Bio- Unit 4 AOS1- Pathogens

Antigen

A molecule that promotes an immune response

MHC Markers (Major Histocompatibility Complex)

a group of proteins present on the surface of all self-cells that enables the immune system to distinguish it from non-self material

Pathogen

the causative agent of an infectious disease

Pathogenic bacteria

Unicellular, prokaryotic organisms that usually produce endotoxins or exotoxins. These toxins affect functioning of cells or cause their death. They typically reproduce asexually through binary fission.

Fungi

Eukaryotic organisms that can be unicellular or multicellular. They contain long, branching filaments called hyphae. They reproduce via asexual reproduction and sexual reproduction called spore formation.

Worms

Multicellular, invertebrate parasites. Development includes egg, larval, and adult stages. They reproduce sexually.

Protozoa

Single-celled eukaryotes that can be free-living or parasitic. They have many different mechanisms of action. They reproduce through both sexual and asexual reproduction

Viruses

Non-living infectious agents composed of genetic material inside a protein capsid. They cannot reproduce independently, instead, they insert their genetic material into a host’s cell and use the cell’s machinery to replicate.

Prions

Abnormally folded proteins that can only effect neural structures in mammals. They are the only known infectious agents that don’t contain nucleic acids. They induce misfolding in nearby proteins, therefore spreading throughout a tissue.

First line of defence

a component of the innate immune system, providing physical barriers, chemical barriers, and microbiological barriers to prevent pathogenic invasioun

Physical barriers in plants

bark, waxy cuticles, cellulose cell walls

chemical barriers in plants

chemicals (e.g. toxins) which are harmful to the pathogen and/or enzymes that affect the functioning or development of the pathogen. Some chemicals can also act to repel insects or animals that may damage the plant. E.g- phenols, glucanases

Physical barriers in animals

intact skin, mucous membranes

mechanical barriers in anmials

sneezing/coughing, diarrhea, vomiting, tears

chemical barriers in animals

stomach acid, lysozyme in tears

microbiota barriers in animals

the human gut contains microbes which exist in a mutualistic relationship with the person. They prevent the growth of colonies of other species of bacteria by outcompeting them for nutrients and adhesion sites, and secreting antimicrobial chemicals that prevent the growth of pathogenic bacteria

Second line of defence

a component of the innate immune system, composed of a variety of cells and molecules that destroy pathogens which have entered the body, preventing the spread of infection

mast cells

Leucocytes that embed themselves in connective tissues. When they detect damage to surrounding cells, they release histamines that have 3 effects, which are referred to as the inflammatory response- vasodilation, increased permeability of blood vessels, and attraction of phagocytes.

phagocytes

Cells that engage in phagocytosis, a process where they consume and destroy foreign or dead material present in the body by engulfing it through endocytosis. Once engulfed, lysosomes containing antimicrobial enzymes called lysozyme present in the cell destroy  the foreign or dead material by fusing with the vesicles containing the engulfed material. The important phagocytes are neutrophils, macrophages, and dendritic cells.

Natural killer (NK) cells

Large, granular, lymphocytes. They are instrumental in destroying self-cells that have been infected by a virus, or which have become cancerous. __ cells, on finding a self-cell displaying non-self antigens on its surface, release a death ligand, which is a signalling molecule that stimulates the cell to die by apoptosis

Eosinophils

Large, granulated cells which contain various toxic chemical mediators such as DNases, RNases, and proteases, which help destroy pathogens. They typically target pathogens which are too large to be phagocytosed by degranulating on contact with them and releasing chemical mediators contained with their granules.

Interferons (INF)

Signalling molecules (cytokines) released from virus-infected host cells. They cause nearby cells to heighten their antivirus defences. Cells stimulated by __ produce various enzymes that inhibit protein synthesis. __ also cause cells to upregulate the production of MHC I markers.

Complement system

A suite of small proteins called complement proteins that are synthesised by the liver, and circulate in the blood in an inactivated state. When activated they achieve 3 primary outcomes; oponisation, chemotaxis, and lysis.

Oponisation

Complement proteins stick on the outside surface of pathogens and make it easier for cells of the immune system, such as phagocytes, to recognize them as foreign

Chemotaxis

Complement proteins gather near a pathogen and attract phagocytes to it, making it more likely to be destroyed.

Lysis

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

Fever

A temporary increase in body temperature. A complex series of responses can raise the set temperature point of the body during a fever, meaning the body will initiate a number of countermeasures to increase core body temp to reach this new setpoint. This is an innate response to potential infection, as many pathogens cannot survive at the elevated temperatures created. Prolonged __ can be detrimental to the body due to the additional stress placed on our cells.

Steps in the inflammatory response

Initiation, vasodilation, migration

Initiation in the inflammatory response

When pathogens break through the first line of defence, macrophages situated in the tissue where the pathogens were introduced become activated and along with damaged cells, release cytokines. Mast cells will also degranulate, releasing histamine.

Vasodilation in the inflammatory response

Histamines from mast cells bind to receptors on nearby blood vessels, causing vasodilation. This increases blood flow to the injury site, causing the swelling, redness, and warmth associated with inflammation. Gaps in the vessel walls also form, increasing permeability to immune cells.

