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

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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.

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

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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

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.

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Related Lectures

• Immunodeficiencies

• Complement system

• Innate immune system

• Adaptive immune system

• Immunoglobulins

• Self-tolerance

• Hypersensitivity reactions

Dr. Yıldıran 28