Week 4 Flashcards
Barrier immunity
Barriers are anywhere that is open to the outside world and interacts with microbes or pollutants
Have a microbiota associated
Rich in immune cells
Mucus and chemical barrier defences help protect barrier organs
The skin barrier
Epidermis made up of keratinocytes a type of stromal cell
Keratinocytes can make antimicrobial peptides
Lower layers (eg dermis) rich in immune cells (macrophages and dendritic cells)
Examples of skin breaches: IV lines, burns, eczema
The respiratory barrier
Epithelium contains cilia, small hair like projections that brush microbes and debris out of the airway
Goblet cells make mucus to act as a a further physical barrier
Many immune cells in the lung, both in airspace’s and surrounding tissue (interstitium)
Airspaces also rich in secreted immune defences such as antimicrobial peptides and antibodies
Breaches may be caused by chronic lung inflammation and excess mucus (eg cystic fibrosis, smoking, COPD)
The gut barrier
Thick layer of mucus to separate the epithelial layer from gut commensals
Commensals are critical for proper development of the immune system
Epithelial layer changes depending on where you are in the gut
Area below the epithelial cells is called the ‘lamina propria’ and is very rich in immune cells
Gut is very concentrated with antimicrobial peptides and goblet cells
Breaches may be caused by antibiotics, surgery, chemotherapy
Innate immune cells key features
No memory
Fast acting
Inherited receptors (pattern recognition)
Often concentrated within barrier tissues
Innate immune cells function
Recognise pathogens:
-professional antigen presenting cells (APCs)
E.g. dendritic cells, macrophages
Engulf and destroy pathogens/sound the alarm:
-Granulocytes e.g. neutrophils, eosinophils, mast cells
-phagocytes e.g macrophages, neutrophils, monocytes
Neutrophils
Short lived (~2 days in blood)
Made in bone marrow (released into blood)
Numerous
Quickly infiltrate infected tissue
Granules
Strong anti-microbial activity
Neutropenia: too few neutrophils
Neutrophilia:too many neutrophils
Cytoplasm has vesicles
Monocytes
Short lived (~2 days in blood)
Made in bone marrow
Numerous
Quickly infiltrate infected tissue
Monocytes in blood, macrophages in tissue
No granules
Differentiate into macrophages once in tissues
Macrophages
Found in every organ of the body
Important for immune surveillance
During infection their numbers increase from monocytes which infiltrate tissues and differentiate into macrophages
Can act as antigen-presenting cells as well as phagocytes
Involved in nearly every aspect of physiology
Dendritic cells
Found in every organ of the body-important for immune surveillance (e.g Langerhans cells in skin)
Specialised at antigen presentation
Engulf pathogens and make peptides from them to present to lymphocytes and activate adaptive immunity
Eosinophils
Granulocyte
Tissue resident cells
Enriched in barrier sites like the gut
Involved in allergy responses, will migrate to lung during a reaction
Killing of antibody-coated parasitic worms
Mast cells
Granulocyte
Tissue resident cells
Enriched in barrier sites like the gut
Granules are full of histamine; important for vasodilation and increased blood flow
The complement system
Ancient part of immune system
Involves a cascade of proteolytic events (a snowball effect)
Uncleaved complement proteins
Broken down into smaller active proteins
Smaller proteins cause more reactions to make new proteins some of which form large complexes
Complement activation and outcomes
3 main pathways that activate the complement system;
-classical antibody binding
-lectin carbohydrate binding
-alternative C3 binding
Activate C3 convertase
3 major outcomes of complement activation:
-inflammation; anaphylatoxins boost inflammation and immune cells recruitment
-pathogen recognition; C3b deposition onto microbes to boost phagocytosis
-membrane attack complex; MAC forms pores in microbes to damage membranes
Pattern recognition receptors PRRs
PRR-PAMP binding
PAMP: pathogen-associated molecular patterns
Intracellular signalling
-antigen presentation and activation of adaptive immunity
-pathogen killing
-gene expression: production of cytokines and chemokines: interferons: switch on antiviral responses, growth factors; boost immune cell numbers , interleukins; direct immune responses, chemokines; co ordinate cell movement
Toll-like receptors TLRs
Really important for antibacterial immunity
Both extracellular and intracellular members
Many signal through similar intracellular signalling pathway using a protein called MyD88
Deficient in MyD88 cant activate immune response downstream from many receptors
C-type lectin receptors CLRs
Really important for anti fungal immunity
Much bigger family than TLRs
Many signal through similar intracellular signalling pathway using a protein called CARD9
CARD 9 deficient unable to activate immune response against fungal infection
NEMO deficiency
NFkB= transcription factor, master regulator of immune responses
Both TLRs and CLRs activate NFkB
Deficiency results in profound immune system defects as well as developmental problems
