Immunology. Overview. Kris.ne Kra1s, M.D.

Immunology Overview Kris.ne Kra1s, M.D.

Immunology Overview Defini.ons Cells Lymphocytes An.gen-presen.ng cells Effector cells Responses The innate immune response Capturing and displaying an.gens Cell-mediated immunity Humoral immunity Immunologic memory

Immunology Overview Defini.ons

Defini.ons Immunity = protec.on against infec.ons Immune system = collec.on of cells and molecules that defend us against microbes Immune deficiencies infec.ons Immune excesses autoimmune diseases

Innate (Natural) Immunity Always present (innate); doesn t change over.me First line of defense when bugs come Major components: Epithelial barriers (skin, GI, respiratory) Phagocytes NK cells Complement

Adap.ve (Acquired) Immunity Second line of defense More specific (adap.ve) and powerful than innate Major components: Lymphocytes Lymphocyte products Two types of adap.ve immunity: Humoral immunity (mediated by an.bodies) Cellular immunity (mediated by T cells)

Immunology Overview Defini.ons Cells Lymphocytes An.gen-presen.ng cells Effector cells

Lymphocytes Present in lymphoid organs and in blood Groups T-lymphocytes (grow up in thymus) B-lymphocytes (grow up in bone marrow) Each one has receptors for a specific an.gen Recognize millions of different an.gens! Diversity generated by: rearrangement of an.gen receptor genes different joining of the gene segments Gene rearrangement studies

Lymphocyte (could be B cell or T cell!)

T Lymphocytes Two basic func.ons: Kill stuff (cytotoxic T cells) Help other cells do their jobs (helper T cells) T-cell receptor (TCR) complex recognizes an.gens Binds an.gen Sends signals to the T cell An.gens must be: Displayed by other cells AND bound to an MHC receptor

The T-Cell Receptor Bound to An.gen Antigen-presenting cell T cell

Cytotoxic T cells surrounding tumor cell

Major Histocompa.bility Complex (MHC) class II MHC genes class III MHC genes class I MHC genes Class II MHC molecule Class I MHC molecule

Class I and II MHC Molecules Class I molecules Display an.gens from within the cell (e.g., viral an.gens) to CD8+ T cells. Present on all nucleated cells! (Good idea.) Class II molecules Display extracellular an.gens (e.g., bacterial an.gens the cell has eaten) to CD4+ T cells Present mainly on an.gen presen.ng cells, like macrophages! (Makes sense.)

B Lymphocytes Basic func.on: make an.bodies B-cell receptor complex recognizes an.gens Binds an.gen Sends signals to B cells An.gens can be free and circula.ng (don t have to be bound to MHCs or displayed by other cells to be recognized!)

Natural Killer (NK) Cells Belong to innate immunity arm Receptors not highly variable (like T and B cell receptors) Main job: recognize and kill damaged or infected cells

Natural killer cell

Natural killer cell (top) killing infected cell (boaom)

Immunology Overview Defini.ons Cells Lymphocytes An.gen-presen.ng cells

An.gen-Presen.ng Cells Main job: catch an.gens and display them to lymphocytes Dendri.c cells Have fine cytoplasmic projec.ons Present all over body: skin, lymph nodes, organs Capture bug an.gens, display to B and T cells Macrophages Macrophages also eat bugs and present an.gens to and T cells Their role in ac.va.ng the adap.ve system is not as pivotal though!

Dendri.c cell surrounded by lymphocytes

Dendri.c cell (right) talking to lymphocyte (le1)

Monocyte Macrophage

Macrophage reaching for bacterium

Macrophage gorging on bacteria

Immunology Overview Defini.ons Cells Lymphocytes An.gen-presen.ng cells Effector cells

Effector Cells These guys carry out the ul.mate immune system task: eliminate infec.on Types of effector cells NK cells Plasma cells T cells (both CD4+ and CD8+) Macrophages Other leukocytes (e.g., neutrophils)

Immunology Overview Defini.ons Cells Lymphocytes An.gen-presen.ng cells Effector cells Responses The innate immune response

The Innate Immune Response Main bug barriers: skin, mucosa If bugs make it through epithelium, they encounter innate immune system What happens in the innate immune system? Phagocytes eat bugs, kill them Cytokines are released Complement is ac.vated The adap.ve immune system is ac.vated

Immunology Overview Defini.ons Cells Lymphocytes An.gen-presen.ng cells Effector cells Responses The innate immune response Capturing and displaying an.gens

Capturing and Displaying An.gens Dendri.c cells in epithelium capture bug an.gens, transport them to lymph nodes Dendri.c cells display an.gens (using their MHC receptors) to T cells B cells in lymph nodes also recognize an.gens An.gens and molecules produced during innate immune response trigger prolifera.on and differen.a.on of B and T cells

Immunology Overview Defini.ons Cells Lymphocytes An.gen-presen.ng cells Effector cells Responses The innate immune response Capturing and displaying an.gens Cell-mediated immunity

Humoral Immunity Cell-Mediated Immunity

Naïve T Cells Turn Into Effector T Cells Naïve T cells are ac.vated by an.gen and cos.mulators in lymph nodes then they proliferate and differen.ate into effector cells that go find the an.gen. CD4+ T cells help macrophages eat bugs CD8+ T cells kill infected cells directly All these steps are dependent upon cytokines

What are cytokines? Polypep.des that do lots of different things: Help leukocytes grow and differen.ate Ac.vate T cells, B cells and macrophages Help leukocytes communicate Recruit neutrophils Made by lymphocytes and macrophages Examples: tumor necrosis factor (TNF), interleukins, interferons

Types of Effector T Cells CD4+ T cells differen.ate helper T cells These guys go to the site of infec.on and help other cells do their thing. CD8+ T cells differen.ate into cytotoxic T cells These guys kill cells that have microbes in their cytoplasm. They are like liale assassins.

Maa Damon and the asset

Cell-Mediated Immunity

Immunology Overview Defini.ons Cells Lymphocytes An.gen-presen.ng cells Effector cells Responses The innate immune response Capturing and displaying an.gens Cell-mediated immunity Humoral immunity

Humoral Immunity Cell-Mediated Immunity

Humoral Immunity B cells are ac.vated by exposure to an.gens (some.mes with the help of CD4+ T cells) B cells differen.ate into plasma cells (which make an.bodies) The an.bodies do nasty things to bugs

What is an an.body? Y-shaped glycoprotein 2 light chains (κ or λ) 2 heavy chains (α, γ, δ, ε, or μ) Constant regions of heavy chain form Fc fragment Binds to APCs Defines isotype (Ig class: IgA, IgE, etc.) Variable regions of both chains form Fab fragments Binds to an.gen Defines idiotype

What do an.bodies do? Bind to and neutralize bugs, so they can t infect cells. Coat ( opsonize ) bugs, making them yummy to macrophages and neutrophils (which have receptors for the Fc por.on of IgG! How handy!). Ac.vate complement.

What is complement? Just give me the boaom line. It s a bunch of proteins that poke holes in cells.

Okay, give me a liale more informa.on. Consists of about 20 plasma proteins (C1, C2, etc.) Can be ac.vated in a few different ways Ac.va.on proceeds in a cascade fashion End results: Cell lysis Chemotaxis Opsoniza.on

Complement, ridiculously oversimplified

Immunologic Memory Most effector lymphocytes die a1er killing the bug. A few memory cells live on for years. Expanded pool of an.gen-specific lymphocytes Respond faster, beaer than naïve cells Vaccines depend on these guys

Summary of the Adap.ve Immune Response