Migration in the inflammatory response

Vasodilation and increased vessel leakiness allow components of the second line of defence to reach the injury site. This includes components such as: Phagocytes, which are guided by cytokines, engulf and digest pathogens using enzymes like lysozymes. Complement proteins also help by marking pathogens for destruction. The response continues until the area is cleared and healed

Third line of defence

it is designed to destroy pathogens that have passed the first line of defence. It has 2 unique features: specificity (the immune system responds to each distinct pathogen in a unique manner), and immunological memory (the adaptive immune system results in the production of memory cells to respond to future re-infections quickly)

Antigen presentation

Antigen-presenting cells engulf pathogens via phagocytosis, displaying pathogenic antigens on their MHC Class II markers. They then travel to the lymph nodes to present foreign antigens on their surface using MHC Class II proteins. Then, they interact with the complementary T cell receptors on the surface of T helper cells, activating the T helper cell. The selected T helper cell can then help initiate the adaptive immune response through the humoral or cell-mediated immune response.

Cell-mediated immune response

This response targets infected or abnormal cells using cytotoxic T cells.
Key steps:

1. Clonal Selection – antigen-presenting cells find a naïve T cell with a matching receptor. T helper cells release cytokines, activating the T cell to multiply and differentiate.

2. Differentiation – The T cell clones become:

   • Cytotoxic T cells, which travel to infection site to kill infected cells

   • T memory cells, which stay in the body to provide long-term immunity

3. Destruction – Cytotoxic T cells bind to infected cells showing the antigen on MHC Class I. They release perforin and other chemicals to trigger apoptosis.

Humoral immunity

This response targets extracellular pathogens using antibodies produced by B lymphocytes.
Key stages:

1. Clonal Selection – A B cell with a matching receptor binds to a pathogen's antigen.

2. Clonal Expansion – A T helper cell releases cytokines, causing the B cell to multiply.

3. Differentiation – The B cell clones differentiate into plasma cells and B memory cells.

4. Response – Plasma cells secrete antibodies to fight infection; memory cells stay in the body for long-term immunity.

Antibodies

Proteins with quaternary structure, arranged into a Y shape. They interact with pathogens in a number of ways; neutralisation, agglutination, immobilisation, oponisation, and the activation of complement proteins.

neutralisation in antibodies

Antibodies can block the sites of pathogens that are used to attack host cells and can block the active sites of toxins

Agglutination in antibodies

Antibodies can bind together with antigens on two separate pathogens, forming large antigen-antibody complexes, making it easier for phagocytes to recognise the pathogens as foreign bodies and destroy them

immobilisation in antibodies

antibodies can restrict the movement of pathogens around the body through the formation of large antigen-antibody complexes

oponisation in antibodies

antibodies can bind directly to the surface of a pathogen to make it easier to phagocytose

activation of complement proteins in antibodies

antibodies attached to the surface of pathogens can facilitate the actions of complement proteins, including the formation of membrane attack complexes.

B memory cells contribution to immunological memory

They rapidly divide and form new antibody-producing plasma cells when they encounter an antigen that matches their receptor, contributing to immunological memory. They also create immunological memory by constantly secreting low amounts of their antibody.

T memory cells contribution to immunological memory

They contribute by proliferating rapidly into T helper cells and cytotoxic T cells upon stimulation by an antigen-presenting cell that is presenting a previously encountered antigen.

Lymphatic system

a network of blind-ended vessels that collect tissue fluid and drain it back to the circulatory system.

Lymph

a pale fluid that flows through the lymphatic system and has a high concentration of leukocytes. It flows through lymph vessels, as a result of the movement of body muscles

primary lymphoid tissues

where lymphocytes are formed and mature. it includes the thymus and bone marrow. all lymphocytes are formed in the bone marrow of the long bones in the body. T lymphocytes then leave the bone marrow and mature in the thymus gland

secondary lymphoid tissues

includes the lymph nodes, tonsils, spleen, Peyer’s patches in the small intestine, and mucosal surfaces.

lymph nodes

a small secondary lymphoid tissue found throughout the body where antigen-presenting cells activate the adaptive immune system. They act as filters for the lymph flowing back towards the heart. __ contain a high concentration of lymphocytes

Artificial immunity

obtained if medical technology is used to deliberately give a person immunity

natural immunity

immunity that results from an unintentional exposure to an antigen

active immunity

immunity obtained when a person’s own immune system produces their antibodies

passive immunity

immunity that occurs when a person has antibodies that were produced by someone else’s immune system

whole pathogen vaccines

vaccines that contain whole pathogens. they include inactivated vaccines and live attenuated vaccines

inactivated vaccines

vaccines that contain whole bacteria or viruses that have been killed or altered so that they cannot reproduce

live attenuated vaccines

vaccines that contain whole bacteria or viruses that have been weakened through genetic modification or other means

subunit vaccines

vaccines that do not contain any whole pathogens, but instead, contain antigens from the pathogen. they include recombinant protein vaccines, toxoid vaccines, virus-like particles, and outer membrane vesicles

