Histological examination of the immune system
The key primary lymphoid organs of the immune system are like thymus and bone marrow, and secondary lymphatic tissues such as spleen, tonsils, lymph vessels, lymph nodes, adenoids, and skin.
Many components of the immune system are actually cellular in nature and not associated with any specific organ but rather are embedded or circulating in various tissues located throughout the body.
Developmental immunology :
The body’s capability to react to antigen depends on a
- person’s age,
- Antigen type,
- Maternal factors
- The area where the antigen is presented.
Neonates are said to be in a state of physiological immunodeficiency, because both their innate and adaptive immunological responses are greatly suppressed. In neonates, opsonic activity and the ability to activate the complement cascade is very limited.
Phagocytic activity is also greatly impaired in newborns.
Maternal factors also play a role in the body’s immune response.
At birth most of the immunoglobulin is present is maternal IgG.
Because IgM, IgD, IgE and IgA don’t cross the placenta
Although some IgA is provided in breast milk. These passively acquired antibodies can protect the newborn up to 18 months, but their response is usually short-live and of low affinity.
During adolescence the human body undergoes several physical, physiological and immunological changes. These changes are started and mediated by different hormones.
Depending on the sex either testosterone or 17-β-oestradiol, act on male and female bodies accordingly, start acting at ages of 12 and 10 years
There is evidence that these steroids act directly not only on the primary and secondary sexual characteristics, but also have an effect on the development and regulation of the immune system.
The female sex hormone 17-β-oestradiol has been shown to regulate the level of immunological response.
Similarly, some male androgens, like testosterone, seem to suppress the stress response to infection; but other androgens like DHEA have the opposite effect, as it increases the immune response instead of down playing it.
As in females, the male sex hormones seem to have more control of the immune system during puberty and the time right after than in fully developed adults.
Other than hormonal changes physical changes like the involution of the Thymus during puberty will also affect the immunological response of the subject or patient.
Clinical immunology :
Clinical immunology is the study of diseases caused by disorders of the immune system (failure, aberrant action, and malignant growth of the cellular elements of the system).
It also involves diseases of other systems, where immune reactions play a part in the pathology and clinical features.
The diseases caused by disorders of the immune system fall into two broad categories:
1) Immunodeficiency, in which parts of the immune system fail to provide an adequate response (examples include chronic granulomatous disease).
2) autoimmunity, in which the immune system attacks its own host’s body (examples include systemic lupus erythematosus, rheumatoid arthritis, Hashimoto’s disease and myasthenia gravis).
Other immune system disorders include different hypersensitivities, in which the system responds inappropriately to harmless compounds (asthma and other allergies) or responds too intensely.
Disorders of human immunity
The immune system is a remarkably effective structure that incorporates specificity, inducibility and adaptation.
Failures of host defense do occur, however, and fall into three broad categories:
Immunodeficiencies occur when one or more of the components of the immune system are inactive.
The ability of the immune system to respond to pathogens is diminished in both the young and the elderly, with immune responses beginning to decline at around 50 years of age due to immunosenescence.
In developed countries, obesity, alcoholism, and drug use are common causes of poor immune function.
However, malnutrition is the most common cause of immunodeficiency in developing countries.
Diets lacking sufficient protein are associated with impaired cell-mediated immunity, complement activity, phagocyte function, IgA antibody concentrations, and cytokine production.
Deficiency of single nutrients such as iron; copper; zinc; selenium; vitamins A, C, E, and B6; and folic acid (vitamin B9) also reduces immune responses.[
Additionally, the loss of the thymus at an early age through genetic mutation or surgical removal results in severe immunodeficiency and a high susceptibility to infection.
Immunodeficiencies can also be inherited Chronic granulomatous disease, where phagocytes have a reduced ability to destroy pathogens, is an example of an inherited,
congenital, immunodeficiency. AIDS and some types of cancer cause acquired immunodeficiency.
Overactive immune responses comprise the other end of immune dysfunction, particularly the autoimmune disorders.
the immune system fails to properly distinguish between self and non-self, and attacks part of the body.
Hypersensitivity is an immune response that damages the body’s own tissues.
They are divided into four classes (Type I – IV) based on the mechanisms involved and the time course of the hypersensitive reaction.
Type I hypersensitivity is an immediate or anaphylactic reaction, often associated with allergy.
Symptoms can range from mild discomfort to death.
Type I hypersensitivity is mediated by IgE, which triggers degranulation of mast cells and basophils when cross-linked by antigen.
Type II hypersensitivity occurs when antibodies bind to antigens on the patient’s own cells, marking them for destruction.
This is also called antibody-dependent (or cytotoxic) hypersensitivity, and is mediated by IgG and IgM antibodies.
Immune complexes (aggregations of antigens, complement proteins, and IgG and IgM antibodies) deposited in various tissues trigger Type III hypersensitivity reactions
Type IV hypersensitivity (also known as cell-mediated or delayed type hypersensitivity) usually takes between two and three days to develop.
Type IV reactions are involved in many autoimmune and infectious diseases, but may also involve contact dermatitis (poison ivy).
These reactions are mediated by T cells, monocytes, and macrophages.
