Adaptive Immunity 1.Vertebrates only 2.Specificity - recognition modules - BCR, Ab and TCR - gene rearrangement is the source of diversity - clonal selection 3.Small lymphocytes - types and sub-types - functions

Recognition concept Receptor or Antibody molecule Antigen - structure recognized by an Ab, BCR or TCR Epitope - particular sub-structure of the Ag that is bound Affinity - how much a molecule likes to bind to a structure

B-cells BCR is Immunoglobulin (Ig) Plasma cells - effector cells that secrete Ab T-cells T c = cytotoxic (CD8+) T H = helper T-cells (CD4+) Th1 (inflammation) Th2 (help B-cells make AB) Small lymphocyte sub-types

Recognition modules of Adaptive immunity B cellsT cells B-cell receptor

B-cellsT-cell Native vs Denatured Antigen processing Major Histocomp -atibility (MHC)

How does MHC work?

Intracellular pathogens All nucleated cells APC Extracellular pathogens Only immune cells Professional APC APC - Antigen Presenting Cells Professional APC - macrophages - B cells - Dendritic cells

Figure 1-26 MHC class I communicates with Tc cells

Figure 1-27 MHC class II communicates with T H cells Dendritic cells interact with naïve T-cells and initiate differentiation

How do Antibodies work?

Parasite + Mast cell Inflammation Mast cell activated Expel and/or destroy pathogen Neutralization Opsonization Inflammation Parasitic infection

Principles of Adaptive Immunity Diversity Specificity Memory Self-tolerance

Gene Rearrangement is the source of Diversity Germline configuration Diversity 1.Alternative combinations 2.Imprecise joints 3.Different types of chains 4.B-cells - somatic hypermutation In the absence of antigen

Clonal Selection 1.Each cell = one receptor 2.Millions of lymphocytes are generated 3.Small subset will recognize a pathogen 4.Proliferation and differentiation 5.Acquired immunity - the adaptive immunity provided by immunological memory

Figure 1-22 Antibodies are usually very specific

Figure 1-30 Few specific lymphocytes Many lymphocytes Some memory lymphocytes Concept Behind Vaccination

Pre-industrialization infants built immunity naturally Post-industrialization polio rate increased in adults hence a need for vaccination

Polio Vaccine - Inactive vs Oral “live” version VDPV - vaccine derived polio virus - mutations can lead to polio at extremely low rate

Principle of Self-tolerance B-cells with BCR that bind to self will undergo Apoptosis More complicated scheme of selection for T cells

Mechanism of Self-tolerance Selection of T cells 1.Thymocytes 2.Positive selection -Self MHC 3. Negative selection

Immunodeficiencies Inherited deficiencies e.g. Bubble boy disease Stress induced nutrition, emotional Pathogen caused deficiencies HIV - attacks CD4 T lymphocyte

Figure 1-32 IgE IgG CD4 T H 1 CD8 CTL Cells and molecules involved in Hypersensitivity Diseases

Figure 1-33 Insulin-Dependent Diabetes Mellitus Beta cells of the Islets of Langerhans

Figure 1-34 Hygiene Hypothesis Inflammatory Adaptive Immune Response