Immunity

Immunity

Immunity Microbiology -Lecture 55 Dr. Bipin Patel INTRODUCTION INTRODUCTION The term immunity is referred to the resistance of an individual towards injury caused by microbial stimuli (microorganisms

& their products) & non-microbial stimuli. INTRODUCTION Microbial Stimuli Examples OBJECTIVES The concepts of innate immunity and acquired immunity The types of innate immunity and acquired immunity

The mechanism of innate immunity The differences between active and passive immunity IMMUNE SYSTEM Immune System Components of immune system are Bone Marrow Thymus

Lymph nodes Lymphoid Tissue Lymphatics Spleen Skin & Mucous membrane Lymphoid tissue is scattered throughout the body and is home to the lymphocytes. Lymphocytes are packed into clusters in the walls of parts of the body that are often exposed to foreign substances.

Primary Lymphoid Tissue Bone Marrow & Thymus Secondary Lymphoid Tissues Lymph nodes Spleen MALT (Mucosal associated lymphoid tissues) Tonsils (& Walderyers Ring) GALT inducing

Peyers Patches Appendix & colonic lymphoid nodules BALT Lymph nodules Diffuse lymphoid tisses Tertiary Lymphoid Tissue Lymph nodules developing at sites of inflamation

Bone Marrow Bone marrow is the primary lymphoid organ .It is a soft tissue within the cavity of bones .Bone marrow is divisible into 2 regions: 1. Vascular region 2. Hematopoietic region.

Red marrow is actively involved in haemtopoiesis. Red marrow contains totipotent cells called stem cells. The devlopment of blood cells from stem cells is called Haematopoies.

Bone Marrow Aspiration Sites Thymus The thymus is a lymphoid organ located in the lower part of the neck and the front of the chest. With age, the thymus becomes smaller and loses most of its active immune cells.

The outside of the thymus contains lymphoid stem cells (which are immature cells, still capable of growing) that divide rapidly, producing cells that mature into T cells. These T cells then migrate to the middle of the thymus. Lymph node

Lymph nodes are small, oval structures that can be anywhere from 1mm to 25mm big. Blood vessels and nerves attach to the lymph nodes, as well as two sets of lymphatic vessels those that enter the lymph node and those that leave it.

99% of all the foreign substances that arrive at the lymph node are removed Spleen The spleen is the largest of the lymphoid organs. It is usually purple in colour, and located in the upper-left of the abdomen (the belly).

The red pulp is named because of its colour and its role is to filter the blood. The white pulp is basically areas of lymphoid tissue in the middle of the spleen. There are areas filled with T cells and B cells. These make up about 5-20% of the spleen.

IMMUNITY DIFFERENCE B/W INNATE & ADAPTIVE IMMUNITY What is innate immunity? Resistance to infections that an individual possesses due to his genetic makeup No relation to prior exposure

No relation with immunization Types of innate immunity: Non-specific innate Immunity Specific Innate Immunity Non-specific innate immunity Nonspecific immunity It indicates a degree of resistance to infections in general. It may of

Species specific Racial specific Individual specific Specific immunity Specific immunity It refers to the resistance to a particular pathogen. It can be Species specific Racial specific Individual specific

Species immunity Species immunity Refers to the resistance to a pathogen shown by all members of a species. For example all human beings are totally unsusceptible to plant pathogens. Racial immunity Racial immunity Different races within a

species, may show differences in susceptibility to infections. For example in some parts of Africa resistance to Plasmodium falciparum malaria is seen. Individual immunity Individual immunity It is the difference in innate immunity shown by different individuals within a race.

Several factors, influence the level of innate immunity in an individual, such as age, hormones and nutrition. Age: The very young and very old are more prone to infectious diseases than the rest. The fetus in utero is normally protected by placental barrier.

But some pathogens cross this barrier. Some, such as rubella virus, herpes viruses, cytomegaloviruses and parasite Toxoplasma gondii, can lead to congenital infections. The increased susceptibility of the fetus to infection is due to immaturity of its immune system. Old persons are more susceptible to infections due to their waning immune responses and other factors, like enlarged prostate leading to stasis of urine. Hormonal influences

Endocrine disorders like Diabetes mellitus, Hypothyroidism, Adrenal dysfunction are associated with increased risk of infections. The increased risk may be related to increased levels of carbohydrate in tissues. Corticosteroids depress the individuals resistance by its anti inflammatory and anti phagocytic effects. The effect of pregnancy & stress in increasing susceptibility to infections may be due to release of

steroids. Nutrition Both cell mediated and antibody mediated immune responses are depressed when there in malnutrition. Cell mediated immune responses such as Mantoux test for tuberculosis becomes negative in severe protein deficiency, as in kwashiorkor.

