Body Lines of Defense - Innate and Acquired Immunity

In order to fight pathogenic invaders like bacteria, viruses, fungi, parasitic worms, aberrant cells, etc., the immune system is made up of a complex network of immune cells that collaborate with proteins like cytokines. With the exception of specific disorders like autoimmune diseases, they have a special capacity to tell self-molecules apart from non-self-molecules. Except for identical twins, each person's bodily cells have a distinct Major Histocompatibility Complex (MHC) protein on their surface, which is used to distinguish between self and non-self. MHC I and MHC II are two different types of MHC proteins that distinguish the body's own cells from foreign or pathogenic cells and display antigen on the cell surface, respectively. MHC II, however, is also present in immune cells called antigen-presenting cells (APCs), which display phagocytosed microbe on the cell surface. Red blood cells do not have MHC proteins.

Table of Contents

- Innate and Acquired Defense Systems
1. First Line of Defense
2. Second Line of Defense
    - Phagocytes (eating cells) and their relatives
    - Mechanism of the second line of defense
3. Third Line of Defense
    - Humoral or antibody-mediated immune response
    - Mechanism of antibody-mediated immune response
    - Cell-mediated immune response
    - Mechanism of cell-mediated immune response

Innate and Acquired Defense Systems

Two forms of bodily defences exist against invaders:

The two types of reactions are acquired (adaptive/specific) and innate (natural/non-specific).

• No matter how often a pathogen is exposed, innate reactions are the same, but acquired reactions are better with each consecutive exposure to foreign particles.
• Phagocytic cells including neutrophils, monocytes, and macrophages as well as Natural Killer (NK) cells are used in innate reactions. However, antigen-specific B and T cells or antigen-presenting cells are involved in adaptive responses (APCs).
• When a foreign attack occurs, innate reactions react right away, but adaptive responses need more time to respond.
• Be a result, learned responses are referred to as particular and innate responses battle against certain sorts of invaders.
• The first and second lines of defence are part of the innate reaction, whereas the third line is part of the learned response.

Basically, there are three types of lines of defense:

1. First line of defense
2. Second line of defense
3. Third line of defense

1. First Line of Defense

It's sometimes referred to as an external defensive system.

The initial line of defence against the invasion of pathogens is composed of physical, chemical, and biological defences; they do not operate separately and may overlap depending on their activities.

i) Physical defenses: 

These include physical obstructions and mechanical defences that prevent infections from entering through healthy skin and mucus.

• Skin: The epidermis, dermis, and hypodermis are the three layers of skin. The epidermis, which is the top layer, is densely covered in keratin and dead skin cells. These defunct cells are constantly being replaced and shed. Because it is mechanically strong and very water-resistant, keratin inhibits the development of microorganisms.
• Nasal Hairs: While tiny cilia along the respiratory system whisk mucus and trap inhaled particles towards body openings where they may be expelled from the body, nasal hairs filter air tainted with bacteria, dust, and dirt.
• Mucous membranes: Mucus, a slimy material produced by the mucous membranes lining the respiratory, urinary, and reproductive systems, collects unwanted particles and guides them out of the body by mechanical processes including shedding, coughing, peristalsis, and flushing of physiological fluids (e.g. urination, tears)

ii) Chemical defenses: 

include substances and enzymes in bodily fluids, a range of plasma protein mediators, cytokines, antimicrobial peptides, and inflammation-inducing mediators that kill pathogens on the surface of the body, at body openings, and on the linings of the inside of the body.

• Sweat, tears, mucus, and saliva: Saliva, mucus, sweat, and tears all have pathogen-killing enzymes. Lysozyme, an enzyme present in saliva, sweat, and tears, may destroy the cell walls of bacteria and eliminate them. Similar to this, secretory IgA function by destroying peptidoglycans in bacterial cell walls. Dermcidin, cathelicidin, defensins, histatins, and bacteriocins are antimicrobial peptides (AMPs). In reaction to pathogens on the skin, AMPs are created.
• Cerumen or ear wax: The fatty acids in cerumen, or ear wax, cause a pH drop to between 3 and 5, shielding the auditory canal from external objects like germs.
• Gastric juice: Pathogens that enter the stomach through the mouth or nose are killed by the extremely acidic nature of gastric juice (pH 2-3).
• Urine: Acidic urine flow kills microorganisms and is directed out of the urethra.
• Serum: Serum (unsaturated fatty acids) is found to include certain molecules that make it easier for some microorganisms to get the nourishment they need while still reducing water loss and inhibiting microbial development.

