Chapter 16 - Part 1 Flashcards
what does mast cell degranulation do? what is it perceived as?
enhance blood flow
itchiness and irritation
what attracts neutrophils to infection sites?
C5a, IL-8, and bacterial products
where are bacterial Ags processed and presented?
local LNs
what are processed bacterial proteins presented to?
Class II MHC molecules for differentiation of naive T cells
TRUE or FALSE:
Initially, IgM class Ab is produced, then affinity maturation, isotype switching, and finally clonal expansion.
FALSE
Isotype switching occurs LAST
in the resolution of an infection, what removes bacterial debris?
local macrophages and neutrophils, or by Abs
infections caused by pathogenic extracellular bacteria have what 2 mechanisms?
- inflammation causing tissue destruction
2. production of toxins with diverse pathological effects
what are bacterial toxins subdivided into?
endotoxins - bacterial cell wall components
exotoxins - secreted by the bacteria
what is a common endotoxin and what does it activate?
what can it lead to?
LPS activates macrophages, DCs and endothelial cells
leads to gram negative sepsis
what are 3 common extotoxins which are cytotoxic? what are their methods of action?
diphtheria - shuts down protein synthesis
cholera - ion/water transport interference
tetanus - inhibits neuromuscular transmission
what can exotoxins stimulate the production of?
cytokines that cause disease
what are the main mechanisms of innate immunity to extracellular bacteria?
complement act.
phagocytosis
inflammation
what activates the alternative complement system?
Peptidoglycans (gram +) and LPS (gram -) bacteria
what does the MAC lyse?
bacteria (Neisseria)
What are the 3 major effectors of the complement system?
anaphylatoxins (C4a/C3a/C5a)
opsonins (C3b)
MAC
What are the 3 mechanisms of prevention of host bystander damage (regulation)?
Factor I cofactor activity
Decay-acceleration activity for C3
Inhibition of lysis
what prevents C3b from forming active convertases?
Factor I
MCP
CR1
Factor H
what prevents C4b from forming an active convertase?
Factor I
MCP
CR1
C4BP
what proteins inhibit the classical pathway?
DAF
CR1
C4BP
what proteins inhibit the alternative pathway?
DAF
CR1
Factor H
What factors inhibit the MAC formation?
CD59
Vitronectin
S protein
Neutrophils and macrophages use surface ______ to recognize extracellular bacteria?
What receptors do they use to recognize bacteria opsonized with Abs and complement proteins?
mannose and scavenger receptors
Fc and complement receptors
what ingests and destroys bacteria?
recruited leukocytes
what does TLR1 and 2 recognize?
lipoprotein
What does TLR4 recognize?
what amplifies the detection?
LPS
CD14
What does TLR5 recognize?
flagellin
what does TLR9 recognize?
CpG DNA
what is the most important activator of the inflammatory response?
what adaptor protein is required?
NF-KB
MyD88
what detects intracellular pathogens?
NOD2 and NLRP3
what inhibits NF-KB activation?
CARD8
what mediates the production of Type I interferon?
TLR4, TLR9, NOD2
the formation of NLRP3 inflammasome results in what?
cleavage of pro-IL-1Beta and pro-IL-18 generating a matured form of cytokines
what is lactorferrin and what does it do?
Fe scavenger/exporter
grabs Fe 2+
iNOS converts what to what?
Citruline to Arginine
what does the NADPH oxidase utilize as a catalyst?
SOD (superoxide dimutase)
what are bacterial defense mechanisms?
modification of their surface
catalase expression, converts reactive species to less harmful compounds
prevention of protein complexes that synthesize RNS or ROS
what kind of bacteria uses resistance to phagocytosis as evasion?
pneumococcus
Neisseria meningitidis
what kind of bacteria uses scavenging of ROS for evasion?
catalase-positive staphylococci
how does humoral immunity function against extracellular bacteria?
block infection, eliminate microbes, neutralize their toxins
ABs responses against extracellular bacteria are directed at what?
cell wall Ags and secreted cell-associated toxins
humoral immunity is the principal mech of defense against what?
TI polysaccharide-rich Ags of encapsulated bacteria
what Ab may IFN-Gamma stimulate production of?
IgGs
what is the major injury in response to extracellular bacteria?
inflammation and septic shock
what causes septic shock?
endotoxin released by killed gram + or - extracellular bacteria, caused by cytokines that are produced by macrophages
what does TNF-alpha upregulate?
Tissue factor (TF) and iNOS
what does IL-18 do?
induces INF-Gamma –> act. macrophages
what cytokines activate neutrophils, lymphocytes and vascular endothelium, upregulate cellular adhesion molecules, induce prostaglandins, etc.
IL-1, 6, 12, 15, 18, TNF-alpha, IL-10 (negative regulator)
What chemokines mobilize and activate inflammatory cells (neutrophils) and act. macrophages?
IL-8, MCP-1, MCP-3
what lipid mediators activate vascular endothelium, regulate vascular tone, act. extrinsic coagulation cascade?
prostaglandins, leukotrienes
what oxygen radicals have antimicrobial properties and regulate vascular tone?
superoxide and hydroxyl radicals, NO
what do superantigens bind to?
class II MHC OUTSIDE the peptide grinding groove binds variable region of diff. TCR Beta chains regardless of specificty
what do superantigens cause?
polyclonal T cell activation
what are some SAgs in human disease?
food poisoning - SEA-SEE and SEG-SEI Toxic shock syndrome (TSS) Streoiciccal toxic shock syndrome (STSS) Acute rheumatic fever (ARF) Kawaski disease (KD) Autoimmune diseases
what causes TSS, what is the result?
S. aureus
capillary leak syndrome
what causes STSS, what is it
S. pyogenes
most severe form of invasive streptococcal infection
what causes ARF?
post-infection cause of preventable pediatric heart disease
what is KD?
acute multi-system vasculitis
what is the major mechanism used by bacteria to evade humoral immunity?
variation of surface Ags
What can activate the alternative or MBL complement system?
what is the result?
surface LPS, C-reactive protein
bacterial lysis
