Fundamental And Principals Of Immunology

IMMUNOLOGY Principles and Fundamentals

Mr. T.A. Premchandani, NMIMS, Shirpur Campus 1

Immunity 

The body’s ability to resist foreign organisms and toxins (poisons) that damage tissues & organs

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Knowledge of immunology is important for pharmacy practice and pharmaceutical research.

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Drugs affecting the immune system can be used for the treatment of immunological diseases such as

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Allergies, Immune deficiencies, and Organ transplantation

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Inside your body there is an amazing protection mechanism called the immune system. It is designed to defend you against millions of – – – – – –

Bacteria Microbes Viruses Toxins and Parasites that would love to invade your body

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When someone dies, its immune system (along with everything else) shuts down.

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In a matter of hours, the body is invaded by all sorts of bacteria, microbes, parasites...

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None of these things are able to get in when your immune system is working, but the moment your immune system stops the door is

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First Line Defences 

The skin is the most difficult surface to penetrate.

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Mucous on mucous membranes helps wash away microbes, in some cases via active propulsion such as via the lung’s mucocilliary escalator.

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Lysozyme, an enzyme that destroys particularly Grampositive cell walls, is found in various body fluids, secretions, and defensive cells.

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Lactoferrin sequesters iron within the body; iron is a key nutrient required for bacterial growth.

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Defensins are small proteins that create pores in bacterial membranes (killing the bacteria).

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Free Fatty Acids essentially are soap.

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Normal flora occupies space, utilizes nutrients, and produces antimicrobial substances that together can prevent pathogen colonization of body surfaces.

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Anatomic Barriers 

In the skin the sebaceous glands produce an oily secretion called sebum.

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Sebum consists of lactic and fatty acids, which maintain the pH of the skin between 3 and 5; this pH inhibits the growth of most microorganisms

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The conjunctivae, the alimentary, respiratory, and urogenital tracts are lined by mucous membranes

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For example, saliva, tears, and mucous secretions act to wash away potential invaders and also contain antibacterial or

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Anatomic Barriers 

The viscous fluid called mucus (epithelial cells) of mucous membranes, entraps foreign microorganisms.

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Some organisms have evolved ways of escaping these defense mechanisms and thus are likely to invade the body through mucous membranes. – For example, influenza virus and the organism that causes gonorrhea.

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Physiologic barriers

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Temperature Normal body temperature inhibits growth of some pathogens (chickenpox and anthrax).

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Fever response inhibits growth of some pathogens.

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Low pH Acidity of stomach contents kills most ingested microorganisms.

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A variety of soluble factors contribute to non specific immunity, more them the soluble proteins lysozyme , interferon, and complement .

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One of the reasons that newborns are susceptible

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When you "get sick", your body is not able to work properly or at its full potential. There are many different ways for you to get sick -- here are some of them: Mechanical damage

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Vitamin or Mineral Deficiency

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Organ Degradation

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Genetic Disease

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 Infection- a condition in which

pathogenic microbes penetrate host defenses, enter tissues & multiply.

 Disease – any deviation from

health, disruption of a tissue or organ caused by microbes or their products (pyrogens) 11

Resident flora 

Includes wide varieties of bacteria

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Most areas of the body in contact with the outside environment harbor resident microbes; large intestine has the highest numbers of bacteria.

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Internal organs & tissues & fluids are microbe-free.

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Bacterial flora benefit host by preventing overgrowth of harmful microbes.

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Portals of entry 

Skin.

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Gastrointestinal tract.

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Respiratory tract.

