IMMUNE SYSTEM Dr. Yıldıran1. 150 different intracellular signaling pathways Dr. Yıldıran2.
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Transcript of IMMUNE SYSTEM Dr. Yıldıran1. 150 different intracellular signaling pathways Dr. Yıldıran2.
IMMUNE SYSTEM
Dr. Yıldıran 1
150 different intracellular signaling pathways
150 different intracellular signaling pathways
Dr. Yıldıran 2
Again turn thy vision a second time; (thy) vision will come back to thee dull and discomfited in a state worn out. (67-4)
Dr. Yıldıran 3
Human
• Genom
• Proteom
• Microbiome
Dr. Yıldıran 4
Microbiome
• More than 100 years ago, the human microbiome was defined as;
• living together with dissimilar organisms (symbiosis), or community of microbes and collection of genomes found in and on the human body.
Relman, 2012Dr. Yıldıran 5
Immunity
• Host can recognize self/strange material from itself (microorganisms, antigens etc) and can destroy or make useful them.
• If this system cannot work properly:– Immune dysregulation
• Autoimmune disorders (more than 100)
• Allergy– Immune deficiencies
Dr. Yıldıran 6
Anatomy
• Lymphoid tissues- primary lymphoid tissues (bone marrow and thymus)- secondary lymphoid tissues
(spleen and lymph node)s)
Dr. Yıldıran 7
Organization of the body’s defenses
• Non-specific defenses: no need to decipher pathogen’s identity. - Physical barriers- Inflammation (in a separate lecture)- Natural cell killers (NK cells)- Complement system
• Specific defenses: Based on recognition of the pathogen’s identity– Humoral immunity– Cell-mediated immunity
Dr. Yıldıran 8
Main physiologic barriers
Hydrochloric acit Ciliar epithelia
Tears Normal floraDr. Yıldıran 9
Non-specific immunity
(Innate) Specific
immunity
(Adaptive)
Immune System
Dr. Yıldıran 10
Stem cell
Myeloid progenitor
Pluripotent Stem cell
Lymphoid progenitor
Thymus
T lr
Granulosit-monosit CFUEozinofil CFUBazofil CFU
NötrofilEozinofilBazofil Monosit
e
B lymphocytes T lymphocytes
NK cells
Granulosit-monosit CFU
Cells of immune response develops from common
stem cell
Dr. Yıldıran 11
Immune Response
Abbas, 2003Dr. Yıldıran 12
Specific Immunity
Abbas, 2003Dr. Yıldıran 13
Weber State UniversityDr. Yıldıran 14
CellularHumoral
(mg/
dl)
Maternal IgG
IgG (in child)
IgG
IgA
IgM
Month Month YearBirth
Mea
n s
eru
m im
mu
ngl
obu
lin
leve
l(m
g/d
l)Maternal IgG
IgG (ço
IgG
IgA
IgM
Y
Age
Postnatal Immunglobulin level changes
Dr. Yıldıran 15
• Chemotaxis
• Adhesion
• Phagocytosis
• Microbicidal killing
Phagocytic system
Mainly bacterial and fungal pathogensDr. Yıldıran 16
Chronic granulomatous diseaseChronic granulomatous disease
Dr. Yıldıran 17
Complement system
• Of nine substantial, many blood proteins
• Opsonization• Chemotaxis• Neutrolization• Lysis of bacteria and
cells• Anaphylotoxin
• Complement system also promotes inflammation
Dr. Yıldıran 18
PIDPrimary Immunodeficiencies
• Rarely seen genetic and variable diseases • Incidense 1/2-10.000 live birth• Most important signal is infection.• More than 200 diseases
Samarghtiean, 2009Dr. Yıldıran 19
Clinical Presentation
• Serious overwhelming recurrent life-threatening infections of predominantly respiratory, GI or skin system.
Dr. Yıldıran 20
Common Infection
• In one year:
– More than two severe infections
– More than three RTI (sinusitis, otitis, bronchitis)
– Antibiotic need more than two months
Dr. Yıldıran Stiehm, Uptodate, 201221
Think imunodeficiency
Dr. Yıldıran
Buckley, IDF, 2009
22
ESID Classification
Primary Immunodeficiencies
1 Predominantly T cell deficiencies
2 Antibody deficiencies
3 Other well defined immundeficiencies
4 Complement deficiencies
5 Phagocytic disorders
6 Autoimmune and immundysregulation disorders
7 Autoinflammatory diseases
More than 200 diseases
More than 200 diseases
Dr. Yıldıran 23
• Common infection• Recurrent absscess• Persistent moniliasis• Persistent diarrhea • Prolonged and/or severe infection• Unusual pathogen• İllness after live vaccine
Need for immunological evaluation
Dr. Yıldıran 24
PID Samples
• Bruton diseases: Agammaglobulinemia
• SCID: T cells absent
• Hereditary Angioedema: C1inh absent
• CVID: B cell dysfunction
• Di George Syndrome: 22q11del, thymus hipoplasia
• CGD: NADPH oxidase deficiency
Dr. Yıldıran 25
Secondary ID
Dr. Yıldıran Stiehm, Uptodate, 201226
AIDS
• HIV destroys CD4 T cells (adaptive immunity!)
• Virus contaminates from blood products, sexually or vertically in delivery of newborn.
Dr. Yıldıran 27
Related Lectures
• Immunodeficiencies
• Complement system
• Innate immune system
• Adaptive immune system
• Immunoglobulins
• Self-tolerance
• Hypersensitivity reactions
Dr. Yıldıran 28