lecture 17 B2: infection & innate immunity Flashcards
What are the main features of innate immunity: speed of response, relationship with time, pathogen to receptor ratio
Innate immunity is first line of defense against infection. Fast. Doesn’t change over time. It recognises traits shared by broad ranges of pathogens using a small set of receptors.
What is the cellular parts of the innate immune system
Cellular is myeloid lineage: leukocytes–esp neutrophils and macrophages, natural killer cells.
What are the humoral (soluble) components of innate immune system
complement, lectin binding proteins that activates complement, antimicrobial peptides that bind to the surface of bacteria causing it to lyse
What are the barrier defenses of the innate immune system
Skin, mucous membranes, the low pH of stomach, secretions like saliva and tears
What is the main point of innate immunity
To discriminate between self and non self
What is the age of innate immunity
500 million years ago. Even in primordial organisms.
What are the 3 interlinked processes of innate immunity
Complement, phagocytosis and Pattern recognition receptors (PRR)
What is complement
opsonisation of microbes by blood proteins and the production of anaphylotoxins that attract and activate phagocytes
What is phagocytosis
engulfment of the microbe by phagocytes (neutrophils and macrophages) that destroy the organism.
What is pattern recognition receptors
receptors found on mainly myeloid cells that recognise complex microbial molecular patterns
What are the three types of pathogens that make different infections that require different immune responses
Viruses, Bacteria yeast and fungi, and Protozoa and other parasites
What type of pathogens are viruses and how does the immune system target it
eg. influenza, HIV, smallpox, polio
intracellular pathogens that use host cell machinery to replicate itself. Need a way to distinguish infected vs normal cells
What type of pathogens are bacteria and how does the immune system target it
eg. cholera, scarlet fever, tb
Mostly extracellular pathogens that are engulfed by phagocytic cells. Most bacteria are distinguished by the Gram strain
What are the two types of gram strain that distinguishes bacteria
Gram + = s. aureus
Gram -= E. coli
Gram positive bacteria have thick cell walls and are resistant to direct complement MAC lysis, require phagocytosis. Gram negative have thinner peptidoglycan layer and an outer membrane and are often more sensitive to complement MAC lysis
What type of pathogens are Protozoa and parasites and how does the immune system target it
eg. malaria, helminths- worms
complex multicellular organisms that require direct killing by basophil, eosinophils and mast cells that release granules filled with cytotoxic chemicals (have to be in contact) Degranulation releases toxic inflammatory chemicals such as histamine
What is the purpose of neutrophil extravasation
It is how neutrophils migrate from the blood capillary to the site of infection/
What are the 5 steps of neutrophil extravasation in order
Activation, tethering, adhesion, diapadesis, chemotaxis
What is activation
Chemokines from tissue injury activate the endothelial cells lining the inside of the adjacent capillary wall.
What is tethering (ne)
Neutrophil slows and tethers to the inside of the capillary wall. mediated by unregulated selectin on endothelial cells and sialyl Lewis X, carb antigen on neutrophils
What is adhesion (ne)
Strong binding between neutrophil integrins and ICAM-1 on the endothelium. Neutrophil flattens out
What is diapadesis (ne)
Neutrophil squeezes between endothelial cells out of the capillary into the tissue into the interstitial space.
What is the chemotaxis (ne) outside the capillaries
Neutrophil migrates along a chemokine gradient to the site of infection
What complement receptors does neutrophils have.
CR1 to C3b complement protein on the surface.
But others CR2. CR3. CR4.
How do neutrophils migrate up the chemo attractant gradient (actin)
they polymerise actin filaments at their leading edge and de-polymerising those filaments
What initiates phagocytosis
The cross linking of the surface complement receptors initiates phagocytosis.
What are complement receptors and what has it
myeloid cell (neutrophils) receptors that bind activated complement components deposited on bacteria.
What is FcR (antibody) mediated phagocytosis (before phagocytosis)
Antibody (IgM and IgG) bind to bacterial antigens. This exposes the antibody Fc region. Neutrophil FcR binds multivalent Fc.
Activates phagocytosis.
What are the 5 steps of phagocytosis
Ingestion, Fusion, Acidification, Digestion and Exocytosis
What is ingestion
the membrane invaginates into a phagosome after the bacteria is captured by receptors.
What is fusion
The phagosome and lysosome fuse to form a phagolysosome
What is acidification
The phagolysosome acidifies, activating protease and stimulates the production of superoxides such as H2O2 and HOCl which kill bacteria.
What is exocytosis
explusion of the digested microbe
What is molecular pattern recognition
What is being bound to what
Innate mechanism where pattern recognition receptor (PRR) bind complex molecules (pathogen associated molecular patterns) (PAMP) that are unique to microbes.
What are the best known PRRs
Toll-Like Receptors (TLR) that are leucine rich repeat receptors that look like slinky.
ACtivation through TLR stimulates what
a strong innate response through an important inflammation pathway
What are PAMPs
recognised by PRRS. Structurally complex, evolutionarily stable. Stimulates the power switch for the adaptive response.
What is the receptor for LPS
TLR4
What is LPS component
A membrane component of all gram negative bacteria. Pyrogen that causes fever and can cause septic shock.
