Immunity: Barriers, Fever and Inflammation

Surface Barriers

If you encounter a pathogen or invader, your skinThe body’s largest organ, providing protection and regulation. provides a very effective barrier.  The many layers of your skin act to prevent entry. Waterproofing from keratinA strong, fibrous protein that forms the structure of skin, hair, and nails. also helps prevent entry. Additionally, the tight junctions of the keratinocytesThe most abundant cells in the epidermis, responsible for producing keratin. in the stratum spinosumA layer of the epidermis with cells connected by desmosomes, giving a spiny appearance. of the epidermisThe outermost layer of the skin, made of stratified squamous epithelium. play a role in prevention.   The skin secretes acidicA solution with a pH below 7, having a higher concentration of H⁺ ions. substances known as the acid mantleA thin, slightly acidic film on the skin that acts as a barrier to bacteria and contaminants..  The acidA substance that releases hydrogen ions (H⁺) in solution. mantle can contain IgAs, among other things. It also contains dermcidin, an antibiotic protein that can denatureThe process in which a protein loses its shape and function due to heat or pH changes. proteinsLarge molecules made of amino acids with various functions in the body. and kill invaders. However, using harsh soaps may wash away this protective layer, reducing its effectiveness. These physical barriers form the first line of defense, preventing entry into the body.

Additionally, respiratory cellsThe basic structural and functional units of life. in areas like the trachea have ciliaHair-like projections on the surface of some cells that move fluids or particles.. They also have a mucus layer. These features are designed to trap and expel foreign particles. IgAs are found in the mucus of the 4 mucus membranes of the body (respiratory, digestive, reproductive and urinary). In this diagram of a mucus membrane, these dendritic cellsImmune cells in the epidermis that help fight infections. are drinking the fluids and ingest a pathogen.  The dendritic cell will travel to a lymph node. It will say, “Hey, I found this. I don’t know what it is, but I thought you’d like to know.”  A B cell living in the lymph node say, “Oh, yeah, that’s bad.”  The B cell differentiates into a plasmaThe liquid component of blood. cell that secretes IgAs into the mucus.  These IgAs, along with antimicrobial proteins are capable of neutralizing the bacteria in the inner mucus layer.

Fever

While inflammation is a localized response, fever is a systemic response—that means it affects your whole body. Fever usually occurs if the infection is widespread and internal. Fever is an increase in the body temperature. This occurs when your internal thermostat—regulated in your hypothalamus—is reset to a higher point. The reason your thermostat gets reset is because leukocytes and macrophages secrete chemicals called pyrogens. Low and moderate fever is an effective immune response. It speeds up the body’s metabolic rate. This, in turn, accelerates the repair process.

Fevers are kind of a genius response of the body and based on a very simple factA statement based on direct observation that is repeatedly confirmed.. Raising your temperature even 1° makes you inhospitable to so many different bacteria. I don’t know about you but I feel like I’m dying when I have a fever. So I bet little tiny bacteria really take a hit with even a 1° increase. What sparks a fever in the 1st place are proteins called pyrogens that are secreted by white blood cells. These pyrogens circulate to the hypothalamusA small but vital brain region controlling hormones, temperature, and autonomic functions. and raise your basal body temperature.

 A fever at first starts like positive feedbackA control mechanism that amplifies a change instead of reversing it.. Getting worse and worse and worse as time goes on. However there’s a plateauing of your fever which is a phase of fever and called the stadium phase. At this point your body thinks that 101.5 is the right temperature and therefore employs mechanisms to keep you fluctuating around 101.5. At some point, your hypothalamus stops receiving pyrogens from the blood. Then, your body temperature lowers again. This is called defer vents.

After my first back surgery I ran a fever for 2 1/2 years. It was awful. I was diagnosed with a condition called fever of unknown origin. This condition is much more common than you would think. FUO or fever of unknown origin can have 4 origins. These include cancer, autoimmune issue, infectious disease, and my last and favorite category: unknown. I found statistics saying that people in the unknown category usually just stop obtaining medical assistance out of frustration. That is certainly what I did.

Inflammation

Inflammation is another genius innate immune response. If a pathogen breaches the skin—like through a cut—damaged tissue releases alarm signals called cytokines, initiating inflammation. Inflammation is beneficial, as it prevents the spread of damaging agents. It also disposes of debris and pathogens. Additionally, it prepares tissues for repair. It acts as both a quarantine and sanitation mechanism. For instance, in our peanut allergy case study, corticosteroidsSteroid hormones from the adrenal cortex, including glucocorticoids and mineralocorticoids. suppress inflammation post-surgery. However, this suppression can reduce the body’s ability to respond to allergens.

There are 3 cardinal signsObjective clinical findings observable by a provider (e.g., edema, fever). of inflammation redness swelling and heat. Some people also use impairment as a sign of inflammation, too. Those are signs because of medical professional would be able to confirm them on the patient. There is one symptom associated with inflammation which is pain. Pain, like all symptomsSubjective experiences reported by the patient (e.g., nausea, fatigue)., must be reported by the patient. It can’t be visually or otherwise confirmed by a medical professional.

All of these signs occur due to the vasodilationThe widening of blood vessels due to relaxation of smooth muscle, decreasing blood pressure and incr of blood vessels in the area. This process allows excess fluids to seep from the blood vessels into the area. As a result, white blood cells and other cells can perform their clean-up process. The excess fluid causes the swelling. The activity of the white blood cells causes the heat. The vasodilation of the blood capillariesThe smallest blood vessels where gas, nutrient, and waste exchange occurs between blood and tissues. causes the redness. Inflammation is not only about gobbling up the pathogen. It is also about initiating tissue repair once the pathogen is cleared. This is why some white blood cells secrete growthAn increase in size and number of cells. factors.

Inflammation

Inflammation begins with a warning siren made up of chemicals secreted by the injured tissues. These chemicals act as a homing beacon for macrophages and mast cells to migrate to the injury site. Macrophages start engulfing bacteria and debris while mast cells secrete histamine. Histamine is a very potent inflammatory chemical. It causes the symptoms we associate with allergies like a runny nose, hives, and watery eyes.

Histamine causes the surrounding arteriolesSmall arteries that regulate blood flow into capillaries through vasoconstriction and vasodilation to dilate. This brings warm blood to the area and increases the local temperature. Local macrophages secrete cytokines when they encounter a pathogen.  These cytokines also enter the blood stream and recruit other leukocytes to the area.

The histamine increases permeability of the local capillaries. This promotes exudation. It involves the leaking of capillary fluid into the tissues. This fluid carries antibodies and clotting factors with it. The dilated capillary allows neutrophils in blood to exit a blood vessel. Monocytes also leave the bloodstream to enter into the local damaged area.  This is what causes the swelling. And the swelling in turn presses on nerves, causing the pain.

If the injury is badly infected, pus can develop. This creamy-yellow substance is a mixture of dead white blood cells, ruined tissue, and living and dead pathogens. If the area is very badly infected, scar tissue can wall it off from the rest of the body. The scar tissue is made from collagenA structural protein in the dermis that provides strength and elasticity. fibers and can form an abscess. At this point, the pus and fluid build-up within the abscess will need to be drained. Only then can the injured area heal properly.