MECHANISM OF INNATE IMMUNITY Epithelial surfaces The intact skin and mucous membrane covering the body protect it against invasion of microorganisms. The bactericidal activity of skin secretions Sweat : High salt concentration Sebaceous secretions: Long chain fatty acids

can be illustrated by frequent fungal and bacterial infections in individuals who immerse their hands in soapy water for long periods of time occupationally for example washer men. Mucosa of Respiratory Tract The mucosa of respiratory tract has several innate mechanism of defense. The structure of nose prevents entry of microorganism to a large extent, inhaled particles being arrested at or near nasal orifices.

Those that pass beyond are held by mucous lining the epithelium, and are swept back to mouth were they tend to be swallowed or coughed out. The cough reflex is an important defense mechanism. The cilia on the respiratory epithelial cells propel particles upwards. Nasal and respiratory secretions contain substances that combine with influenza and some other viruses. Particles that manage to reach alveoli are ingested by alveolar macrophages.

Digestive Tract The mouth is continuously bathed by saliva which has inhibitory effect on many microorganisms. Particles deposited in the mouth are swallowed and subjected to action of digestive juices and high acidity of stomach. The intestinal mucosa is covered by lacelike network of mucus. Particles get trapped in the mucus and form small masses which are propelled

by peristalsis. Conjunctiva The conjunctiva is freed of foreign particles by flushing action of lachrymal secretions. The eye becomes susceptible to infection when lachrymal secretions are absent. Tears contain antibacterial

substance lysozyme, which acts on cell walls of susceptible bacteria. Genitourinary system The flushing action of urine eliminates many bacteria from the urethra. Zinc present in semen has antibacterial activity. The acidity of adult vagina (fermentation of

glycogen in epithelial cells by bacilli) makes it resistant to many pathogens. Antibacterial substances in blood and tissues Several substances possesses bactericidal activity. Blood components like complement system Beta lysine, leukins from Leukocytes, Plakins from Platelet in blood and

Lactic acid in muscle tissue & inflammatory areas, Lactoperoxidase in milk Interferon possess antiviral properties. Microbial antagonisms The skin and mucous membrane have resident bacterial flora which prevents colonisation by pathogens. Alteration of normal resident flora may lead to

invasion by pathogenic microorganisms, causing serious diseases such as staphylococcal intestinal infections following oral antibiotics. Cellular factors in innate immunity

Natural defense against the invasion of blood and tissues by microorganisms and other foreign particles is mediated to a large extent by phagocytic cells which ingest and destroy them. Phagocytic cells are Macrophages and Microphages (Neutrophils). Macrophages consists of Histiocytes in tissues,

Reticuloendothelial cells and Monocytes in blood. Cellular factors in innate immunity Phagocyte reach the site of inflammation in large numbers attracted by chemotactic substances, and ingest particulate material. Microorganisms are more

readily phagocytosed when trapped against a firm surface like alveolar wall than when they are free in tissue fluids. Cellular factors in innate immunity Bacteria are phagocytosed into a vacuole (phagosome), which with lysosomes to form phagolysosomes. The bacteria are subjected to the

action of the lytic enzymes in the phagolysosomes and are destroyed. Some bacteria like lepra bacilli resist intracellular digestion and may multiply inside phagocytes. A class of lymphocytes called natural killer (NK) cells are important in defense against viral infections and tumours. Inflammation Tissue injury or irritation initiated by the entry of

pathogens or other irritants, leads to inflammation. The arterioles at the site constrict initially and then dilate leading to an increase in blood flow. There is a slowing of blood flow and margination of the leucocytes, which escape into the tissues and accumulate in large numbers, attracted by the chemotactic substances released at the site of injury. Microorganisms are phagocytosed and destroyed. Fever

Fever: A rise of temperature following infection is a natural defense mechanism like Accelerates physiological processes Destroys infecting pathogen Fever stimulates production of interferon , hence helping in recovery from viral infections Therapeutic induction of fever was used in syphilis patients before use of penicillin.

Acute Phase Proteins Acute phase proteins: Infection or injury leads to a sudden increase in the plasma concentration of certain proteins, collectively called acute phase proteins. These include C-reactive protein (CRP) Mannose binding protein Alpha 1 acid glycoprotein Serum amyloid P component

They are believed to Activate the alternative complement pathway, enhance host resistance, prevent tissue injury and promote repair of inflammatory lesions. ACQUIRED IMMUNITY What is acquired immunity? The resistance that an individual acquires during life is known as acquired immunity. Acquired immunity is of two types:

Active immunity Natural Artificial Passive immunity Natural Artificial Active immunity Active immunity is the resistance developed by

an individual as a result of an antigenic stimulus. This involves the active functioning of the hosts immune apparatus leading to the synthesis of antibodies and the production of immunologically active cells. Active immunity sets in after a latent period which is required for the immunological machinery to sets in motion. Active immunity

Once developed active immunity is long standing. If an individual who has been actively immunised against an antigen is exposed to same antigen again, the immune responses occur quickly and abundantly than during the first encounter. This is known as secondary response. Active immunity is associated with immunological memory. This means that the immune system is able to retain for long periods the memory of prior antigenic exposure. Active immunity confers better protection then passive

immunity. Natural active immunity Active immunity can be natural or artificial. Natural active immunity results from either a clinical or an inapparent infection by a microorganism. Such immunity is usually long lasting but the duration varies with the type of pathogen. Immunity is lifelong following viral diseases like measles and chickenpox.

