Immune system

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Dr.P.S.N.Raju P.G in Physiology Andhra Medical College Visakhapatnam A.P , India

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THE IMMUNE SYSTEM The Latin term “IMMUNIS” means EXEMPT, referring to protection against foreign agents. Immunity is the ability of the body to specifically counteract foreign organisms or substances, called antigens.

Specific Defenses of the Host:The Immune Response: 

Specific Defenses of the Host:The Immune Response Acquired immunity Developed during an individual's lifetime

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ANATOMY OF THE IMMUNE SYSTEM

DEFENCE: 

DEFENCE COUNTRY ATTACKED TWO WAYS TO FIGHT HIRE A TRAINED FORCE - QUICK PREPARE OWN FORCE – TAKES TIME WHICH IS BEST?

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ATTACK INFECTION INFECTION INFECTION INFECTION

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DEFENCE HIRE (PASSIVE) MAKE OWN (ACTIVE) PHYSICAL (SKIN)

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Cells of Immune System

Lymphocytes: 

Lymphocytes Large nuclei Capable of proliferation Extensive Rough ER Synthesize antibodies Phagocytosis Direct killing of target cells Modulation of the immune response

Naturally Acquired immunity.: 

Naturally Acquired immunity. B-cells : humoral immunity (blood-specific immunity ) Secrete antibodies into blood stream Ingest, digest and display parts of antigens T-cells : cell mediated immunity T cells secrete lymphokines - activate / repress immune response. (e.g. interleukin-2) Direct cell-cell contact Bind to infected cells, deliver toxins, Induce apoptosis

Distinct Cells in Immune System: 

Distinct Cells in Immune System Lymphocytes ( B cells, T cells ) Determining specificity of immunity Monocyte/macrophage, dendritic cells, natual killer cells and other members of myeloid cells Antigen presentation Mediation of immunologic functions Specialized epithelial and stromal cells Providing anatomic environment

Acquired immunity.: 

Acquired immunity. Characteristics: Immunological recognition . Discrimination between self & non-self. Depending on displaying of specific markers Capacity to make Immune response to foreign Ag is developed in late foetal stage or after birth. Immunilogical Silence. Immunological specificity . Immunological memory .

Acquired immunity.: 

Acquired immunity. Immune system mounts immune response . Immune response must: Recognise micro-organism / parasite as foreign. Respond by production specific antibodies & lymphocytes. Mediate elimination of organisms.

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The discovery of B cell immunity 1954 - Bruce Glick, Ohio State University Studies on the function of the bursa of Fabricius, a lymphoid organ in the cloacal region of the chicken Bursectomized chickens were later used in experiments to raise antibodies to Salmonella antigens None of the bursectomized chickens made anti-Salmonella antibodies Bursa was later found to be the organ in which antibody producing cells developed – antibody producing cells were thereafter called B cells Mammals do not have a bursa of Fabricius

1. Cellular immunity - B lymphocytes.: 

1. Cellular immunity - B lymphocytes. Found in lymph nodes, liver & spleen. Bone marrow-derived. Mature in Peyers ’ Patches of Intestine . During maturation, antigen-specified Ab displayed on cell surface. If the cell activated by antigen, B cells secrete antibody.

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B cell development in the bone marrow B Regulates construction of an antigen receptor Bone Marrow provides a MATURATION & DIFFERENTIATION MICROENVIRONMENT for B cell development Ensures each cell has only one specificity B Checks and disposes of self-reactive B cells B Exports useful cells to the periphery B Provides a site for antibody production B

Major Histocompatibility Complex (MHC): 

Major Histocompatibility Complex (MHC) The major histocompatibility complex ( MHC ) is a large genomic region or gene family found in the short arm of chromosome 6. HLA antigen system-Group of genes present in MHC mol. The proteins encoded by the MHC are expressed on the surface of cells Class MHC I – found in every cell , presents Ag to Cytotoxic T cells Class MHC II – on B cells , otherAPC , Presents A g to T H cells

Humoral Immunity: 

Humoral Immunity Antibody (Ab) Proteins made in response to exposure to bacteria and other pathogens, toxins, plant polen and red blood cells that the body recognized as alien, or nonself Antigen (Ag) A substances that causes the body to produce specific antibodies or sensitized T cells

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An antigen (or immunogen) is a chemical substance that causes the body to produce specific antibodies ( anti body g en eration) As a rule, antigens are proteins or large polysaccharides . Antibodies are formed against specific regions on antigens called epitopes , or antigenic determinants. The Nature of Antigens

Haptens: 

Haptens A hapten is a low-molecular-weight substance that cannot cause the formation of antibodies unless combined with a carrier molecule; once the antibody against hapten has been formed haptens will react with their antibodies independent of the carrier molecule. Figure 17.4

The Nature of Antibodies: 

The Nature of Antibodies An antibody, or immunoglobulin (Ig), is a protein produced by B cells in response to an antigen and is capable of combining specifically with that antigen . Antibodies recognize and react with antigenic determinants or epitopes . Figure 17.3

Antibody Structure: 

Antibody Structure Figure 17.5a-c

Generation of immune response. : 

Generation of immune response. ~ 4-7 days to generate immune response. > 7 days get primary immune response . 1 st IgM produced then IgG. After ~3 weeks primary immune response turned off. Ab producing cells & memory B cells formed. Memory B cells secrete ab when same agent encountered again. This is secondary immune response . Memory lasts weeks / years.

