Bio immunity

Self/non-self, cellular/non-cellular, Pathogens and Allergens

•The body’s ability to defend against invasion by pathogens depends your immune system distinguishing ‘self’ from ‘non-self’.

•Antigens are markers that are unique molecules on the surface of all cells that are used by immune system in recognition of self from non-self

Self: Self-antigens originate from inside the body and are found on the surface of cells that make up the organism.

Non-self: Antigens found on the surface of all pathogens (or any other foreign cell) are identified as non-self and initiate an immune response when detected.

Pathogens: Disease-causing agents

Allergens: Antigens that cause allergic reactions.

Cellular pathogens: Living, independent organisms that can replicate. E.g. Bacteria, fungi, parasitic worms, protozoa.

Non-cellular pathogens: Non-living, rely on a host organism to reproduce and replicate. E.g. Viruses, Prions.

Innate Immune System (non-specific)

“A component of the immune system that is composed of generalised and non-specific defences and/or responses to pathogens”

• First (barriers) and Second (leukocytes) Line of Defences.

• Non-specific response to foreign antigens, responding the same way regardless of the type of pathogen or antigen present.

• Responds to injury and antigens very quickly- within minutes to hours they begin to limit the spread of infection or stimulate local changes at the site of infection.

First Line of Defence: Physical, chemical and microbiota barriers as preventative mechanisms of pathogenic infection in animals and plants

• the first line of defense of the innate immune system involves physical, chemical and microbiological barriers to keep pathogens out of the host organism.

Barrier types

• Physical- solid or fluid obstacles that block pathogens from entry

• Chemical- enzymes, toxins and acids that kill pathogens

• Microbiological- presence of normal flora which limits the growth of pathogenic bacteria

Plants:

• Physical barriers- thick bark of trees, waxy cuticles of leaves, closing of stoma, thorns and trichomes, formation of galls

• Chemical barriers- production of various chemicals/toxins that repell or kill invading pathogens/microorganisms. E.g. enzymes that have antifungal properties

• Microbiological barriers-

Animals:

• Physical barriers- mucus secretions, intact skin, cilia

• Chemical barriers- stomach acid, lysozymes/digestive enzymes, acidic sweat

• Microbiological barriers- flora on skin. gastrointestinal tract

Second Line of Defense: Leukocytes, Phagocytes, APC’s

• Involves a variety of different leukocytes/white blood cells

• Key innate immune cells- Macrophages, Dendritic cells, Mast cells, Eosinophils, Neutrophils and NK cells.

Phagocytes & Phagocytosis

• Phagocytosis: process in which phagocytes consume and destroy foreign or dead material present in the body by engulfing it through the process of endocytosis.

• Key phagocytes- macrophages, dendritic cells, neutrophils.

• To communicate with the immune system, phagocytes release a number of substances such as cytokines to guide immune cells to the site of infection to defend against pathogens.

Phagocytosis steps:

1. Pathogen is recognised by pattern recognition receptors on a phagocyte’s plasma membrane and is engulfed by the out-foldings of the membrane.

2. Pathogen is fully enclosed in vesicle (the phagosome)

3. Lysosomes containing toxic chemicals fuse with the vesicle

4. Pathogen is digested and some partially digested proteins are kept for antigen presentation.

5. Indigestible material/debris is discharged by the phagocytic cell via exocytosis.

NK cells

• Large granulated cells which target abnormal and infected cells. This is achieved through the presence of two receptors: Killer inhibitory receptor- examines the surface of cells for MHC class I markers. The Killer activation receptor- binds to certain molecules which appear on infected or cancerous cells to undergo apoptosis

• If the killed inhibitory receptor detects a sufficient number of MHC I markers, it overrides the killer activation signal, preventing apoptosis.

• When there are insufficient for the killer inhibitory receptor to bind to MHC I markers, due to infected or cancerous cells, the activation receptor is activated, initiating apoptosis.

• The presence of MHC I markers may be absent due to the presence of a viral infection, which can destroy or suppress their production.

• The gene expression of MHC I markers may also be affected in cancerous cells, leading to its absence.

Mast cells

• Reside in connective tissues throughout the body

• When they detect injury to surrounding cells or are stimulated by antigens/allergens, they activate and degranulate, releasing histamine, which plays a big part in the inflammatory response.

Eosinophils

• large granulated cells containing toxic chemical mediators such as Dnase, Rnases, Proteases, which help destroy invading pathogens that are too large to be phagocytosed (parasites) via degranulation which releases the chemical mediators into the pathogen upon contact.

Neutrophils

• The “first responders” and the most abundant leukocyte in the body (50-70%).

• They rapidly travel to the site of infection to trap and engulf the pathogen, destroying it via phagocytosis.

Non-cellular components of the innate immune system

Interferons

• A type of cytokine called interferons released by a cell when infected by a virus. Interferons interact with the receptors of neighbouring cells and signal them to undergo a number of changes that make them less susceptible to viral infection, preventing spread of the virus between cells.