iii) Biological defenses: 

are supplied by pleasant and helpful living microbes. These are naturally occurring organisms that live on our skin, in our bowels, and in various other locations, including the mouth, stomach, reproductive system, etc. These stop pathogen adhesion and colonisation by occupying accessible cellular binding sites, generating an acidic environment by the fermentation of carbohydrates to acids, and outcompeting them for resources. As a result, the local normal microbiota helps to chemical defences by producing bacteriocins, which have antibacterial properties.

2. Second Line of Defense

The immune system is another name for it.

When the first line of protection is breached, the second line of defence within our body "kicks" in and becomes active. In other words, when the pathogens successfully overcome the first line's barriers, the second line of defence then comes into contact with them. To identify and get rid of any non-specific pathogens that are ingested into the body, this system requires the engagement of mostly immune cells, primarily white blood cells (leucocytes), such as phagocytes, NK cells, dendritic cells, mast cells, and complement proteins. Immunological memory doesn't exist.

Phagocytes (eating cells) and their relatives

• Basophils: These make up only 1% of WBCs. Since they emit heparin and histamine when activated, they are renowned for their inflammatory response linked to allergies and asthma.
• Mast cells: Despite being tissue-based, they have functional similarities with basophils. As a result of being activated by various inflammatory mediators and antigens, they exhibit an inflammatory response. Once it detects pathogens, it produces granules that contain inflammatory histamine.
• Monocytes: They are referred regarded as the "trash trucks" or "vacuum cleaners" of the immune system and are associated with scavenging. These make up between 2 and 6% of the WBCs in the blood. The biggest WBCs are made up of these cells. They enter tissues in response to inflammation and undergo differentiation into macrophages and dendritic cells after leaving the circulation.
• Macrophages: These are present in the tissues and organs and engulf and digest pathogens missing certain surface proteins to healthy body cells, such as malignant cells, bacteria, cellular debris, etc. They discharge a variety of compounds, including enzymes and complement proteins, as well as regulatory substances like interferons, interleukins, etc. Since these processes absorbed antigens and presented them to T cells, these active T cells and consequently the adaptive immune system by serving as "antigen-presenting cells."
• Dendritic cells: These can be distinguished from monocytes, which are found in tissues that come in touch with the outside world, such as the skin, nose, lungs, etc. Innate immunity and adaptive immunity are connected by these cells. When they locate foreign particles, they go to lymph nodes where they engage with T and B cells to deliver the antigen and start an immune response. These are referred to as dendritic in that their cellular architecture resembles a "tree-like" structure.
• Neutrophils: These make up around 65% of WBCs and are the first immune cells to react to invaders. They deliver messages to other immune cells and squeeze out through capillaries into the infection location. Therefore, they are often referred to as "patrol tissue." They have a brief life expectancy of about eight hours after being expelled from bone marrow.
• Natural Killer (NK) cells: These cytotoxic lymphocytes are the only ones in the innate immune system that may act quickly against tumour or virus-infected cells without priming or prior activation. These are most recognised for their "natural" propensity to kill, which subsequently aids in the detection and management of early cancer indications.

Mechanism of the second line of defense

Neutrophils mobilise to engulf and eliminate pathogens that have invaded the entrance site. If they manage to avoid the activity of neutrophils, then dendritic cells and macrophages enter the fray, aiding in the phagocytosis of antigens and their presentation to T cells. The second line of defence also involves phagocytosis, NK cells, an inflammatory response, fever, and the complement system. Immune cells as well as infected cells release various cytokines that increase the amount of cytokine production. This results in capillary dilatation, an inflammatory response, and enhanced capillary wall permeability. Macrophages play a role in cellular debris removal and the healing of the inflamed area. Fever is a consequence of cytokines raising core body temperature. This raised temperature expedites healing and repair procedures while preventing germ development. Apoptosis is triggered when NK cells identify malignant or virally infected cells. Similar to this, several complement proteins that are contained in blood serum are drawn to pathogens that have been recognised by the adaptive immune system. Pathogens are coated by a cascade of complement protein binding, which acts as a flag to identify pathogens in phagocytes and their breakdown during the phagocytosis process.