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Urogenital tract. 13

Portals of exit 

Respiratory, saliva

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Skin scales

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Fecal exit

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Urogenital tract 14

Infectious dose (ID) 

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Minimum number of microbes required for infection to proceed Microbes with small IDs have greater virulence – 1 rickettsial cell in Q fever – 10 bacteria in TB, giardiasis – 109 bacteria in cholera

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Lack of ID will not result in infection

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Overview of infection

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Patterns of infection 

Localized infection– microbes enters body & remains confined to a specific tissue

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Systemic infection– infection spreads to several sites and tissue fluids usually in the bloodstream

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Focal infection– when infectious agent breaks loose from a local infection and is carried to other

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True pathogens – capable of causing disease in healthy persons with normal immune defenses – Influenza virus, plague bacillus, malarial protozoan

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Opportunistic pathogens – cause disease when the host’s defenses are compromised or when they grow in part of the body that is not natural to them – Pseudomonas sp & Candida albicans

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Organs and Cells in the Immune System – – – – –

Bone marrow, Thymus gland, Spleen, and Lymph nodes are organs that are necessary for the normal functioning of the human immune system.

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These organs are connected by a network of lymphatic vessels

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Lymphatic fluid moves from organ to organ in a fashion analogous to the circulation of blood in the vascular network. 20

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Lymphatic fluid is devoid of erythrocytes, being only enriched with leukocytes.

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Divisions of the Immune System 

Immunity in vertebrates can be divided into different sections.

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By the processes involved in the immune Response  Innate immunity and  Acquired immunity or Adaptive Immunity.

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By the components involved in the immune response,  Humoral immunity and  Cellular immunity.

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By the location of the immune response  Serosal immunity and  Mucosal immunity 23

Major properties of the innate and adaptive Immune systems

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INNATE IMMUNITY 

Faster-acting

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Non-specific

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No stimulation needed for activation

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Present from birth (Congenital)

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Active round the clock 25

INNATE IMMUNITY 

First-line defenses :

1: physical and chemical barrier – skin and mucus coating of the gut and airways 2: the stomach secretes gastric acid

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INNATE IMMUNITY 

Second-line defense: Phagocytic cells: 1: Phagocytic cells ( macrophages and neutrophil granulocytes) that can engulf (phagocytose) 2: Phagocytosis involves chemotaxis – chemotactic chemicals – adhesion -by opsonization, opsonins-ingestion-reactive 27 oxygen species and proteases

ACQUIRED IMMUNITY 

Adaptive immune system

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Ensure full/partial immunity against reinfection by the same organism

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Based on specialized cells called lymphocytes ,produced by stem cells in the bone marrow

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Lymphocytes - two major types: B cells and T cells

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ACQUIRED IMMUNITY 

Roughly 80% of them are T cells, - 15% B cells and - 5 % are null Lymphocytes. - B cells produce plasma cells which then produce antibodies - T cells become T helper (CD4) or cytotoxic (CD8) lymphocytes

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ACQUIRED IMMUNITY 

If acquired immunity is due to B cells or antibodies (IgA,IgG,IgM,IgD andIgE) it is also called Humoral immunity. -If acquired immunity is due to T cells it is also called Cellular immunity

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Immune Response

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Humoral and Cellular Immunity 

Humoral immunity is mediated mainly by B cells and circulating antibodies.

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Cellular immunity is mediated by T cells, Which synthesize and release various cytokines that affect other cells. These two immunities interact with each and collaborate to achieve final goal of eliminating the antigen. 32

Humoral Immunity 

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Humoral immunity is mediated by serum antibodies “immunoglobulins secreted by B cells in response to antigen” Antibodies are a group of glycoprotein's which are present in serum, as well as in almost all physiological fluids. The simplest structure of an immunoglobulin molecule consists of – Two identical short polypeptide chains, the light chains – Two identical long polypeptide chains, the heavy chains,

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Structure of Immunoglobulins (Igs)

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The two amino terminal regions from one light chain and one heavy chain form a binding site for the antigen.

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The amino terminal of Light Chain (VL) and Heavy chains (VH) are referred to as variable regions.

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The carboxyl terminal regions of light chains (CL) and heavy chains (CH) are referred to as constant regions. 39

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The peptide sequence in the center of a heavy chain CH1 and CH2, is called the hinge region Hinge regions can provide flexibility for antibodies to bind two separate but identical antigenic structures, or epitopes, with various distances. Antibodies can be divided into several classes. In humans, antibodies consist of five classes: – immunoglobulin A (IgA), – immunoglobulin D (IgD), – immunoglobulin E (IgE),

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Characteristics of Each Class of Immunoglobulin

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Immunoglobulin A 

IgA is the major secretory antibody. It is present in dimeric form.

