Intro and Innate immunity Flashcards by Kirsty Welshman

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)

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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

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What are the two types of immunity?

Innate and adaptive

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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

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What does the innate immune system comprise of?

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

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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

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What is adaptive immunity made up of?

Lymphocytes:

T-cells and B-cells

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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

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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

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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

Autoimmunity
Joint issues, type 1 diabetes

Transplant rejection

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What are the two parts to innate immunity?

Steady state - immediate

Inflammatory - early host defences

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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

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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

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Describe a neutrophil?

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

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Describe a dendritic cell?

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

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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?

Killing 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

What is the inflammatory phase?

The second phase of innate immunity Process: infection, recruitment of effector cells, recognition of PAMPs/activation of effector cells and inflammation, removal of infectious agent

What is inflammation?

The acumulation of fluid, plasma proteins and leukocytes, initiated by physical trauma, infection or local immune response Signs: swelling, pain, redness, heat and loss of function Acute inflammation - less than 6 weeks Chronic inflammation - more than 6 weeks

What are the stages of the inflammatory phase?

Initiation Recuitment of effector cells (mainly neutrophils) Resolution (switching off and removal of cells)

Describe initiation of the inflammatory phase?

An edema forms, activating a macrophage Then complementation activation (releasing soluble molcules: anaphylatoxins) - to help reduce swelling Chemoattractants are then released Bacterial uptake by macrophages and mast cell degranulation lead to increase in vessel permeability Increased permeability leads to increase in soluble components from blood, antibodies and complement Chemokines and bacterial products facilitate chemotaxis Inflammatory cytokines up regulate adhesion molecules on the endothelium and neutrophils allowing the recruitment of cells from the blood

Describe recruitment of the inflammatory phase?

1 Rolling 2 Activation (by chemokines) 3 Firm Adhesion 4 Extravasation (diapedesis - the passage of blood cells into a capillary) of neutrophils Leukocyte adhesion and migration mediated via cell surface adhesion receptors and chemokine receptors found on leukocytes and endothelial cells

Describe resolution of the inflammatory phase?

Neutrophils remove the infection via: NADPH oxidase-derived reactive oxygen species (ROS) Cytotoxic granule components Antimicrobial peptides Neutrophil extracellular traps (NETs) To generate a highly lethal environment that is essential for efficient microbe killing and degradation

What are some types of neutrophils?

``` Primary granules Secondary granules Tertiary granules Calprotectin Myeloperoxidase ```