Humoral and Cellular Immunity Dr Yldran Kaynak Abbas

Humoral and Cellular Immunity Dr. Yıldıran Kaynak: Abbas 2003, Male 2006, Le Bien Blood 2008 1

Presentation Plan • • Basics of immune response Lymphocyte types Primary and secondary lymphoid tissues Development of B lymphocyte functions Development of T lymphocytes Receptors of lymphocytes and activation Dr. Yıldıran 2

Objectives of this lecture You can tell: • Development of B lymphocytes • Functions of B lymphocytes • Development of T lymphocytes • Functions of T lymphocytes You can explain: • Humoral immunity • Cellular immunity Dr. Yıldıran • Differencies between both of them 3

Dr. Yıldıran 4

Immune System Specific immunity (Adapttive) Non-specific immunity (Innate) Phagocytes NK cells Complement system Dr. Yıldıran T and B lymphocytes MEMORY! 5

Pathogen • Extracellular • Intracellular • Toxin Immune System Microbiome Lactobacillus Flora Dr. Yıldıran 6

Immune Response Antigen presenting cell Dr. Yıldıran Abbas, 2003 7

Adaptive immunity Dr. Yıldıran 8

Specific Immunity CD 19 Dr. Yıldıran CD 3 CD 4 CD 3 CD 8 9 Abbas, 2003

Maturation of Lymphocytes • B lymphocytes in bone marrow • T lymphocytes in thymus • Then they include circulation as naive lymphocytes • IL-7 is essential in this process. • If naive lymphocytes don’t encounter to any foreign antigen they go to apopitosis (programmed death). Dr. Yıldıran 10

• Primary Lymphoid Tissues – Thymus Development of T lymphocytes Antigens are – Fetal liver and postnatal bonecatched marrow and processed here Development of B lymphocytes • Secondary Lymphoid Tissues – Spleen – Lymph nodes – MALT (mucosa associated lymphoid tissue) Dr. Yıldıran 11

B lymphocyte development Early Pre-B cell Stem cell Fetal Liver LAte Pre-B cell Pre-BCR Pro-B cell Antigen independent Bone marrow Immatüre B cell Mature B cell Plasma cell Antigen dependent

Markers CD 10+ Conley 2003

Genetic defects of B cell development

• Class (isotype) switching (CSR): B cell produce firstly Ig. M, then switch this molecule to other Ig’s. • Somatic hypermutation involves a programmed process of mutation affecting the variable regions of immunglobulin genes immune repertoire Dr. Yıldıran 15

Antigen specific receptor • Somatic recombination provides this with RAG (Recombination activating gene) ensyme • If this gene disrupted, the result is severe combined immunodeficiency (SCID). Dr. Yıldıran 16

Immunglobulin Molecule Antigen binding site (Fab) Fc receptor and complement binding site Disulphit links Carbohydrate Heavy chain Light chain Ig domains Dr. Yıldıran 17

Functions of antibodies Neutrolastion of microorganisms and toxins Antibodies B lymph Opsonisation and phagoctosis Microorganism Lysis Phagocytosis of opsonised microorganism by complement Complement activation Surface antigen Ig. G Fc. RIII Inflammation Antibody dependent cellular cytotoxicity Dr. Yıldıran NK cell 18

Maturation of T lymphocyte CD 4+ T hücresi (Thelper=Th) CD 8+ T cell Cytotoxic T cell Dr. Yıldıran 19

Selection of T lymphocyte DP DN Zone 1 -4 SP AIRE Dr. Yıldıran 20

Receptors CTLA-4=CD 152 Inhibitor Dr. Yıldıran 21

Activation Dr. Yıldıran 22

Activated Lymphocytes • Activation markers – CD 25 and CD 69 • Effector molecules – CD 40 L (=CD 154) activates B lymphocytes, dendritic cells, endothelial cells – Fas (CD 95) apopitosis Dr. Yıldıran 23

Peptide Antigen catch Dr. Yıldıran 24

IL-2, Antigen processing. CD 4 IFNG CD 8 Perforin, granzym Antigen Presentig Cell ER: Endoplasmic Reticulum Dr. Yıldıran 25

Signaling IL-2, IL-4, IL-5, IFN secreted Dr. Yıldıran 26

Functions of T Lymphocytes • Defense to intracellular microorganisms – Th cytokine secretion, stimulation of macrophages • Activation of B lymphocytes and phagocytes – Th • Killing of infected cells – Ts • Memory – Th – Ts Dr. Yıldıran 27

memory T • TCR specifity and diversity, recognize 107109 different antigens.

Flowcytometry