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BASIC IMMUNOLOGY PowerPoint PPT Presentation


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BASIC IMMUNOLOGY. Prepared by: Dr. D. L. Boyd, DDS Oral & Maxillofacial Pathologist Associate Professor Reference: Kaplan Review Notes. IMMUNE SYSTEM. Collection of Organs, Tissue, & soluble Factors to defend against Bacteria, Viruses, & Tumor cells. Consist of:

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BASIC IMMUNOLOGY

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Basic immunology l.jpg

BASIC IMMUNOLOGY

Prepared by: Dr. D. L. Boyd, DDS

Oral & Maxillofacial Pathologist

Associate Professor

Reference: Kaplan Review Notes


Immune system l.jpg

IMMUNE SYSTEM

  • Collection of Organs, Tissue, & soluble Factors to defend against Bacteria, Viruses, & Tumor cells.

  • Consist of:

    • Primary (central) Lymphoid Organs in which Leukocytes develop

    • Secondary (peripheral) Lymphoid Organs & Tissues in which Immune Response occur.

    • Leukocytes in Blood

  • Mature in Marrow (B cell) or Thymus (T-cell)


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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 (lymphokine)


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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 (TNFα) Lipase


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MONOCYTES / MACROPHAGES

Have on cell surface:

Fc Receptors  allow uptake of Immune Complexes

Class 11 MHC molecules  present Antigenic peptides to T-cells

Monocytes  Macrophage with different names:

Kupffer cell in sinusoid of Liver

Alveolar macrophage in Lung

Microglial in Brain


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MONOCYTES / MACROPHAGES

  • Morphology:

  • Epithelioid: (From Monocytes)

    • In Granulomas

    • Activated by immune response to Antigen

  • Multinucleated Giant Cells formed by fusion of Macrophages


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MONOCYTES / MACROPHAGES

  • Activation:

  • Stimulated by Lymphokines (γ-Interferon)

  • Kill Microbs + Tumor cells

  • When activated:

    • Have increased lysosomal hydrolytic enzymes

    • Increase Chemotactic response to C5a & Cytokines from Lymphocytes, Neutrophils & Fibroblasts


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MONOCYTES / MACROPHAGES

  • Activation (cont)

  • Opsonization can occur:

    • Phagocytosis of Antigen coated with C3b and Antibody

  • Increase in Size, and Number of Pseudopodia + Pinocytotic vesicoles


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MONOCYTES / MACROPHAGES

  • Present Antigens to T-Lymphocytes:

    • Antigen undergo phagocytosis or pinocytosis

    • Antigen degraded in cytoplasm to small Peptides

    • Peptides non-covalently bind to Class 11 MHC molecules in Endosomal vesicle  complex transported to cell surface  stimulate Class 11-restricted Antigen-specific Helper T cells (CD4)


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MONOCYTES / MACROPHAGES

  • Pocess Exogenous Ag  present Epitopes in groove of Class 11 MHC

  • CD4 T cells with receptors specific for the Epitope react with Epitope-MHC complex and release Lymphokines

  • Pocess Endogenous Ag  presented to CD8 T cells on Class 1 MHC


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MACROPHAGES & NEUTROPHILS

  • Phagocytize Bacteria coated with Complement

  • C3b binds to Bacteria Opsonized by Ab  binds to Receptor on Phagocytic cell  Phagocytosis

  • Fc receptor on Macrophage useful for Opsonization of Bacteria by Ab  hold bacteria close  Engulfment  Phagocytosis


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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)


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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)


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GRANULOCYTES

  • NEUTROPHIL – SUMMARY

  • Kill microbes by:

    • Toxic Oxygen molecule

    • Digestive Enzymes stored within Lysosomal granules


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GRANULOCYTES

  • EOSIONPHILS (1 –3% of leukocytes)

  • Have receptors for Complement

  • Bi-lobed nucleus + red granules (Giemsa stain)

  • Chemotactic factors for Eosinopkils:

    • HistamineC5aLTB4PAF

    • ECF-A (anaphylaxis)

  • Mostly in parasitic(*MBP)& allergic conditions

  • Contents & Functions: Histaminase

    Pyrogen (fever)Peroxidase (kill bacteria)

    Aryl sulfatase (degrade LT) *Major Basic Protein


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EOSIONPHILS

  • CLINICAL CORRELATION

  • Classically seen with:

    • Atopic allergies

    • Worm infections

    • Collagen Vascualr diseases

    • Neoplastic disorders

    • Skin rash

  • Granules (histaminase, arylsulfatase) help control allergic reactions


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CELLS OF THE IMMUNE SYSTEM

  • BASOPHILS (1% of leukocytes) (smallest)

  • Contain much granules with:

    • RNAMucopolysaccharide

    • Histamine (hypersensitivity madiator)

  • Have receptors for Fc portion of IgE

  • IgE binding  degranulation  Histamine allergic reactions


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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


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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


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CELLS OF THE IMMUNE SYSTEM

  • Natural killer (NK) cells(10 -15% of Lymphocytes)

  • Kill Tumor cells

  • Defend against Viral infections

  • Recognize Foreign Ag independent of MHC

  • Mediate Ab-dependent cellular toxicity (ADCC)

    • Kill Opsonized or Ab-coated cells

  • Activated by Cytokines (γ- Interferon)


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LYMPHOCYTES

  • SUMMARY:

  • T Helper cell  CD4+

  • Cytotoxic T cells  CD8+

  • TDTH cell  delayed-type Hypersensitivity

    • Has CD$ in its membrane

  • Antibody-Dependent cellular toxicity (ADCC)

    • Linked to NK cells, Neutrophils

      • Have Fc Receptors


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LYMPHORETICULAR SYSTEM

  • Primary (central) Lymphoid Organs:

    • Bone marrow & Thymus (child & adult)

    • Hematopoiesis & Lymphopoiesis occur here

  • Secondary (peripheral) Lymphoid Organs:

  • Lymph NodesSpleen

  • Mucosa-Associated Lymphoid Tissue (MALT)

    • Waldeyers Ring: Lingual Tonsil + Soft Palate LNS + Tonsils + Adenoids

  • Gut- Associated Lymphoid Tissue (GALT)

    • Peyer’s patch


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LYMPHORETICULAR SYSTEM

  • Secondary (peripheral) Lymphoid Organs:

  • Bronchus-Associated Lymphoid Tissue (BALT)

  • Trap & present Ag to Lymphocytes  Immune Response

  • Protect all surfaces and fluids of the body

  • Extracellular fluid or Lymph filtered thru LNs, and tissues of MALT

  • NOTE: Primary filter of Blood = Spleen + Liver


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LYMPHORETICULAR SYSTEM

  • BONE MARROW

  • A primary organ

  • Site for Hematopoiesis + B cell maturation

  • Site of origin of Stem cell  T-cell production

  • A secondary organ: site for Plasma cell  Ab

  • Contains activated T cells


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LYMPHORETICULAR SYSTEM

  • BONE MARROW STRUCTURE

  • Very large tissue (3 – 5% body mass)

  • In Long bones + Cranium + Ribs + Iliac crest

  • Two Functional Parts:

    • Vascular + Adipose

    • Hematopoietic

      • Blood cells from single Stem cell


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LYMPHORETICULAR SYSTEM

  • HEMATOPOIETIC CELL DIFFERENTIATION

  • Pluripotent Stem cell  Myeloid + Lymphoid progenitor cells

  • Myeloid Stem cell give rise to:

    • Monocyte  Macrophage

    • Eosinophil

    • Basophil

    • Megakaryocyte  Platelet

    • Erythroblast  Erythrocyte


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LYMPHORETICULAR SYSTEM

  • Lymphoid Stem cell give rise to:

    • Pre-B cell  Late pre-B cell  Immature B cell  Mature B cell  Plasma cell  Abs

    • Pre-T cell (enters Thymus)  Helper T cell + Cytotoxic T cell + TDTHcell

    • NK cell

  • Stimuli for Differentiation:

  • Colony-stimulating Factors Erythropoietin Thymosin Ags (self or foreign)


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LYMPHORETICULAR SYSTEM

  • After maturation in Thymus or Bone marrow, Lymphocytes migrate to Spleen + LNs + MALT

  • THYMUS

  • Development:

    From 3rd + 4th Pharygeal Pouches

    Located in Mediatinum

    Maximum weight in Puberty, slowly involutes


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LYMPHORETICULAR SYSTEM

  • THYMUS (cont)

  • Organization:

    • Stroma:

      • Connective tissue capsule  invaginates into Parenchyma as Septa  divides into Lobules

    • Cortex:

      • Differentiating Thmocytes surrounded by meshwork of Epithelial Reticular cell + Macrophages


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LYMPHORETICULAR SYSTEM

  • THYMUS

  • Organization: (cont)

    • Medulla:

      • Epithelial Reticular cells + Mature T cells

      • Hassall corpuscles = concentrically arranged dead / dying Reticular cells + Macrophages + Neutrophils + Nuclear material ?origin


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LYMPHORETICULAR SYSTEM

  • THYMUS (cont)

  • THYMECTOMY result in:

    • Poor development of other Lymphoid tissue

    • Absence of cell-mediated immunity

    • DeGeorge syndrome (congenital absence)

      • Decrease B and T cells  increase infections  death

      • Also Hypoparathyroidism  Tetanus


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LYMPHORETICULAR SYSTEM

  • THYMOSIN

  • Lymphokine that stimulate Thymus-dependent zones in Lymphoid tissues

  • Produced by Thymic Epithelium

  • LYMPHATICS

  • Plasma filtered from Capillaries  Tissues  Veins  Interstitial Fluid  Excess (Lymph) Lymphatic vessels  LNs  Lymphatic vessels  Thoracic Duct  Left Subclavian Vein


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LYMPHORETICULAR SYSTEM

  • LYMPH NODES

  • Most common site for adaptive immune response

  • Filters Lymph of Foreign bodies

  • Encapsulated, kidney shaped, concave side with Hilum (entry & exit of Blood vessels + Nerves)


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LYMPHORETICULAR SYSTEM

LYMPH NODES (cont)

  • Stroma:

    • CT capsule extends into and divides the parenchyma

    • Reticular cells  Reticular fibers  network  filters Lymph + suspend Lymphocytes & Macrophages

    • Facilitates cell-to-cell & Ag-receptor interactions


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LYMPHORETICULAR SYSTEM

  • LYMPH NODES (cont)

  • Cortex:

    • Composed of Lymphatic nodules (B cells)

    • Diffuse Lymphatic tissue (T cells)

      • Mixes with Supcapsular & Peritubular Sinuses (Macrophages)

      • Lymphatic Sinuses:

        • Lymphatic passageways

        • Lined with Endothelial cells

        • Receive Lymph  Medulla


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LYMPHORETICULAR SYSTEM

  • LYMPH NODES

  • Cortex: (cont)

    • Germinal centers:

      • Inside Nodules of Cortex

      • Mainly B cells  Plasma cells  Abs

      • Where Ags are processed  increase in number + develpoment of Germinal centers


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LYMPHORETICULAR SYSTEM

  • LYMPH NODES

  • Medulla:

  • In center of LN

  • Contain medullary cords of Lymphoid tissue  extend into Cortex

  • Medullary Sinuses transmit Lymph to Hilium  exists thru Efferent Lymphatics


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LYMPH NODES

  • CLINICAL CORRELATION:

  • Receive Lymph from defined and limited regions of the Body

    • Example: Pericoronitis around Mandibular 3rd molars  Submandibular LNs

  • Neoplasms can metastasize to via LNs

    • Example: Breast, Lung, GIT, Prostate, Kidney cancer  Jaws


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LYMPHORETICULAR SYSTEM

  • SPLEEN

  • Peripheral (Upper Left Quadrant of Abdomin)

