Acquired Immune Response Sanjaya Adikari Department of Anatomy

Acquired Immune Response Sanjaya Adikari Department of Anatomy

Immune Response n Defense against foreign invaders or cancer cells Immune Response Innate Response Acquired Response Antibody Response Cell mediated Response

Innate Response Adaptive Response

Cells of the immune system

Properties of Immune cells Inactive/Naive Few surface molecules Activated cells Effector cells Many surface molecules Becomes larger in size Proliferate and produce more cells Release peptides and lipids Increased ability to migrate

epithelium Macrophage

Macrophage Common receptors for immune cells of many animals Detect pathogen associated molecular patterns

epithelium Opsonization by Complement proteins Toll-like receptor Macrophages

Toll-like receptors Pathogen-associated molecular patterns

Lysosomes Phagosome Phagolysosome H 2 O 2 - NO Activated macrophage Prostaglandins, Leukotrienes and Platelet activating factor

Flow increased Velocity reduced Lipid mediators of inflammation Increased diameter Increased permeability

Increased expression of adhesion molecules

Lysosomes Phagosome Phagolysosome H 2 O 2 - NO Activated macrophage Cytokines Chemokines

Cytokines Proteins released by cells that affect the behavior of other cells that bear receptors for them Chemokines Proteins released by cells that attract other cells that bear receptors for them A A

Neutrophil H 2 O 2 O 2 - NO

Body tissue

Cytokines activated Chemokines Mediators of infl. Cytokines activated Cytokines Chemokines Mediators of

Pus cells

Natural Killer cells Also called NK T cells Larger than T and B cells Activated during the innate response by macrophage derived cytokines Eg. IL-12 and Interferons Produce IFN- when activated Kills cells infected with intracellular pathogens Mechanism of Killing is similar to that of cytotoxic T cells

Complement system n Augments the opsonization of bacteria by antibodies. Hence, the name, meaning that it complements the antibodies n Large number of plasma proteins that react with each other following a trigger n Most of them are proteases that are themselves activated by proteolytic cleavage

Complement system…. cont. n Precursor proteins are widely distributed in body fluids and tissues n Only activated on the surface of the pathogens n Once triggered it becomes a huge reaction in its successive steps

Trigger

Innate immunity - summary n Immune cells identify the ‘pathogen-associated molecular patterns’ on the cell membrane of pathogens n Pathogen is immediately destroyed n Neutrophils and macrophages are key players n Complement system plays an important role n Activated dendritic cells present antigens

Body cells Kill

Body cells Kill

From Innate to Adaptive n Cells activated during the innate immune response bridge the gap between the innate and the adaptive systems n Dendritic cells and Macrophages

Adaptive Immune Response

epithelium Dendritic cells

Toll-like receptors Dendritic cell or macrophage Antigen presentation Antigen presenting cells (APC) T T T Clonal expansion of lymphocytes

Dendritic Cells (DC) n Most potent APC (>>> macrophages) n Designated as professional APC n Main function is to control T and B cells through presentation of different antigens

Mature DC T B B T B T B Circulation T T Immature DC T B B B

Jefford et al. , Lancet, June 2001

Surface molecules on DC and T cells n Cell-cell interaction molecules n Receptors for cytokines n Receptors for chemokines n Cell adhesion molecules

Cell-cell interaction molecules on DC and T cells Antigen presenting cell MHC II MHC I CD 4 CD 8 B-7 TCR CD 28 B 7= CD 80 & CD 86 CD 4+ helper T cell CD 8+cytotoxic T cell

MHC molecules n Two types: MHC type I and MHC type II n MHC type I: Expressed in all body cells n MHC type II: Expressed in some immune cells n n Dendritic cells, macrophages and B cells Human counterpart is called HLA MHC – Major histocompatibility complex HLA – Human leukocyte antigen

DC-T cell interaction Dendritic cells send two signals to T cells n 1 st signal – determines antigen specificity n 2 nd signal – triggers T cell proliferation

immature DC CD 4 MHC II 1 st signal TCR CD 4+ helper T cell

mature DC B-7 MHC II CD 4 2 nd signal TCR CD 28 CD 4+ helper T cell Increase proliferation Secrete IL-2 (growth factor of T cells)

Cell-cell interaction molecules on DC and T cells Antigen presenting cell MHC II MHC I CD 4 CD 8 B-7 TCR CD 28 B 7= CD 80 & CD 86 CD 4+ helper T cell CD 8+cytotoxic T cell

Intravesicular pathogens Extracellular pathogens Toxins Vesicle Cytoplasm MHC II CD 4 TCR APC CD 8 TCR

Th 1 cells T helper cells (Th cells) Th 2 cells Th 0 cells

Cytokines Cytokines Cytokines IFN- IFN- IL-5 IL-10 IL-4 IL-10 Th 1 cells Macrophage Activation IL-4 IL-10 IL-5 Th 2 cells B cell Activation

Th 1 cells Produce IFN- , the main macrophage-activating cytokine. It inhibits B cells Th 2 cells Produce IL-4, IL-5 that activates B cells and IL-10 that inhibits macrophages Th 0 cells Produce both Th 1 and Th 2 cytokines and therefore have a mixed effect

Clinical relevance of Th 1 vs Th 2 Mycobacterium leprae grows in macrophage vesicles. To destroy bact. need to activate macrophages by Th 1 cells Th 2 response is a waste Th 2 response Lepromatous leprosy Th 1 response Tuberculoid leprosy - Numerous live bacteria - Few live bacteria - Lot of Ab in serum (ineffective) - Little Ab in serum - Gross tissue damage & death - Skin & PN damage due to Mac. activation - Slow disease, patient survives

Humoral immune response

BCR B cell MHC II

BCR MHC II

BCR MHC II

B cell MHC II CD 4 IL-10 TCR CD 4+ T helper cell Th 2 IL-4 IL-5 IL-6

IL-4, IL-5, IL-10 Plasma cell B cell Ab mediated response (Humoral immunity)

B cell MHC II CD 4 Inhibition IFN- TCR CD 4+ T helper cell Th 1

Cell mediated response

immature DC CD 8 MHC I 1 st signal TCR CD 8+cytotoxic T cell

mature DC B-7 MHC I CD 8 2 nd signal TCR CD 28 CD 8+cytotoxic T cell Increase proliferation Secrete IL-2

mature. Tissue DC Infected MHC I CD 8 Kill IFN- TCR effector CD 8+cytotoxic T cell

Kills virus or intracellular pathogen infected body cells MHC I CD 8 T cells Cell mediated response Immunological memmory cytokines MHC II chemokines cytokines CD 4 T cells chemokines B cells Antibody mediated response

Immunological memory n n n The ability of the immune system to respond more rapidly and effectively to pathogens that have been encountered previously Both T cells and B cells are left behind as memory cells following the primary immune response These are a distinct populations of long lived cells, without the need to getting exposed to residual antigen, in the body

Immunological memory…cont. n In the presence of memory T and B cells, the naïve T and B cells are not activated upon exposure to the same antigen again (would be a waste)

Adaptive immunity - summary n The immune cells need to specifically identify the pathogen n Clonal expansion of specific immune cells n Takes few days to build up n T and B lymphocytes are key players n Leaves behind memory cells