Fundamentals and Principles of Immunology

Basics of Immunology: Immune System

Immunology is the study of an immune system which provides resistance to disease caused by the micro-organisms and their products like toxins. This resistance is termed as immunity and this also provides resistance even to cancer cells.

Immune system mainly works on following principle strategies −

• It prevents the pathogen entry into the body

• Eliminates the invaded pathogens by involving different immune cells.

• Preventing the attack on the host’s own or self-cells.

• Stored memory of previously invaded pathogens by T and B cells.

• Should able to limit its immune response once the pathogen is eliminated.

Defense Mechanisms of Host

Host exhibits defense against pathogens by an intricate network of immunological organs and the cells. This host defense is mainly categorized into 2 groups of defense mechanisms to prevent the entry of pathogen and to eliminate it. They are :

• Natural resistance which is usually provided by barriers of host. This forms the part of the external defense mechanism.

• Internal defense mechanism which includes both non-specific innate immunity and specific acquired immunity.

Barriers/1^st Line of Defense/External Defense of Host

This includes three different factors which acts like a barriers and as a 1st line of defense mechanisms.

• Physical Factors – This includes skin, saliva, nose hair and mucus.

• Chemical Factors – Includes Sweat and oil.

• Biological Factors – Includes good bacteria which are the normal flora present within the body and do not cause any infection. These normal flora produces substances which can kill pathogens and are mainly found in skin, stomach and intestine.

  • Lysozymes which are secreted by the cerebro-spinal fluid (CSF) in brain helps to prevent the infections caused by microbes.

  • Mucus which is secreted in the mouth helps in trapping the microbes and this mucus has enzymes which can kills these microbes.

  • Cilia which lines the trachea entraps the microbes preventing its entry into liver to case infections if inhaled by the host.

  • Sebaceous glands which produce sebum form an oily layer on the skin reducing the pH thereby preventing alkaline bacteria.

  • Due to acids secreted in stomach, all the neutrophilic or alkaline bacteria gets killed.

  • Normal flora presents in GIT and vagina also provide defense against microbes.

Role of White Blood Cells

So in the case of damage to the skin, pathogen invades the host cell making it a site of entry. Then the white blood cells come into the role which exhibits both 2nd line and 3rd line of defense against the pathogen.

This mainly includes 2 types of cells.

• Granulocytes – Noticeable granules are present in these cells. Granules are the small vesicles that contains substances which helps in defending against pathogen.

• Agranulocytes – These do not possess any granules.

Innate Immunity/2^nd Line of Defense/Non-specific Internal Defense

• It is a general and immediate response towards the invaded pathogens.

• It has no memory hence is response remains the same.

• Involves innate immune cells like neutrophils, basophils, eosinophils, mast cells etc.

• Some of the phagocytes like neutrophils can kill the pathogens by a process called phagocytosis which is the ingestion of pathogen.

• Other innate immune cells like eosinophils can kill pathogen by degranulation which is the process of releasing contents of granules.

• Basophils release a chemical called histamine in response to an infection and leads to the inflammation which is a normal response to any infection. Inflammation results in widening the space between the capillary cells allowing the white blood cells to move from capillaries to tissues.

• Mast cells which are formed in the tissues also release histamines and kills the pathogens through degranulation.

• NK cells involved in innate immunity and kills the infected cells by degranulation process.

• Monocyte which is the largest white blood cell in the blood kills pathogens by phagocytosis. These monocytes when moved into tissues it becomes dendritic cells and macrophages. These cells are mainly involved in innate immunity.

• Dendritic cells act as a link between innate and adaptive immunity. When innate immunity fails to eliminate the pathogens then these dendritic cells activates the adaptive immunity. Once the pathogen is ingested this cell breaks don it into tiny particles and present them on their surface MHC molecules.

Non-specific defense is mainly provided by the following mechanisms.

Phagocytosis

It is also called cell eating. Monocytes, basophils and neutrophils causes phagocytosis of invaded pathogen. Most of the gram positive bacteria are killed by this process.

Natural Killer cells

Exact mechanism for killing of microbes by these cells is unknown. These can kill cancer cells and virus infected cells without ingesting them.

Interferons

Eukaryotic cells produce some proteins upon exposure to the viral infections called as interferons. These are of 3 types, alpha, beta and gamma. These induce the host cells to produce non-specific viral proteins. These can resist viral infections, inhibits cell proliferation and promote cytotoxic activity of NK cells.

Inflammatory Responses

First when there is any tissue injury, it leads to irritation as the microbes enter through the damaged site. Arterioles at this site then dilate resulting in increased blood flow. Then the large number of immune cells accumulate near the infection site and kill if any pathogen presents there.

Fever

Following the infection, there is a rise in temperature observed which again a natural defense mechanism as it can kill pathogens. Also stimulates the production of the interferons. Endotoxins released by the microbes and the IL-1 mainly causes the fever.

Complement System

It is also called as C system which is one of the internal defense mechanism. This system refers to many factors which occur in normal serum and are mainly activated when there is an antigen antibody interaction. It can subsequently mediate number of biological significant consequences.

It mainly consists of 9 proteins C1 to C9 and C1 is made up of 3 subunits. These are mainly synthesized in different sites.

• Intestinal epithelium – C1

• Macrophages – C2, C4

• Spleen – C5, C8

• Liver – C3, C6, C9

Complement system causes bacteriolysis and cytolysis. Complement binding to Ag-Ab complex adhere to erythrocyte phagocytosis.

Adaptive Immunity/3rd Line of Defense/Specific Internal Defense of Host

• This is a specific response and needs to be activated first hence provide delayed response towards the invaders.

• It has a memory hence results in improved responses when a same kind of pathogen invaded again.

• Immune cells like T and B lymphocytes are involved in the adaptive immune responses.

• There are 2 types of T cells cytotoxic T cells (Tc) and helper T cells (TH).

• Tc cells kill the infected cells by degranulation here as TH cells recognizes the tiny pieces provided by the dendritic cells on their MHC molecules and activate the TC cells and other white blood cells like B cells.

• B cells are differentiated into plasma cells which can produce antibodies against the pathogens.

• Provides immune response by 2 different mechanisms, they are cell-mediated immunity which involves TC and TH cells and humoral immunity mediated by production of antibodies specific to invaded pathogen.

Conclusion

Science of immunology is a rapidly expanding subject which provides scope for knowledge and research. Immunology is the study of an immune system which not only encompasses the immune responses against microbes but also extensively involved in tumor recognition and subsequent rejection, rejection of transplanted organs and tissues, elimination of parasites, allergies and autoimmunity. Host’s Immune system provides defense mainly by 2 types of mechanisms which are external defense mechanism and internal defense mechanisms. Internal defense mechanisms of host include non-specific (Innate immunity) and specific (acquired) defense mechanisms which are discussed below.