Principles of Immunology

This post is part of a series of brief summaries condensing the core principles of what I learned in each class this semester.

The human immune system is exactly that–a system. This system grows and develops from birth, learns and evolves through time, adapts and remembers with experience, and wears and tears from use. There are different regions of the body in which this system is developed and maintained. The primary immune sites are localized in the bone marrow and thyroid, and are responsible for immune cell maturation. The secondary immune sites are more dispersed throughout the body (located in regions called lymph nodes) and are responsible for immune cell activation. After immune cells mature, they must be activated in order to perform specific effector functions within the body.

To begin with, the immune system relies heavily on the body’s fundamental response to physical damage: inflammation. Inflammation is a process in which fluids flow to saturate an area of damage, causing increased metabolism, vasodilation (enlarging of vessels) and the influx of various repair cells. This inflammation response is critical to the activation of immunity, and many immunosuppressant drug inhibit the immune system through blocking this process.

The innate immune response is what results when the body fights off pathogens at a site of inflammation. The most important fighters of this response are neutrophils and macrophages. Neutrophils are messay tanks that cause a lot of damage to the body through the spewing of enzymes such as Reactive Oxygen Intermediates (targets of anti-oxidants). Macrophages perform the same function of spewing enzymes, but macrophages can also phagocytize pathogens, taking them in to digest them. Other cells of the innate immune system include mast cells and eosinophils, and all of these cells react most immediately upon inflammation.

The adaptive immune response is what results when the body learns to react, adapt, and develop a memory towards certain molecules (called antigens and epitopes). The adaptive immune response involves B-cells and T-cells. B-cells are best used to develop antibodies towards pathogens, with different types of antibodies serving different functions at different locations in the body. For instance, the IgA antibody is found in mucosal tracts; IgG is found throughout the body, and all antibodies serve the functions of neutralizing pathogens, causing opsinization (uptake by macrophages), and assisting ADCC (Antibody dependent cell-mediated cytotoxicity). T-cells are split into T-helper cells and T-cytotoxic cells. T-helper cells produce cytokines (activating enzymes) that activate more T-cells and B-cells, and the T-cytotoxic cells are known as silent assasins (or CTLs), and they kill self-cells that have been invaded by foreign pathogens by triggering programmed cell death (apoptosis).

As it was mentioned, adaptive immune cells must be ‘activated’ by certain molecules called antigens in order to respond. Antigen Presneinting Cells like Macrophages and Dendritic Cells serve this function of presenting molecules to activate the adaptive immune response. This activation process involves the coming together of the Antigen Presenting Cell with the Adaptive Immune cells (T/B cells) with the facilitation of MHC (Major Histocompatibility). The MHC has two classes: Class I MHC is found on most cells, and it is a way to emit a distress signal to CTLs; Class II MHC is found only on Antigen Presenting Cells, and they are used to bind with T/B cells for activation.

When a pathogen enters the body, it is usually faced with antibodies, macrophages, and dendritic cells. After the pathogen is killed, the APCs present the pathogen’s antigen to the adaptive immune system, resulting in the creation of more antibodies and T-cells that respond to that specific pathogen from which the antigen originated. Pathogens come in all shapes and sizes, and the more complex a pathogen, the more potential antigens it has to trip off the adaptive immune system.

Pathogen are either intracellular or extracellular, and depending on which, there are different immune responses. Extracellular pathogens like bacteria, protozoa, and worms, are usually attacked by antibodies and macrophages. Intraceullular pathogens like viruses are attacked by CTLs and Mast Cells. Many times, an individual may be infected with a pathogen but not express disease. Whether a pathogen expresses disease is dependent on the host’s immune status, the pathogen’s virulence, and the dosage of the pathogen.

A functional immune system ideally reacts to the molecules of pathgoens such a bacteria and viruses and fights it off; however, certain disease also result when the adaptive immune system begins to respond to the innocuous molecules on one’s own body. The most general categories of such responses are transplant rejections, Hypersensitivity, autoimmunity diseases, Cancer, and stress.

In particular, hypersensitivty is seperated into four types: type I is the classic allergic response (allergy to pollen, drugs, dust, etc); type II is a response to blood transfusions; type III is a response to immune complex disease; and type IV, also known as delayed type hypersensitivity, is a response to contact dermatitis (Poison oak, metal, latex, etc).

Autoimmunity are caused by T/B-cells. B-cell autoimmune disease occur when antibodies block or activate certain receptors, triggering damage in the area caused by enzymes spewed by phagocytes, and resulting in permanent damage to specific functions (Graves Disease, Myastavia Gravis, Hashimoto Thyroditis, Rhematoid Arthritis, Systemic Lupus). T-cell immunity is when the CTLs kill off important self cells, resulting in disease such as Multiple Sclerosis and Type I diabetes).

Cancer is a result of rampant cell growth, caused by the mutation of a gene and facilitated by excessive damage and repair. Genes that control cell death can be turned on/off to cause over/under development; genes that suppress tumors can be turned off; etc. Tumors occur when self cells are no longer being regulated correcly and begin to grow rampantly throughout the body. Often times, tumors are engaged in a vicious cycle in which the destruction of certain tumors will result in the increased likelihood of developing future tumors.

In sum, the human immune system is an evolved, programmed system that responds to and attacks certain targets based on the antigens it is activated by. Depending on whether that antigen is foreign or self, the immune system can either fight off disease or cause disease as a result.