Introduction to innate immunity Flashcards
What is immunology?
The study of physiological mechanisms that humans and other animals use to defend their bodies from invading organisms.
e.g.
- Bacteria
- Viruses
- Fungi
- Parasites
- Toxins
What are some passive defence mechanisms?
Skin
Mucous membranes
Both first lines of defences. Anatomical and secretory barriers that protect against pathogen entry
What is the first line of defence?
Protection against pathogen entry e.g. skin and mucous membranes
How does skin protect against pathogen entry
Acts as an external barrier
Also have a large variety and diversity of microbes on the skin surface which helps with being a first line of response as they can act on the pathogens before the enter the body.
What are some chemical and bacterial barriers?
Where are they found?
Oral cavity
- Saliva 00> 95% H2O, immunoglobulin A (identifies pathogens), amylase and lipase.
- Bacteria from the oral cavity can resist gastric acid and colonise in intestines
Stomach
- Gastric acid (pH2/3 –> aid digestion and protection)
Intestines
- Variety of microbes
Skin
- Sweat gland (pH5) –> secrete a wide array of antimicrobial peptides which restrain growth of various microbes on the skin
Lungs
- Mucus –> first line of innate defence, provides an essential first host barrier to inhaled pathogens that can prevent pathogen invasion and subsequent infection
Eyes
- Tears –> contains a substance called lysozyme which has antibacterial action and works to prevent invasion and infection by microbes
What is second line innate immunity?
Non-specific responses
- Innate immune cells
- Inflammation
- Complement
- Antimicrobial substances
May take a few days to become activated
What is part of 3rd line adaptive/ acquired immunity?
Specific responses
Specialised lymphocytes
1. B cells –> produce antibodies
2. T Cells –> T Helper cells –> T Killer cells
What are tissue resident cells?
Cells that live close to areas where defence is required, e.g. lungs, gut, eyes, skin
What are immune cells
Stem cells synthesised in the bone marrow
1. Lymphoid stem cells
- T Lymphocyte (thymus)
- B Lymphocyte –> Plasma cell (mature in circulation)
- NK Lymphocyte
- Myeloid stem cells
- Erythrocyte
- Megakaryocyte (blood clotting)
- Monocyte –> macrophage
- Granulocytes
What are mast cells?
Tissue resident cells.
Granules rich in histamine (vasodilator) and heparin.
Key role in inflammation, wound healing and angiogenesis.
Immune tolerance and defence against pathogens.
When the is damage, mast cells release histamine which is a vasodilator which increase blood vessel permeability allow immune cells to move to area of damage from circulation.
Also encourages angiogenesis –> synthesis of new capillaries –> more immune cells can reach infection site.
What are some examples reasons of acute inflammation?
- Allergic reaction
- Chemical irritants
- Infection
- Trauma injury
- Burns
- Laceration, cuts, wounds
- Frostbite
What are some examples of reasons for chronic inflammation?
- Cardiovascular disease
- Neurological disease
- Autoimmune disease
- Rheumatoid arthritis
- Cancer
- Systemic Lupus Erthymatosus
- Fibromyalgia
- Chronic fatigue syndrome
What are dendritic cells?
Innate cells found in nearly all peripheral tissues
Engulfs pathogens via phagocytosis and kills them
Tissue resident cells
Antigen-presenting cells –> when activated they engulf pathogens, then travel through lymphatic system (absorbed into lymphatic vessels, e.g. thymus), where they encounter T-cells.
Connect second line of defence to the third line - can activate third line cells, especially T cells. Present antigen to the cells, where the T cells can then begin adaptive immune response.
Surface protein expression and cytokine production activates T cells for third line of response.
Particularly susceptible by viruses - viral infections can kill these cells and may compromise immune capacity.
What are natural killer cells?
Innate cells
Can be found in the tissue and also the circulation.
The main cells recognising cells that have been infected by viruses e.g. COVID-19.
Useful to recognise tumoural cells
Their activation depends on other innate cells e.g. mast cells and dendritic cells that release cytokines
Once activated they have the capacity to recognise infected cells, they release Granzyme B and Perforin which opens the infected cell’s cell membrane and causing apoptosis.
They also increase the production of cytokines, amplify the innate response which helps with B cells and T cell activation - activate the adaptive immune response
What do natural killer cells produce?
What does that do?
Granzyme B and Perforin –> open the infected cell’s cell membrane and causes apoptosis.
Increase pro-inflammatory cytokine production –> amplifies immune response by activating the adaptive immune response which involves B and T cells.
What are macrophages?
Tissue resident innate cells.
Small quantities in the circulation.
Monocyte (non-mature macrophages) are circulating cells that once they move to the tissue, the express all their organelles and become mature.
Recognise pathogens and induce phagocytosis (engulf pathogen) –> Pseudopodia are receptors that identify antigen –> the site that activate phagocytosis.
Can place some molecule from pathogen into a membrane receptor and travel to lymphatic system/ lymphatic organs to present antigen to adaptive cells (t cells) –> antigen presenting cells.
When active they produce large quantities of free radicals (hydrogen peroxide, nitric oxide) to increase vasodilation and arrival of immune cells to the site. Free radicals such as nitric oxide have anti-microbial capacity, can kill pathogens on their own by destroying their membrane.
What are the main antigen presenting cells in the immune system?
Macrophages and dendritic cells
What are antigen-presenting cells?
Macrophages and dendritic cells.
Connect 2nd line of defence to 3rd line by placing a molecule of the pathogen into the cell membrane receptor then travelling in the lymphatic system to lymphatic organs where they present the antigen to adaptive cells such as T-cells
What does the production of free radicals from macrophages do?
Increase vasodilation and arrival of immune cells to the site so more immune cells can work and fight the pathogens.
