Inflammation

Introduction

Inflammation is part of the complex biological reaction of the tissues of the body to harmful stimuli, such as bacteria, damaged cells or irritants, and is a defensive reaction involving immune cells, blood vessels and molecular mediators. 

Inflammation has the purpose of removing the initial cause of cell injury, clearing necrotic cells and damaged tissues from the initial insult and inflammatory process, and initiating tissue repair.

Inflammation is a generalized response, and thus, opposed to adaptive immunity, which is unique to each pathogen, it is regarded as a mechanism of innate immunity. Too little inflammation could cause the harmful stimulus (e.g. bacteria) to slowly kill tissue and threaten the organism’s survival.

There are two main types of inflammation:

1. Acute inflammation: It typically occurs for a short time (though sometimes severe). In two weeks or less, it generally resolves itself. Symptoms soon emerge of an injury or illness after acute inflammation is seen in the body.

2. Chronic inflammation: It is a slower form of inflammation and usually less severe. Usually, it lasts longer than 6 weeks. Even when there is no prominent disease, injury or illness, it can happen, and it doesn’t necessarily stop when the disease or injury is cured. Autoimmune conditions and even prolonged stress have been associated with chronic inflammation.

Inflammation symptoms

The five major signs that indicate the presence of inflammation are:

• heat
• pain
• redness
• swelling
• loss of function

Symptoms widely depend on the stage and condition that causes the inflammation in the body. Other symptoms that are observed in chronic inflammation include:

• body pain
• constant fatigue and insomnia
• depression, anxiety, and other mood disorders
• gastrointestinal issues, like constipation, diarrhea, and acid reflux
• weight gain
• frequent infections

Causes that lead to inflammation in the body

There are different factors which cause inflammation in the body. 

This include:

• Acute and chronic disorders 
• Some drugs 
• The body cannot quickly remove exposure to irritants or foreign materials. 

A chronic inflammatory response may also arise from repeated episodes of acute inflammation. 

In persons with autoimmune conditions, there are also certain forms of foods that can induce or exacerbate inflammation. 

These foods include:

• sugar
• refined carbohydrates
• alcohol
• processed meats
• trans fats

Treatment of Inflammation

There are a number of tests that can be carried out which show the presence of inflammation in the body. It can be as easy to combat inflammation as improving one’s diet.Inflammation is greatly subsided by eliminating sugar, trans fats, and processed foods. Some common anti-inflammatory foods are:

• berries and cherries
• fatty fish
• broccoli
• avocados
• green tea
• Tomatoes

Other remedies that can be practiced are:

• Consistently take required vitamins. 
• To decrease swelling and pain,  hot or cold treatment for physical wounds can be used.
• Exercise more often.
• Manage and lower the levels of stress. 
• Stop smoking. 
• Treat any preexisting conditions and control them.

Other treatment options:

NSAIDs and aspirin

In treating short-term pain and inflammation, non-steroidal anti-inflammatory drugs (NSAIDs) are typically the first line of protection. It is an over the counter drug.

NSAIDs that are popular include: 

• Aspirin
• ibuprofen (Advil, Motrin, Midol) 
• naproxen (Aleve)

Corticosteroids 

Corticosteroids are a form of steroid widely used to treat allergic reactions as well as swelling and inflammation. 

Typically, corticosteroids come as either a nasal spray or an oral pill. 

Article By- Ria Fazulbhoy (MSIWM031)

Adaptive Immunity

BY: SAI MANOGNA (MSIWM013)

Adaptive immunity is capable of identifying unique foreign microorganisms and molecules (i.e., foreign antigens) and selectively eliminating them. In comparison to innate immune responses, in all members of a species, adaptive immune responses are not the same but are reactions to particular antigenic challenges.

Four characteristic attributes represent adaptive immunity:

a. Antigen specificity

b. Diversity

c. Immunologic memory

d. Recognition of Self/non-self

The immune system’s antigenic specificity enables it to discern subtle distinctions between antigens. Antibodies can differentiate between two molecules of protein that differ by only one amino acid. In its recognition molecules, the immune system can produce immense complexity, enabling it to identify billions of unique structures for foreign antigens. If an antigen has been recognized and reacted to by the immune system, it exhibits immunological memory; that is, a second encounter with the same antigen causes an increased immune reactivity state. Because of this feature, after an initial experience, the immune system will confer life-long immunity to several infectious agents. Finally, the immune system typically only responds to foreign antigens, suggesting that it can recognize itself. The immune system’s ability to differentiate oneself from non-self and react only to non-self molecules is necessary. The result of an inappropriate reaction to self-molecules may be fatal.

