7A – Antigens, the markers, types of pathogens

• Pathogen: an agent that causes disease in a host

• antigen: any molecule that may trigger an immune response

2 functions of the immune system:

1. recognise foreign cells as antigens and eliminate them

2. recognise their own body cells as self and not attack

MHC

• a group of receptor proteins present on the surface of body cells

• help the immune system to distinguish the body’s proteins from foreign proteins

• 2 types of MHC:

  • MHC-I

  • MHC-II

MHC-I

• found on all nucleated body cells

• mark cells as self so the immune system doesn’t attack them

MHC-II

• found on antigen-presenting cells (APCs)

• interact with T helper cells during antigen presentation

Types of Pathogens

• non cellular agents: prions and Viruses

• Cellular agents: bacteria, fungus, protists, insects

Non-cellular

• Prions

  • normal, harmless proteins found in the nervous system

  • change in shape and become infectious

  • makes all proteins it contacts change shape

  • cannot be cured

    e.g. scrapie, CJO

• Viruses

  • An infectious agent composed of genetic material (DNA or RNA) inside a protein coat (capsid).

  • In some instances, the protein coat is surrounded by a lipid envelope.

  • Viruses cannot independently reproduce, instead, they insert their genetic material into a host’s cell and use the cell to replicate.

  • Viruses can cause disease through the lysis of cells during viral replication

    e.g The flu, Covid

Cellular

• Bacteria

  • Unicellular prokaryotes can infect almost any part of the body.

  • Bacteria can cause disease through the production of toxins and enzymes which either affect the functioning of cells or cause their death

  • reproduces through binary fission

    e.g. Meningitis, Tetanus

• Worms

• Fungi

7B- The First Line of Defence

Plants

Chemical barriers

• Defensins – small peptides that are toxic to microbes and fungi

• Glucanases – defend plants against fungi

Physical Barriers

• Thick bark

• Waxy cuticles of leaves

• Closing of stomata to prevent pathogen invasion during carbon dioxide uptake

Animals

Physical

• intact skin

• mucus secretion

Chemical

• tears and saliva

• sweat

• stomach acid

• earwax

Biological

• bacteria on skin

• gut microbiota

7C- The Second Line of Defence.

NK cells

• Destroys infected or abnormal cells with insufficient MHC Class I markers

Mast cells

• Causes inflammation through the release of histamine

Phagocytes

phagocytosis: consume and destroy foreign or dead material present in the body by engulfing it

• Neutrophils

  • Phagocytosis of pathogens

• macrophages

  • engages in phagocytosis and antigen presentation

• dendritic cells

  • engages in phagocytosis and antigen presentation

  • connects the innate immune response with the adaptive immune response

Inflammation

• the first reaction when an injury is caused

1. initiation

   • in response to injury macrophages activate and along with damaged cells release cytokines. mast cells release histamines

2. vasodilation

   • histomines travel to the blood vessels and bind to receptors causing vasodilation, increasing blood flow to the injury site. gaps form in the vessel wall, increasing permeability for immune cells

3. Migration

   • complement proteins such as macrophages are guided by the cytokines to the injury site where they phagocytose pathogens and digest them using enzymes such as lysosomes

Complement proteins

• 25 proteins form a complement system

• react with each other in the presence of pathogens

• 3 major outcomes:

1. opsonisation

   complement proteins bind to the surface of the pathogen making it easier for immune cells to recognise it as foreign

2. chemotaxis

   they gather near a pathogen and attract phagocytes making it more likely to be destroyed

3. lysis

   • join on the surface of the pathogen to form a membrane attack complex (MAC)

   • forms a pore on the pathogen membrane allowing fluid to enter it

   • the pathogen swells and bursts

7D- Third Line of Defence

Antigen presentation

1. an APC engulfs and processes the antigen

2. MHC II binds to a small piece of the antigen presented by the APC

3. A T cell receptor on a T_H cell binds to the antigen if it is complementary

4. When this interaction occurs, the T helper cell becomes activated

5. The activated T helper cell can then help initiate the adaptive immune response through either the humoral or cell-mediated immune responses

Lymphocytes

• memory B cells: keep a memory of the pathogen

• Plasma B cells: secrete antibodies to destroy the antigen

• T helper cells: coordinate the actions of the immune system: activate naive B cells and cytotoxic T cells

• cytotoxic T cells: target intracellularly infected cells, inducing cell death

Humoral immunity

• targeted towards extracellular pathogens

1. a naive B-cell that can recognise an antigen presented by an APC gets selected (B-Cell clonal selection)

