Human Body Systems Print

9.3 First Line of Defence: The Innate Immune Response Against Bacteria

We said your immune system has two parts: the innate and adaptive immune systems. Using a bacterial infection as an example, let’s look at your innate immune response. Please remember that this is a very simplified explanation.

Your innate immune system is your body’s first line of defence against pathogens. It contains all the defences you were born with and can be employed seconds after an attack. 

Part of your innate immune system is your physical barrier, your skin, which is hard to breach if it is intact and healthy. It protects you from invading microorganisms, extreme temperatures, radiation, and chemicals. The weak points for infections are the entry points lined with mucous membranes, like your nose, windpipe, lungs, mouth, stomach and intestines, as well as your eyelids, reproductive tract and bladder. All places that come into contact with the outside world, even if some of them do not come directly into contact with the outside world. Your windpipe and lungs receive the air you breathe, and your gut gets the foods you eat. Hence, they could be considered the outside inside of you. At these points, a chemical barrier provides protection. Mucus containing immune cells, enzymes, and antibodies trap and remove pathogens. Enzymes, antimicrobial peptides, and the acidic pH in other body fluids, like tears, stomach or pancreas juices, prevent the growth and survival of pathogens.

The innate system goes back to the very first multicellular animals on earth and is critical for your survival. It is a brilliant system that can distinguish between the ‘self and other’; once it detects ‘other’, it will immediately react. 

How it can detect the ‘other’ is a fundamental question. 

All life on earth is made from the same fundamental molecule types arranged in different ways: carbohydrates, lipids, proteins, and nucleic acids. You may recall that proteins make up life’s essential building blocks. 

Bacteria use the same building blocks. There are billions of different protein building blocks with various shapes and sizes. However, certain proteins are necessary for bacteria to move, and because our immune system evolved alongside bacteria, our cell receptors can recognise these proteins. Since human cells do not use these proteins to move around, our cell receptors can recognise them as ‘others’. 

They can even identify pathogens they haven’t come into contact with through the odour they leave behind. Microorganisms are living things that sweat and need to expel waste just like we do, but on a much smaller scale, our cells pick up that smell as ‘other’. 

Your immune cells have millions of receptors that can smell the ‘other’. Another way of smelling the other is through cytokines, which are tiny proteins your cells release to convey information. Immune cells encountering bacteria release cytokines as a cry for help. Different immune cells pick up that smell and come to the rescue. The more cytokines are released, the more pungent the smell. 

Your cells, however, have a certain threshold for action so as not to overreact to faint cries of maybe only a few left-over cytokines from a previous attack. When a cell smells cytokines with its receptors, partly outside and inside the cell, they trigger pathways inside that cell, changing its gene expression and, hence, its behaviour. Some of these cytokines act as a navigation system, and your cells follow the smell toward where they need to go.

The intensity of the smell is a crucial component. If the smell is intense, help will be called, but the immune response will shut down if the scent lessens. Both a quick reaction and a shutdown are crucial for proper immune function. If that system breaks down and too many cytokines float around your immune system, it can go wild, leading to a cytokine storm. This means your cells release too many cytokines even though there is no more danger, engaging your immune cells all over your body and leading to a rise in inflammation. Immune cells flood affected organs and can cause significant damage. Blood vessels all over your body get leaky, with fluid rushing into tissues and out of blood vessels, decreasing blood pressure. This means organs are oxygen-starved and will start to shut down, which could prove deadly. Cytokine storms, though, only happen if things go completely wrong.

Your innate immune system does not have specific weapons against specific enemies. It fights invaders, providing nonspecific protection against various potential threats. Most microorganisms that successfully invade you are killed by your innate immune system without you even knowing about it. Let’s look at the different ways your innate immune system defends yourself.

Sentinel cells are a specialised subset of immune cells that act as the first line of defence in detecting and responding to potential threats, particularly at infection or tissue damage sites. These cells are strategically positioned in tissues and organs throughout your body to monitor the local microenvironment for signs of infection, inflammation, or tissue injury. These cells also include phagocytic cells called phagocytes, a type of immune cell that specialises in engulfing and destroying foreign particles like bacteria, viruses, cellular debris, and other microorganisms. 

Monocytes are the biggest WBC and differentiate into macrophages or dendritic cells. Macrophages are the largest immune cells in your body. If an average cell is as big as a human, a macrophage would be the size of a Hippopotamus compared to a bunny-sized bacterium. Macrophages are part of phagocytes, meaning they devour dead cells and living pathogens. They also help coordinate defences, produce inflammatory mediators, and present antigens to activate other immune cells and heal wounds.

Dendritic cells are efficient phagocytes located in tissues exposed to the external environment, like your skin mucosal surfaces, such as the nose lining, where microorganisms can penetrate your body. Unlike your other phagocytes, your dendritic cells don’t demolish your enemies. They take them apart and prepare samples. Your dendritic cells are your messenger cells. Once they collect dead samples of your invaders, ‘the other’ also called antigens, they will bring them primarily to your lymph nodes, where they present the antigens to T cells. This interaction between dendritic cells and T cells is pivotal for launching adaptive immune responses against specific pathogens or foreign substances.

Neutrophils are the most abundant white blood cells circulating in your bloodstream and are highly effective at combating bacterial infections. They can rapidly migrate to sites of infection or tissue damage. They are also part of your phagocytes; once activated, they destroy invaders without much consideration for collateral. They have only a certain amount of time to destroy enemy bacteria as they will run out of energy and die or self-sacrifice by releasing antimicrobial substances that form extracellular traps that trap and kill pathogens.

Mast Cells are tissue-resident immune cells primarily found in connective tissues, particularly near blood vessels and mucus areas. They are large, bloated cells containing tiny bombs with extremely potent chemicals, histamine and cytokines that cause rapid and massive local inflammation. You may have felt their effect after a mosquito bite. The itching afterwards was probably caused by chemicals your mast cell released.

Inflammation can be caused by mast cells, macrophages, and neutrophils and is a key feature of your innate immune system. It’s a universal response to all kinds of breaches. Inflammation is the red swelling and itching after an insect bite or sore throat when you have a cold. The purpose of inflammation is to restrict an infection from spreading, to help remove damaged and dead tissue, and to increase blood flow. New blood brings extra body heat and helps immune cells and attack proteins to get to the site of damage faster. Most microorganisms do not like heat. Making the injured area hotter will slow pathogens down.

Chemicals released by inflammation make nerve endings more susceptible to pain. Inflamed parts also make it harder to move; both are intended to make humans slow down so that the body can do its job and heal. Repair cells, on the other hand, like the extra heat. It makes them work faster. Inflammation, however, needs to be requested consistently by your immune cells; otherwise, it dissipates.

On top of being your first line of defence, your innate immune system decides how dangerous an invasion is and will figure out who attacks you and what other weapons are needed to defend you.

9.4 The Complement System: Amplifying the Body’s Defence Mechanisms