PANCU DANIEL FLORIN

UMF CRAIOVA / MEDICINA GENERALA

IMMUNE SYSTEM

An immune system is a system of biological structures and processes within an organism that protects
against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from
viruses to parasitic worms, and needs to distinguish them from the organism's own healthy cells and tissues in
order to function properly. Detection is complicated as pathogens can evolve rapidly, and adapt to avoid the
immune system and allow the pathogens to successfully infect their hosts.
To survive this challenge, multiple mechanisms evolved that recognize and neutralize pathogens. Even
simple unicellular organisms such as bacteria possess enzyme systems that protect against viral infections.
Other basic immune mechanisms evolved in ancient eukaryotes and remain in their modern descendants, such
as plants and insects. These mechanisms include antimicrobial peptides called defensins, phagocytosis, and the
complement system. Jawed vertebrates, including humans, have even more sophisticated defense mechanisms.
The typical vertebrate immune system consists of many types of proteins, cells, organs, and tissues that interact
in an elaborate and dynamic network. As part of this more complex immune response, the human immune
system adapts over time to recognize specific pathogens more efficiently. This adaptation process is referred to
as "adaptive immunity" or "acquired immunity" and creates immunological memory. Immunological memory,
created from a primary response to a specific pathogen, provides an enhanced response to secondary encounters
with that same, specific pathogen. This process of acquired immunity is the basis of vaccination. Primary
response can take 2 days and up to 2 weeks to develop. After the body gains immunity towards a certain
pathogen, when infection by that pathogen occurs again, the immune response is called the secondary response.
Disorders in the immune system can result in disease, including autoimmune diseases, inflammatory
diseases and cancer. Immunodeficiency diseases occur when the immune system is less active than normal,
resulting in recurring and life-threatening infections. Immunodeficiency can either be the result of a genetic
disease, such as severe combined immunodeficiency, or be produced by pharmaceuticals or an infection, such
as the acquired immune deficiency syndrome (AIDS) that is caused by the retrovirus HIV. In contrast,
autoimmune diseases result from a hyperactive immune system attacking normal tissues as if they were foreign
organisms. Common autoimmune diseases include Hashimoto's thyroiditis, rheumatoid arthritis, diabetes
mellitus type 1, and lupus erythematosus. Immunology covers the study of all aspects of the immune system,
having significant relevance to health and diseases. Further investigation in this field is expected to play a
serious role in promotion of health and treatment of diseases.
Leukocytes (white blood cells) act like independent, single-celled organisms and are the second arm of the
innate immune system. The innate leukocytes include the phagocytes (macrophages, neutrophils, and dendritic
cells), mast cells, eosinophils, basophils, and natural killer cells. These cells identify and eliminate pathogens,
either by attacking larger pathogens through contact or by engulfing and then killing microorganisms. Innate
cells are also important mediators in the activation of the adaptive immune system.
Phagocytosis is an important feature of cellular innate immunity performed by cells called 'phagocytes' that
engulf, or eat, pathogens or particles. Phagocytes generally patrol the body searching for pathogens, but can be
called to specific locations by cytokines. Once a pathogen has been engulfed by a phagocyte, it becomes
trapped in an intracellular vesicle called a phagosome, which subsequently fuses with another vesicle called a
lysosome to form a phagolysosome. The pathogen is killed by the activity of digestive enzymes or following a
respiratory burst that releases free radicals into the phagolysosome. Phagocytosis evolved as a means of
acquiring nutrients, but this role was extended in phagocytes to include engulfment of pathogens as a defense
mechanism. Phagocytosis probably represents the oldest form of host defense, as phagocytes have been
identified in both vertebrate and invertebrate animals.
