INTRODUCTION TO IMMUNOLOGY

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INTRODUCTION TO IMMUNOLOGY: 

INTRODUCTION TO IMMUNOLOGY BY MANOJ KUMAR.M

CONTENTS: 

CONTENTS IMMUNE SYSTEM TYPES OF IMMUNE SYSTEM CELLS OF IMMUNE SYSTEM IMMUNE RESPONSE TYPES OF IMMUNE RESPONSE REGULATION OF IMMUNE RESPONSE REFERENCES

IMMUNE SYSTEM: 

IMMUNE SYSTEM Collection of Organs, Tissue, & soluble Factors to defend against Bacteria, Viruses, & Tumour cells. Consist of: Primary (central) Lymphoid Organs in which Leukocytes develop Secondary (peripheral) Lymphoid Organs & Tissues in which Immune Response occur. Leukocytes in Blood

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The immune system Immune system Anatomic barriers (Skin , mucous membranes) Physiological barriers (temperature, pH) Phagocytic Barriers (cells that eat invaders) Inflammatory barriers (redness, swelling, heat and pain) Antigen specificity Diversity Immunological memory Self/nonself recognition Innate (non-specific) immunity Adaptive (specific) immunity

CELLS OF THE IMMUNE SYSTEM: 

CELLS OF THE IMMUNE SYSTEM MONOCYTES & MACROPHAGES Control infections not overcome by Neutrophils Associated with chronic infections Main role in cell-mediated immunity Act as Ag presenting cell to T-Lymphocyte Activated by γ - Interferon (lymphocyte)

MONOCYTES / MACROPHAGES: 

MONOCYTES / MACROPHAGES Formation: Stem cell  Monoblast  Promonocyte  circulating Monocyte  tissue Macrophage Mature in the Blood Secrete Inflammatory Mediator & Cytokines Interleukins (IL-1, 8, 12) Prostaglandin (PG) Thromboxane (TBx) Leukotriene (LT) Interferon (IF) Collagenase Elastase Complement components Lysozymes Tumor Necrosis Factor (TNF α ) Lipase

MACROPHAGES & NEUTROPHILS: 

MACROPHAGES & NEUTROPHILS Phagocytise Bacteria coated with Complement C3b binds to Bacteria Opsonised by Ab  binds to Receptor on Phagocytic cell  Phagocytosis Fc receptor on Macrophage useful for Opsonisation of Bacteria by Ab  hold bacteria close  Engulfment  Phagocytosis

DENTRITIC CELLS : 

DENTRITIC CELLS Present in Blood, LNs, Epithelial cells Digest & process Ag to present to T-cells Examples: Langerhan cells (resides within Epithelium) Veild cells (Afferent Lymphatics) Interdigitating reticular cells (Spleen & LNs)

GRANULOCYTES : 

GRANULOCYTES NEUTROPHILS (PMNs) 60% of leukocytes (white blood cells) Have receptor for Fc region of IgG & C3b Release Matrix Metalloproteinase (MMP) First to arrive in acute inflammation, actively killing bacteria, by generation of Hydrogen peroxide & Oxygen free radicals releasing LPS. Cytoplasm contain Lysosomal Peroxidase + Acid Hydrolases Cytoplasmic granules contain digestive enzyme (Myeloperoxidase) & Lactoferrin (binds Fe)

CELLS OF THE IMMUNE SYSTEM: 

CELLS OF THE IMMUNE SYSTEM BASOPHILS (1% of leukocytes) (smallest) Contain much granules with: RNA Mucopolysaccharide Histamine (hypersensitivity mediator) Have receptors for Fc portion of IgE IgE binding  degranulation  Histamine allergic reactions

CELLS OF THE IMMUNE SYSTEM (cont): 

CELLS OF THE IMMUNE SYSTEM (cont) LYMPHOCYTES (30% of circulating WBC) B Lymphocytes: Differentiate into Plasma cells  Antibodies CDb5-positive  IgM CDb5-negative  IgG, IgA, IgE Memory B cells: generated after exposure to Ag Mature B cell: have surface IgM & IgD that bind Ag  cause B cell  Ab B cell respond to: T-cell-independent Ag  Ig without CD4 cells T-cell –dependent Ag  regulate T-cells  B cell Ab

CELLS OF THE IMMUNE SYSTEM : 

CELLS OF THE IMMUNE SYSTEM T LYMPHOCYTES : Helper T cells (CD4 positive) Stimulate B-Lymphocytes  Plasma cell  Ab Promote cytotoxic T- cell (CD8) response Activation due to recognition of Class 11 MHC on Antigen-presenting cells Produce Lymphokines, Differentiation Factors, Inflammatory Cytokines (IL-2) Cytotoxic T cell (CD 8 +) Recognize Foreign Ag & Class 1 MHC Lyse virus infected cells & tumor cells