Activation of B cells to produce antibodies: 

Activation of B cells to produce antibodies T- dependent antigen

Activation of B cells to produce antibodies: 

Activation of B cells to produce antibodies T independent antygen -Antigens that stimulate B cells without help of T cells Repeating subunits – polisaccharides or lipopolisaccharides Can bind multiple receptors

Helper T Cells: 

Helper T Cells Figure 17.13

Stages of Humoral Immune Response: 

Stages of Humoral Immune Response

Two-Signal Model of Humoral Immune Response: 

Two-Signal Model of Humoral Immune Response

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FUNCTIONING OF THE IMMUNE SYSTEM

Antigen Receptors: 

Antigen Receptors The humoral and cell-mediated responses both rely on antigen receptors Receptor versus Ligand An antigen receptor is a receptor whose ligand is an antigen Antibodies are only one class of antigen receptors

Receptor-ligand interactions “lock and key”: 

BINDING NO BINDING BACTERIA RECEPTOR LIGAND LYMPHOCYTE LYMPHOCYTE RECOGNIZES BACTERIA DOES NOT RECOGNIZE BACTERIA Receptor-ligand interactions “lock and key”

IgG antibodies: 

Monomer 80% of serum antibodies Fix complement In blood, lymph, intestine Cross placenta Enhance phagocytosis; neutralize toxins & viruses; protects fetus & newborn Half-life = 23 days IgG antibodies

IgM antibodies: 

Pentamer 5-10% of serum antibodies Fix complement In blood, lymph, on B cells Agglutinates microbes; first Ab produced in response to infection Involved in response to ABO blood group Half-life = 5 days IgM antibodies

IgA antibodies: 

Dimer 10-15% of serum antibodies In secretions, mucus, salvia, tears, and brest milk Mucosal protection Half-life = 6 days IgA antibodies

IgD antibodies: 

Monomer 0.2% of serum antibodies In blood, lymph, on B cells On the surface of B cells, initiate immune response Half-life = 3 days IgD antibodies

IgE antibodies: 

Monomer 0.002% of serum antibodies On mast cells and basophils, in blood Allergic reactions; lysis of parasitic worms Half-life = 2 days IgE antibodies

Ag-Ab Binding: 

Ag-Ab Binding Antigen-antibody complex Affinity Specificity

The Results of Ag-Ab Binding: 

The Results of Ag-Ab Binding Figure 17.9

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Immunity General Categories of Immunity Disorders Hypersensitivity Autoimmunity Immunodeficiency

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Immunity HYPERSENSITIVITY overactive or hyperactive state of the immune system. Four Mechanisms of Hypersensitivity Type 1 Hypersensitivity (Anaphylactic) Type 2 Hypersensitivity (Cytotoxic) Type 3 Hypersensitivity (Immune Complex Mediated) Type 4 Hypersensitivity (Cell Mediated)

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Immunity Type 1 Hypersensitivity (Anaphylactic) mediated by IgE, formed in response to a particular antigen (allergen) bound to mast cells and basophils (release vasoactive amines and cytokines) 2 phases: Initial (rapid) response Second (delayed) phase

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Immunity Type 1 Hypersensitivity (Anaphylactic) 2 Types of Anaphylaxis Local Anaphylaxis Asthma, rhinitis, angioedema, urticaria Systemic Anaphylaxis Life threatening Laryngeal edema, bronchospasm, pulmonary edema, hypotension

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Immunity Type 2 Hypersensitivity (Cytotoxic) mediated by antibodies against intrinsic or extrinsic antigens adsorbed on the cell surface or on other tissue components. Transfusion reactions Erythroblastosis fetalis Certain drug reactions Good Pasteure Disease Myasthenia Gravis Graves Disease

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Immunity Type 3 Hypersensitivity (Immune-Complex) Mediated by antigen-antibody complexes-immune complexes forming either in the circulation or at extravascular sites of antigen deposition Rheumatic fever

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Immunity Type 4 Hypersensitivity (Cell mediated) Initiated by specifically sensitized T-lymphocytes Delayed type of hypersensitivity Tuberculosis T-cell mediated cytotoxicity Viral infections, graft rejection

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Immunity AUTOIMMUNITY result from breakdown in “self-tolerance” which is the lack of responsiveness to one’s own antigen The body’s own immune system recognize itself as foreign Systemic Lupus Erythematosus, inflammatory myopathies, Mixed connective tissue disease

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Immunity IMMUNODEFICIENCY Subdivided into: Primary hereditary loss of immune system Secondary acquired

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Immunity IMMUNODEFICIENCY Subdivided into: Primary Bruton’s disease (deficient B cell) DiGeorge Syndrome (deficient T cell) Isolated IgA Deficiency Severe combined Immunodeficiency X-linked agammaglobulinemia (XLA) patients don’t have any mature B cell - can't make antibodies

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Autoimmune disorder Symptoms Target of Antibodies Glomerulonephritis Lower back pain Kidney cell antigen that resembles Streptococcus antigen Graves disease Restlessness, weight loss, irritability, increased heart rate and blood pressure Thyroid gland antigen Myasthenia gravis Muscle weakness Nerve message receptors on skeletal muscle cells Pernicious anemia Fatigue and weakness Binding site for vitamin B on cells lining stomach Rheumatoid arthritis Joint pain and deformity Cells lining joints Systemic lupus erythematosus Red rash on face, fever, weakness and kidney damage DNA, neurons, blood cells Type I diabetes Thirst, hunger, weakness, emaciation Pancreatic beta cells Ulcerative colitis Lower abdominal pain Colon cells

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Thank You