Complement proteins

• within the blood, different proteins together form the complement system. In the presence of certain pathogens, these proteins begin reacting with eachother, in a series of reactions called the “complement cascade”, which has 3 major outcomes:

1. Opsonisation- complement proteins stick on the surface of pathogens and make it easier for the immune system to recognise them as foreign (tagging).

2. Chemotaxis- complement proteins gather near a pathogens, break and diffuse from the pathogen. This leaves a trail of complement protein which attracts phagocytes to the pathogen, making it more likely to be destroyed.

3. Lysis- complement proteins can join together on the surface of pathogens, forming a membrane attack complex (MAC), which creates pores in their membrane and causes lysis via the sudden influx of fluid into the pathogen, causing it to burst and destroys it.

Innate Inflammatory response

Fever

• A temporary increase in body temperature caused by a complex series of immune responses that raise the set temperature points.

• Is an innate response to potential infection as many pathogens cannot withstand the elevated temperatures.

• Prolonged fevers are detrimental to the body due to the additional stress placed on cells, which are no longer functioning at their optimal temperature.

Inflammatory response

1. Initiation- An injury pierces the skin, damaging cells and introduces pathogens into the body. Macrophages situated in the tissue are activated and along with the damaged cells, release cytokines. Mast cells degranulate and release histamine.

2. Vasodilation- The histamine released travels to nearby blood vessels and binds to specific receptors, causing vasodilation. Blood vessels widen, increasing blood flow to the site of injury, causing swelling, redness and warmth. The formation of gaps in blood vessels increases their permeability to cells of the immune system.

3. Migration- increases permeability allows for innate immune system components to leave blood stream and enter site of injury. Phagocytes are guided by the cytokines secreted by activated macrophages and damaged cells to the site of injury and perform phagocytosis.

Adaptive immune system

• Is specific- responds to each distinctive pathogen in a unique, tailored manner.

• Has immunological memory- the adaptive immune system results in the production of cells that allow the body to respond to future reinfections to a previously encountered pathogen quickly and effectively.

Antigen Presenting Cells (APC)

• Macrophages and dendritic cells are known as professional antigen presenting cells as they not only consume and destroy foreign material, but also present antigens from consumed pathogens on their surface via MHC II markers.

Antigen presentation & processes

• A key process in the initiation of the adaptive immune system, involving T helper cells- a type of T lymphocyte, via the process of antigen presentation.

• Each T helper cell has a unique set of T cell receptors for a single antigen on its surface, facilitating the specificity of the adaptive immune system.

• After phagocytosis, APC’s travel via the lymphatic system to lymph nodes to present foreign antigens on their surface using their MHC class II markers. These interact with and bind to complementary T cell receptors on the surface of T helper cells, cytokines are released by the T helper cell which activating itself, which is then said to be ‘selected’ (Clonal selection) and can then initiate the adaptive immune response through either humoral or cell mediated responses.

Cell Mediated Immunity

• Involves the destruction of infected or abnormal cells via the clonal selection of a Cytotoxic T cell- A differentiated T lymphocyte

1. Pathogen is recognised as non-self and phagocytosed by an APC. The antigens from the pathogen are presented on the MHC II markers of the APC and the APC travels to the lymph nodes.

2. After being activated via clonal selection, the T helper cell undergoes a series of cell divisions (Clonal expansion), resulting in more T helper cells and differentiation which produces Cytotoxic T cells and T memory cells.

3. A Cytotoxic T cell with a complementary receptor to the antigen being presented binds to the APC and is fully activated when it receives cytokines from a nearby T helper cell.

4. The cytotoxic T cells travel to the site of infection and release granzymes and perforin, destroying the infected cells.

Humoral Immunity

• Involves the production of antigen-specific antibodies by B cells

• Response can be initiated the same way as the humoral response (phagocytosed by APC), or a pathogen can directly enter the lymph node (phagocytosed and presented by B cell)

• Pathogen arrives at lymph node and is phagocytosed by a B cell, which then displays its antigens on their MHC II markers.

• A T helper cell with a complementary receptor to the antigen binds to the antigen being displayed by the B cell and releases cytokines which activates the B cell.

1. Activated B cells rapidly multiply via clonal expansion and differentiate into plasma B cells and B memory cells

2. The plasma B cells produce antibodies that are released from the lymph node and travel around the body.

3. The antibodies specifically bind to the antigen, resulting in agglutination, opsonisation and neutralisation.

4. Plasma B cells remain in the lymph node for long periods of time and are important for a rapid immune response upon reinfection with the same pathogen.

Emergence of disease

Emerging infectious disease: new, previously unknown diseases in humans, that have increased in incidence virulence.

Re-emerging infectious disease: known diseases that once had a dramatic decline in cases, but have returned and are increasing in number or spreading across areas.

Epidemic- the rapid spread of an infectious disease to a large number of people within a population.

Pandemic- the rapid spread of an infectious disease to a large number of people across multiple countries or continents.

Endemic- infectious disease that stays steady, with a predictable baseline in a specific area or community.