Acquired Immune Response

Sanjaya Adikari Department of Anatomy

Immune Response

 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 Activated cells Effector cells Few surface molecules 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

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

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

Increased expression of adhesion molecules

Phagosome Phagolysosome H 2 O 2 O 2 NO Activated macrophage Lysosomes 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

H 2 O 2 O 2 NO Neutrophil

Body tissue Body tissue Body tissue

Cytokines activated Chemokines Mediators of infl.

Cytokines Cytokines activated Cytokines activated Chemokines Cytokines Chemokines Mediators of

Pus cells 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

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

Complement system….cont.

 Precursor proteins are widely distributed in body fluids and tissues  Only activated on the surface of the pathogens  Once triggered it becomes a huge reaction in its successive steps

Trigger

Innate immunity - summary

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

Body cells

Kill

Body cells

Kill

From Innate to Adaptive

 Cells activated during the innate immune response bridge the gap between the innate and the adaptive systems 

Dendritic cells

and Macrophages

Adaptive Immune Response

epithelium

Dendritic cells

Antigen presenting cells (APC)

Toll-like receptors Dendritic cell or macrophage

Antigen presentation T T T T T

Clonal expansion of lymphocytes

Dendritic Cells (DC)

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

Mature DC T T T T B B T B B T T B T B

Circulation

T T T B B B Immature DC

Jefford et al., Lancet, June 2001

Surface molecules on DC and T cells

 Cell-cell interaction molecules  Receptors for cytokines  Receptors for chemokines  Cell adhesion molecules

Cell-cell interaction molecules on DC and T cells Antigen presenting cell CD4 CD8 B-7 B7= CD80 & CD86 CD28

CD4 + helper T cell

CD28

CD8 + cytotoxic T cell

MHC molecules

 Two types: MHC type I and MHC type II  MHC type I: Expressed in all body cells  MHC type II: Expressed in some immune cells  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  1 st signal – determines antigen specificity  2 nd signal – triggers T cell proliferation

1 st signal immature DC CD4

CD4 + helper T cell

B-7 mature DC CD4 2 nd signal CD28 Increase proliferation

CD4 + helper T cell

Secrete IL-2 (growth factor of T cells)

Cell-cell interaction molecules on DC and T cells Antigen presenting cell CD4 CD8 B-7 B7= CD80 & CD86 CD28

CD4 + helper T cell

CD28

CD8 + cytotoxic T cell

Intravesicular pathogens Extracellular pathogens Toxins CD4 CD8 APC

T helper cells (Th cells) Th1 cells Th2 cells Th0 cells

Cytokines Cytokines Cytokines Cytokines Cytokines Cytokines

IFN  IFN  IFN  IFN IFN   Th1 cells Macrophage Activation

Cytokines Cytokines Cytokines Cytokines Cytokines

IL-5 IL-10 IL-4 IL-4 IL-10 IL-4 IL-10 Th2 cells IL-5 B cell Activation

Th1 cells Produce IFN  , the main macrophage-activating cytokine.

It inhibits B cells Th2 cells Produce IL-4, IL-5 that activates B cells and IL-10 that inhibits macrophages Th0 cells Produce both Th1 and Th2 cytokines and therefore have a mixed effect

Clinical relevance of Th1 vs Th2

Mycobacterium leprae grows in macrophage vesicles.

Th2 response To destroy bact. need to activate macrophages by Th1 cells Th2 response is a waste Th1 response Lepromatous leprosy - Numerous live bacteria - Lot of Ab in serum (ineffective) - Gross tissue damage & death Tuberculoid leprosy - Few live bacteria - Little Ab in serum - Skin & PN damage due to Mac. activation - Slow disease, patient survives

Humoral immune response

B cell

IL-10 B cell CD4 IL-4 IL-5 IL-6

CD4 + T helper cell

Th2

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

Inhibition IFN  B cell CD4 Inhibition IFN 

CD4 + T helper cell

Th1

Cell mediated response

1 st signal immature DC CD8

CD8 + cytotoxic T cell

B-7 mature DC CD8 2 nd signal CD28 Increase proliferation

CD8 + cytotoxic T cell

Secrete IL-2

CD8

IFN-



Kill effector CD8 + cytotoxic T cell

MHC I MHC II CD8 T cells cytokines chemokines Kills virus or intracellular pathogen infected body cells MHC I Cell mediated response Immunological memmory CD4 T cells cytokines chemokines B cells Antibody mediated response

Immunological memory

 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.

 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



The immune cells need to specifically identify the pathogen

 Clonal expansion of specific immune cells  Takes few days to build up  T and B lymphocytes are key players  Leaves behind memory cells