Dr.P.S.N.

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

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

Acquired immunity

Developed during an individual's lifetime

ANATOMY OF THE IMMUNE SYSTEM

DEFENCE

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

ATTACK

INFECTION

INFECTION

INFECTION

INFECTION

 DEFENCE

MAKE OWN (ACTIVE)

HIRE (PASSIVE)

PHYSICAL (SKIN)

Cells of Immune System

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.

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

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

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 antiSalmonella 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.

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.

B cell development in the bone marrow

B B

Regulates construction of an antigen receptor Ensures each cell has only one specificity hecks an isposes of self-reactive cells

Exports useful cells to the periphery Provi es a site for antibo y pro uction

T R TI

one arro provi es a IFFERE TI TI I R E for cell evelop ent

IR

E T

Markers of Self
Epithelial cell Muscle cell

Leukocyte Nerve cell

Class I MHC self-marker protein

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Mar
Bact ria

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AR

ir s

lf

A tig

it A tib d

Non-self ner e cell

lf l

A tig

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lass I MHC r t i

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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 Ag to TH cells

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

The Nature of Antigens

An antigen (or immunogen) is a chemical substance that causes the body to produce specific antibodies (antibody generation) As a rule, antigens are proteins or large polysaccharides. Antibodies are formed against specific regions on antigens called epitopes, or antigenic determinants.

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

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

Figure 17.5a-c

Generation of immune response.

~ 4-7 days to generate immune response. > 7 days get primary immune response. 1st 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

T- de endent anti en

F i u re 1 7 .4 - O v e rv iew

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

Fig re

.6

Helper T Cells

Figure 17.13

Stages of Humoral Immune Response

Two-Signal Model of Humoral Immune Response

FUNCTIONING OF THE IMMUNE SYSTEM

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

RECEPTOR LIGAND BINDING

NO BINDING

BACTERIA LYMPHOCYTE LYMPHOCYTE

RECOGNIZES BACTERIA

DOES NOT RECOGNIZE BACTERIA

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

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

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

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

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

Ag-Ab Binding

Antigen-antibody complex
Affinity Specificity

The Results of Ag-Ab Binding

Figure 17.9

General Categories of Immunity Disorders 1.Hypersensitivity 2.Autoimmunity 3.Immunodeficiency

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

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

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

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

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

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

AUTOIMMUNITY result from breakdown in self-tolerance which is the lack of responsiveness to ones own antigen The bodys own immune system recognize itself as foreign Systemic Lupus Erythematosus, inflammatory myopathies, Mixed connective tissue disease

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

IMMUNODEFICIENCY Subdivided into: Primary Brutons 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

Autoimmune disorder
Glomerulonephritis

Target of Antibodies Symptoms

Lower back pain Kidney cell antigen that resembles Streptococcus antigen

Graves disease

Restlessness, weight loss, irritability, Thyroid gland antigen increased heart rate and blood pressure Muscle weakness Fatigue and weakness Joint pain and deformity Red rash on face, fever, weakness and kidney damage Lower abdominal pain Nerve message receptors on skeletal muscle cells Binding site for vitamin B on cells lining stomach Cells lining joints DNA, neurons, blood cells

Myasthenia gravis Pernicious anemia Rheumatoid arthritis Systemic lupus erythematosus Type I diabetes Ulcerative colitis

Thirst, hunger, weakness, emaciation Pancreatic beta cells Colon cells