1.1.3 Innate Immunity Flashcards
What are the hallmarks of innate immunity?
Immediate response, same response to repeat encounters, respond to invariable structure and does not react to host
What is the role of the epithelial barrier?
It is a physical barrier, killing microbes by locally produced anti-biotic peptides, and killing by lymphocytes
Neutrophil characteristics?
Most abundant leukocyte in the blood, 1st responder to bacterial and fungal infection, and ingest and destroy pathogens
What are neutrophils stimulated by?
G-CSF
Increased number of band neutrophils is a sign of what?
Infection
What is severe congenital neutropenia and how is it currently treated?
Dysfunction in neutrophil generation leading to recurrent severe bacterial and fungal infections. Currently treated with G-CSF.
What is the basic role of monocytes and macrophages in innate immunity?
These ingest and destroy microbes and produce cytokines to regulate other cells
What are PAMPs?
Pathogen associated molecular patterns
What is the importance of PAMPs?
These are structures that are shared by classes of microbes and are not present in normal cells. These are required for survival and infectivity
What are some examples of PAMPs?
LPS, peptidogylcans, terminal mannose, and Unmethylated CpG rich oligonucleotides
What are PRRs?
These recognize PAMPs. Referred to as Pattern recognition receptors.
TLR-2 recognizes
Bacterial lipoglycans and peptidoglycans
TLR-4 recognizes
LPS
TLR-5 recognizes
Flagellin
TLR-9 recognizes
Unmethylated CpG rich oligonucleotides
What is the TLR signaling pathway?
MyD88 interacts with IRAK which leads to activation of NF-kB. This will create inflammatory cytokines
What is the pathway of NOD-like receptors?
NLRP3 (inflammasome) activates caspase-1 which will then cleave Pro-IL-1B to IL-1B which will activate acute inflammation.
What is important about the complement pathway
This will lead to a deposition of C3b on the surface of microbe leading to MAC complex formation
What is the basic role of CRP?
It can activate proteins of the complement pathway
What is the role of TNF and what is it secreted by?
It is secreted by macrophages and T-cells and it leads to endothelial activation, neutrophil activation, and acute phase proteins
What is IL-1 function and what is it secreted by?
Macrophages secrete it and these activate acute inflammation
What are the function of chemokines and what are they secreted by?
Many cells secrete this including endothelial cells and fibroblasts. These lead to increased integrin affinity
What is the role of IL-6?
Liver synthesis of acute phase proteins and B cell proliferation of antibody producing cells
What is the process of extravasation?
Chemokines lead to integrin activation, then leukocytes adhere , and when stable adherence in achieved they will migrate into the tissue
What are the clinical signs of inflammation?
Heat and redness - cause by vasodilation Swelling, pain and loss of function - caused by increased permeability Pain - Swelling and stimulation of pain receptors
What is opsonization?
Marking of a pathogen for ingestion or destruction by a phagocyte
What is leukocyte adhesion deficiency?
Inherited deficiency in intergrin and selectin ligands leading to increased susceptibility to bacterial infections
What is the process of microbial destruction by phagocytosis?
Ingestion of microbe and creation of phagosome. This will fuse with a lysosome and create a phagolysosome which will destroy the pathogen.
What are some important enzymes associated with the phagolysosome?
NADPH oxidase - creates ROS iNOS - creates NO Lysosomal proteases
What is chronic granulomatous disease?
It is an inherited NADPH deficiency which will make it difficult to destroy the microbe
What is the role of NK cells with microbes?
These respond to a macrophages that have phagocytosed microbes. The macrophage will secrete IL-12 and interact with the NK cell. The NK cell will then secrete IFN gamma which will lead to the killing of phagocytosed microbes
What is the role of IFN-Gamma
It is secreted by NK cells to signal to macrophages to kill ingested microbes
How are viruses detected?
Mainly by TLRs that are recognized by MDAS, RIG-1, MAVS, and STING
What are some of the effects of Type I interferons (IFN alpha/beta)?
Induce resistance to viral replication, Increase expression of ligands for receptors on NK cells, Activate NK cells to KILL
What is recurrent HS encephalitis?
This is cause by a defect in the production or recognition of Type I IFNs leading to HSV in the brain
NK receives what signal from macrophages?
IL-12
What will lead to inactivation of NK cells?
MHC class I signaling
What are DAMPs?
Damage associated molecular pathogens
What interleukin is a regulator of inflammation?
IL-10 in an anti-inflammatory
What are some mechanisms of microbial evasion?
Resistance to phagocyte destruction - listeria Cell walls that are resistant to complement - staph Degradation of NKG2D ligands - cytomegalovirus
What are two important activating receptors on NK cells?
NKG2D and ADCC
How is gout an example of innate immunity gone bad?
Recognition of urate crystals and inflammation mediated by inflammasome
What is SIRS and its characteristics?
Systemic inflammatory response syndrome. Fever of more the 38 Heart rate higher than 90 BPM High respiratory rate and low CO2 Abnormal white blood count (high or low)
What is sepsis?
SIRS with a documented or presumed infection. Also has organ dysfunction and hypotension
What are the characteristics of septic shock?
Sepsis-induced hypotension Persistent hypotension and perfusion abnormalities despite having adequate fluid resuscitation.
What is septic shock caused by?
High levels of TNF-alpha
The patient has periodic fever syndrome
IL-1 antagonist
IFN-alpha
What are detectins?
Dectin-1 (dendritic cell–associated C-type lectin 1) and dectin-2 are dendritic cell receptors that serve as pattern recognition receptors for two life-cycle stages of fungal organisms.
What are defensins?
Antimicrobial peptides that are produced by the epithelial cells of mucosal tissue
What is the sequence of events in the migration of blood leukocytes to sites of infection?
At sites of infection, macrophages and dendritic cells that have encountered microbes produce cytokines (e.g., tumor necrosis factor [TNF] and interleukin-1 [IL-1]) that activate the endothelial cells of nearby venules to produce selectins, ligands for integrins, and chemokines. Selectins mediate weak tethering and rolling of blood neutrophils on the endothelium, integrins mediate firm adhesion of neutrophils, and chemokines activate the neutrophils and stimulate their migration through the endothelium to the site of infection. Blood monocytes and activated T lymphocytes use the same mechanisms to migrate to sites of infection. PECAM-1, platelet-endothelial cell adhesion molecule-1.
What is the role of C-reactive protein?
Opsonin; fixes complement and facilitates phagocytosis
