicidins in paneth cells
In crypts of small intestine
Large quantities of defensisns
Suppress growth of commensals and pathogenic in mucosal tissue
defensisns and cathelicidns in keratinocytes
Decrease the growth of pathogens on the surface of the skin
Collectins
antimicrobial
form trimer with ficolin and then higher order complex
increase phagocytosis or complement binding
ficolins
antimicrobial
form trimer with collectins and then higher order complex
increase phagocytosis or complement binding
antimicrobial proteins
ficolins
Surfactants
Mannose binding lectins
collectins
function of collectins and ficolins
form trimers and higher order complex to increase phagocytosis and complement binding
avidity effect
increase affinity of entire complex by forming higher order structures
what do ficolins bind to
N acetyl glucosamine
what do mannose bind to
mannose derivatives
what do surfactants A and D bind to
mannose and glucose derivatives
what do human glycoproteins contain
galatose, fructose, and sialic acid
how do collectins and ficolins find pathogens
different sugars on surface than humans
n acetyl glucosamine, mannose, glucose
vs.
galatose, fructose, sialic acid
complement system
30 proteins produced by liver
protein pathway in the innate response
kill pathogens and enhance immune function
what increases expression of complement protiens
infection and inflammation
3 methods of complement activation
lectin, classical, alternative
4 outcomes of complement activation
inflammation and chemoattraction
phagocytosis
membrane attack complex
antibody production
common complement cascade starting at C3
C3 cleavage into C3a and C3b
C3b stays on pathogen and coats it to enhance phagocytosis (opsinization)
C3b recruits C5 and cleaves into C5a and C5b
C5b recruits C6, 7, 8, 9
C9 forms a pore
C3a and C5a function as inflammatory mediators and chmoattractans
membrane attack complex
formed from polymerization of C9, bursting pathogen cells
effective against gram negative and enveloped virus
gram positive is immune
activators of classical pathway
antibodies IgM, IgG1, IgG3, or pentraxin
IgA and IgE do not activate
steps in classical pathway
binding of antibody/pentraxin recruit C1 complex (C1q, C1s, C1r)
recruitment of C1 complex cleaves C4 into a and b
C4b binds and cleaves C2
C4b/C2b complex serves as C3 convertase complex
pentraxins
proteins found in blood that resemble antibodies
C reactive protein
C1q
classical pathway
binds antibodies or pentraxin
steps in lectin pathway
activated by collectins or ficolins which are bound to MASP 2 and 3 which cleave C4
C4b stays and binds C2 which gets cleaved
C4b/C2b form C3 convertase complex
activators of lectin pathway
collectins or ficolins to sugar residues
steps in spontaneous activation pathway
C3 spontaneously cleaved by water, C3b binds to nearest surface
C3b binds complement factor B which cleaves into Bb and Ba
C3b/Bb form C3 convertase complex
goals of spontaneous activation pathway
amplify classical and lectin pathways
antibody independent pathway
regulators of classical and lectin complement pathway
C1 INH, C4bp inhibit C1 complex and C4b
regulators of spontaneous complement pathway
Cr1, DAF, MCP on surface of cells and factor H and I in blood
lack of complement proteins
increased bacterial infections
deficiencies of proteins in classical pathwya
autoimmune disorders
polymorphisms in suppressive factors
age related macular degeneration
atypical hemolytic uremic syndrom
deficiency in what factors cause increased susceptibility to infections
B, D, 3, 5, 6, 7, 8, 9
especially Neisseria
deficiency in what factors cause disease that resembles lupus
1, 2, 4
