Chapter 17 Adaptive Immunity: Specific Defenses of the Host

Opsonization: (from greek to cater)

Coat bacteria with antibodies that enhance ingestion and lysis by phagocytes

17-1 Compare and contrast innate and adaptive immunity

Innate Immunity: Adaptive immunity - exposure to a disease can make a person "immune " to that disease when encountered later (led to vaccination).

Activation of B cells (T-dependent)

Once a B-cell is activated by binding its specific antigen it divides rapidly (often with the assistance of a T-helper cell (TH) cell to make many copies of that one cell - clonal selection Each antibody producing cell is called a plasma cell (2000 molecules per second!) - a primary response (write out the steps)

17-18 Describe the role of antibodies and natural killer cells in antibody-dependent cell-mediated cytotoxicity.

Protozoans and helminths are too large to be phagocytized Protozoan or helminth target cell is coated with antibodies Immune system cells attach to the Fc regions of antibodies Target cell is lysed by chemicals secreted by the immune system cell

Antibody-dependent Cell-Mediated Cytotoxicity

Target organism is coated with antibodies but destruction of the target cell is mediated by cells that remain outside the target cell

Adaptive immunity:

- developed over the course of a lifetime Natural acquired immunity: -actively acquired when individual is exposed to a new antigen -passively acquired when antibodies are passed from mother to fetus via placenta or in the mother's milk Artificially acquired immunity: -actively acquired following vaccination

IgM (macro) antibodies

--IgM (M for macro - large size - pentamers) ~6% of serum proteins --Found in blood, lymph and on B cells -- effective against bacteria and agglutinating antigens, 1st antibodies produced in infection - half-life of 5 days

IgG (gamma) antibodies

--Monomer 80% of serum proteins --IgG - Fixes complement, --enhances phagocytosis, neutralizes toxins & viruses, and protects fetus and newborn - only Ig to be transferred across placenta, long half-life of 23 days

Foreign substances provoking an immune response are called --

--antigens The body produces specific antibodies against these antigens that tag them for destruction

Cellular Immunity

Accidental finding in 1956 that birds without this kind of organ (the Bursa of Fabricus) could not produce antibodies (immunoglobulins)! In mammals B cells mature in the bone marrow. Until 1950's the thymus had no known function ! Inspired by removal of the BoF -removal of Thymus in mice resulted in a lymphocyte deficiency - subsequently named T-cells -because they mature there Lead to idea that antibodies signaled white blood cells (lymphocytes) to produce more antibodies. Now know that T cell receptors (TCRs) on the T cell surface contact antigens, causing the T cells to secrete cytokines instead of antibodies - used mainly to fight infections inside of cells

Antibody Structure

Antibodies recognize and interact with a region on an antibody called an epitope. Four protein chains form a Y-shape. Two identical light chains and two identical heavy chains joined by disulfide links The variable (v) region of each antibody allows for a huge number of epitopes to be recognized by the body. Constant (Fc) region is the stem, which is identical for a particular Ig class.

17-16 Define antigen-presenting cell.

Antigen Presenting Cells (APCs) T-cells interact with specific antigens that must be displayed on a cell surface. Macrophages or dendritic cells after digestion display fragment of antigen on their surface near self MHC (major histocompatibility complex) Dendritic cells (DCs) Engulf and degrade microbes and display them to T cells Found in the skin, genital tract, lymph nodes, spleen, thymus, and blood Macrophages Activated by cytokines or the ingestion of antigenic material Migrate to the lymph tissue, presenting antigen to T cells

17-4 Define antigen, epitope and hapten

Antigens: substances that cause the production of antibodies. Usually components of invading microbes or foreign substances Antibodies interact with epitopes, or antigenic determinants, on the antigen Haptens: antigens too small to provoke immune responses; attach to carrier molecules, e.g. penicillin

Neutralization:

Block viruses from attaching to host receptors - can neutralize toxins in a similar manner

17-14 Differentiate TH1 and TH2 and TH17 cells T cells interact more directly with antigens rather than producing more antibodies T cells are classified based on surface glycoproteins that help attach to membrane receptors (clusters of differentiation or CD)

CD4+ T helper cells (TH) Cytokine signaling with B cells; interact directly with antigens Bind MHC class II molecules on B cells and APCs CD8+ Cytotoxic T lymphocytes (CTL) Bind MHC class I molecules

Agglutination:

Causes antigens to clump together - more easily digested by phagocytes e.g. IgG can bind 2 cells IgM with many binding sites is even more efficient at aggregating many antigens

17-12 Describe at least one function of each of the following: M cells, TH1 cells, CTLs, Treg cells, NK cells.