Adaptive immunity is not autonomous from innate immunity. In initiating the particular immune response, the phagocytic cells critical to non-specific immune responses are closely involved. Conversely, it has been shown that various soluble factors released by a specific immune reaction increase these phagocytic cells’ activity. For instance, as an inflammatory response grows, soluble mediators are created that attract immune system cells. In exchange, the immune reaction may help to monitor the strength of the inflammatory response. The two mechanisms function together to remove a foreign invader through the carefully controlled inter-play of adaptive and innate immunity.

Lymphocytes and Antigen-presenting cells Co-operate in Adaptive immunity :

Two main classes of cells are involved in a successful immune response: T lymphocytes and antigen-presenting cells. Lymphocytes are formed by the hematopoiesis process in the bone marrow. Lymphocytes leave the bone marrow, circulate and remain in various lymphoid organs in the blood and lymphatic systems. Lymphocytes mediate the distinguishing immunological characteristics of specificity, diversity, memory, and self/non-self recognition since they generate and exhibit antigen-binding cell-surface receptors.

B LYMPHOCYTES

1. B lymphocytes mature within the bone marrow. Each expresses a specific antigen-binding receptor on its membrane when they leave it.

2. A membrane-bound antibody molecule is this antigen-binding or B-cell receptor. 3. Glycoproteins consisting of two identical heavy polypeptide chains and two similar light polypeptide chains are antibodies.

4. Disulfide bonds join each heavy chain with a light chain, and additional disulfide bonds hold the two pairs together.

5. A cleft within which antigen binds forms the amino-terminal ends of the pairs of heavy and light chains.

6. The antigen-binding to the antibody causes the cell to divide rapidly when a naive B cell (one that has not previously experienced antigen) first encounters the antigen that matches its membrane-bound antibody. Its progeny differentiates into memory B cells, and plasma cells called effector B cells.

7. Compared to naive cells, memory B cells have a longer life span, and parent B cells release the same membrane-bound antibody.

8. The antibody is formed by plasma cells in a form that can be secreted and has little to no membrane-bound antibodies. While plasma cells live for only a few days, they secrete enormous amounts of antibodies during this period.

9. It has been calculated that more than 2000 antibody molecules per second can be secreted by a single plasma cell. The main effector molecules of humoral immunity are secreted antibodies.

T LYMPHOCYTES

1. T cells move to the thymus gland to mature, unlike B cells, which mature within the bone marrow.

2. The T cell expresses a unique antigen-binding molecule, called the T-cell receptor, on its membrane during its maturation within the thymus.

3. T-cell receptors can recognize only antigens connected to cell-membrane proteins called major histocompatibility complex (MHC) molecules, unlike membrane-bound antibodies on B cells that can recognize antigen alone.

4. The polymorphic (genetically diverse) glycoproteins found on cell membranes are MHC molecules that act in this recognition case called “antigen presentation.”

MHC molecules are of two types:

1. Class I MHC Molecules
2. Class II MHC Molecules

Class I MHC molecules consist of a heavy chain linked to a small invariant protein called 2-microglobulin, expressed by almost all vertebrate organisms’ nucleated cells. Only antigen-presenting cells release Class II MHC molecules, consisting of an alpha and a beta glycoprotein chain. T cells proliferate and differentiate into memory T cells and multiple effector T cells when a naive T cell encounters an antigen mixed with an MHC molecule on a cell.

5. Two well-defined subpopulations of T cells exist T helper cells (Th) and T cytotoxic cells (Tc). While the third type of T cell has been postulated, called a T suppressor (Ts) cell

6. The presence of CD4 or CD8 membrane glycoproteins on their surfaces will differentiate T helper and T cytotoxic cells from one another.

7. T cells that display CD4 typically act as Th cells, whereas those that express CD8 usually operate as Tc cells.

8. The cell is activated after a Th cell recognizes and interacts with an antigen-MHC class II molecule complex, which becomes an effector cell that collectively secretes different growth factors known as cytokines.

9. In activating Tc cells, B cells, macrophages, and numerous other cells involved in the immune response, the secreted cytokines play an essential role.

10. Various types of immune reactions arise from variations in the pattern of cytokines generated by activated Th cells.

11. Tc cell recognizes an antigen-MHC class I molecule complex proliferates and differentiates into an effector cell called a cytotoxic T lymphocyte (CTL), under the influence of Th-derived cytokines.

12. The CTL does not typically secrete many cytokines, unlike the Tc cell, and exhibits cell-killing or cytotoxic activity instead.

13. The CTL plays a crucial role in tracking the body’s cells and removing any antigen-showing cells, such as virus-infected cells, tumor cells, and foreign tissue graft cells.

14. Cells exhibiting foreign antigen complexed with an MHC molecule of class I are referred to as altered self-cells; these are CTL targets.

IMMUNOLOGY

BY- SREELAKSHMI (MSIWM012)

Immunology is the branch of science dealing with the study of immunity. Louis Pasteur is considered as the Father of Immunology.

HISTORY OF IMMUNOLGY

 Immunology started from the observation of people who recovered from certain infectious diseases and who never got infected with the same.

