Responding To Antigens

First Line of Defense

Mechanisms used to prevent pathogens from entering the body in the first place

(physical, chemical, and microbiotal barriers)

Physical Barriers

(animals and plants)

Solid or fluid obstacles that block pathogen entry

• For animals → INTACT skin, mucus secretions & cilia

• For plants → Thorns and trichomes, closing of stomata, waxy cuticles or leaves, thick bark, formation of galls

Chemical Barriers

(animals and plants)

Chemicals are used to inhibit the growth or development of pathogens and/or destroy pathogens

• For animals → Lysozymes & digestive enzymes, stomach acid, acidic sweat, antibacterial proteins in semen

• For plants → Production of various chemicals

Microbiotal Barriers

(animals)

The presence of normal flora prevents the growth or colonisation of microorganisms that may be pathogenic

• For animals → Flora, non-pathogenic organisms in the vagina

The Innate Immune Response

Includes all the nonspecific cellular and molecular responses to pathogens that have entered the body (breached the first line)

Non-adaptable and doesn't change in an individual's lifetime

Cellular components in the second line of defence

All cells involved in the innate immune response are leukocytes (white blood cells):

• Phagocytes (neutrophils, macrophages, dendritic cells)

• Mast cells

• Eosinophils

• Natural killer (NK) cells

Phagocytes

• Leucocytes capable of engulfing and destroying foreign matter through endocytosis

  • Include: Neutrophils, Macrophages, Dendritic cells

• Release cytokines

  • Important cell-signalling molecules

  • They stimulate, recruit and proliferate other immune cells

    Can help guide them to the site of infection or injury.

Macrophages

• A type of phagocyte that is found at the sites of infection throughout the body

• Amoeboid type of movement.

• Type of Antigen-Presenting Cell (APC)

• Key roles:

  • Phagocytosis to consume and destroying foreign material

  • Have a role in recruiting other immune cells to the infection site.

  • Uses MHC II markers to display antigens from consumed pathogens on their surface, allowing interaction with the adaptive immune system

Dendritic Cells

• Star-shaped phagocyte

• Tends to be found on or near the body’s surfaces (skin, lining of nose, lungs and digestive tract)

• Type of Antigen-Presenting Cell (APC)

• Key roles:

  • Phagocytosis to consume and destroying foreign material

  • Uses MHC II markers to display antigens from consumed pathogens on their surface, allowing interaction with the adaptive immune system

  • Act as messengers between the innate and adaptive immune system

  • Ingest antigenic material and present this to T cells

Steps of Phagocytosis and Antigen Presentation

1. Phagocytosis of a pathogen

2. Fusion with the lysosome

3. Enzymes start to degrade the pathogen

4. Pathogen broken into small fragments

5. Fragments of antigen presented on cell surface

APCs and Initiation of the Adaptive Immune Response

• Macrophages and Dendritic cells are antigen-presenting cells (APCs)

• They present the antigens from the pathogen they’ve phagocytosed on MHC II markers

  • In doing so, they initiate the adaptive immune response (3rd line of defence)

Neutrophils

• Circulate in the bloodstream

• Most abundant circulating white blood cells (30 – 80%)

• A type of phagocyte that contains granules (containing toxic chemicals, e.g. enzymes & defensins)

• Engulf microbes and kill them with toxic chemicals

• The first cells to arrive at an infection site in response to chemical signals from other cells

• Release cytokines which amplify the immune response and attract other cells to the infection site.

Mast Cells

• Found between connective tissues, especially close to the external environment (where pathogens are likely to enter)

• Alert the rest of the immune system

• Degranulate and release histamines when they detect injury to surrounding cells or are stimulated by antigens or allergens

• Histamines cause:

  • Vasodilation

  • Increased permeability of blood vessels

  • Attraction of phagocytes

Eosinophils 

• Large granulated cells containing various toxic chemical mediators which help destroy invading pathogens (e.g DNases, RNases, and proteases) 

• Generally found in tissues

• Typically target pathogens too large to be phagocytosed

  • Especially effective in combating multicellular parasites

• Degranulate on contact with pathogens, releasing the chemical mediators contained within their granules

Natural Killer Cells

• Circulate in the bloodstream and are responsible for the recognition and destruction of damaged and/or infected self/host cells

• Recognition and destruction of damaged and/or infected host cells is achieved via two receptors 

  • killer inhibitory receptor → examine the surface of cells for MHC I markers

  • killer activation receptor → binds to certain molecules which appear on cells undergoing cellular stress (e.g. infected or cancerous cells)

• If there are insufficient MHC I markers on a cell (often due to viral infection or cancer), the killer inhibitory receptors are unable to bind, and cell death is initiated

Non-cellular Components In The Second Line of Defence

Specific non-cellular components that you are expected to have an understanding of include:

• Complement Proteins

• Interferons

Complement Proteins

• Different complement proteins within the blood form the complement system

• In the presence of pathogens, complement proteins interact with each other in a series of complex reactions called a complement cascade

• This “complements” the function of immune cells in three main ways:

1. Opsonisation of pathogens

2. Chemotaxis

3. Lysis

Opsonisation of pathogens

Complement proteins stick to the surface of pathogens, making them more susceptible to phagocytosis because they are easier to recognise

Chemotaxis

Complement proteins gather near a pathogen and attract phagocytes, increasing the chance of it being destroyed

Lysis

Complement proteins join together to form a membrane attack complex (MAC) on the surface of pathogens, destroying them via lysis

Interferons (INFs)

• Cytokines called interferons are released when a cell is infected by a virus

• They interact with receptors on neighbouring cells, increasing the viral resistance of these neighbouring cells

• This helps to stop the spread of a virus between cells

Inflammatory Response Purpose

• Defend against potential pathogens

• Eliminate the effects of injury

• Clear out damaged or destroyed cells and initiate repair

Stages of The Inflammatory Response

1. Initiation

2. Vasodilation

3. Migration

Initiation

• Damage occurs

  • Immune cells nearby OR damaged tissue/cells release cytokines (chemical signals)

  • Most cells also degranulate

    • Histamine is released

Vasodilation

• Histamine released from mast cells binds to coreceptors on nearby blood vessels

• This results in 

  • Vasodilation, 

  • Increased permeability of blood vessels

  • Attraction of phagocytes

Migration

• Vasodilation + increased permeability of blood vessels allow many components of the innate immune system to leave blood vessels & enter the injury site

• Including: Phagocytes are attracted by cytokines and complement proteins

What Else Might You Find At The Site Of Infection

Pus (dead immune cells and pathogens)

Types of Pathogens

• Cellular (bacteria, fungi, parasites, protists)

• Non-cellular (viruses, prions)

Cellular Pathogens

Causative agents of disease that have a cellular structure and are living

(bacteria, fungi, parasites, protists)

Non-cellular Pathogens

Causative agents of disease that do not have a cellular structure and are non-living

(viruses, prions)

Allergens

Antigens that cause an allergic reaction

Self vs Non-self Antigens

• Immune system uses antigens to recognise if a cell or molecule is self or non-self

  • If identified as non-self, an immune response is initiated

• The immune system protects our body by scanning for and destroying pathogens, and it must recognise a vast variety of different pathogens while ensuring that it doesn’t harm any of our own self-cells

It does this by using antigens

Antigens

Any molecule that may trigger an immune response

2 types:

• Self

• Nonself

Self Antigens

• Located on the surface of cells

• Mark the cells of organisms as ‘self’ so the immune system doesn’t attack it

• In vertebrates, the most important self-antigens take the form of major histocompatibility complex (MHC) markers

• Self-markers are proteins on the surface of all nucleated cells in the body

  • MHC Class I markers

    • Expressed on all nucleated cells

    • Therefore, all cells in humans except those without a nucleus (e.g. red blood cells)

  • MHC Class II markers

    • Found on specialised cells of the immune system

      • Macrophages

      • Dendritic cells

      • Blymphocytes

Non-self Antigens

• Antigens that the immune system reads as ‘foreign’ or not belonging to that individual

• If a non-self antigen is recognised within the body, the immune system is activated and attempts to eliminate it

Bacteria

Unicellular Prokaryotes

• Have DNA but no Nucleus

• Only a small percentage are pathogens

• On average, bacteria can reproduce every 20 – 30 minutes via binary fission

• Rapid development of infection 

• E.g. Meningitis, Tetanus 

Fungi

Unicellular or Multicellular Eukaryotes

• Most fungal diseases are superficial and non-life-threatening

• Include yeasts (unicellular) and moulds

• Other fungi contain long, branching filaments called hyphae

• Fungi pathogens are not so common in animals, more so in plants

• Often reproduce by forming spores

• E.g. tinea and thrush

Parasites

Unicellular or Multicellular Eukaryotes

• Live in or on a host organism

• Endoparasites → live in the body (e.g. tapeworms and roundworms) 

• Worms reproduce sexually (egg, larval and adult forms) or asexually by breaking off proglottid segments at the end of the trunk 

• Ectoparasites → live on the body (e.g. ticks, lice and fleas)

Protists

Unicellular Eukaryotes

• Typically live in a host

• Can reproduce by binary fission or budding

• E.g. malaria,  giardiasis, toxoplasmosis, and African sleeping sickness

Prions

• Abnormally folded proteins that can cause nearby normal proteins to misfold

• Non-living, no genetic material (i.e. nucleic acids)

• Only found in mammals and affect the brain

• Smaller than viruses

• E.g. Mad cow disease (BSE), Creutzfeldt-Jakob Disease (CJD), Scrapie

Viruses

• Composed of genetic material (DNA or RNA) inside a protein coat (capsid)

• When outside a host cell → referred to as a virion

• Also contains enzymes necessary for the reproduction of the virus

• Cannot reproduce independently - inject genetic material into a host’s cell and use the cell to replicate

• Often causes disease through the lysis of cells during viral replication

• Retroviruses insert negative-sense RNA, where the host transcribes the RNA backward into DNA (e.g. HIV, influenza)

• Positive-sense RNA viruses → RNA is read directly by the tRNA in the host cell (e.g. coronavirus)