CELLS OF THE IMMUNE SYSTEM : 

CELLS OF THE IMMUNE SYSTEM Natural killer (NK) cells (10 -15% of Lymphocytes) Kill Tumour cells Defend against Viral infections Recognize Foreign Ag independent of MHC Mediate Ab-dependent cellular toxicity (ADCC) Kill Opsonised or Ab-coated cells Activated by Cytokines ( γ - Interferon)

LYMPHOCYTES: 

LYMPHOCYTES SUMMARY: T Helper cell  CD4+ Cytotoxic T cells  CD8+ T DTH cell  delayed-type Hypersensitivity Has CD$ in its membrane Antibody-Dependent cellular toxicity (ADCC) Linked to NK cells, Neutrophils Have Fc Receptors

IMMUNE RESPONSE: 

IMMUNE RESPONSE NATURAL IMMUNITY (innate immunity) Present at birth Immediate response to Pathogens  Inflammation Does not increase with repeated exposure First line of defense: Skin + Mucous membrane Effected by: Antibodies Macrophages PMNs Eosinophils Natural Killer cells Saliva Tears

IMMUNE RESPONSE (cont): 

IMMUNE RESPONSE (cont) ACQUIRED IMMUNITY (Late in Fetal life) Stimulated by repeated exposure to foreign Ag Response specific to individual Antigen (Ag) Antigen eliminated due to specific Antigen recognition & Lymphocytes activated into Effectors and Memory cells  Anamnestic Response SELF TOLERANCE: Absence of immune response to one’s own tissue Antigens. Necessary to prevent auto-immune diseases

IMMUNE RESPONSE : 

IMMUNE RESPONSE Antigen : any substance that can specifically bind to an Antibody or T cell receptor. Examples: Proteins , LPS , DNA , Lipid , Haptens (small molecules act as Ab epitope) Immunogen : that which induces an immune response . Epitope (Antigenic Determinant) Specific site on Ag that is recognized by the immune system, where Ab binds Antibody: able to bind to epitopes

IMMUNE RESPONSE : 

IMMUNE RESPONSE Major Histocompatibility Complex (MHC) In Humans the MHC called HLA Genes that encode proteins that regulate the immune response. Class 1: located on surface of all Nucleated cells + Platelets (HLA –A, HLA-B, HLA-C) Associated with Cytotoxic T cell Class 11: located on Langerhan cells & activated Macrophages (HLA-DR, HLA-DQ) Associated with Th & T DTH cells

IMMUNE RESPONSE : 

IMMUNE RESPONSE ANTIBODY STRUCTURE Ag Binding Site Ag Binding Site Variable Heavy Chain Amino acid End Constant Heavy Chain Carboxyl End Variable Light Chain Constant Light Chain Hinge Region Complement Binding Site Cell Receptor Binding Region

IMMUNE RESPONSE : 

IMMUNE RESPONSE ANTIBODIES (Ab): Act on Ag-specific receptors on B cells Secreted by Plasma cells and mediate Humoral responses (Antibodies in blood) 20% of plasma proteins Ag  B cell  Ab Bind Epitopes on Ag Activate Complement Binds Fc receptors on other Lymphoid cells

IMMUNE RESPONSE : 

IMMUNE RESPONSE ANTIBODIES Structure: 4 polypeptide chains (2 identical Light + 2 identical Heavy), bound by disulfide bonds Have Hyper variable regions at Amino acid end (responsible for Ag-binding) Have Constant regions at Carboxyl end Light chains 2 types: kappa & lambda

IMMUNE RESPONSE : 

IMMUNE RESPONSE ANTIBODIES (cont) Heavy Chains: IgG – gamma heavy chain IgA – alpha heavy chain IgM – Mn heavy chain IgE – epsilon heavy chain IgD – delta heavy chain

IMMUNE RESPONSE : 

IMMUNE RESPONSE ANTIBODY-BINDING SITES: Found at Variable Region at Amino acid terminal end of Heavy & Light chains Variability of Amino acid sequence gives Ag- binding specificity Different structurally related Ags can cross- react & bound by same Ag-binding site on & different Abs Important in Rheumatic Fever – Strep Ags structurally related & cross react with Myosin.

