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Physiology of the Human Immune System

As a biology major, Christina loves exploring the sciences and applying them to everyday life.

Innate Immunity vs Acquired Immunity

There are two main sections of the immune system: the innate immunity and the acquired (also referred to as adaptive) immunity. The innate immunity includes phagocytic cells, skin, and mucous membranes. The adaptive immunity includes lymphocytes, specifically B cells, helper T cells, and cytotoxic T cells.

All plants and animals have an innate system while only vertebrates have both an innate system and an adaptive system. Innate immunity has the same response to pathogens no matter how many times the same pathogen is encountered, while the adaptive immunity has a stronger and faster response when encountering the same pathogen again.

Innate Immunity System

The first defenses of the innate immunity system are the skin and mucous membranes. The skin defends against pathogens due to its acidity and its ability to dry out the pathogens. Mucous membranes, such as the naval cavities, release secretions containing lysozymes, which breakdown bacterial walls, and trap and rinse out the pathogen. If a pathogen makes it past the skin and mucous membranes, it meets the leukocytes.

Leukocytes use toll-like receptors (TLRs) to identify pathogen-associated molecular patterns (PAMPs) on macromolecules that are never present naturally in the human body; for example, people don't naturally create double-stranded RNA or the protein flagellin, so when leukocytes find those particular macromolecules, it's clear that they are part of foreign bodies. When TLRs recognize a PAMP, a phagocytic leukocyte consumes the pathogen via phagocytosis.

Types of phagocytic leukocytes:

  • neutrophils- short-living phagocytes that are typically the first to respond to pathogens
  • macrophages- large phagocytes than can eat bigger things than neutrophils
  • eosinophils- targets multicelluar parasites
  • dentritic cells- activates the adaptive immunity

Another part of the innate immunity system are natural killer cells, which target infected or cancerous cells, and antimicrobial proteins and peptides. Interferons, a chemical released by infected cells, inhibits how fast a viral infection spreads by alerting non-infected cells. The complement system, on the other hand, is a combination of approximately 30 proteins that attack microbes that don't belong in the body.

Acquired Immunity System

Significant qualities of the acquired immunity system:

  • specificity
  • diversity
  • memory
  • self/nonself recognition

The main components of the acquired immunity system are lymphocytes. There are three main types of lymphocytes: B lymphocytes (or B cells), cytotoxic T cells, and helper T cells.

Helper T cells act like field generals; they are an additional check against the immune system accidentally attacking the body. When helper T cells recognize a pathogen, they release cytokines, a protein triggering B cells and cytotoxic T cells to activate.

Specificity of the Acquired Immune System

Pathogens have thousands of antigens, and parts of those antigens are called epitopes. The T cell receptors recognize a particular epitope, and all cell receptors on one T cell recognize the same epitope. On the other hand, B cell receptors recognize whole antigens; this is due to B cells screen the body fluids while T cells screen cells via major histocompatibility complex (MHC) molecules.

MHC molecules are located in the cytoplasm of all cells, and they come in two classes, each class presenting epitopes from molecules inside the cell to outside the cell membrane. Class I MHC molecules are present in the majority of cells, and they randomly scoop up part of a protein from things synthesized within the cell and present that to cytotoxic T cells. If a cytotoxic T cell recognizes the epitope presented, it means the cell is creating things it's not supposed to, so the cell is killed.

Class II MHC molecules, found in phagocytic cells, present epitopes from molecules the cell has consumed through phagocytosis. Class II MHC molecules present to helper T cells.

Phagocytic cells have both Class I and Class II MHC molecules.

Diversity and Self/Nonself Recognition of the Acquired Immunity System

The diversity is the result of each lymphocyte screening for one particular epitope. During development, when these lymphocytes are maturing, they are tested for self-reactivity. If any lymphocyte reacts to a molecule naturally occurring in the body, it is inactivated, resulting in self-tolerance.

Clonal Selection and Memory of the Acquired Immune System

Clonal selection is the process that demonstrates the memory of the acquired immune system. When the receptors on a lymphocyte is exposed to a pathogen containing the epitope it recognizes, the lymphocyte undergoes clonal selection, a process in which the cell makes short term cells (called plasma cells if its a B cell or effector T cells if its a T cell) and long term cells (called memory cells), which stay in the body for decades. If the same pathogen gets introduced to the body again, these memory cells creates the body's secondary immune response.