  • Filters Blood of old + defective RBCs

  • Protects against Blood-borne pathogns

  • Stroma:

    • Dense CT capsule containing Smooth muscle

    • Trabeculae branches off Capsule  partition parenchyma of Splenic Pulp

    • Delicate meshwork of Reticular CT filters Blood


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LYMPHORETICULAR SYSTEM

  • SPLEEN (cont)

  • Splenic Parenchyma (White & Red Pulp)

    • White Pulp:

      • Lymphatic tissue arranged in Sheaths

      • Increases with Antigenic stimulation

      • Periarteriolar Lymphocyte Sheath (PALS)

        • Rich in T cells

        • Marginal zone mostly B cells  form Primary follicles + Ag  Secondary follicles with Germinal centers (B cells)


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LYMPHORETICULAR SYSTEM

  • SPLEEN

  • Splenic Parenchyma

    • White Pulp (cont)

      • In Marginal Zone, Dendritic cells trap & process Ag, and migrate to PALS to present Ag to Antigen-specific cells

    • Red Pulp

      • Mostly RBC-filled sinusoids + Macrophage in Reticular fiber network

      • Most of Filtration occur here


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LYMPHORETICULAR SYSTEM

  • SPLEEN

  • Splenic Parenchyma

    • Red Pulp (cont)

      • Sinuses of various sizes separated by Pulp (Billroth) cords

      • RBCs + Platelets exposed to Macrophages in Pulp cords, which phagocytize worn-out or damaged cells

      • Sinusoids lined by endothelial cells with numerous fenestrations  filtration


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LYMPHORETICULAR SYSTEM

  • SPLEEN

  • Splenic Parenchyma

    • Red Pulp (cont)

    • Phagocytosis mainly by Macrophages outside the sinusoids, by extending finger-like projections into the sinusoids, that push thru the fenestrations between the endothelial cells


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SPLEEN

  • CLINICAL CORRELATION

  • Patients with Sickle cell anemia undergo gradual infarction of the Spleen  increase risk for septicemia (S. pneumoniae), and other opportunistic infections (Salmonella, meningococci, H. Influenza)

  • NOTE:

  • In White Pulp, T cell mostly in central portion of PALS, B cells mostly in marginal zone


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LYMPHORETICULAR SYSTEM

  • GUT-ASSOCIATED-LYMPHOID TISSUE

  • Non-encapsulated

  • Located in the Submucosa + Lamina propria

  • Site of immune responses to ingested Microbs + Food antigens

  • Structure:

    • Large follicular aggregates

      • Peyer patches (Small Intestine – villi))

    • Intraepithelial Lymphocytes


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LYMPHORETICULAR SYSTEM

  • GALT (cont)

  • Function:

    • Ag-presenting cells (M cell) in the Mucous Membranes endocytose Microbes + Ags  which are presented to T Lymphocytes between the Lymphoid follicles

    • B cell become activated  form Germinal Centers  become Plasma cells  IgA


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LYMPHORETICULAR SYSTEM

  • GALT

  • Function (cont)

    • IgA react with receptor on Intestinal Epithelial cells  crosses cytosol of epithelial cell  cleaved  excreted into lumen of intestine as secretory IgA (sIgA)  protected against hydrolysis by intestinal fluids  destroy Microbes.

    • sIgA also found in Saliva


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LYMPHORETICULAR SYSTEM

  • BRONCHUS-ASSOCIATED LYMPHOID TISSUE (BALT)

  • Lymphoid tissue beneath Respiratory mucosa

  • Tonsils

  • Organization:

    • Aggregates of B cells  Plasma cells  Abs  Humoral immune response


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LYMPHORETICULAR SYSTEM

  • Types of Tonsils:

  • Palatine Tonsils:

    • Bilateral in the Oropharynx

    • Dense Lymphoid tissue with Germinal centers

    • Numerous Epithelial invaginations (crypts)

  • Lingual Tonsils:

    • Base and Posterior Lateral Tongue

    • With an Inflamed Lingual Tonsil, Squamous cell carcinoma MUST be R/O


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LYMPHORETICULAR SYSTEM

  • Types of Tonsils (cont)

  • Pharyngael Tonsils (Adenoids)

    • Unpaired aggregate of Lymphoid tissue in the Posterior Wall of the Nasopharynx

    • Surfaced by Pseudostratified Columnar Epithelium with Cilia + Goblet cells

  • Waldeyer’s Ring = Ring of Lymphoid tissue located on Soft Palate + Floor of Mouth + Palatine Tonsil + Lingual Tonsil


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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:

    • AntibodiesMacrophages

    • PMNsEosinophils

    • Natural Killer cells SalivaTears


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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 Anatigen recognition & Lymphocytes activated into Effector and Memory cells  Anamnestic Response

  • SELF TOLERANCE:

  • Absence of immune response to one’s own tissue Antigens.

  • Necessary to prevent auto-immune diseases


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IMMUNE RESPONSE

  • Antigen: any substance that can specifically bind to an Antibody or T cell receptor.

    • Examples: ProteinsLPSDNALipidHaptens (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


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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 & TDTH cells


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IMMUNE RESPONSE

  • Class 111 encode Complement proteins

    • Associated with C2 & Factor B

    • Not related to Transplant acceptance or rejection

  • HLA diseases:

  • Arthritis (HLA DR4)

  • Sjogren’s syndrome (HLA DR3)

  • IDDM (HLA DR3 & 4)


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IMMUNE RESPONSE

  • ANTIBODY STRUCTURE

Ag Binding Site

Ag Binding Site

Variable Heavy Chain

Amino acid End

Constant Heavy Chain

Carboxyl End

Variable Light Chain

Hinge Region

Constant Light Chain

Complement Binding Site

Cell Receptor Binding Region


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IMMUNE RESPONSE

  • ANTIBODIES (Ab)

  • Act on Ag-specific receptors on B cells

  • Secreted by Plasma cells and mediate Humoralresponses (Antibodies in blood)

  • 20% of plasma proteins

  • Ag  B cell  Ab

  • Bind Epitopes on Ag

  • Activate Complement

  • Binds Fc receptors on other Lymphoid cells


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IMMUNE RESPONSE

  • ANTIBODIES (cont)

  • Structure:

  • 4 polypeptide chains (2 identical Light + 2 identical Heavy), bound by disulfite bonds

  • Have Hypervariable regions at Amino acid end (responsible for Ag-binding)

  • Have Constant regions at Carboxyl end

  • Light chains 2 types: kappa & lamda


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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


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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.


