understanding immunology for internists 1

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Understanding Immunology

Dr. Ahmed Elshebiny , MDDr. Ahmed Elshebiny , MDLecturer of Internal MedicineLecturer of Internal Medicine

Faculty of Medicine, Menoufyia UniversityFaculty of Medicine, Menoufyia University

Former Clinical Research FellowFormer Clinical Research Fellow,,Joslin Diabetes Center, Harvard UniversityJoslin Diabetes Center, Harvard University

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Immunology Course Basics:

Immune system and disease Diseases:

Immunopatholy Applications:

Therapeutic applications

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Immune system and disease Immunity Immune system Innate Immunity Adaptive Immunity Immune Recognition

Cells of the Immune system Complement Immunoglobulins Cytokines

Human disease & Immunity Immunopathology Diagnostics Therapeutic applications

Structure andFunction of The

System

Cells and Molecules of

Immunity

Introduction toClinical

Immunology

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Immunity

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Immunity is characterized by:1. Specificity – activated by and responds to a

specific antigen

2. Versatility – is ready to confront any antigen at any time

3. Memory – “remembers” any antigen it has encountered

4. Tolerance – responds to foreign substances but ignores normal tissues

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History of discovery of immunity “Immune” meaning Noticing immunity centuries ago Small pox Edward Jenner Recent developments

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1st Line defense: Physical and chemical barriers

Skin – acts as a barrier to invasion Sweat – has chemicals which can kill different

pathogens. Tears - have lysozyme which has powerful digestive

abilities that render antigens harmless. Saliva – also has lysozyme. Mucus - can trap pathogens, which are then sneezed,

coughed, washed away, or destroyed by chemicals. Stomach Acid – destroys pathogens

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Innate Adaptive

Immunity

Immunity

Cellular HumoralCellular Humoral

Let us see this video about immunity

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Inflammation

Inflammation is a nonspecific response of living tissue to localize and eliminate the injurious agent

Immune Response

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Inflammation The word inflammation means "setting on

fire" (16th century), and the process has been known since ancient Egyptian times (c. 2500 B.C)

The cardinal signs of redness, swelling, heat, and pain were described by Celsus (first-century A.D.), and loss of function was added by Galen (130-200 A.D)

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Acute phase changes characterized by pronounced behavioral,

physiologic, biochemical and nutritional changes

Acute phase reactants Acute phase proteins

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C-reactive protein named for its capacity to precipitate the

somatic C-polysaccharide of Streptococcus Pneumoniae.

Systemic marker of inflammation produced by hepatocytes, predominantly

under transcriptional control by the cytokine IL-6

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The Immune system The immune system

recognizes, attacks, destroys, and remembers each pathogen that enters the body.  

It does this by making specialized cells and antibodies that render the pathogens harmless.

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Questions? What Happens during an infection ?

How can immune cells distinguish foreign invaders from our own cells ?

How can we make 100,000,000 different antibodies with only 30,000 genes ?

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Cells of the immune system

T-cell development

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Cells of the immune system

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Polymorphonuclear cells1- Neutrophils

Stored in bone marrow Released in response to infection Have surface receptors for IgG,

IgA, complement Phagocytose and destroy bacteria Short lived Dead neutrophils make a part of

pus

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Polymorphonuclear cells2-Basophils and mast cells

Basophil circulate Mast cells are tissue bound Released in response to infection Have surface receptors for IgE, complement C3, C5 Produce histamine, prostaglandins, leukotrienes and

proteases Involved in immune response to parasites Involved in immediate hypersensitivity

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Polymorphonuclear cells3-Eosinophils

Allergy Have surface receptors for IgG, complement

C3, C5 Also binds to IgE but less than mast cells or

basophils Phagocytose antigen antibody complexes

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Macrophage In the tissues Long lived Initiate immune responses as they display antigens

from the pathogens to the lymphocytes.

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Phagocytosis

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Lymphocytes B and T cells mature then

circulate in the blood and lymph

B-cells mature in bone marrow

T-cells mature in thymus

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B-Lymphocytes The huge variety is caused

by genes coding for abs changing slightly during development.

The number of plasma cells goes down after a few weeks

Antibodies stay in the blood longer but eventually their numbers go down too.