In influenza immunity is short lived due to antigenic variation, so as to immunity following the first infection is not effective against second infection caused by antigenically novel virus. In syphilis, a special type of immunity known as premunition is seen. Here, the immunity to reinfection lasts only as long as original infection remains active. Artificial active immunity Artificial active immunity is the resistance induced by the vaccines.

Vaccines are preparations of live or killed microorganisms or their products used for immunization. Examples of vaccines are as follows: Bacterial vaccines live (BCG for tuberculosis), bacterial products (Tetanus toxoid) Viral vaccines live (Oral polio vaccine Sabin), killed (Injectable polio vaccine Salk), subunit (Hepatitis B vaccine) Live vaccines initiate an infection without causing any injury or

disease. The immunity following live vaccine parallels that after natural infection though it may be of lower order. Killed vaccines are generally less immunogenic than live vaccines, and protection lasts only for a short period. They therefore, to be given repeatedly; generally at least two doses are required. The first dose is called primary dose and the subsequent doses as booster doses. Passive immunity Passive immunity is the resistance transmitted passively to

an individual in a readymade form. There is no antigenic stimulus; instead, preformed antibodies are administered. There is no latent period, protection being effective immediately. The immunity is transient, no secondary response in passive immunity. It is less effective then active immunisation. The main advantage of passive immunisation is that it acts immediately and, therefore, can be used when immediate effect is desired, for example antidiphtheritic serum given to a child

presenting with diphtheria. Natural passive immunity Natural passive immunity is the resistance passively transferred from mother to baby. In the human infants, maternal antibodies are transmitted predominantly through the placenta. It is only by the age of three months that the infant acquires some measure of immunological independence.

Artificial passive immunity Artificial passive immunity is the resistance passively transferred to a recipient by the administration of antibodies. The agents used for this purpose are hyperimmune sera of animal or human origin (Anti tetanus serum, ATS, prepared from hyperimmune horses) and pooled human gammaglobulin (tetanus immuneglobulin, TIG). Sometimes a combination of active and passive

immunization is used, known as combined immunization. For example, protection of a nonimmune individual with a tetanus prone wound (both TIG and Tetanus toxoid is given). Adoptive immunity A special type of immunity mediated by immunologically competent lymphocytes, known as adoptive immunity. Two types of lymphocytes involved in adaptive immunity are

B Lymphocytes and T Lymphocytes Adoptive immunity B cells secrete antibodies, highly specific protein molecules that bind to a specific pathogen. These antibodies bind specific parts of pathogens known as antigens - either presented extracellularly on infected cells or free-floating in the body. Antibody binding attracts mechanisms that will then

attack and destroy the infected cell or pathogen. Some of these B cells become memory cells, which help the body remember the disease and prevent re-infection. Adoptive immunity T cells can either be helper T cells or cytotoxic T cells, and bind pathogens via the T-cell receptor (TCR), which senses specific protein sequences. Helper T cells activate B cells, attract

macrophages, and secrete cytokines. Cytotoxic T cells create pores in infected cells through which they introduce chemicals that trigger apoptosis, thus actively killing the cell. Measurement of immunity A simple method of testing immunity is to relate its level to some convenient indicator, such as demonstration of the specific antibody. The antibodies may be demonstrated by a variety of techniques such as

Agglutination, Precipitation, Complement fixation, Hemagglutination inhibition,

Neutralisation, Enzyme linked immunosorbent assay (ELISA). Where protection is associated with cell mediated immunity, below mentioned tests are used as an indicator of immunity Skin tests for delayed hypersensitivity and In vitro tests Local immunity In poliomyelitis systemic immunity provided by

active immunization with the killed vaccine neutralises the virus when it enters the bloodstream, but it does not prevent multiplication of virus at the site of entry (the gut mucosa) and its fecal shedding. This is achieved by local intestinal immunity either acquired by infection or immunisation with live oral vaccine. A special class of immunoglobulins (IgA) forms the major component of local immunity.

Herd immunity This refers to the overall level of immunity in a community. When a large proportion of individuals in a community (herd) are immune to a pathogen, the herd immunity to the pathogen is satisfactory. Eradication of communicable diseases depends on the development of a high level of herd immunity rather than on the development of a high level

of immunity in individuals. Development of Innate v/s Adaptive Immunity in an individual Innate v/s Adaptive Immunity

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