IMMUNE RESPONSE Dr Mohit Bhatia Assistant Professor Department

IMMUNE RESPONSE Dr. Mohit Bhatia Assistant Professor Department of Microbiology AIIMS, Rishikesh

LAYOUT • INTRODUCTION • ANTIGEN PRESENTATION • CELL MEDIATED IMMUNE RESPONSE • HUMORAL IMMUNE RESPONSE • AN OVERVIEW OF CYTOKINES

INTRODUCTION • Immune response refers to highly coordinated reaction of the cells of immune system and their products • Cell mediated immune response: T cells • Humoral immune response: Antibodies

ANTIGEN PRESENTATION

ANTIGEN PRESENTING CELLS

DIFFERENCES BETWEEN DIFFERENT APCs

PATHWAYS OF ANTIGEN PRESENTATION

ENDOGENOUS (MHC I) EXOGENOUS (MHC II)

CELL MEDIATED IMMUNE RESPONSE

Development of αβ T cells

Positive & Negative selection of thymocytes results in mature T cells that are both self-MHC restricted & selftolerant

INSTRUCTIVE & STOCHASTIC MODELS

T CELL RECEPTOR-CORECEPTOR COMPLEX & OTHER SURFACE MOLECULES

INTERACTIONS BETWEEN T CELLS & APCs

OVERVIEW OF TCR MEDIATED SIGNALING

TH-cell activation requires a co-stimulatory signal provided by APCs

CONCEPT OF CLONAL ANERGY

Super-antigen mediated cross-linkage of T-cell receptor and class II MHC molecules TSST-1 EXFT SPE- A, B, C, D

üActivation of TH cells by signal 1 & co-stimulatory signal 2 up-regulates expression of IL-2

FEATURES OF NAÏVE & EFFECTOR T CELLS

EFFECTOR MOLECULES PRODUCED BY EFFECTOR T CELLS

GENERATION OF EFFECTOR CTLs

STAGES IN CTL MEDIATED KILLING OF TARGET CELLS

CTL MEDIATED PORE FORMATION IN THE TARGET CELL MEMBRANE

PATHWAYS OF TARGET CELL APOPTOSIS STIMULATED BY CTLs

ASSESMENT OF CMI • Mixed lymphocyte reaction • Cell mediated lympholysis • Graft versus host reaction

NK CELL MEDIATED KILLING: OPPOSING SIGNALS MODEL

Antibody-Dependent Cell-Mediated Cytotoxicity(ADCC)

ANTIBODY DEPENDENT CELL MEDIATED CYTOTOXICITY (ADCC)

HUMORAL IMMUNE RESPONSE

OVERVIEW OF B CELL DEVELOPMENT

Pro-B CELL & BONE MARROW STROMAL CELL INTERACTION

B-CELL RECEPTOR-CORECEPTOR COMPLEX

THYMUS INDEPENDENT & DEPENDENT ANTIGENS

PROPERTIES OF TI & TD ANTIGENS

B-CELL MEDIATED IMMUNE RESPONSE

B-CELL MEDIATED RESPONSE

üSchematic diagram of a peripheral lymph node showing anatomic sites at which various steps in B-cell activation, proliferation and differentiation occur. üThe cortex is rich in B cells & the paracortex in T cells. üBoth B and T cells are present in large numbers in the medulla. üA secondary follicle contains the follicular mantle and a germinal center.

OVERVIEW OF CELLULAR EVENTS WITHIN GERMINAL CENTERS

The interactions of numerous cytokines with B cells generate signals required for proliferation and class switching during the differentiation of B cells into plasma cells

NAÏVE & MEMORY B CELLS

PRIMARY & SECONDARY IMMUNE RESPONSE

COMPARISON OF PRIMARY & SECONDARY IMMUNE RESPONSES

EFFECTOR FUNCTIONS OF HUMORAL IMMUNITY

Neutralization Toxin receptors Bacterial toxins Host cell Neutralization by antibody Fc Forming phagosome receptor Phagocytosis of antibody-antigen complex by macrophage

Opsonization Extracellular bacteria Opsonization Macrophage Ingestion by macrophage Digestion in lysosom

Complement Activation Bacteria in plasma Lysis and ingestion C 1 C 2 C 4 C 1 C 2 C 4 Complement activation Digestion in lysosom

TRANSCYTOSIS

AN OVERVIEW OF CYTOKINES

INDUCTION & FUNCTION OF CYTOKINES

ATTRIBUTES OF CYTOKINES

Interaction of antigen with macrophages and the subsequent activation of resting TH cells leads to release of numerous cytokines (blue arrows), generating a complex network of interacting cells in the immune response.

SUMMARY OF CYTOKINES