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T-Lymphocytes CD3 in all types CD4 in helper CD8 in cytotoxic

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Natural killer cells Large granular lymphocytes Recognize and destroy cells bedaring viral or

tumor surface markers

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Complement Definition : series of heat-labile serum proteins

Site : serum and all tissue fluids except urine and CSF

Synthesis : in liver – appear in fetal circulation during 1st 13 W Function : Responsible for certain aspects of immune response and inflammatory response

Activation : antigen-antibody complex or endotoxin, capsule series of proteins activated sequentially

Inactivation: inhibitors in plasma (short lived)

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Complement system Plasma protein sequence cascade Triggered by

Classic pathway Alternative pathway Lectin binding

Complement

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Complement ActivationComplement ActivationClassical PathwayClassical Pathway CC11

CC4 4 CC22

CC3 3 Alternative pathwayAlternative pathway CC55

CC66

CC77

CC88

CC99

Membrane damageMembrane damage

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Classic And Alterenative pathwaysClassic And Alterenative pathways

Classic Pathway Alternative pathwayClassic Pathway Alternative pathway

* Specific acquired immunity * Non-specific innate immunity* Specific acquired immunity * Non-specific innate immunity

* Initiated by antibody * Bacterial endotoxin, capsule* Initiated by antibody * Bacterial endotoxin, capsule

* Interaction of all components * C1, C4, C2 are by-passed* Interaction of all components * C1, C4, C2 are by-passed

* Properdin system not involved * Properdin system is involved* Properdin system not involved * Properdin system is involved

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Complement and disease Complement difficiency Difficiency of classic pathway components C3 difficiency Terminal complement protein difficiencies Difficiency of regulatory proteins

Heriditary angioedema PNH Complement consumption as in SLE

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Functions of Complement Biologically active complement products

have 3 main functions Opsonisation …… C3b Chemotaxis and inflammation……C3a, C5a Cell lysis……….. C5,C6,C7,C8,C9

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Immunoglobulins

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Immunoglobulins & age

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Plasma protein electrophoresis

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Antigens Antigens are macromolecules that elicit an immune

response in the body. The most common antigens are proteins and polysaccharides.

Hapten: incomplete Ag which can be conjugated with a carrier protein to form a complete Ag.

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Cytokines hormone-like soluble low molecular weight

protein molecules that act, generally in a paracrine fashion, to regulate immune responses

They are secreted not only by lymphocytes and macrophages but also by endothelial cells, adipocytes, neurons, glial cells, and other types of cells

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Chemokines cytokines that regulate cell movement and

trafficking; they attract neutrophils and other white blood cells to areas of inflammation or immune response.

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Interferons are potent cytokines that possess antiviral,

immunomodulating, and antiproliferative activities Interferon-α, Interferon-β & Interferon-γ Recombinant, natural, and pegylated IFNs currently

are available for treatment of condyloma acuminatum, chronic HCV infection, chronic

HBV infection, Kaposi's sarcoma in HIV-infected patients, other malignancies, multiple sclerosis

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Tolerance It is a specific immunologic unresponsiveness Unresponsiveness to self antigens is known as

auto tolerance

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ToleranceB-cells become tolerant to self by two mechanisms: 1) Clonal deletion Probably while B-cell precursors are in bon marrow

2) Clonal anergy B cells in the periphery

Tolerance in B-cells is less complete than in T-cells

The most autoimmune diseases are mediated by antibodies

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Factors affecting induction of tolerance Maturity of the immune system Antigen complexity Antigen dose Continuous presence of antigen Immunosuppressive drugs

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Clinical importance of tolerance Organ transplantation Tumor development Autoimmune diseases

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Autoimmune Diseases Autoimmune diseases occur due to breakdown of

the mechanisms that maintain auto tolerance

Auto-antibodies and self reactive T-cells are produced, resulting in tissue damage by several mechanisms

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References Lecture notes: Immunology 2010 Essential revision notes for MRCP 2009 Merck manual : online textbook Kumar & Klark : Clinical Medicine 2009 Other Web Resources & books

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Understanding Immunology(2)

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Immunodeficiency

Immunopathology

Immunopathology

Autoimmunity

Hypersensitivity

LymphoproliferativeDiseases

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References Lecture notes: Immunology 2010 Essential revision notes for MRCP 2009 Merck manual : online textbook Kumar & Klark : Clinical Medicine 2009 Other Web Resources & books

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Understanding Immunology

(3)

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References Lecture notes: Immunology 2010 Essential revision notes for MRCP 2009 Merck manual : online textbook Kumar & Klark : Clinical Medicine 2009 Other Web Resources & books

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