• The earliest written evidence on immunology is by Thucydides during 430 BC .He was describing about a plague in Athens where he mentioned that people who recovered from plague could only nurse the sick because they won’t get the disease again.
• The first recorded attempt was by Chinese and turks in the 15 century. Dried crusts of from smallpox pustules was inhaled through nostrils or inserted into cuts in the skin. They used in this technique called variolation  to prevent the deadly and fatal smallpox.
• Variolation technique was later improved by Edward Jenner in 1718.
• Next major advancement was that success of Louis Pasteur in growing bacterium responsible for fowl cholera in chicken. After completing, he concluded that ageing weekend the virulence of pathogen. He called the attenuated strain as vaccine .he named it so in honor of Jenner’s technique of cowpox inoculation.
• Next decade various researchers demonstrated that an active component from the serum of immune animals are capable neutralizing toxins, precipitating toxins and occlude rich bacteria. They were termed as angio toxin precipitating and agglutinating respectively. Gamma –globulin present in serum is responsible for this activities. This active molecule is called as antibody.

DIFFERENT TYPES OF IMMUNE RESPONSE

1. Inherent Immunity

It’s a first line of defense mechanism and non-specific. Inherent immunity include physical barriers (e.g., skin, saliva etc.)and cells (e.g. Macrophages, neutrophils, basophils, mast cells etc.).It is active for first few days during infection period.

• Adaptive Immunity

It is the second line of defense. It responds to anything that is foreign and also remembers it.It involves antibodies and lymphocytes. Active and passive immunity comes under Acquired immunity

ANTIGEN

It can be any substance that can be recognized by immunoglobulin receptor of B-cells or by the T-cell receptor when complexes with MHC. Antigens include toxins, bacteria, foreign blood and the cells of transplanted organs.

   TYPES OF ANTIGENS

• Exogenous Antigen: Antigens that have entered the body from outside either by inhalation, ingestion or injection .Immune response to these antigens is often sub-clinical. Some Exogenous Antigen later become endogenous Antigens.
• Endogenous Antigens: They are generated within an individual normal cells as a result of cell metabolism. Endogenous antigens include xenogenic, autologous and idiotypic antigens.
• Tumour Antigens: They are present on the surface of tumor cells. They can sometimes be presented only by tumour cells and never by the normal ones due to some tumour specific mutations, such antigens are called Tumour specific Antigens (TSAs).Commonly these antigens are presented by both tumour cells and normal cells, and they are called Tumour Associated Antigens.

       ANTIBODIES (IMMUNOGLOBULINS)

         

They are group of glycoproteins which are present in the serum and tissue fluids of all mammals. They are produced by the immunocompetent B-cells called as plasma cells .Some of these antigen-binding proteins are carried on the surface of B-cells, where they act as receptors for specific antigens and thus, confers antigenic specificity on B-cells.

Structure of Antibodies: It is Y-shaped in appearance whose arms can swing at an angle of 180 degree. It consist of two identical light chains and heavy chains which are linked by disulphide bonds and non-covalent interactions such as hydrogen bonds, salt bridges and hydrophobic bonds in the form of heterodimer.

TYPES OF ANTIBODIES

• Immunoglobulin G (IgG): It is a major immunoglobulin present in serum. It is the major Ig produced during the secondary response. It is the only Ig which can cross placenta. It also helps in the activation of classical compliment pathway.

• Immunoglobulin A (IgM): It accounts for approximately 5%-10% of the total serum immunoglobulin with an average serum concentration of 1.5 mg/mL is the first immunoglobulin to be synthesized by the newborn. It is confined to the intravascular pool only. IgM are capable of agglutinating the antigen as well as it can neutralize the viral particles.IgM is also more efficient activator of the classical complement pathway.

• Immunoglobulin a (IgA): It constitutes only 10%-15% of the total immunoglobulin in serum. It served as a first line of defense against the microbial invasion at the mucosal surfaces. Secretory IgA present in breast milk protect the newborn against infection during the first month of life.

• Immunoglobulin E (IgE): It’s present in extremely low in serum. It mediate the immediate hypersensitivity reactions or allergic reactions. On the exposure of allergen, IgE will be produced which binds to Fc receptors present on the membranes of blood basophils and tissue mast cells. It also plays a major role in parasitic infections

• Immunoglobulin D (IgD): It constitutes only 0.2% of the total immunoglobulin in serum. It is expressed by mature B-cells on its surface together with IgM.

SCOPE OF IMMUNOLOGY

Immunology is a diverse and growing discipline. It plays an important role in the development vaccines. Immunology is associated with the treatment of allergy and asthma. It plays a major role in the disciplines of medicine especially for organ transplantation, oncology, virology, bacteriology. Immunoinformatics is special stream which link immunology and bioinformatics.Majorily for vaccine design.