immunodeficiency syndromes: part one: primer on immunology

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Immunodeficiency Syndromes:

Part One:

Primer on Immunology

May 23, 2012

Roy C. Maynard, M.D.

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Objectives

• Understand basic concepts in immunology

• Anatomy of the immune system: be able to

identify primary and secondary lymphoid organs

• Role of the innate immune system in prevention

of disease

• Describe aspects of the adaptive immune

system as related to vaccines

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Immunology

• Definition: Study of the immune system,

both in wellness and disease

- Infectious disease

- Autoimmune disease

- Oncology

- Medical diagnostics

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Anatomy of the Immune System

• Primary

- Thymus

- Bone marrow

• Secondary

- Spleen

- Lymph nodes

- Mucosa-associated lymphoid tissue

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Lymphoid Organs and Tissues

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Cells of the Immune System

http://www.hhmi.org/biointeractive/disease/immunology_primer/01.html

Accessed on 5/1/12

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Innate Immune System

• Relatively non-specific antimicrobial systems that are innate in the sense they are not intrinsically affected by prior contact with the infectious agent

• Active all the time

• External and internal

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Innate Immune System

• External

- Barrier functions

- Physical and chemical

- Skin: lactic acid, pH, fatty acids

- Mucous membranes: mucus contains

bactericidal components

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Innate Immune System

• Internal

- If microorganisms penetrate the external barriers, then cells of the innate immune system come into play

• 2 major defense strategies

- Phagocytic cells

- Soluble bactericidial chemical factors

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Phagocytic Cells

• Neutrophils

• Eosinophils

• Basophils

• Lymphocytes

• Macrophages

• Mast cells

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Phagocytic Cells

• Neutrophils

– Short-lived

– Pyogenic organisms

– Granules

• Myeloperoxidase

• Cathepsin G

• Lysozyme

• Lactoferrin

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Phagocytic Cells

• Macrophages

– Monocytes, microglia, kupffer cells, histiocytes, osteoclasts, glomerular mesangial cells

– Longer half-life

– Intracellular pathogens

– Pattern recognition receptors (toll-like receptors)

– Release cytokines

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Phagocytic Cells

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Innate Immune System

• NK Cells (natural killer cells)

– Granular leukocytes

– Recognize molecules surface virally infected cells

– Become activated and release cytokines (perforin, granzyme) to attack target cell

– Target cell death results by programmed cell death and viral particle reproduction ends

– May be involved in cancer surveillance

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Natural Killer Cells

http://arapaho.nsuok.edu/~castillo/NotesImages/Topic17NotesImage2.jpg

Accessed 5/18/12

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Innate Immune System

• Eosinophils

– Parasites

– Allergies

– Autoimmune disease (Churg-Strauss syndrome)

– Cytokines (major basic protein, eosinophilic cationic protein)

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Complement System

• Complex series of 20 proteins in plasma

• Enzyme activation of cascade

• Complement facilitates phagocytosis

• Complement (C3b) binds to bacteria and allows recognition by phagocytes to engulf

• May stimulate (C3a and C5a) phagocytes make reactive oxygen intermediates and enhance expression of cell surface receptors

• Trigger degranulation of mast cells and granulocytes

• MAC (membrane attack complex)

• Attract other inflammatory cells

• Part of anaphylaxsis

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Complement System

http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookimmun.html

Accessed on 5/18/12

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Ontogeny of Immune Cells

• T cells processed in the thymus

• B cells processed in fetal liver then in bone marrow

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Adaptive Immune System

• Antibody Production

– Antibody molecule evolved as a specific adaptor to attach to microorganisms which do not activate the complement pathway or prevent activation of macrophages

– Supplementary route into the acute inflammatory response enhanced by antibodies which activate mast cells, form immune complexes that stimulate cytokine from macrophages

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Antibodies or Immunoglobulins

• Immune proteins

• Manufactured by B cells and plasma cells

• First function to recognize and bind to foreign material (antigen)