Neutrophils and macrophages are phagocytes that travel throughout the body in pursuit of invading
pathogens. Neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte,
normally representing 50% to 60% of the total circulating leukocytes. During the acute phase of inflammation,
particularly as a result of bacterial infection, neutrophils migrate toward the site of inflammation in a process
called chemotaxis, and are usually the first cells to arrive at the scene of infection. Macrophages are versatile
cells that reside within tissues and produce a wide array of chemicals including enzymes, complement proteins,
and regulatory factors such as interleukin 1. Macrophages also act as scavengers, ridding the body of worn-out
cells and other debris, and as antigen-presenting cells that activate the adaptive immune system.
Dendritic cells (DC) are phagocytes in tissues that are in contact with the external environment; therefore,
they are located mainly in the skin, nose, lungs, stomach, and intestines.[45] They are named for their
resemblance to neuronal dendrites, as both have many spine-like projections, but dendritic cells are in no way
connected to the nervous system. Dendritic cells serve as a link between the bodily tissues and the innate and
adaptive immune systems, as they present antigen to T cells, one of the key cell types of the adaptive immune
system.
Mast cells reside in connective tissues and mucous membranes, and regulate the inflammatory response.
They are most often associated with allergy and anaphylaxis. Basophils and eosinophils are related to
neutrophils. They secrete chemical mediators that are involved in defending against parasites and play a role in
allergic reactions, such as asthma. Natural killer (NK cells) cells are leukocytes that attack and destroy tumor
cells, or cells that have been infected by viruses.
Adaptive
For more details on this topic, see Adaptive immune system.
The adaptive immune system evolved in early vertebrates and allows for a stronger immune response as
well as immunological memory, where each pathogen is "remembered" by a signature antigen. The adaptive
immune response is antigen-specific and requires the recognition of specific “non-self” antigens during a
process called antigen presentation. Antigen specificity allows for the generation of responses that are tailored
to specific pathogens or pathogen-infected cells. The ability to mount these tailored responses is maintained in
the body by "memory cells". Should a pathogen infect the body more than once, these specific memory cells are
used to quickly eliminate it.
Lymphocytes
The cells of the adaptive immune system are special types of leukocytes, called lymphocytes. B cells and T
cells are the major types of lymphocytes and are derived from hematopoietic stem cells in the bone marrow. B
cells are involved in the humoral immune response, whereas T cells are involved in cell-mediated immune
response.
Both B cells and T cells carry receptor molecules that recognize specific targets. T cells recognize a “non-
self” target, such as a pathogen, only after antigens (small fragments of the pathogen) have been processed and
presented in combination with a “self” receptor called a major histocompatibility complex (MHC) molecule.
There are two major subtypes of T cells: the killer T cell and the helper T cell. Killer T cells only recognize
antigens coupled to Class I MHC molecules, while helper T cells only recognize antigens coupled to Class II
MHC molecules. These two mechanisms of antigen presentation reflect the different roles of the two types of T
cell. A third, minor subtype are the γδ T cells that recognize intact antigens that are not bound to MHC
receptors.
In contrast, the B cell antigen-specific receptor is an antibody molecule on the B cell surface, and recognizes
whole pathogens without any need for antigen processing. Each lineage of B cell expresses a different antibody,
so the complete set of B cell antigen receptors represent all the antibodies that the body can manufacture.
Killer T cells
Killer T cells directly attack other cells carrying foreign or abnormal antigens on their surfaces.
Killer T cell are a sub-group of T cells that kill cells that are infected with viruses (and other pathogens), or
are otherwise damaged or dysfunctional. As with B cells, each type of T cell recognises a different antigen.
Killer T cells are activated when their T cell receptor (TCR) binds to this specific antigen in a complex with the
MHC Class I receptor of another cell. Recognition of this MHC:antigen complex is aided by a co-receptor on
the T cell, called CD8. The T cell then travels throughout the body in search of cells where the MHC I receptors
bear this antigen. When an activated T cell contacts such cells, it releases cytotoxins, such as perforin, which
form pores in the target cell's plasma membrane, allowing ions, water and toxins to enter. The entry of another
toxin called granulysin (a protease) induces the target cell to undergo apoptosis. T cell killing of host cells is
particularly important in preventing the replication of viruses. T cell activation is tightly controlled and
generally requires a very strong MHC/antigen activation signal, or additional activation signals provided by
"helper" T cells (see below).