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IMMUNE RESPONSE

  • IDIOTYPE = areas on the Variable Region responsible for Ag Specificity

  • ISOTYPE = subclass of Igs that are distinguished by unique Constant Regions encoded by Heavy chain gene

  • ALLOTYPE = protein product of an Allele that may be detected as an Ag by another member of the same species

  • It involves different Alleles at a specific site on the Constant Region of the Heavy chain.


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IMMUNE RESPONSE

  • IMMUNE SERUM contain a mixed population of Abs with varying affinity for Ags

  • MONOCLONAL ANTIBODIES

  • Specific for a Single Epitope

  • Produces in Lab by Hybridomas (fusion of activated B cells to Plasma cell)


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IMMUNE RESPONSE

  • PROPERTIES OF IMMUNOGLOBULINS

  • IgG:

    • Major defense against Bacterie & 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


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IMMUNE RESPONSE

  • IgM: (only Ig produced by the Fetus)

    • Primary respone 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


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IMMUNE RESPONSE (cont)

  • IgA:

  • Important barrier function on mucosalsurfaces

  • Function in secretory immune response

  • Secretory IgA (sIgA) found in Tears, Saliva, Colostrum, Breast Milk)

  • Produced by Plasma cells in GIT & URT


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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 Basophils & Mast cells  Histamine, LT, ECF, Heparin  Immediate Hypersensitivity reaction


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HYPERSENSITIVITY REACTIONS

  • Type Antibody Complement Cells Examples

  • 1 IgE No Basophil Allergies, Anaphylaxis Asthma

  • 11 IgG, M Yes PMN, MO Autoimmnue (Cytotoxic)NKdiseases Transfusion reactions HDNB

    Graft rejectionGoodpasture ds Rheumatic fever


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HYPERSENSITIVITY REACTIONS

  • Type Antibody Complement Cells Examples

  • 11 IgG No 0 Myastemia (non-cytoxic)Gravis

    Graves disease

    Type 2 DM

    111 IgG, M Yes PMN, MO SLE, RA (immune complex) PolyarteritisnodosaPost-Strep glomerulonephritis

    Arthus RxSerum sickness


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HYPERSENSITIVITY REACTIONS

  • Type Antibody Complement Cells Examples

  • 1V 0 0 CTL, Th, MO TB test (delayed, TB DTH) Leprosy Hashimoto thyroiditis Poison Ivy (contact dermatitis)Acute Graft rejectionGVHD, IDDM


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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


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TYPES OF IMMUNE RESPONSES

  • INFLAMMATION

  • Caused by infection or injury to tissues

  • Enhance Ag delivery Dendritic cells + Monocytes  Lymphocytes  recruit NK cells

  • Activation & clonal expansion of Ag-specific Lymphocytes require several days to generate enough Effector Lymhocytes & Memory cells

  • Effector Lymphocytes extravasate at site of Infection


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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)


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TYPES OF IMMUNE RESPONSES

  • HUMORAL RESPONSE (cont)

  • Secondary Immune Response

    • Anamistic to priviously 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


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TYPES OF IMMUNE RESPONSES

  • CELLULAR IMMUNE RESPONSE

  • Functions of Effector (activated) T cells:

    • Activate B cells, Cytotoxic T Lymphocytes

    • Kill Virus infected cells & some Tumor 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


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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.


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REGULATION OF IMMUNE RESPONSES

  • IMMULOGIC TOLERANCE

  • Specific supression 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


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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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REGULATION OF IMMUNE RESPONSES

  • IMMUNE SUPRESSION (cont)

  • Physical Immune Suppression:

    • X-ray & Ulltaviolet Radiation

      • Destroy Lymphocytes

      • Bone marrow & Lymphoid Tissue very sensitive

  • Surgical removal of Thymus, Spleen, LNs


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REGULATION OF IMMUNE RESPONSES

  • IMMUNE SUPRESSION (cont)

  • Chemical Agents:

    • Corticosteroids:

      • Cause Lymphopenia

      • Inhibit DNA & RNA synthesis

      • Decrease Macrophage response

      • Decrease Monocyte chemotaxis

      • Decrease IgG response


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REGULATION OF IMMUNE RESPONSES

  • IMMUNE SUPRESSION

  • Chemical Agents: (cont)

    • Purine or Pyrimidine Analogs (Azathioprine) inhibit IgG response

    • Folic acid Antogonist block DNA & Protein synthesis in Lymphocytes

    • Alkylating Agents (Cyclophosphamide) reduce number of Lymphocytes in the Spleen.