recombinant protein vaccines

vaccines made by genetically modifying harmless yeast or bacteria, so they produce a surface protein of the pathogen. This causes an effective immune response without actually exposing the body to the pathogen

toxoid vaccines

some bacteria cause disease by releasing toxins. a toxoid is an inactivated version of the toxin

virus-like particles

molecules that closely resemble viruses but are non-infectious because they contain no genetic material. it still has the antigen on the surface, allowing the body to produce an immune response without getting sick

outer membrane vesicles

vaccines naturally produced by bacteria and are essentially a bleb of the bacterial outer cell membrane

nucleic acid vaccines

vaccines that provide genetic instructions for making the protein antigen. they include RNA vaccines, DNA vaccines, and viral vector vaccines

RNA vaccines

vaccines that use RNA in a lipid membrane. The RNA, once inside a cell, enters a ribosome where it is translated to make the protein

DNA vaccines

vaccines that are currently not in use, but are being developed

viral vector vaccines

vaccines that contain a recombinant harmless virus that retains the ability to reproduce, but contains the genetic instructions for making antigens from a different virus

herd immunity

resistance to the spread of an infectious disease within a population that is based on pre-existing immunity of a high proportion of individuals

emerging diseases

infectious diseases that have recently appeared within a population

zoonosis

a disease that move from another species of animal into a human

antigenic shift

when there is a sudden change in the antigens on a pathogen, meaning that most people won’t have immunity to the new illness

antigenic drift

an accumulation of small mutations in the viral genes that code for the surface proteins that host antibodies recognise

strategies that help authorities assess risk

• testing

• contact tracing

• wastewater testing

strategies that reduce the chance of infection when in contact infected individuals

• public education about personal hygiene

• vaccination programs

strategies to manage illness in the infected

• GP’s

• hospital care

• antiviral drugs being developed

immunotherapy

a form of medical treatment that modulates the functioning of the immune system in order to treat disease. the two broad categories are activation immunotherapies, and suppression immunotherapies.

monoclonal antibodies

antibodies produced in a lab that bind to specific antigen. They can be used to target specific types or parts of ells for a variety of therapeutic purposes.

production of monoclonal antibodies

1. scientists identify and isolate an antigen that is present on a desired target cell

2. scientists vaccinate an animal with an antigen. the vaccination stimulates an immune response against the antigen and results in the selection and proliferation of a B lymphocyte that matches the antigen

3. scientists extract these B lymphocytes from the spleen of the animal

4. the extracted B lymphocytes are fused with cancerous human cells known as myeloma cells. The products are called hybridomas

5. hybridomas are screened so that only the cells with the appropriate antibody are selected. the hybridomas that produce the specific antibody are cloned, which results in the mass production of these antibodies

6. antibodies are then collected and purified before being administered to a patient

cancer

Cancer is a group of diseases caused by uncontrolled cell replication. It results from DNA mutations that bypass normal cell cycle checkpoints, and sometimes evades or suppresses the immune system

activation immunotherapy in the use of cancer treatments

can be used to help the immune system to recognise and destroy cancerous cells. there are 2 types of monoclonal antibodies used in immunotherapy; naked monoclonal antibodies, and conjugated monoclonal antibodies

naked monoclonal antibodies

antibodies that don’t have any drugs or added materials attached to them. They have 3 mechanisms against cancer; antibody-dependent cell-mediated cytotoxicity, complement activation, and checkpoint inhibition

antibody-dependent cell-mediated cytotoxicity

Monoclonal antibodies bind to cancer cells and interact with cells of the immune system, particularly NK cells, causing them to recognise the antibody-coated cancer cell as foreign and kill it.

complement activation

Monoclonal antibodies bind to cancer cells and interact with complement proteins. Complement proteins can then go on to destroy the cancerous cell either by forming a membrane attack complex (MAC) or by enhancing the function of other immune cells

checkpoint inhibition

Immune checkpoints are regulators in the immune system that, when activated, suppress the immune system. Monoclonal antibodies can be used to block immune checkpoints, meaning the immune system is able to function at a greater capacity and destroy cancer cells easier

conjugated monoclonal antibodies

monoclonal antibodies that have other molecules attached to them

suppression immunotherapy in the use of autoimmune disease treatment

Can be used to dampen the immune system and reduce its ability to attack self-cells, leading to immunosuppression. Monoclonal antibodies can be used to reduce the immune response in a few different ways; cytokine inhibition, and B cell and T cell depletion and inhibition

cytokine inhibition

cytokines are messenger molecules used by the immune system to coordinate its response. Monoclonal antibodies that bind to and inhibit cytokines can be used to reduce the immune response

B cell and T cell depletion and inhibition

monoclonal antibodies that bind to autoreactive B and T cells can be used to either inhibit these cells or stimulate other immune cells to destroy them

immunotherapy and traditional autoimmune disease treatment

Traditional treatments involve broad immunosuppression, which can weaken the whole immune system, increasing the risk of infections and cancer. Immunotherapy is a new approach which aims to specifically only target autoreactive immune cells.