Innate Immune System Flashcards
What is the role of the immune system?
Defence against threats of disease of pathogens and some tumors
What are the two arms of the innate immune system?
Cellular and humoral
What does the humoral response utilise?
Utilises pattern receptors, enzymes and cytokines
What does the cellular response utilise?
Utilise phagocytes and naturka killer cells
4 signs of inflammation?
Rubor (redness)
Tumor (swelling)
Calor (heat)
Dolor (pain)
How is inflammation caused?
When skin is damaged histamine (or another chemical sugnal) is released. This causes dialation and icnreased permiability if local blood vessels cause migration of phagocytes to consume bacteria and cell debris
What is PRR?
Pathogenic recognition recpetors
What an example of a PRR?
Toll like receptor
What are the parts if bacteria that PRR recognise?
Theyre called PAMPs pathogen associated molecular patterns
What is an example if a PRR and PAMP couple?
PRR- toll like recpetor 4 TR4
PAMP-lipopolyaacchride found on bacteria membranes
When PAMPs bind to TRs what are the two pathways?
MyD88 and TRIF pathways
What does the MyD88 pathway trigger?
This pathway triggers the TF, NF-KB which increases transcription aof inflammatory genes.
What does the TRIF pathway trigger?
TRIF pathway triggers TFs called IRFs which increase expression of interferons.
What is the MyD88 pathway?
MyD88 uses a universal TIR adaptor to bind to the TLR. MyD88 promotes association of IRAK1 and 4. 4 phosphorylates 1 allowing binding if TRAF6 once dimerise with IRAK1. Complexes wirh TAK1 which activates NGkappaB and MAP kinase pathways increasing transcription.
Whats thep prpose of an NK cell (natural killer)?
Immune surveillance of cancer and viral infected cells
What is a dendritic cell?
Antigen presenting cell can also produce cytokines
Whats the purpose of a macrohpage?
Phagocytosis and cytokine production
What is the purpose of a neutrophil?
Phagocytosis and enzyme production
What do cytokine receptors signal too?
JAKs and STATS
What is a JAK?
Janus kinase- molecules when active (by cytokines) have tyrosine kinase activity phosphorylating allowing for SH2 binding if STATs
What are STATs?
Signal transducing and activator of transcription molecules- a tf that bonds DNA sequence that promotes transcription of GAS elements
What are GAS elements?
Gamma interferon activation sites
What two effects can cytokines cause?
Systemic or local
Whats are local effects of cytokines?
Adhesion molecules, permeability ,flow rate and chemokine expression
What are systemic effects of cytokines?
Liver (acute phase proteins)
Hypothalamus (fever)
Bone marrow (mobilisation)
Name 5 cytokines:
IL-1beta TNF-alpha IL-6 IL-12 CXCL8
What does cytokine IL-1beta do?
Activates vascular ednothelium,lymphocytes, local tissue destruction ans increases acess of local effector cells
What does cytokine TNF-alpha do?
Increase vascular permeability, entry of IgG and incressed fluod drainage by lymphocytes
What does cytokine iL-6 do?
Activated lymphocyte production/activation and increase antibody production
What does cytokine CXCL8 do?
Chemotactic factor recruits neutrophils,basophils and Tcells to infection site
What does cytokine IL-12 do?
Activates NK cells imduces differentiation of CD4 Tcells into T1 cells
What is complement activation?
Complement activation is when one zymogen precursor is cleaved leading to the next cleavage and next after that .
What are the 3 mamillian complement pathways?
Classic activation pathway
Mannose-lectin activation pathway
Alrernative activation pathway
What complement components are used in the classic activation pathway?
-C1q,C1r, C1-S, C4,C2 and C3
What complement componentd are used in the mannose-lectin activation pathway?
-MBL MASP1, MASP2, C4 ,C2 and C3
What complement components are used in the alternative activation pathway?
C3, B,P and D
Where do all complement pathways converge?
Proteolytic activation of C3
What does C3 cause?
Proteins C5,C6,C7 and C8 complex to form poly-C9 (membrane attack complex) forms pores in membrane leading to lysis
What does complement lead to?
Membrane attack complex making pores ending in lysis
What is poly-C9?
Membrane attack complex
What are neutrophils?
Also known as polymorphnuclear leuocyte (PMN) are recruited first ton infections by interlupin 8 they detect a phagocytose pathogen with lysosomal killing mechanisms
What are neutrophils known as?
Polymorphnuclear leuocyte
How od neutrophils kill?
Lysosomal killing machanisms
What is leukocyte extravation?
The movement of leukocytes outo f the circularory system and towards sore of tissue damage and infection
What are the steps of leukocyte extravasation?
1) chemoattraction
2) tethering and rolling
3) migration througg cell wall
What is chemoattraction in leukocyte extravasation?
The leukocyte stops moving with the blood and moves to vessel wall due to chemokines
What is the tethering and rolling stage of leukocyte extravasation?
Leukocytes have L-selectin which bind onto the P and E selectins in the vessel wall. Both also bind to sialyl lewis X glucan epitope present on leukocyte
How does full arrest of leukocyte movement occur in leukocyte extravasation?
Conformation change of integrin LFH-1 allows toght binding to ICAM-1 on endothelial cells
How does the extravasation step of leukocytes occur?
Neutrophils squeeze between endothelial cells into tissue attracted by chemokines ar site of infection
Name 4 types of macrophages?
Kuppfer cell
Microglia
Osteoclast
Alveolar macrophage
Where do you find the kuppfer macrophage?
In the liver
Where do you find the microglia macrophage?
The Brain
Where do you find osteoclast macrophage?
In the bone
Where do you find alveolar macrophage?
The Lung
What is phagocytosis?
The ingestion of bacteria or other material by phagocytes
How does phagocytosis occur?
Chemotaxis and adherence of the microbe, then you have ingestion of the microbe by pseudopods - forming a phagosome. The phagosome then fuses with a lysosome forming a phagolysosome. Microbe is digested forming a residual body that is then expelled
Mechanism of destruction for pathogens in phagocytosis?
Acidification Toxic oxygen derived products Toxic nitrogen oxide Antimocrobial peptides Enzymes