2. the naive B-cell gets activated by the T helper Cell with the same receptor

3. the naive b cell differentiates and proliferates into plasma b cells and memory b cells

4. memory B cells keep a memory of the pathogen for future infection and plasma B cells secrete antibodies to destroy the antigen

Cell-mediated immunity

• targeted towards intracellular pathogens

  • viruses

  • cancers

1. The activated T helper cells rapidly divide, differentiating into memory T cells and more T helper Cells

2. The T helper Cell activates cytotoxic T Cells which then proliferate into more Cytotoxic T cells and T memory cells

3. infected self-cells present the antigen of the intracellular pathogen on their MHC I markers

4. Cytotoxic T cells detect the non-self antigens presented on the MHC I markers and kill the infected cells via apoptosis or lysis

Antibodies

• composed of four polypeptide chains,

  • including two heavy chains and two light chains, arranged into a ‘Y’ shape

• The two heavy chains are joined by a disulphide bond

• The ‘stem’ of the antibody is known as the constant region

• the tops of the ‘arms’ are known as the variable region

• These regions come together to form two identical binding sites for the same specific complementary antigen.

• This allows antibodies to bind with antigens on the surface of pathogens

• can bind with 2 pathogens at once

Functions

• Immobilisation

  • Antibodies can restrict the movement of pathogens around the body through the formation of large antigen-antibody complexes.

• Activation of complement proteins

  • Antibodies attached to the surface of pathogens can facilitate the actions of complement proteins, including the formation of membrane attack complexes (MACs).

7E- Lymphatic system

Primary lymphoid tissue

Bone Marrow

• b and T cells are produced

• B cells mature

Thymus

• T cells mature

Secondary lymphoid tissue

Lymph nodes

• filter the lymph (cancer cells, Pathogens, infected cells)

• where antigen is presented by APC to the lymphocytes

Spleen

• B cells also mature here

8A- Immunity

Types of immunity

active immunity: memory cells are produced

• antibodies produced in a person’s own body

• natural

  • catch the disease

  • make your own antibodies

• artificial

  • vaccination which contain dead or treated pathogens

  • symptoms of disease do not generally occur

passive immunity: no memory of infection

• antibodies from another organism enter the body

• natural

  • from mother to foetus through placenta

  • in breast milk

• artificial

  • antibodies obtained from another organism are injected into patient

  • blood plasma

Vaccinations

• designed to stimulate a person’s adaptive immune system to create immunity to a pathogen without actually causing disease

primary immune function

• After a person receives their first vaccination, there is a delay in the adaptive immune system’s response

• Eventually, a primary immune response takes place in which a moderate number of antibodies and memory cells are formed

• these quickly diminish over time.

secondary immune function

• Upon receiving a second vaccination, the memory cells created by the first vaccine quickly recognise the antigen in the vaccine

• This results in the generation of a large number of antibodies and memory cells that go on to create long-lasting immunity.

Herd Immunity

• when the majority of the population is immune to a particular pathogen, helping to prevent the spread of the pathogen to those who haven’t been vaccinated or who haven’t already been infected with the pathogen.

• important because it protects people in the community who have no immunity towards a particular disease

8D- Immunotherapy

treating cancer (naked and conjugated monoclonal antibodies).

Immunotherapy: a form of medical treatment that modulates the functioning of the immune system to treat disease.

• dendritic cell therapy

• Car T therapy

• cytokine therapy

• monoclonal antibodies

Monoclonal antibodies

• laboratory-made proteins that can be used to treat a number of different diseases.

Produced:

1. mouse injected with antigen X, activates production of B cells that produce specific antibodies

2. the mouse spleen is removed and the cells are removed and cultured

3. myeloma cells are added to the culture

4. myeloma cells fuse with the B cells to form hybridoma cells

5. the hybridoma cells are cultured and allowed to divide repeatedly to produce multiple copies of each hybridoma cell

6. each clone is screened for the presence of antibodies against antigen X. The hybridomas that produce the specific antibody are cloned, which results in the mass production of these antibodies.

7. Antibodies are then collected and purified before being administered to a patient.

Naked Monoclonal antibodies

• there are no additional molecules added

• can bind to cancer cells and interact with complement proteins to for MAC

conjugated monoclonal antibodies

• have other molecules such as chemotherapy or radiotherapy drugs added

• can be used to deliver chemotherapy drugs or radioactive isotopes directly to cancer cells