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Flashcards in Intro and Innate immunity Deck (37)
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What is immunology?

the study of the molecules, cells and tissues concerned with the defence of the body against any substance that is foreign to the body (non-self)


What does the immune system defend against?

Viruses: Influenza virus (flu)
Bacteria: Clostridium tetani (tetanus)
Protozoa: Plasmodium (malaria)
Fungi: Candida albicans (Candidiasis, also known as thrush)
Helminths: Tapeworms


What are the two types of immunity?

Innate and adaptive


What is innate immunity?

You are born with it
Represents the most ancient form of immunity and is present in some form in all animals
Is able to respond immediately to presence of pathogen: the first line of defence


What does the innate immune system comprise of?

Physical barriers
Inflammatory response of tissues, such as:
Biochemical factors - complement
Cells - neutrophils, macrophages, eosinophils and natural killer cells


What is adaptive immunity?

Acquired by experience - you trigger it upon exposure
It is specific for an antigen
It takes a number of days to respond to exposure of a pathogen but subsequent responses are greater in amplitude and more rapid: MEMORY


What is adaptive immunity made up of?

T-cells and B-cells


What are antigens?

Foreign antigens - non-self molecular configurations recognised by B and T lymphocytes
They activate the adaptive response
Lymphocytes do not recognise whole antigens, they recognise small non-self molecular portions of antigens that are known as epitopes


What are lymphocytes?

Possess protein surface receptors that recognise epitopes - however each one only has one specificity of a receptor - therefore one epitope
There are therefore millions of different clones of lymphocytes - immunological repertoire


Describe some immunological dysfunctions?

Too Much - Hypersensitivity
Can't detect between dangerous and helpful foreign material, therefore food allergies can arise

Too little - Immunodeficiency
Very susceptible to disease

Joint issues, type 1 diabetes

Transplant rejection


What are the two parts to innate immunity?

Steady state - immediate
Inflammatory - early host defences


What are haeatopoietic stem cells?

They are multipotent cells, capable of renewal
All differentiated blood cells from the lymphoid and myeloid lineages arise from HSCs
They influence transcription factors to determine what kind of white blood cell is formed


What types of myeloid cells are involved in innate immunity?

Phagocytes: neutrophil, dendritic cell and macrophage
Secretory cells - eosinophil and mast cells
Lymphoid secretory cells - natural killer (NK) cell


Describe a neutrophil?

Short lived, found normally in the blood
Migrate during inflammation
High phagocytic granulocyte
Produces vast repertoire of antimicrobial factors


Describe a dendritic cell?

Found throughout the body
Link between innate and adaptive immune response, via secretion of cytokines and antigen presentation (to T-cells)


Describe a macrophage?

Found in most if not all tissues
Highly phagocytic and antimicrobial
Directs both innate and adaptive through secretion of cytokines and antigen presentation
Important for non-inflammatory clearance of apoptotic cells


Describe eosinophil cells?

Found in blood, gut, lungs and urogenital tract
Important in helminth infection (worms)
Involved in allergy and asthma
Contains toxic granules and inflammatory mediators


Describe mast cells?

Found in tissues
Involved in allergy and histamine release (increases vessel permeability)


Describe Natural killer cells?

Found in blood and tissues
Cells are crucial for recognising changes in tumour cells and virally infected cells - target and kill these cells
They either detect the lack of host proteins or the induction of stress proteins

They have both activating and inhibitory receptors
When activated they produce granules containing perforin and granzyme B that will kill the tumour cells
Perforin forms pores to allow entry of granzyme B, which then triggers apoptosis of target cells


What is steady state response?

Immediate innate response (0-4 hours)
After infection, recognised by pattern recognition receptors, complement and then the infection is removed


Examples of pre-inflammatory defences?

Structural barriers: skin and mucosal pH
Soluble molecules:
Defensins (antimicrobial peptides), secreted by epithelial cells etc
Lysozyme secreted by macrophages
The complement system


How does innate immunity recognise pathogens?

Pathogen associated molecular patterns - PAMPs
Components unique to microbe- not normally produced by the host
Essential for microbial survival
Difficult to mutate to escape (evade) the immune response
We have receptors that recognise PAMPs - pattern recognition receptors


What are some classes of pattern recognition receptors? What do they survey?

Toll-like receptors
Carbohydrate binding lectins

All cellular environments: soluble (blood), intracellular and vacuolar sensors


How can we discover immune genes?

Loss of function - to see if the gene necessary
Gain of function - to see if the gene sufficient


What can enhance the immune system?

DAMPs - Damage associate molecular patterns
When dying they could release: HSPs, ATP, nuclear proteins and extracellular matric components (hyaluronic acid)
Therefore they can identify naturally dying cells - as these chemicals aren't normally released when undergoing apoptosis


What is the size of particles that phagocytosis will take up?

Large particles - >0.5µm


What happens in phagocytosis?

The phagocyte is attracted to the pathogen from the chemoattractants
Receptors (either antibody-coated particles or complement-coated particles) bind to the surface of the pathogen
The phagocyte invaginates around the virus which engulfs it
The lysosomes move towards the pathogen and eventually forms a phagosome
The lysosomes release hydrolytic enzymes which breaks down the pathogen
Waste products will be discharged eventually


How are hydrolytic enzymes in phagocytosis activated? What do they do?

Proton pumps are are used to make the vacuoles more acidic and activate certain hydrolytic enzymes: protinases, lipases and hydrolytic enzymes

The low pH aids the killing of microbes as well as the activation of degrading enzymes


What are the killing mechanisms of macrophages and dendritic cells?

Proteolytic and hydrolytic enzymes
Reactive oxygen species/reactive nitrogen species - superoxides and hydrogen peroxide (toxic to the cell)
Antimicrobial peptides - target the differences in bacterial membranes
Nutrient deprivation


What is the outcome of phagocytosis by macrophages and dendritic cells?

Presentation (activation of T cells, future lectures)
Removal of apoptotic cells
Production of cytokines (group of soluble proteins that have various immunomodulating effects) and inflammatory molecules- critical for inflammation