Due to memory cells, if the body gets exposed to the same pathogen again, the secondary immune response is faster and more amplified than the primary immune response.

Helper T and Cytotoxic T Cell Activation

When a helper T cell recognizes an antigen, its antigen receptor connects to the Class II MHC molecule. The accessory protein CD4, which is part of the helper T cell, stabilizes the class II MHC molecule-antigen complex. This activates the helper T cell, and it releases cytokines, (proteins that act as a signal for activating lymphocytes) resulting in the activated helper T cells to undergo clonal selection.

Cytotoxic T cell activation is very similar to helper T cell activation. The significant distinctions are the accessory protein CD8 stabilizes the class I MHC molecule-antigen complex.

Activation of a Cytotoxic T Cell

The protein CD8 stabilizes the antigen-Class 1 MHC molecule complex, resulting in the release of perforin and granzyme, which are virtually serving same function as cytokines.

The protein CD8 stabilizes the antigen-Class 1 MHC molecule complex, resulting in the release of perforin and granzyme, which are virtually serving same function as cytokines.

Comparison of B Cells, Helper T Cells, and Cytotoxic T cells

 B cellHelper T cellCytotoxic T cell

Where it matures

bone marrow



shape of molecule

Y shaped

I shaped

I shaped

what class of HMC molecules it reads


Class II

Class I

name of accessory protein




what is screens

bodily fluids



name of short term cells from clonal selection

plasma cells

effector T cells

effector T cells

Role of Antibodies

Antibodies result from B cells undergoing clonal selection. There are many components to an antibody, including the two antigen-binding sites, the disulfide bridge, the constant regions, the variable regions, the light chain, and the heavy chain. The variable regions are what code for a specific epitope, and the constant region determines the class of the antibody.

The Structure of the Antibody

Antibody Classes



first antibody class produced


most abundant antibody class in blood, often used in research


membrane-bound antibodies


found in secretions and body fluids


associated with allergic reactions

Antibody- Mediated Disposal of Antigen

Antibodies neutralizes pathogens in various ways. Antibodies can inhibit a pathogen's ability to bind to a host cell by adding "tags"; this process is called neutralization. Opsonization is essentially enhanced phagocytosis by macrophages and neutrophils. In addition, antibodies activate the complement system, which pokes holes in the pathogen's membrane. Natural killer cells also get recruited by antibodies; antibodies attach to the pathogen, and natural killer cells attack the antibody-attached cells.

Autoimmunity vs Immunodeficiency

Autoimmune diseases turns the immune system against itself: the body loses its ability to differentiate between pathogens and the body's own cells. While infected by an autoimmune disease, antibodies against cells naturally occurring in the body. For example, in Type 1 Diabetes, the immune system attacks the body's own beta cells in the pancreas, inhibiting the ability to create insulin.

Immunodeficiency infects the adaptive immunity system. Primary immunodeficiency is caused by genetic defect while secondary immunodeficiency is immunodeficiency that occurs later in life, which is typically caused by immunosuppressants, stress, or other things. An example of a secondary immunodeficiency is AIDS (acquired immunodeficiency syndrome), which is caused by the human immunodeficiency virus (HIV) destroying the helper T cells.

Active vs Passive Immunity

Active immunity is the result of recovery from infectious diseases as it's dependent on a person's own immune system. This irmmunological memory, which is again the result of the acquired immunity system,can be naturally acquired, when there is a natural expose to the pathogen, or artificially acquired, like a vaccination or immunization.

Passive immunity, on the other hand, is the short term transference of immunity from one individual to another. This is includes pregnancy, nursing, and anti-venom, as anti-venom has antibodies from other animals who are naturally immune.

© 2019 Christina Garvis


Christina Garvis (author) from United States on May 23, 2019:

@Brain Leekley I do plan on adding information about vaccination at a national/global level at some point, although I hadn't decide whether to have that in another article or adding it to this one. I have to admit I would love to explore the related topics you mentioned- thank you for suggesting them!

Brian Leekley from Bainbridge Island, Washington, USA on May 22, 2019:

Thanks, Christina, for this clear overview of the immune system. I hope you will post follow-up articles on how best—at individual, household, community, national, and global levels—to enhance the immune system and to avoid damaging it. What daily habits help? Should children be raised in a sanitized environment or be encouraged to play in the dirt? What public health actions, such as vaccinations and clean water, are helpful? And so on. There are a myriad of related topics.