IMMUNE RESPONSE : 

IMMUNE RESPONSE PROPERTIES OF IMMUNOGLOBULINS IgG: Major defense against Bacteria & Toxins Only Ig to cross the human placenta, protecting newborn for 4 – 6 months. Associated with Opsonization Associated with Complement activation Important in Secondary immune response to Ag  provides Long-lasting immunity

IMMUNE RESPONSE : 

IMMUNE RESPONSE IgM: (only Ig produced by the Fetus) Primary response to Antigens First Ab detected in serum post Viral infection Rheumatoid factor & Heterophile Abs are IgM Found on B cell membranes Very efficient activator of Complement

IMMUNE RESPONSE (cont): 

IMMUNE RESPONSE (cont) IgA: Important barrier function on mucosal surfaces Function in secretory immune response Secretory IgA (sIgA) found in Tears, Saliva, Colostrums, Breast Milk) Produced by Plasma cells in GIT & URT

IMMUNE RESPONSE : 

IMMUNE RESPONSE IgD: (very low concentration in serum) Cell surface Ag receptor on naive B cells Primary receptor for Ag on B cells Stimulate B cell proliferation IgE: (very very low concentration in serum) Allergic & immediate Hypersensitivity Fc region of IgE binds to surface of Basophiles & Mast cells  Histamine, LT, ECF, Heparin  Immediate Hypersensitivity reaction

HYPERSENSITIVITY REACTIONS: 

HYPERSENSITIVITY REACTIONS T-cell Receptors (TCR) Ag-specific in concert with MHC molecules Allow T cells to function in cell-mediated responses Types of Immune Responses Involve Inflammation + adaptive response Extracellular vaccine or pathogen  Humoral response Intracellular pathogen  Humoral + cell-mediated response

TYPES OF IMMUNE RESPONSES : 

TYPES OF IMMUNE RESPONSES INFLAMMATION: Caused by infection or injury to tissues Enhance Ag delivery Dendrite cells + Monocytes  Lymphocytes  recruit NK cells Activation & clonal expansion of Ag-specific Lymphocytes require several days to generate enough Effector Lymphocytes & Memory cells Effector Lymphocytes extravagate at site of Infection

TYPES OF IMMUNE RESPONSES : 

TYPES OF IMMUNE RESPONSES HUMORAL RESPONSE: Require Antibodies Primary Immune Response Lag Phase: 3 – 4 days, no measurable Ab T helper & B cells activated Activated B cell  Plasma cells Log Phase: detectable Ab in serum IgM mostly produced Later IgG & sIgA ( Ag acting on mucosa)

TYPES OF IMMUNE RESPONSES: 

TYPES OF IMMUNE RESPONSES HUMORAL RESPONSE (cont): Secondary Immune Response Animistic to previously encountered Ag Memory B & T cells involved High-affinity IgG & IgA rise rapidly Ability to respond may persist for years Explains the efficacy of Booster injections Response to extracellular particles [helminths, pollen, enzymes (cat saliva)]  IgE

TYPES OF IMMUNE RESPONSES: 

TYPES OF IMMUNE RESPONSES CELLULAR IMMUNE RESPONSE: Functions of Effector (activated) T cells: Activate B cells, Cytotoxic T Lymphocytes Kill Virus infected cells & some Tumour cells T cell Activation: Require presentation of Foreign peptides on HLA Class 11 proteins on Ag-presenting cell Release cytokines  differentiation & proliferation of Lymphocytes, MO, PMNs Excess Macrophage activation  DTH

TYPES OF IMMUNE RESPONSES: 

TYPES OF IMMUNE RESPONSES CLINICAL CORRELATION: Some allergies can be controlled by the ingestion of Allergen. This can help patients with Pollen allergen, by eating Honey) Frequently given Low doses of Ag may explain why large organ transplants (e.g. Liver) survive well in most recipients.

REGULATION OF IMMUNE RESPONSES: 

REGULATION OF IMMUNE RESPONSES IMMULOGIC TOLERANCE: Specific suppression of Immune response caused by previous Ag exposure – the opposite to Immunity Factors that affect Tolerance: Form of Ag Route of Exposure Age of person Dose of Ag

REGULATION OF IMMUNE RESPONSES: 

REGULATION OF IMMUNE RESPONSES IMMUNE SUPRESSION: Active non-response to interaction of normal cells with suppressor cells Physical or Chemical agents interactions with immune cells Suppression by CD*+ cells affect functions of T helper cells (CD4+), B Lymphocytes, Macrophages

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REFERENCES WWW.WIKIPEDIA.COM IMMUNOLOGY BY KUBY 5 TH EDITION IMMUNOLOGY AN INTRODUCTION BY TIZARD