3. Third Line of Defense

It is sometimes referred to as the adaptive immune system since it develops through time rather than at birth. These develop long-lasting immunity, a potent immune response, and immunological memory and only target particular infections. Innate immunity takes a long time to develop since there is a lag between exposure and the maximum response. However, they respond fast to remove when exposed to the same antigen repeatedly. It helps you recognise, dismantle, and retain principles. Only when infections get beyond the first and second lines of protection does it become active. Antigen-presenting cells (APC), B lymphocytes, and T lymphocytes are three types of cells that participate in the third line of defence. 

T cells, B cells, and NK cells, which make up 20–30% of white blood cells (WBCs) and are located in the lymph, are referred to as lymphocytes. T and B cells are among them, and as was already said, NK cells are a part of the innate immune response. This defence includes humoral and cell-mediated immune responses.

Humoral or antibody-mediated immune response

When B cells come into touch with a pathogen, they get activated and release antibodies into the circulation as part of an antibody-mediated response. After Max Cooper's work in the 1960s to examine the function of B cells, in which he showed that surgical ablation of the Bursa of Fabricius, the main location of B cell growth in birds, entirely abolished antibody production in irradiated chicken, the designation "B cell" was created. They both develop and begin in the bone marrow. On their outer surface, B cells produce a variety of antigen-specific molecules that aid in antigen identification. Thus, naïve B cells undergo clonal growth and some of these clones develop into Memory B cells and Plasma B cells (Plasmocytes/Effector B cells) when they come into contact with an antigen in the lymphatic system.

• Plasma B cells: These eject immunoglobulins, which are antibodies (Igs).
• Memory B cells: They provide the immune system a durable memory.

Mechanism of antibody-mediated immune response

When B cells are exposed to an antigen that matches their receptor, the antigen is internalised, digested, and displayed as fragments on their surface attached to specific MHC II molecules. These cells release cytokines, interleukins, and other substances. This complex draws mature matched helper T cells. As a result, secreted substances aid in B cells' proliferation by stimulating mitosis. Some B cells develop into memory and plasma cells. Antigen-antibody complexes are formed when plasma cell-secreted antibodies bind to antigens and are later removed by the complement cascade, neutralisation, agglutination, precipitation, etc.

Cell-mediated immune response

T lymphocytes, APCs such macrophages, B cells, and dendritic cells, as well as a number of cytokines, are the main players in this immune response. Antibodies are not used. It mostly eliminates malignant cells and viruses. T lymphocytes come in four different subtypes: T-helper, T-killer, T-suppressor, and T-memory cells.

• TH /T helper cells (CD4+): These cells release cytokines that promote clonal development of TH cells, activation of macrophages to cause phagocytosis, and B cell division and maturation into plasma and memory cells.

• Tc (T- killer/cytotoxic) cells (CD8+): These cells cause the pathogen's DNA to be destroyed by secreting cytotoxin or by puncturing the membrane of the pathogen with perforin. Cell lysis or apoptosis is the effect of this.
• T-suppressor cells/Treg/Regulatory T cells: are a component of the body's self-check system that shuts down T cell-mediated immunity once the pathogen has been eliminated. They also aid in the prevention of autoimmune illnesses.
• T-memory cells: These cells don't proliferate unless they have already been exposed to an antigen. When the same antigen surfaces again, they are stimulated to differentiate into cytotoxic T cells and eradicate the infection.

Mechanism of cell-mediated immune response

Naive T cells connect with the MHC II- Ag complex with their T cell receptor (TCR) when APCs display antigenic fragments associated with MHC II protein on their surface. This contact also results in a number of costimulatory interactions. APCs start releasing interleukins, and T cells start secreting cytokines and interferons, which cause them to differentiate into various subsets of effector T cells. Helper T cells are activated by the IL-1 that T cells release, and cytotoxic T cells and B cells multiply as a result of the IL-2. Since TH cells encourage B cells to differentiate into plasma and memory cells, they are linked to indirectly enhancing both cellular immunity and humoral immunity. Cytotoxins and perforins secreted by TC cells kill pathogens or diseased cells.