Helper T cells
Function of T helper cells: Antigen-presenting cells (APCs) present antigen on their Class II MHC
molecules (MHC2). Helper T cells recognize these, with the help of their expression of CD4 co-receptor
(CD4+). The activation of a resting helper T cell causes it to release cytokines and other stimulatory signals
(green arrows) that stimulate the activity of macrophages, killer T cells and B cells, the latter producing
antibodies. The stimulation of B cells and macrophages succeeds a proliferation of T helper cells.
Helper T cells regulate both the innate and adaptive immune responses and help determine which types of
immune responses the body will make to a particular pathogen. These cells have no cytotoxic activity and do
not kill infected cells or clear pathogens directly. They instead control the immune response by directing other
cells to perform these tasks.
Helper T cells express T cell receptors (TCR) that recognize antigen bound to Class II MHC molecules. The
MHC:antigen complex is also recognized by the helper cell's CD4 co-receptor, which recruits molecules inside
the T cell (e.g., Lck) that are responsible for the T cell's activation. Helper T cells have a weaker association
with the MHC:antigen complex than observed for killer T cells, meaning many receptors (around 200–300) on
the helper T cell must be bound by an MHC:antigen in order to activate the helper cell, while killer T cells can
be activated by engagement of a single MHC:antigen molecule. Helper T cell activation also requires longer
duration of engagement with an antigen-presenting cell. The activation of a resting helper T cell causes it to
release cytokines that influence the activity of many cell types. Cytokine signals produced by helper T cells
enhance the microbicidal function of macrophages and the activity of killer T cells. In addition, helper T cell
activation causes an upregulation of molecules expressed on the T cell's surface, such as CD40 ligand (also
called CD154), which provide extra stimulatory signals typically required to activate antibody-producing B
cells.
γδ T cells
γδ T cells possess an alternative T cell receptor (TCR) as opposed to CD4+ and CD8+ (αβ) T cells and share
the characteristics of helper T cells, cytotoxic T cells and NK cells. The conditions that produce responses from
γδ T cells are not fully understood. Like other 'unconventional' T cell subsets bearing invariant TCRs, such as
CD1d-restricted Natural Killer T cells, γδ T cells straddle the border between innate and adaptive immunity. On
one hand, γδ T cells are a component of adaptive immunity as they rearrange TCR genes to produce receptor
diversity and can also develop a memory phenotype. On the other hand, the various subsets are also part of the
innate immune system, as restricted TCR or NK receptors may be used as pattern recognition receptors. For
example, large numbers of human Vγ9/Vδ2 T cells respond within hours to common molecules produced by
microbes, and highly restricted Vδ1+ T cells in epithelia will respond to stressed epithelial cells.
An antibody is made up of two heavy chains and two light chains. The unique variable region allows an
antibody to recognize its matching antigen.
B lymphocytes and antibodies
A B cell identifies pathogens when antibodies on its surface bind to a specific foreign antigen. This
antigen/antibody complex is taken up by the B cell and processed by proteolysis into peptides. The B cell then
displays these antigenic peptides on its surface MHC class II molecules. This combination of MHC and antigen
attracts a matching helper T cell, which releases lymphokines and activates the B cell. As the activated B cell
then begins to divide, its offspring (plasma cells) secrete millions of copies of the antibody that recognizes this
antigen. These antibodies circulate in blood plasma and lymph, bind to pathogens expressing the antigen and
mark them for destruction by complement activation or for uptake and destruction by phagocytes. Antibodies
can also neutralize challenges directly, by binding to bacterial toxins or by interfering with the receptors that
viruses and bacteria use to infect cells.