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CLINICAL CORRELATION

  • Opportunistic Infections a serious complication of Immunosuppression

  • Recurrent CMV infection major cause of morbidity in Bone marrow transplant patients


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CELLULAR INTERACTIONS

  • ANTIGEN PROCESSING

  • How Ag is taken in & re-expressed on Antigen-presenting cells (APC) membranes in associiation with MHC Class 1 & 11 molecules

  • Exogenous route:

    • Cell takes in Foreign Ag by phagocytosis or pinocytosis

    • Taken into Endosomes  digested by Proteolytic enzymes  small peptides


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CELLULAR INTERACTIONS

  • ANTIGEN PROCESSING

  • Exogenous route: (cont)

    • Endosomes fuse with exocytic vesicles that carry MHC Class 11 molecules

    • Peptide epitopes bind to the Ag-binding groove of the Class 11 molecule

    • Endosomes travel and fuse to cell membrane  MHC-peptide expressed on the surface


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CELLULAR INTERACTIONS

  • ANTIGEN PROCESSING

  • Endogenous route:

    • Ag processed inside the cell

      • Example: Tumor Ag + Viral proteins

    • Peptides transported to lumen of Endoplasmic Reticulum (TAP peptide transporter complex)  MHC Class 1 molecules  MHC Class 1-peptide complex  transported thru Golgi complex to cell surface


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CELLULAR INTERACTIONS

  • T cell Receptor Interaction with Antigen

    • Ag (epitope) specific

    • Bind to epitope in groove of MHC 1 or 11

    • Non-covalent bond to CD3  CD3 transmit signals to interior of cell

    • CD4 respond to Ag processed by MHC 11

    • CD8 respond to Ag processed by MHC 1


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CELLULAR INTERACTIONS

  • Requirement for Activation of Cytotoxic T cell

    • Tc do not secrete enough IL-2 for own growth

    • Require activated CD4 (Th1) to supply IL-2

  • Requirement for Activation of B cells

    • Interaction with naïve (unprocessed) Ag and Ag receptor

    • Activated T cell supply CD4 (Th1) cytokines (IL-2, IL-4, IL-5, Il-6, IL-10)


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CELLULAR INTERACTIONS

  • Requirement for Activation of Tc cell: (cont)

    • Some Ag (polysaccharide) stimulate B cell with help of T cell (Thymus independent Ag)

    • Ab produced = IgM only

    • Protein Ag are Thymus dependent  all Ig


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CELLULAR INTERACTIONS

  • CYTOKINES

  • Regulate Immunologic + Inflammatory responses to injury

  • Macrophage  IL-1 + TNFα  activate Th cells

  • Th1 cell  IL-2  B cell proliferation  Plasma cell

  • Th2 cell  IL-4, IL-6  CD8 response

  • Autocrine effect = effects on same cell

  • Paracrine effecct = effect over distance on other cells


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INTERLEUKINS

  • IL-1:

    • Stimulate cells to proliferate, activate, and chemotax

    • Stimulate IL-2 secretion (MO)

    • Pyrogenic (fever inducing)

  • IL-2:

    • Produced by activated T cells

    • Stimulate T cells (CD4, CD8 & NK cells)

    • Stimulate B cells  Plasma cells  Abs


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INTERLEUKINS

  • IL-3:

    • Secreted by activated T cells

    • Stimulate Bone Marrow Stem cells

  • IL-4:

    • Secreted by activated CD4 (helper) cells + Mast cells

    • Stimulate B cells

    • Increase IgG & IgE production


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INTERLEUKINS

  • IL-5:

    • Secreted by activated CD4 cells

    • Promotes B cell proliferation

    • Increase IgA & Eosinophils

  • IL-6:

    • Stimulates Acute-phase Reactant production

    • Stimulate B cells


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INTERLEUKINS

  • IL-7: Stimulate pre-B cells & pre-T cells

  • IL-8: Stimulate Chemotaxis & Ahesion of Neutrophils to Endothelial cells

  • IL-10:

    • Stimulate Cytokine release from Macrophage

    • Inhibits Interferon synthesis by Th1 cells


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INTERLEUKINS

  • IL-12:

    • Activates Natural Killer cells

    • Induces Th cells  Th1 cells

    • Increases CTL cells (cytotoxic T cell) & DTH cells (Delayed Type Hypersensitivity)


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COMPLEMENT & INFLAMMATION

  • Inflammation an integral part of the immune response (redness, swelling, pain, heat)

  • Activation of Complement Cascade major way to initiate inflammation.

  • Complement  opsonins, chemoattractants, anaphylatoxins, mediate killing of cells

  • Complement: a system of proteins &

    glycoproteins found in Blood & Tissue fluids.

    Complement opsonize FB for phagocytosis after Ab activation (C3)

    End result is Membrane Attack Complex


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COMPLEMENT

  • CLASSIC PATHWAY:

  • Main Ab-directed mechanism for complement activation

  • Most rapid& efficient pathway

  • Complement recognizes Ab-Ag complexes (IgG or IgM)

  • Ag-Ab complexes bind to C1  cascade activated

  • C1q  C1r  C1s  C4  C2  C3


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COMPLEMENT

  • ALTERNATE PATHWAY(C3b)

  • Activated as result of binding directly to surface of infectious organisms.

  • Slow & less effective

  • Initiators of Alternative Pathway:

    • LPS Bacterial & Plant polysaccharides

    • Cell membrane constituents

    • Aggregated IgA, IgG, IgE, IgM

    • Cobra venumEndotoxins

  • Protects body in absence of Ab


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COMPLEMENT

  • MEMBRANE ATACK COMPLEX (MAC)

  • Formed from the reactions among C5, C6, C7, C8 & C9  MA C  cell lysis

  • Products of complement cascade involved in:

  • Viral neutralization

  • Lysis of infected cells

  • Direct lysis of pathogens. Promote phagocytosis

  • Focus Ag on Macrophage & Lymphocytes

  • Anaphylaxis Smooth muscle contraction

  • Vasodilation ChemotaxisKinin activity


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COMPLEMENT

  • SUMMARY

  • C2a & C4a weak anaphyatoxins

  • C3a & C5a strong anaphylatoxins

  • C5a potent chemotoxin

  • C3b potent opsonin


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COMPLEMENT

  • CLINICAL CORRELATION

  • C3 deficiency  increased susceptibility to Pyogenic infections

  • C2 deficiency  increased Connective Tissue disorders

  • C5 to C8 deficiencies  recurrent Neisseria infections

  • C1 Esterase Inhibitor deficiency  Hereditary Angioneurotic Edema


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INFLAMMATION

  • Characterized by pain, redness, heat, swelling.

