Notes

IMMUNOLOGY

Latin-immunis meaning free from burden, freedom from disease.
It is defined as the state of resistance or insusceptibility exhibited by the host to toxic molecules, microorganism and foreign cells.
Immunity can be broadly classified in to two types:

1. Innate (non-adaptive): resistance with which a person or a lower animal is born.
• First line of immune response
• Relies on mechanisms that exist before infection (already formed components)
• Based on genetic make-up
• Rapid response: within minutes of infection
• Not specific
• Same molecules / cells respond to a range of pathogens
• Has no memory
• Same response after repeated exposure
• Does not lead to clonal expansion

Types of Innate immunity:

Species immunity

• This refers to the total or relative refractoriness to a pathogen, shown by all members of a species.
• For example anthracisinfects human but not chicken, birds are immune to tetanus.
• The exact mechanism of species immunity is not understood the physiological and biochemical differences between tissues of different species may be responsible.

Racial immunity

• This is the difference in innate immunity exhibited by different individuals in a race.
• This type of immunity is commonly observed in an epidemic outbreak of an infection.
• Certain individuals may be found within a highly susceptible population, who unaccountably cannot be infected by some microorganisms even though they have no previous contact with the same.

Factors affecting Innate Immunity

AGE: The two extremes of life, i.e. foetus (immune apparatus is immature) and old person (immune response is waning) carry high susceptibility of infectious diseases.

The foetus in utero is normally protected by placental barrier from maternal infection. Certain pathogens, e.g. Rubella, Cytomegalovirus, Toxoplasma gondii cross the placental barrier leading to congenital malformation.

Hormonal influences: Endocrine disorders like diabetes mellitus are associated with increased risk of infections.The increased risk may be related to increased levels of carbohydrate intissues.

Corticosteroids depress the individuals resistance by its anti inflammatory and anti phagocytic effects. The effect of stress in increasing susceptibility to infections may be due to release of steroids.

NUTRITION: In general, both humoral and cell mediated immune process are reduced when there is malnutrition and thus predisposes host various infections like bacterial septicaemia, tuberculosis, herpers virus infection, measles, candidiasis.

Innate immunity: mechanisms

• Physiochemical barriers

• skin, acidic pH in stomach, cilia

• Humoral mechanisms

• lysozymes, basic proteins, complement, interferons

• Cellular defense mechanisms
  • natural killer cells, neutrophils, macrophages, mast cells, basophils, eosinophils
  • Phagocytes such as neutrophils, macrophages including monocytes are the main component of innate immunity.

Phagocytosis is the process of endocytosis in which the cell engulfs the foreign particles in a phagocytic vacuole and kills or inactivates them. A wide range of phagocytic cells are involved in the process such as blood monocytes, tissue macrophages, dendritic cells, nutrophils etc.

Steps of phagocytosis:

1. Chemotaxis
2. Attachmnent
3. Engulfment (endocytosis)
4. Intracellualr killing

• Oxygen dependent killing (respiratory bursting)
• Oxygen independent mechanism

Natural Killer (NK) cells: They are a class of lymphocytes that kill virus infected cells and tumor cells.

Mast cells: They are present lining the respiratory & other mucosa.

They are activated by microbial products binding to toll-like receptors or by IgE antibody dependent mechanism, following which they release abundant cytoplasmic granules rich in histamine, prostaglandins & cytokines that initiate inflammation &proteolytic enzymes that results in killing of bacteria.

Dendritic cells: they respond to microbe by producing numerous cytokines that initiate inflammation. They also serve as vehicle in transporting the antigens from the skin and mucosal sites to lymph nodes where they present antigens to T cells.

• Inflammation
  • Tissue injury or irritation initiated by the entry of pathogensor other irritants,leads to inflammation.The arterioles at the site constrict initially and then dilate leading to an increase in blood. There is as lowing 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

It is also an important physiological barrier. Fever results in the increase body temperature which enhances the rate of synthesis of leukocytes and inhibit the further amplification of the pathogens.

Acquired immunity

Acquired (adaptive): resistance acquired by an individual during life.

• Second line of response (if innate fails)
• Relies on mechanisms that adapt after infection
• Handled by T- and B- lymphocytes
• One cell determines one antigenic determinant
• Specific in nature
• Inoculation can transfer long-life immunity in most of the cases
• Have memory in most of the cases
• Inoculation of booster doze enhances the immune response.
• Are of two types: active immunity and passive immunity.

Active immunity

It is the immunity acquired by the individual by the inoculation of antigen or by the infectious microbes. In this type, the host immune response is provoked (activated) by the microbes or their components (Antigen).

• Passive immunity
• It is the resistance that is transmitted passively to a recipient in a ‘readymade’ form.
• The recipient’s immune system plays no active role.
• However, it acts as important tools for the protection of immuno-compromised individuals.

Adaptive immunity: mechanisms

• Cell-mediated immune response (CMIR)
  • T-lymphocytes
  • eliminate intracellular microbes that survive within phagocytes or other infected cells
• Humoral immune response (HIR)
  • B-lymphocytes
  • mediated by antibodies
  • eliminate extra-cellular microbes and their toxins

Main components of innate and acquired immunity that contribute to humoral and cell-mediated immunity. Table below compares the differences between these two types of immunity.

Immunity type	Humoral immunity	Cell-mediated immunity
Innate immunity	Complement neutrophils	Macrophages Natural killer cells
Acquired immunity	B-cells Plasma cells	Helper T cells Cytototoxic cells

Cell-mediated immune response

T-cell

• recognizes peptide antigen on macrophage in association with major histo-compatibility complex (MHC) class
• identifies molecules on cell surfaces
• helps body distinguish self from non-self

T-cell goes into effectors cells stage that is able to kill infected cells

2 types

• helper T- lymphocytes (CD4+)
  • CD4+ T cells activate phagocytes to kill microbes
• cytolytic T-lymphocyte (CD8+)
  • CD8+ T cells destroy infected cells containing microbes or microbial proteins

Types of immune response in active immunity vary depending upon the microbial exposure that occurs the first time (Primary immune response) and subsequent time (Secondary immune response).

Primary response

• production of specific clones of effector T cells and memory clones
• develops in several days
• does not limit the infection

Secondary response

• more pronounced, faster
• more effective at limiting the infection

Example - cytotoxic reactions against intracellular parasites, delayed hypersensitivity (e.g., Tuberculin test) and allograft rejection

B cells

1. B lymphocytes recognize specific antigens
• proliferate and differentiate into antibody-secreting plasma cells
2. Antibodies bind to specific antigens on microbes; destroy microbes via specific mechanisms
3. Some B lymphocytes evolve into the resting state - memory cells

Difference between active and passive immunity

Active immunity	Passive immunity
Produced actively by host's immune system.	Received passively. No active host participation.
Induced by infection or by immunogens.	Readymade antibody transferred.
Durable effective protection.	Transient, less effective.
Immunity effective only after lag period.	Immediate immunity.
Immunological memory present.	No memory.
Booster effect on subsequent dose.	Subsequent dose less effective.
Negative phase may occur.>	No negative phase.
Not applicable in the immunodeficient.	Applicable in the immunodeficient.

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, enzymelinked immunosorbent assay (ELISA). Where protection is associated with cell mediated immunity, skin tests for delayed hypersensitivity and invitro tests are used as an indicator of immunity

Local immunity

In poliomyelitis systemic immunity provided by active immunisation 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.