1 of 45
Immunodeficiency Syndromes:
Part One:
Primer on Immunology
May 23, 2012
Roy C. Maynard, M.D.
2 of 45
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
3 of 45
Immunology
• Definition: Study of the immune system,
both in wellness and disease
- Infectious disease
- Autoimmune disease
- Oncology
- Medical diagnostics
4 of 45
Anatomy of the Immune System
• Primary
- Thymus
- Bone marrow
• Secondary
- Spleen
- Lymph nodes
- Mucosa-associated lymphoid tissue
5 of 45
Lymphoid Organs and Tissues
6 of 45
Cells of the Immune System
http://www.hhmi.org/biointeractive/disease/immunology_primer/01.html
Accessed on 5/1/12
7 of 45
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
8 of 45
Innate Immune System
• External
- Barrier functions
- Physical and chemical
- Skin: lactic acid, pH, fatty acids
- Mucous membranes: mucus contains
bactericidal components
9 of 45
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
10 of 45
Phagocytic Cells
• Neutrophils
• Eosinophils
• Basophils
• Lymphocytes
• Macrophages
• Mast cells
11 of 45
Phagocytic Cells
• Neutrophils
– Short-lived
– Pyogenic organisms
– Granules
• Myeloperoxidase
• Cathepsin G
• Lysozyme
• Lactoferrin
12 of 45
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
13 of 45
Phagocytic Cells
14 of 45
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
15 of 45
Natural Killer Cells
http://arapaho.nsuok.edu/~castillo/NotesImages/Topic17NotesImage2.jpg
Accessed 5/18/12
16 of 45
Innate Immune System
• Eosinophils
– Parasites
– Allergies
– Autoimmune disease (Churg-Strauss syndrome)
– Cytokines (major basic protein, eosinophilic cationic protein)
17 of 45
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
18 of 45
Complement System
http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookimmun.html
Accessed on 5/18/12
19 of 45
Ontogeny of Immune Cells
• T cells processed in the thymus
• B cells processed in fetal liver then in bone marrow
20 of 45
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
21 of 45
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
22 of 45
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
23 of 45
Immunoglobulin Classes
• IgM
– Pentameric
– Interacts with complement
– Early immune response
– First line defense against bacteremia
24 of 45
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
25 of 45
Anatomy of an Immunoglobulin
http://www.emc.maricopa.edu/faculty/farabee/biobk/ANTIBODY.gif
Accessed on 5/1/12
26 of 45
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
27 of 45
Serum Immunoglobulin Ontogeny
28 of 45
Immunoglobulin Switching
29 of 45
Antibody-Producing Cells
30 of 45
Primary and Secondary Response
31 of 45
Monoclonal Antibodies
32 of 45
Ontogeny of Immune Cells
• T cells processed in the thymus
• B cells processed in fetal liver then in bone marrow
33 of 45
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
34 of 45
Antigen-Presenting Cell
http://en.wikipedia.org/wiki/Antigen-presenting_cell
Accessed on 5/18/12
35 of 45
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
36 of 45
Hypersensitivity (Type I)
37 of 45
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
38 of 45
Hypersensitivity (Type II)
39 of 45
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)
40 of 45
Hypersensitivity (Type III)
41 of 45
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
42 of 45
Hypersensitivity (Type IV)
43 of 45
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
44 of 45
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
45 of 45
Q & A
Questions?
Thank you for attending!