  • Due to increase vascular permeability infiltration of WBCs  Cytokines which enhance the inflammatory response

  • VASOACTIVE & SMOOTH MUSCLE CONSTRICTORS:

  • Histamine: (Skin, GIT, Lungs)

  • Stored in Mast cells, Basophils & Platelets

  • Released when Ag contact IgE on Mast cell

  • Released by Trauma or Cold

  • Concentration falls within hours


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INFLAMMATION

  • VASOACTIVE & SMOOTH MUSCLE

  • CONSTRICTORS:

    • Histamine: (cont)

      • Plus H1 receptor results in:

        • Smooth muscle contraction

        • Increased vascular permeabitily

        • Elevated intracellular cyclic GMP


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INFLAMMATION

  • VASOACTIVE & SMOOTH MUSCLE

  • CONSTRICTORS:

    • Histamine: (cont)

      • Plus H2 receptor results in:

        • Increase Gastric acid secretion

        • Increase Respiratory mucous production

        • Increase intracellular cyclic AMP

      • Plus H3 (found in CNS) act as negative feedback inhibition of Histamine release

      • Adenosine: inflammatory agent from Mast cell


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INFLAMMATION

  • VASOACTIVE & SMOOTH MUSCLE CONSTRICTORS (cont)

  • Arachidonic Acid (AA) Products:

  • AA from cell membrane phospholipids

  • LPS  AA  Prostaglandin (PGE2) + Thromboxane A (TXA) via Cyclooxygenase pathway

  • LPS AA  Leukotrienes (LT) via Lipooxygenase pathway

  • Leukotrienes = slow-reacting substance of Anaphylaxis


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INFLAMMATION

  • VASOACTIVE & SMOOTH MUSCLE CONSTRICTORS (cont)

  • Platelet Activating Factor PAF)

  • From cell membrane lipid (LPS)

  • Synthesized by Basophils, PMNs, Monocytes & Epithelial cell

  • Activates Platelets by initiating the release of Platelet granule components  Clot

  • Stimulates synthesis of PG & LT

  • Increase adhesiveness of PMNs to Endothelial cells


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INFLAMMATION

  • CHEMOTACTIC FACTORS

  • Eosinophlic Chemotactic Factors (ECF)

    • E.g. Histamine

  • Neutrophil Chemotactic Factors (NCF)

    • E.g. IL-1 & IL-2

  • ENZYME MEDIATORS

    • Neutral Protease produced by Mast cells

    • Acid Hydrolases found in Lysosomes degrade Chondroitin sulfate (membranes)


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INFLAMMATION

  • PROTEOGLYCANS

  • Function in storage & release of mediators

  • Heparin: Anticoagulant, affects Tryptase activity

    • Tryptase:

      • Major protein of human Lung Mast cells  activate C3 directly in absence of Heparin

      • Stored in Mast cell with Histamine

  • Chondroitin Sulfate (structural protein) act as binding site for mediators


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    INFLAMMATION

    • TOXIC OXYGEN MOLECULES

    • Kill microorganisms

    • Activate PMNs, Eosinophils, Mast cells

    • Examples:

      • Superoxide oxygenHydrogen peroxide

      • Hydroxyl radical (OH-)

    • KININS: (polypeptide) act similar to Histamine

    • Bradykinin:

    • Vasodilator  increased capillary permeability

      ErythemaEdemaSM contraction


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    INFLAMMATION

    • SUMMARY

    • Inflammatory response can be triggered by local tissue damage that results in enzyme activation or Mast cell degranulation caused by anaphylatoxin interaction with specific receptors (e.g. C3a, C5a) on the cytoplasmic membrane.

    • Allergen reacting wiith cell-bound IgE can also trigger degranulation of Mast cells.


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    CLINICAL CORRELATION

    • Eosinophils are important cells of the immune system as they contain proteins in their granules that are toxic to worms (metazoans) and fungi.

    • Enzymes activated during the Complement Cascade or as part of the Inflammatory response can activate the Clotting system (Hageman factor) leading to Disseminated Intravascular Coagulation (DIC)


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    HYPERSENSITIVITIES

    • TYPE 1 HYPERSENSITIVITY (Anaphylactic)

    • Require initial esposure to Ag to be sensitized

    • Re-exposure to Ag causes cross-linking of IgE receptors on Basophils & Mast cells  Inflammatory mediator

    • Systemic response in minutes:

      • SM contraction  Bronchial constriction

      • Increase vascular permeability  Edema

      • Skin “wheal & flare” (“hives” or Urticaria)

      • E.g. Asthma, Allergic Rhinitis (hay fever)


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    HYPERSENSITIVITIES

    • TYPE 11 HYPERSENSITIVITY

    • Antibody-mediated cytotoxicity

    • May be associated with Auto-immune diseases

    • IgG or IgM reacts with membrane-associated Ag on surface of cells  activation of Complement  cell death

    • Examples:

      • Drug allergies

      • Blood Transfusion reaction

      • Hemolytic disease in Newborn (incompatible Rh factor)


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    HYPERSENSITIVITIES

    • TYPE 111 HYPERSENSITIVITY

    • Immune-complex-mediated

    • Caused by antibodies to foreign Antigens or autoantigens such as DNA

    • Occur only with complement-fixing Ab (IgG, M

    • E.g Arthritis

    • TYPE 1V HYPERSENSITIVITY

    • Delayed-type reaction mediated by T cells

    • E.g Tuberculin Skin Testing (PPD)


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    AUTOIMMUNE DISEASES

    • Immune responses to Ag present in host tissue

    • Mediated by:

      • Humoral (circulating Ab & Immune complexes)

      • Cellular (delayed hypersensitivity)

    • Theories;

      • Overactive T helper cells due to coupling of chemicals, drugs or viruses to self-antigen

      • EBV or polyclonal B cell activation by LPS

      • Inability of T suppressor cells at response to self-antigen


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    AUTOIMMUNE DISEASES

    • Theories (cont)

      • Release of sequestered Ag (lens of eye, sperm) not normally presented to immune system.

