Immune System

Introduction to the immune system 

• body is constantly exposed to a vary of pathogens

• Body needs to have mechanisms to protect itself form pathogens that may cause infections

• some of these mechanisms are non-specific

• some are specific for certain pathogens

• has a mechanism to remember specific pathogens for a faster and more effective response during later infections

Innate Immunity

• The primary protective mechanism for the body. It includes two key aspects: first line of defence (skin and mucous membranes) and second line of defence (internal defences)

• Key features: it is fast - able to provide rapid initial response but it is non-specific.

• refers to wide variety of body responses that serve to protect against invasion of a wide variety of pathogens and toxins.

• We are born with this immunity. 1st line of defence (skin and mucous membranes) 2nd line of defence (internal defences)

Epidermis of skin

• Forms physical barriers to entrance of microbes

• Keeps pathogens on the outside of the body or neutralises them before infection begins.

• Skin: the epidermis - closely packed outer epithelial layer of the skin, key physical barrier against the entry of microbes as intact skin is very difficult to penetrate. Damage leads to risk of infection.

Mucous membranes

• inhibit entrance of many microbes, but not as effective as intact skin

• Keeps pathogens on the outside of the body or neutralises them before infection begins.

• Mucous membranes: line the surface of GI tract and respiratory tract and genitourinary tract, slightly less effective than physical barrier.

Mucous

traps microbes in respiratory and gastrointestinal tracts.

Hairs

Filter out microbes and dust in nose/ from the nasal passage

Cilia

together with mucous, trap and remove microbes and dust from upper respiratory tract

Lacrimal apparatus

tears dilute and wash away irritating substances and microbes

tears wash microbes and particles from the eyes

Saliva

washes microbes from surfaces of teeth and mucouse membranes of mouth

Urine and perspiration

urine: Washes microbes from urethra

perspiration: washes microbes from the skin

Defecation and vomiting

Expels microbes from body

Chemical factors of first line of defence

• Sebum - forms protective acidic film over skin surface that inhibits growth of many microbes

• Lysozyme - antimicrobial substance in perspiration, tears, saliva, nasal secretions and tissue fluids. enzyme which breaks down cell wall of some bacteria.

• Gastric juice - destroys bacteria and most toxins in stomach

• vaginal secretions - slight acidity discourages bacterial growth,, flushes microbes out of vagina.

Second line of defence - antimicrobial substances

• Interferons (IFNs) - secreted by certain virus-infected cells, lymphocytes and macrophages. protect uninfected host cells from viral infection. Interfere with viral replication in neighbouring cells.

• Complement system - causes cytolysis of microbes; promotes phagocytosis; contributes to inflammation

• iron-binding proteins - inhibit growth of certain bacteria by reducing amount of available iron

• Antimicrobial proteins (AMPs) - have broad-spectrum antimicrobial activities and attract dendritic cells and mast cells. Short peptides that can kill a wide range of microbes 

Natural killer cells (NK)

• Kill infected target cells by releasing granules that contain perforin and granzymes; phagocytes then kill released microbes

• Are specific type of white blood cell (leukocyte)

• kill a wide variety of infected body cells and some tumour cells

Phagocytes

• ingest foreign particulate matter

• various types of white blood cells can act as phagocytes

• mainly neutrophils and macrophages

• neutrophils early in infection and macrophages dominate later in infection

• ‘Phago’ (eat) and ‘cyto’ (cell)

• Migrate to the infected area and are involved in clearing debris of denatured proteins, dead body cells and microorganisms. 

Inflammation

• Confines and destroys microbes; initiates tissue repair

• A non-specific defensive response to tissue injury

• limits the effects on the body by confining or walling off the area

• involves the release of chemical by stressed or damaged cells (phagocytes are then attracted to the area via chemotaxis). vasodilation and increased permeability of blood vessles, movement of phagocytes from the blood to the interstitial fluid and tissue repair.

• conditions involving inflammation are given the suffix -itis

• PRISH (pain, redness, immobility, swelling and heat)

Fever

• Intensifies effects of interferons; inhibits growth of some microbes; speeds up body reaction that aid repair.

• a systemic response to tissue damage

• the hypothalamus (body’s thermostat) is usually set at 37C

• during fever the hypothalamus is “reset: to a higher temperature which is thought to intensify the effect of anti-viral substances and increase the production of iron-binding proteins which reduces the availability of iron for bacterial growth

• if body temperature rises too much, deaths results (44-46C)

Adaptive immunity 

Is induced when innate immunity cannot control the situation.

It is also know as third line of defence and has two key components:

• antibody-mediated immunity (also known as humoral immunity) which involves B cells (also known as B lymphocytes).

• Cell-mediated immunity (also known as cellular immunity) which involves T cells (also known as T lymphocytes)

• slower, more specific to type of pathogen and has memory component

Key features of adaptive immunity

• specific recognition of foreign molecules known as antigens (antibody generator molecules)

• includes a memory component that allows for faster and more effective response to the same pathogen in the future.