Physiological regulation :
Hormones can act as immunomodulators, altering the sensitivity of the immune system.
female sex hormones are known immunostimulators of both adaptive and innate immune responses.
Some autoimmune diseases such as lupus erythematosus strike women preferentially, and their onset often coincides with puberty.
By contrast, male sex hormones such as testosterone seem to be immunosuppressive.
Other hormones appear to regulate the immune system as well, most notably prolactin, growth hormone and vitamin D. Conversely, some hormones are regulated by the immune system, notably thyroid hormone activity
The age-related decline in immune function is also related to dropping vitamin D levels in the elderly.
As people age, two things happen that negatively affect their vitamin D levels. First, they stay indoors more due to decreased activity levels.
This means that they get less sun and therefore produce less cholecalciferol via UVB radiation.
Second, as a person ages the skin becomes less adept at producing vitamin D.
Sleep and rest.
Complex feedback loops involving cytokines, such as interleukin-1 and tumor necrosis factor-α produced in response to infection, appear to also play a role in the regulation of non-rapid eye movement (REM) sleep.
Nutrition and diet :
The functioning of the immune system, like most systems in the body, is dependent on proper nutrition.
It has been long known that severe malnutrition leads to immunodeficiency.
Overnutrition is also associated with diseases such as diabetes and obesity, which are known to affect immune function.
More moderate malnutrition, as well as certain specific trace mineral and nutrient deficiencies, can also compromise the immune response.
Specific foods may also affect the immune system; for example, fresh fruits, vegetables, and foods rich in certain fatty acids may foster a healthy immune system.
Likewise, fetal undernourishment can cause a lifelong impairment of the immune system.
In traditional medicine, some herbs are believed to stimulate the immune system,such as echinacea, licorice, ginseng, astragalus, sage, garlic, elderberry, and hyssop, as well as honey although further research is needed to understand their mode of action.
Medicinal mushrooms like Shiitake, Lingzhi mushrooms, the Turkey tail mushroom, Agaricusblazei, and Maitake have shown some evidence of immune system up-regulation in in vitro and in vivo studies, as well as in a limited number of clinical studies.
Manipulation in medicine
The immune response can be manipulated to suppress unwanted responses resulting from autoimmunity, allergy, and transplant rejection, and to stimulate protective responses against pathogens that largely elude the immune system
Immunosuppressive drugs are used to control autoimmune disorders or inflammation when excessive tissue damage occurs, and to prevent transplant rejection after an organ transplant.
Anti-inflammatory drugs are often used to control the effects of inflammation.
The glucocorticoids are the most powerful of these drugs; however, these drugs can have many undesirable side effects (e.g., central obesity, hyperglycemia, osteoporosis) and their use must be tightly controlled.
Therefore, lower doses of anti-inflammatory drugs are often used in conjunction with cytotoxic or immunosuppressive drugs such as methotrexate or azathioprine.
Cytotoxic drugs inhibit the immune response by killing dividing cells such as activated T cells. However, the killing is indiscriminate and other constantly dividing cells and their organs are affected, which causes toxic side effects.
Immunosuppressive drugs such as ciclosporin prevent T cells from responding to signals correctly by inhibiting signal transduction pathways.
In some cases, the drug itself is not immunogenic, but may be co-administered with an immunogenic compound, as is sometimes the case for Taxol.
Manipulation by pathogens :
The success of any pathogen is dependent on its ability to elude host immune responses.
Therefore, pathogens have evolved several methods that allow them to successfully infect a host, while evading detection or destruction by the immune system.[
An evasion strategy used by several pathogens to avoid the innate immune system is to hide within the cells of their host (also called intracellular pathogenesis).
Here, a pathogen spends most of its life-cycle inside host cells, where it is shielded from direct contact with immune cells, antibodies and complement.
Some examples of intracellular pathogens include viruses, the food poisoning bacterium Salmonella and the eukaryotic parasites that cause malaria (Plasmodium falciparum) and leishmaniasis (Leishmania spp.).
Other bacteria, such as Mycobacterium tuberculosis, live inside a protective capsule that prevents lysis by complement.
Many pathogens secrete compounds that diminish or misdirect the host’s immune response.
Some bacteria form biofilms to protect themselves from the cells and proteins of the immune system.
Such biofilms are present in many successful infections, e.g., the chronic Pseudomonas aeruginosa and Burkholderiacenocepacia infections characteristic of cystic fibrosis.
Other bacteria generate surface proteins that bind to antibodies, rendering them ineffective; examples include Streptococcus (protein G), Staphylococcus aureus (protein A), and Peptostreptococcusmagnus (protein L).
The simplest approach is to rapidly change non-essential epitopes (amino acids and/or sugars) on the surface of the pathogen, while keeping essential epitopes concealed.This is called antigenic variation. An example is HIV, which mutates rapidly, so the proteins on its viral envelope that are essential for entry into its host target cell are constantly changing. These frequent changes in antigens may explain the failures of vaccines directed at this virus. In HIV, the envelope that covers the viron is formed from the outermost membrane of the host cell; such “self-cloaked” viruses make it difficult for the immune system to identify them as “non-self” structures.