What is the first line of defence for the body?
Physical barriers:
Skin - turn over rate means microorganisms are shed; low pH; sweat glands secrete protective oils
Mucous - traps foreign particle in mucociliary escalator; has antimicrobial properties
Commensal bacteria - on skin and in GI tract compete with pathogens
What is the immune system?
Network of specialised cells, tissues and soluble factors cooperating to kill disease-causing pathogens and cancer cells
What are the major components of the immune system?
Wbcs
Soluble/humoral factors
What are the wbcs?
Phagocytes (neutrophils, monocytes/macrophages, dendritic cells)
Lymphocytes (T and B cells, Natural Killer cells)
Mast cells
Eosinophils
Basophils
What are soluble/humoral factors?
Antibodies
Complement System proteins
Cytokines (involved with cell signalling)
Acute Phase Proteins
What are antibodies? What do they do?
Immunoglobins (glycoproteins) produced in response to an antigen and bind to it
Provide defence against extracellular pathogens and toxins
What is an antigen?
Substance that can stimulate immune response
Have an EPITOPE, that is complementary to the antibody
What is the complement system? What is the function?
Family of around 30 different proteins produced in the LIVER.
Helps/complements ability of antibodies/phagocytes to clear pathogens
How do complement proteins work?
Enter infected/inflamed tissue and activated
Can enzymatically cleave and activate other downstream complement proteins in a biological CASCADE (capacity for HUGE AMPLIFICATION of response)
What are cytokines and when are they produced?
Small proteins involved with cell signalling and have a short half-life
Produced in response to infection, inflammation, tissue damage
Give examples of cytokines and what they do
Interferons - anti-viral activity
Tumour Necrosis Factor α (TNFα) - pro-inflammatory cytokine
Chemokines - control and direct cell migration via chemotaxis
Interleukins - various functions
Where do cells of the immune system originate from?
From haematopoietic stem cells
What are the phagocytic cells and what do they do?
Monocytes, macrophages (in tissue), neutrophils
Ingest and kill bacteria/fungi (phagocytosis)
Ingest and clear debris, like dead/dying apoptotic cells and immune complexes (antigen/antibody complexes)
Sources of cytokines that regulate acute inflammatory responses
What do monocytes do?
Circulate in blood (5% of all wbcs)
Migrate into peripheral tissues and differentiate into MACROPHAGES
What are the macrophages?
Long-lived tissue resident phagocytes: Kupffer cells Alveolar macrophages Mesangial cells Microglial cells
What do macrophages do, in addition to phagocytosis?
Limit inflammation
Involved in tissue repair and wound healing
Involved in antigen presentation
What are neutrophils? Where do they go once out of blood?
AKA polymorphnuclear cells (PMNS). Short-lived cells (half-life of 6 hrs in blood)
Phagocytic cells circulating in blood (50-70% of wbcs)
Rapidly recruited into inflamed, damaged and infected tissues
What are dendritic cells?
Antigen presenting cells (enable antigen recognition by T cells)
How do dendritic cells work?
Present in peripheral tissues in “immature” state
Phagocytose antigens
Mature and migrate into secondary lymphoid tissues (play key role in antigen presentation)
Dendritic cells, macrophages and neutrophils in order of killing ability?
Neutrophils
Macrophages
Dendritic cells
Dendritic cells, macrophages and neutrophils in order of ability to present antigens?
Dendritic cells
Macrophages
Neutrophils
What are mast cells? Function?
Reside in tissues and protect mucosal surfaces
What do basophils and eosinophils do?
Circulate in blood until recruitment to infected sites by inflammatory signals
What do mast cells, basophils and eosinophils have in common?
Highly granular cells and are the defence system against large pathogens that cannot be phagocytosed, like parasitic worms
Release chemical, like histamines , heparin and cytokines - involved with acute inflammation
Key role in mediating allergic response (overactive immune response to harmless substances)
Anti-histamines