Third Line of Defence

B and T cells are the key cell types involved in adaptive immunity. We don’t need to fully understand the complex mechanism shown in the figure below, but there are some key important points we need to understand

Key important points:

• B and T cells arise from stem cells in the bone marrow

• B cells mature in the bone marrow whereas T cells mature in the thymus

• B cells are activated to produce specific antibodies in response to recognition of antigens on the surface of pathogens

• T cells are activated in response to recognition of pathogen antigens presented on the surface of antigen presenting cells

• Activated B and T cells produce memory cells which enable faster and more effective responses to subsequent exposure to the same antigen in the future.

The immune system is highly….

• Interconnected

• interactive

• cooperative

• as a whole can produce a more protective response than any individual component on its own

• complex!

First line of defence

• keeps pathogens on the outside or neutralises them before infection begins. The skin, mucous membranes and certain antimicrobial substances are part of these defences.

Second line of defence

• slows and contains infections when first-line of defence fails. They influence proteins that produce inflammation, fever and enhance cytokine activity, and phagocytes and NK cells, which attack and destroy cancer cells

Third Line of defence

• includes lymphocytes and target specific pathogens for destruction when the second line of defence fails or don’t contain infections. It includes memory components that allow the body to be more effective when responding to the same pathogen in the future. (also known as adaptive immunity)

Skin and mucous membranes

• the skin and mucous membranes are in contact with our environment, thus they are critical in protecting us from pathogens and foreign substances entering our bodies.

• They provide protection in two key ways: mechanical (physical barriers where physical processes remove microbes from the body’s surfaces) and chemical protection where substances are produced.

Normal microbiome and innate immunity

• Although not considered part of the innate immune response, your normal flora (microbiome) can also play a protective role.

• can compete with potentially pathogenic microorganisms by competing for available nutrients and space.

• some bacteria of the normal flora produces substances that can inhibit the growth or kill other microorganisms.

• Has an impact on the development of the immune system starting from before birth

Innate immunity - 2nd line of defence - internal defences

• antimicrobial substances

• defensive cells

• inflammation

• fever

Defensive cells

• are principally white blood cells

• there are different types of white blood cells which have different roles in the innate and or adaptive immune response

• are involved in defence against different types of infections (bacteria, viruses and parasites).

Two difference of adaptive immunity to innate immunity

• Specificity for a particular foreign molecule: antibody generator molecules → antigens

• Memory as a result of previously encountered antigens

• Third line of defence is designed to distinguish between “self” and “non-self”

• Antigen = the invader, foreign molecules

• antibody = the defender, produced by B cells, specific for different antigens

• Easy trick to remember": A before B → antigen before antibody. Antigen enters first (trigger) and antibody comes after (response)

• epitopes = specific regions of the antigen that is recognised by antibodies

Humoral and cellular

Humoral (antibody-mediated) immunity

• involves B cells which produce antibodies (immunoglobulins, Ig) and defends against extracellular threats (type of white blood cell - B lymphocytes) which are primarily found in the blood and lymphoid organs. Antibodies recognise foreign molecules known as antigens.

Cellular (cell-mediated) immunity

• involves T cells, defends against intracellular threats and induces other cells to perform a function

Humoral immunity continued/antibody-antigen interactions

• B cells are initially coated on the surface with antibodies corresponding to a specific antigen

• once activated B cells secrete the same specific antibody

• targets extracellular pathogens: extracellular bacteria and viruses before they enter cells (virons or viral particles)

• There are millions of B cells, all with different antibodies on their surfaces, once they encounter an antigen thats a match they clone themselves. Both memory B cells and plasma cells are produced and plasma cells produce large amounts of identical antibodies.

• Antibodies can inactivate antigens by binding to them and interfering with their usual functions which enhances phagocytosis

Antibody-antigen interactions

• Antibodies inactivate antigens, bind to them to interfere with usual functions.

• Inactivation can occur by neutralisation, agglutination or precipitation. This enhances phagocytosis

• The binding to antigens can activate the complement system leading to: cell lysis and the enhancement of phagocytosis and inflammation.

Immunological memory

• Subsequent antibody responses to the same antigen are: faster and stronger

Cell mediated immunity/cellular immunity

• involves T cells (T lymphocytes)

• mature in the thymus

• Mature T cells are found in the blood and lymphoid organs

• T cells recognise antigenic peptides presented to them by antigen presenting cells

• Like B cells, T cells are also specific for a single antigen

Self-recognition and self-tolerance

Major histocompatibility complex (MHC) molecules.

• molecules on the surface of body cells to help the immune system recognise them as “self”

• Two difference classes of MHC molecules:

1. MHC class l = present on all nucleated body cells

2. MHC class ll = used by antigen presenting cells to present antigens on their surfaces

MHC class l picture

MHC class ll picture

Types of adaptive immunity

Naturally acquired:

• Active = antigens enter the body naturally; body induces antibodies and specialised lymphocytes

• Passive = antibodies pass from mother to fetus via placenta or to infant via milk

Artificially acquired:

• Active = antigens are introduced in vaccines; body produces antibodies and specialised lymphocytes

• Passive = performed antibodies in immune serum are introduced by injection