      • Molecular mimicry by microbal Ag

      • Inappropriate expression of Class 11 MHC

        • Pancreatic cells of IDDM have high levels


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    AUTOIMMUNE DISEASES (cont)

    • Genetic Predisposition

    • Clear role associated with MHC genes which code for Class 11 Ag that are important in the presentation of Antigens

    • Higher frequency in Females ages 20 – 40 y o

      • Lupus 4 – 6 times than in men

      • Rheumatoid arthritis 3 – 4 times than in men


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    AUTOIMMUNE DISEASES

    • SYSTEMIC LUPUS ERYTHEMATOSIS

    • F:M 9:1.

    • More common in people of African decent

    • Clinical Manifestations:

    • Facial erythematous rash (“butterfly” rash)

    • Alopecia Photosensitivity

    • Oral ulcerationsArthritis ( no deformity)

    • PsychosisSeizures


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    AUTOIMMUNE DISEASES

    • SCLERODERMA

    • Progressive systemic fibrosis

    • F:M 3:1

    • Affects:

      • Skin (“mask-like expression of Face)

      • Kidney Lung Muscle HeartGIT

    • CREST SYNDROME:

    • Calcinosis Raynaud phenomena

    • Esophageal dysfunction Sclerodactyly Telengiectasia


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    AUTOIMMUNE DISEASES

    • SJOGREN’S SYNDROME

    • Clinical Manifestations:

      • Middle ages females

      • Keratoconjunctivitis (dry eyes)

      • Xerostomia (dry mouth)

      • Arthritis

      • Increased risk for developing Lymphoma


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    TRANSPLANT IMMUNOLOGY

    • Autograft:

      • From one site of the body to a next

      • No immune response

    • Allograft:

      • Foreign tissue  Immune response

    • Xenograft: synthetic material  rejected early


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    TRANSPLANT IMMUNOLOGY

    • Donor-Recipient Workup

    • ABO blood group

    • Class 1 & 11 HLA tissue typing

    • Transplant Rejection:

    • T cell mediated rejection in 10 –14 days

    • Antibody mediated rejection

    • Method to Minimize Rejection:

    • Matching at least 4 of the HLA antigens

    • Immunosuppression


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    TUMOR IMMUNOLOGY

    • Tumor-associated antigens (TAA)present in both normal & tumor cells.

    • Tumor-specific antigens (TSA) only found in tumor cells.

    • Tumor-specific transplantation antigen (TSTA) are specilized forms of TSA which the immune system responds to.

    • Antigens of Chemically Induced Tumors:

      • TSTA unique for each tumor

      • Tumor antigens due random mutational events.


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    TUMOR IMMUNOLOGY

    • Antigens of Virally Induced Tumors:

      • TSTA result of oncogenes

    • Oncofetal Antigens:

      • Normally present on tissues duringfetal development but repressed before birth.

      • Alpha Fetoprotein (AFP) (Hepatoma)

      • Carcinoembryonic Antigen (CEA)

        • Colon, Lung, Breast, Prostate carcinomas


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    TUMOR IMMUNOLOGY

    • Leukemia Antigen:

      • Terminal deoxynucleotidyl Transferase (TdT)

      • Common Acute Lymphoblastic Leukemia Antigen (CALLA)

    • Immune surveillance: Natural killer T cells

    • Mechanism for Rejection of Tumors:

      • Antibody & Complement

      • Cytotoxic T cells (CD8+) (Tc)

      • Helper T cells (CD4+)

      • Activated Macrophages


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    TUMOR IMMUNOLOGY

    • Factors that favor tumor growth:

    • Tumor cell heterogeneity allow tumor cells to escape Tc cells.

    • Rapid growth outstrip the immune response by producing growth-promoting factors, e.g. Epithelial Growth Factor (EGF)

    • Shedding of Antigens

    • Serum-blocking Factors block Tc cells


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    HIV & AIDS

    • HIV/AIDS emerged during the 1980s

    • Impact on Dentistry immediate & significant

    • AIDS transmitted via contact with Blood or other Body Fluids

    • Syndrome first noted in American male homosexuals:

      • Oral & Pharygeal Candidiasis

      • Purple Tongue (Kaposi sarcoma)

      • Unusual pneumonia (PCP)

      • Severe weight loss


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    HIV & AIDS

    • CAUSATIVE AGENT:

    • Human Immunodeficiency Virus (HIV)

    • C-type Retrovirus (Lentivirus family)

    • RNA core surrounded by Lipid envelope made from host plasma membrane

    • Viral membrane contains a transmembrane protein gp160 (detected by Western Blot assay as 2 fragments gp41 & gp120

    • Core protein include Reverse Transcriptase + 2 non-glycosylated proteins p18 & p24


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    HIV & AIDS

    • RISK GROUPS

    • Homosexual men

    • Heterosexual transmission increasing

    • Intravenous drug users

    • Children born to infected women

    • Sexual partners of people in high risk groups

    • Recipients of infected blood products or secretions


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    HIV & AIDS

    • MECHANISM OF TRANSMISSION

    • Contaminated needles among IV drug users

    • Sexual contact

    • Exposure to blood during birth

    • Injury with contaminated instruments


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    HIV & AIDS

    • MECHANISM OF INFECTION

    • Severe loss of CD4 T cells

    • Virus bind to CD4 molecule on T cell by gp120

    • Other CD4+ cells (Macrophage + Astrocytes) also infected

    • Viral RNA is reverse transcribed & integrated in host DNA

    • T cell activation by cytokines or Ags  activation of Virus via stimulation of virally encoded genes  viral replication


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    HIV & AIDS

    • CELLULAR CONSEQUENCE

    • T cells:

      • Loss of CD4+ T Helper cells

      • Decrease in response to Antigens

      • Decrease production of cytokines (IL-1 + IFN-γ)

    • B cell: decrease response to Ag

    • Macrophage: HIV enter by binding of gp120 to CD4 + CCR5 (membrane receptor)


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    HIV & AIDS

    • NATURAL PROGRESSION OF HIVD

    • Group 1:

      • Acute infections

      • Infectious mononucleosis-like symptoms:

        • Skin rashSore throat

        • FeverAseptic meningitis

    • Group 11:

      • Asymptomatic infections

      • Disease clinically latent for 7 – 10 years


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    HIV & AIDS

    • Group 111:

      • Persistent generalized Lympadenopathy

      • FeverRash Fatigue

      • AIDS-related Complex (ARC)

        • AIDS prodrome with non-specific cluster of signs & symptoms with no decrease in CD4+ cells’. Any 1 or 2 of the following:

          • FatigueFeverWeight loss

          • Persistent Skin rashHerpes

          • Oral Hairy Leukoplakia + Candidiasis


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    HIV & AIDS

    • Group 1V:

      • Generalized disease

      • Opportunistic infections:

        • Protozoa: Toxoplasma gondii, Crytosporidia

        • Fungi: Cryptococcus, Candida, Pneumocystis carinii

        • Bacteria: Mycobacterium

        • Virus: CMV, Herpes, Vaaricella-zoster


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    HIV & AIDS

    • Group 1V:

      • Secondary Neoplasms:

        • Kaposi sarcoma

        • Non-Hodgkin Lymphoma

      • CNS: Dementia due to opportunistic infections (Toxoplasmosis)


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    HIV & AIDS

    • DIAGNOSIS

    • Antibodies appear 6 weeks to 6 months after exposure

    • Ab against p24 (core) & gp41 (transmembrane protein) appear before Ab to pol gene products


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    HIV & AIDS

    • HIV TESTING

    • For Ab to virus (not virus itself)

    • Shows exposure to virus

    • ELISA (enzyme-linked immunosorbent assay

    • ELISA confirmed by Western Blot Test  serves to eliminate false-positive ELISA

    • Viral load (viral count) and CD$ count used to Stage disease process & indicate when to start treatment


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    HIV & AIDS

    • TREATMENTS

    • Enzymes to interfere with HIV genome:

      • Reverse transcriptase , Intergrase, Protease

    • AZT, ddl, 3TC (NRTIs – nucleoside reverse transcriptase inhibitors) block Reserse transcriptase

    • Protease inhibitors:

      • Indinivir (Crixivan)Ritonavir

      • Saquinavir


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    HIV & AIDS

    • TREATMENTS

    • Combined Therapy:

      • 2 NRTIs + 1 Protease Inhibitors (“drug cocktails”)

        • Attach virus at 2 points of Life cycle

      • HAART (highly active antiviral therapy)

    • Antiviral “cocktails” started early in disease process


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    HIV & AIDS

    • POSTEXPOSURE HIV FOLLOWUP:

    • Needlestick & other accidents

    • 1. First Aid (soap & Water or Eye Eash)

    • 2. Evaluate Wound (superficial or deep, intact or broken Skin)

    • 3. Evaluate Fluid (Blood + Saliva)

    • 4. Evaluate Patient (HIV+/-, member of risk group)


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    HIV & AIDS

    • POSTEXPOSURE HIV FOLLOWUP:

    • Deep Wound + Blood on Needle + HIV+ source, early prophylactic use of Antivirals recommended.

    • If unvaccinated for HBV give HBIG (hepatitis B immune Ig) + HB vaccine


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    HIV & AIDS

    • BODY FLUID & HIV SPREAD

    • Blood & Semen: contain HIV virus & mostly highly infectious)

    • Saliva & Tears: contain virus , not infectious

      • No evidence of transmission thru dental procedures & kissing)

    • “Saliva in a Dental Setting”:

      • Usually mixed with Blood


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    HIV & AIDS

    • PEDIATRIC AIDS

    • HIV passed to child in three ways:

      • Blood mixing in Placenta in late pregnancy

      • Via Mucus in Vaginal canal during birth

      • Breast milk

    • Signs & Symptoms same as adult + bacterial sepsis, Hepatosplenomegaly, failure to thrive.

    • Newborns testing HIV+ may have received Abs from mother or Abs made by infant.

    • If infant is infected Ab will remain


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    COMMON DISORDERS IN HIV PATIENTS

    • Oral thrush (Candida)

    • Esophagitis (Candida, CMV, HSV)

    • Diarrhea:

      • Bacterial (Salmonella, Shigella, Campylobacter, Mycobacterium, Clostridium difficile)

      • Viral (CMV colitis)

      • Fungal (Candida)

      • Parasitic (Cryptosporidium, Isospora, Giardia, Entamoeba)


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    COMMON DISORDERS IN HIV PATIENTS

    • Intestinal Neoplasms (Lymphoma, Kaposi sarcoma)

    • Pulmonary Neoplasms (Lymphoma, Kaposi sarcoma)

    • Pneumonias (Pneumocystis carinii)

    • Tuberculosis

    • Fungal Respiratory infections (Histoplasmosis, Coccidiodomycosis)

    • Hematologic disorders (anemia, leukopenia, thrombocytopenia)


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    COMMON DISORDERS IN HIV PATIENTS

    • Neurologic:

      • Cryptococcal meningitis

      • Toxoplasmosis

      • Progressive multifocal leukoencephalopathy

      • CVM encephalopathy

      • CMV retinitis

      • AIDS dementia

      • CNS Lymphoma


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    COMMON DISORDERS IN HIV PATIENTS

    • Sexually transmitted diseases:

      • Skin:

        • Shingles

        • Kaposi sarcoma

        • Seborrheic dermatitis

        • Herpes simplex

        • Molluscum contagiosum

    • Disseminated infections: CMV, Mycobacterium avium-intrcellulare, Histoplasmosis


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