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

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Anatomy

• Lymphoid tissues- primary lymphoid tissues (bone marrow and thymus)- secondary lymphoid tissues

(spleen and lymph node)s)

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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

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Main physiologic barriers

Hydrochloric acit Ciliar epithelia

Tears Normal floraDr. Yıldıran 9

Non-specific immunity

(Innate) Specific

immunity

(Adaptive)

Immune System

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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

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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

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• Chemotaxis

• Adhesion

• Phagocytosis

• Microbicidal killing

Phagocytic system

Mainly bacterial and fungal pathogensDr. Yıldıran 16

Chronic granulomatous diseaseChronic granulomatous disease

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Complement system

• Of nine substantial, many blood proteins

• Opsonization• Chemotaxis• Neutrolization• Lysis of bacteria and

cells• Anaphylotoxin

• Complement system also promotes inflammation

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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.

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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

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• Common infection• Recurrent absscess• Persistent moniliasis• Persistent diarrhea • Prolonged and/or severe infection• Unusual pathogen• İllness after live vaccine

Need for immunological evaluation

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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

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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.

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Related Lectures

• Immunodeficiencies

• Complement system

• Innate immune system

• Adaptive immune system

• Immunoglobulins

• Self-tolerance

• Hypersensitivity reactions

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