• Second function to trigger elimination of foreign material

• Five classes of immunoglobulins

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Immunoglobulin Classes

• IgG

– 4 subclasses: IgG1, IgG2, IgG3 and IgG4

– Monoclonal disease – multiple myeloma

– Recombinant antibody technology

– Major antibody in plasma and tissue

– Major “memory” antibody

– Fc and complement interaction

– Primary component of gammaglobulin infusions

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Immunoglobulin Classes

• IgM

– Pentameric

– Interacts with complement

– Early immune response

– First line defense against bacteremia

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Immunoglobulin Classes

• IgA

– Monomer in plasma, dimer in secretions

– Major defensive antibody in mucous secretions

• IgE

– Binds to mast cells

– “Allergic” antibody

– Parasitic infections

• IgD

– Surface of naïve B cells

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Anatomy of an Immunoglobulin

http://www.emc.maricopa.edu/faculty/farabee/biobk/ANTIBODY.gif

Accessed on 5/1/12

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Anatomy of an Immunoglobulin

http://upload.wikimedia.org/wikipedia/commons/thumb/3/31/Mono-und-Polymere.svg/170px-Mono-und-Polymere.svg.png

Accessed on 5/1/12

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Serum Immunoglobulin Ontogeny

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Immunoglobulin Switching

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Antibody-Producing Cells

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Primary and Secondary Response

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Monoclonal Antibodies

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Ontogeny of Immune Cells

• T cells processed in the thymus

• B cells processed in fetal liver then in bone marrow

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T Lymphocytes

• CD4 – helper T cells, activate B lymphocytes to make antibody or activate cytotoxic T cells (CD8)

• CD8 – cytotoxic T cells, involved in killing viral infected cells and cancer surveillance

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Antigen-Presenting Cell

http://en.wikipedia.org/wiki/Antigen-presenting_cell

Accessed on 5/18/12

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Hypersensitivity (Type I)

• Type 1

• Anaphylactic hypersensitivity

• IgE mediated cross-linking of receptors on mast cells

• Triggers explosive release of histamine

• Hypotension (vasodilitation), bronchoconstriction (smooth muscle)

• death

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Hypersensitivity (Type I)

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Hypersensitivity (Type II)

• Type II

• Antibody-dependent cytotoxic hypersensitivity

• Antibody binds to target cell and either

activates complement system or effector cell

to kill target cell

• Transfusion reactions, drug reactions, RhD

disease of newborns, ITP

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Hypersensitivity (Type II)

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Hypersensitivity (Type III)

• Type III

• Immune Complex-Mediated Hypersensitivity

• Antigen and antibody combine and trigger

activation of inflammatory disease

• Hypersensitivty pneumonitis, immune complex

kidney disease, Autoimmune disease (rheumatoid

arthritis, SLE)

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Hypersensitivity (Type III)

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Hypersensitivity (Type IV)

• Type IV Cell Mediated Hypersensitivity

• Exaggerated interaction between antigen and the

normal cell-mediated immune mechanisms

• Memory T cells stimulated to release cytokines that

activate other cell types

• Tissue damage

• Basis for PPD (mantoux) reaction

• Contact dermatitis, sarcoidosis

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Hypersensitivity (Type IV)

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Hypersensitivity (Type V)

• Type V Stimulatory Hypersensitivity

• Antibody mediated stimulation of a hormone

receptor on cell surface

• Grave’s disease – autoimmune antibody

triggers thyroid cells to produce excess thyroid

hormone

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Conclusions

• The immune system developed for your protection

• Involves complex interactions between antigens, immune cells and cytokines

• Responsible for killing bacteria, viruses, fungi and parasites

• Deficits within the immune system may be congenital or acquired and lead to immunodeficiency

• Relative to transplantation and tumor immunology

• Imbalances in the regulatory mechanisms of the immune system may lead to organ-specific or nonorgan-specific autoimmune diseases

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Q & A

Questions?

Thank you for attending!