Free radical such as nitric oxide also has anti-microbial capacity and can kill pathogens on their own by destroying their cell membranes.
What is a monocyte?
A non-mature macrophage.
In circulation –> becomes mature when at tissues and has fully expressed organelles.
Doesn’t have pseudopodia which is the receptor that identifies antigen and the site that activates phagocytosis.
3-9% of white blood cells in the body
2nd to respond to infection or tissue damage
Cytokines can attract monocytes to damage site
What are granulocytes?
Circulatory innate cells
Neutrophils eosinopgils
Cytoplasmic granules
What are neutrophils?
Innate granulocytes - in circulation
Main immune cell in the body - 54-62% of white blood cells in the body
1st to response to chemotaxis –> signalling response to cytokines –> in response to cytokines they move to the area that has been damaged/ infected.
Short half life (last a few hours) - constant production.
Small amount in liver, spleen and lungs
What are basophils?
Innate granolocyte
<1% of white blood cells in body.
Can release histamine which enhances blood vessel permeability and vasodilation to amount of immune cells reaching the infection site. Can also cause smooth muscle contraction.
Also releases cytokines IL-4 and IL-13, they can enhance activation of T cells (Th2 lymphocytes) and IgE production (immunoglobulins) - activate adaptive response
What are eosinophils?
1-3% of white blood cells in the body
Have immune regulatory functions
Control inflammatory response –> produce anti-inflammatory cytokines that down regulate immune cells (e.g. mast cells, macrophages and dendritic cells), reduce pro-inflammatory cytokine production and overall inflammatory response.
Can be pro-inflammatory in the first hour, then become anti-inflammatory.
Host protective
- defence against mucosal pathogens –> cytoxicity by granule proteins, mitochondrial DNA traps, respiratory burst and nitric oxide release
What are some symptoms of acute inflammation?
Redness (Rubor) –> increased blood flow (close to skin) to area of damage
Swelling (Tumor) –> ‘’ ‘’
Pain (Dolor) –> Pro-inflammatory cytokines increase metabolism
Heat (Calor) –> ‘’ ‘’
Loss of function (Functio Laesa) –> muscle damage, increased inflammation
How can you test for inflammation?
Describe ESR
Elevated inflammatory markers
- CRP
- ESR –> quicker the RBC fall to the bottom, the higher the inflammation (pro-inflammatory cytokines bind to erythrocytes and causes them to be heavier and fall quicker than without)
- PV
What can explain the symptom of redness?
Higher blood flow at skin due to increased vasodilation and angiogenesis from heparin, histamine and some other compounds.
Also increased blood vessel permeability allows immune cells to move from circulation to area of damage.
This occurs when the area of damage/ infection is close to the skin.
Why does swelling occur?
Increased blood vessel permeability increases the amount of fluid.
Same response and redness –> vasodilation and angiogenesis.
Dilation and increased leakiness of local blood vessels - migration of phagocytes to the area
Why is pain and heat a symptom of damage/infection?
Pro-inflammatory cytokines up-regulate the immune system which increases the metabolic rate.
Immune cells become more active and consume more energy.
Why is loss of function a symptom of damage?
Can be to prevent further damage and allow rest of muscles and tissues.
Acute –> DOMS (delayed onset muscle soreness)
How is acute inflammation stopped?
Eosinophils down-regulate all innate activity and reduce production of pro-inflammatory cytokines.
Transition from M1 to M2 macrophages, which produce anti-inflammatory cytokines.
What are M1 macrophages?
Involved in the first stages of damage/ infection - first release macrophages
Pro-inflammatory macrophages
As damage is improving –> will release less cytokines and encourage shift to M2 macrophages
What are M2 macrophages?
Anti-inflammatory macrophages that release anti-inflammatory cytokines.
Increases EL-10
Which of the following does not protect against pathogens?
A. Skin
B. Mucus
C. Gastric acid
D. Salivary amylase
E. Gut microflora
D - Salivary Amylase
Does not have any anti-microbial properties
Acute inflammation is initiated by:
A. Mast cell activation
B. Influx of neutrophils
C. An increase in vascular permeability
D. B-cells
E. T-cells
A - Mast cell activation
Usually first cells to become active when a pathogen is recognised.
Release histamine and heparin
Which if the following are effective against viral infected cells and tumour cells?
A. Neutrophils
B. Eosinophils
C. Macrophages
D. Natural killer cells
E. Mast cells
D. Natural killer cells
What are some of the key functions of the lymphatic system?
- Fluid balance –> pick up fluid in the interstitial tissue, out of circulation, recover fluid back to the circulation
- Fat absorption –> gut fatty acid absorption goes to lymphatic vessels and then the liver
- Immunological defence
What are the primary lymphoid tissues?
Site of lymphocyte production
- Bone marrow
- Thymus
Play a key role in maturation and differentiation of B cells and T cells
What are some secondary lymphoid tissues>
Site of lymphocyte activation
- Lymph nodes
- Peyer’s patch –> located in the gut, control mucus secretion in the gut
- Spleen –> B cells, and reservoir of red blood cells, old RBC are removed by the spleen and some parts are reused to synthesise other proteins.
Contain B and T cells that can be activated
Discuss the location of the lymphatic system?
Located in parts of the body that can be infected with microbes and the brain as protection.
Make sure that is pathogens enter, there can be a quick immune reaction.
What are Peyer’s Patches?
Secondary lymphoid tissues that are found in the small and large gut that enhance mucus secretion –> prevent pathogen entry into circulatory system.
What is the spleen’s role in the lymphatic system?
- Dispose of worn out erythrocytes
- Cleanses the blood of foreign invaders
- Reservoir of oxygen-rich blood