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Present in tears, saliva, gastrointestinal fluids, milk, and other mucus fluids.

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IgA is also present in the serum at a concentration about 1 to 2 mg/ml.

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IgA can neutralize microorganisms and toxins before those pathogens can enter into or cross epithelia.

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IgA in the milk can provide neonatal immunity.

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Immunoglobulin D 

It is found predominantly on the surface of B cells.

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It is present in serum with very low concentrations (<0.1 mg/ml) and short durations (half-life <3 days).

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It binds antigen molecules on the cell surface to stimulate the activation of the B cells.

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Immunoglobulin E 

Found almost exclusively on the surface of mast cells.

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Upon binding to antigen molecule, IgE can cross-link with each other on the surface of the mast cell and stimulate the release of many allergic mediators. Eg Histamine, IL-2, TNF etc

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Immunoglobulin G 

It is the most predominant immunoglobulin in the serum.

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Normal serum contains approximately 15 mg/ml

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It is about 75% of total serum immunoglobulin.

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IgG also possesses the longest half-life of all classes of immunoglobulin in the blood, i.e., 3 weeks.

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Capable of crossing the placenta and the immature intestinal epithelium to provide

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Immunoglobulin M 

IgM is the first antibody produced by the fetus and is also the first antibody to respond when presented with a new antigen challenge.

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The production of IgM decreases when the production of IgG increases

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IgM in the serum amounts only about 1.5 mg/mL with a half-life in the blood of less than a week 46

Functions of Immunoglobulins 1. Recognize and bind specifically epitope that differ by only a single amino acid often can be distinguished from each other 2. Perform a common biologic function after combining with the antigen for production of immunoglobulin molecule. 

The binding between antigen and antibody is not covalent but depends on many relatively weak forces, such as – Hydrogen bonds, – Van der waals forces, and – Hydrophobic interactions.

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Cell Mediated Immunity 

The Basis behind this type of immunity is that there is generation of variety of cells which includes

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Cell Mediated Immunity There are various types of lymphocytes and

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they are divided into either bursa- (B) or thymus- (T) lymphocytes.

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B-lymphocytes or plasma cells produce and secrete antibodies, which are used to neutralize foreign invaders and serve as a chemo attractant for cellular elements of the immune defense.

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T-lymphocytes can be further divided into either regulatory or effector cells. Regulatory T-lymphocytes can be subclassified as either

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– Helper T-cells (TH: activate the immune system) or49 – Suppressor T-cells (Ts:Downregulators of immune

Cell Mediated Immunity 

The effector cells such as – cytotoxic T-lymphocytes (CTLs) and – Natural Killer cells (NK)

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Responsible for eradication of virallyinfected or tumor cells.

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The role of NK cells is to eliminate antibody coated pathogen by antibody dependent cell-mediated cytotoxicity

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Functions of various subsets of T cells 

Co-operation with B cells to enhance the production of antibodies. T cells release cytokines “lymphokines”, which activate B cells. A group of low molecular weight cytokines are called chemokines, they play a role in inflammatory response.

2. Inflammatory effects: on activation, a certain T cell subpopulation releases cytokines, which induce the migration and activation of monocytes and macrophages, leading to delayed-type hypersensitivity in 51 inflammatory reactions

Functions of various subsets of T cells 

Cytotoxic effects: On contact with their target TC cells (CD8+) are able to deliver a lethal hit leading to the death of the target cells.

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Regulatory effects: TH cells can be divided into different functional subsets, which are defined by the cytokines they release “ TH1, TH2” , they have regulatory properties mediated by the cytokines they release. – –

Th1 cells control (cell mediate immunity) and TH2 that control (humoral immunity)

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