Cell mediated immune system mediated by T-cells mostly. Lose ability to make T cells with age. Deals with pathogens inside of cells T cells develop from stem cells in the bone marrow and mature in the thymus (Hence T) (where 98% are eliminated by clonal deletion) Like B cells, T cells produce a single antibody that can react with a single antigen. Clonal selection occurs to stimulate proliferation of activated T-cells (effector cells). Some become memory cells

17-3 Identify at least one function of each of the following: cytokines, interleukins, chemokines, interferons, TNF and hematopoietic cytokines

Cytokines: are chemical messengers produced in response to a stimulus Interleukins: cytokines between leukocytes Chemokines: induce migration of leukocytes Interferons (IFNs): interfere with viral infections of host cells Tumor necrosis factor (TNF): involved in the inflammation of autoimmune diseases Hematopoietic cytokines: control stem cells that develop into red and white blood cells Overproduction of cytokines leads to a cytokine storm

IgA (alpha) antibodies

Dimer ~13% of serum antibodies IgA - protection on mucosal surfaces, saliva, tears and breast milk -Prevent microbial attachment to mucous membranes - dimers acquire a secretory polypeptide protecting it from enzymatic degradation - half-life of 6 days

17-7 Compare and contrast T-dependent and T-independent antigens. 17-8 Differentiate plasma cell from memory cell. 17-9 Describe clonal selection

Each B cell carries immunoglobulins on it surface that are part of its makeup. Major histocompatibility complex (MHC) genes encode molecules on the cell surface Class I MHC are on the membrane of nucleated animal cells Identify "self" Class II MHC are on the surface of antigen-presenting cells (APCs), including B cells

Fig 17.12 Activation of CD4 helper T cells.

Fig 17.12 Activation of CD4 helper T cells. To activate a CD4+ T helper cell at least 2 signals are required: the first is the binding of the TCR to the processed antigen, and the second signal requires a costimulating cytokine such as IL-2 and others. Once activated, the TH cell secretes cytokines that affect the effector function of multiple cell types of the immune system.

17-17 Describe the function of natural killer cells.

Granular leukocytes called NKs can attack parasites much larger than bacteria. They can detect if cell produces MHC class I self antigens - if not they attack like CTLs. Reduction in the normal levels of surface class I MHC, a mechanism employed by some viruses and certain tumors to evade CTL responses, activates NK cell killing. Not always stimulated by an antigen Form pores in the target cell, leading to lysis or apoptosis

17-2 Differentiate humoral from cellular immunity

Humoral - from body fluid (humors) - also called antibody-mediated immunity - antibodies are found extracellularly in serum, lymph and mucous - originally these are produced by B-lymphocytes that are created and mature in the bone marrow (Named for bursa of Fabricius in birds) -works primarily against microbes freely circulating in body fluids

IgD antibodies Monomer, 0.2% of serum antibodies IgD - presence on B-cells functions in initiation of immune response (as antigen receptors), unknown function in serum, only 0.2 % of serum antibodies. May be involved in clonal deletion. half-life 3 days

IgE antibodies Monomer:0.0002% of serum antibodies On mast cells and basophils, in blood. Allergic reactions; When antigen (e.g. pollen)cross links to IgE on mast cell, histamine is released - allergic reaction Promotes lysis of parasitic worms. Half-life = 2 days

Activation of Complement system:

IgG and IgM bind and allow C1 to bind and start complement cascade. Lysis of the microbe attracts phagocytes to the site of infection

17-5 Explain antibody function, and describe the structural and chemical characteristics of antibodies

Immunoglobulin Classes: Blood proteins separated by electrophoresis fall into several classes (Fig 17-9) Antibodies are globular proteins called immunoglobulins (Ig) Valence is the number of antigen-binding sites on an antibody. Bivalent antibodies have two binding sites

Clonal Selection

Interaction with a specific antigen triggers the proliferation of a cell that is specific for that antigen with the same specificity - hence clonal selection The B-cells proliferate but some become memory cells responsible for the long term secondary response. Clonal deletion eliminates harmful B cells. T-dependent antigen Antigen that requires a TH cell to produce antibodies T-independent antigens Stimulate the B cell without the help of TH cells. Provoke a weak immune response, usually producing IgM No memory cells generated

17-15 Define apoptosis Apoptosis = Programmed cell death (PCD)

Prevents the spread of infectious viruses into other cells Cells cut their genome into fragments, causing the membranes to bulge outward via blebbing

17-19Distinguish a primary from a secondary immune response.

Primary response: For first 4 to 7 days after exposure to an antigen there are no detectable antibodies. Then an increase in IgM and IgG peaking at about 2 weeks. This is followed by a decline. Secondary (anamnestic) response: Also called the memory response - occurs more rapidly following a 2nd exposure to an antigen - reaches a peak in only 2 to 7 days.

17-14 Differentiate TH1 and TH2 and TH17 cells

TH17 cells produce IL-17 and contribute to inflammation if in high amounts. Helps combat bacteria and fungi. TH1 cells produce IFN-g, which activates macrophages, enhances complement, and stimulates antibody production that promotes phagocytosis TH2 cells activate B cells to produce IgE; activate eosinophils T regulatory cells (Treg) Subset of CD4+ cells; carry an additional CD25 molecule Suppress T cells against self; protect intestinal bacteria required for digestion; protect fetus

Activated macrophage -

are activated by ingestion of antigenic material. Important for removal of cancer cells and viral infected cells.

Dendritic cells

are plentiful in lymph nodes, spleen and skin. They are poorly phagocytic.

Immunity

is a specific defense response to an invasion by foreign organisms/substances