17 Adaptive Immunity: Specific Defenses of the Host

Student Learning Outcomes Differentiate between innate and adaptive immunity, and humoral and cellular immunity. Define antigen, epitope, and hapten. Explain the function of antibodies and describe their structural and chemical characteristics. Name one function for each of the five classes of antibodies. Compare and contrast T-dependent antigens and T-independent antigens. Differentiate between plasma cell and memory cell. Describe clonal selection. Describe four outcomes of an antigen-antibody reaction. Differentiate between helper T and cytotoxic T Define apoptosis. Define antigen-presenting cell. Describe the role of antibodies and natural killer cells in antibody-dependent cell-mediated cytotoxicity. Identify at least one function of each of the following: cytokines, interleukins, interferons. Distinguish a primary from a secondary immune response. Contrast the four types of adaptive immunity.

Immune System Overview Def. of innate immunity: __________________ Adaptive immunity: “Ability of the body to react to specific microbial infection”. Adaptive immunity is…. ag specific and has ______________ made up of two branches ____________ Immunity (B cell mediated) ____________ Immunity (T cell mediated) integrated with _______________ has ability to ignore healthy “self” molecules (tolerance)

Vocabulary Antigen (ag): Molecule (or part of molecule) that initiates production of specific antibodies or sensitized T cells. Antibody (ab): Proteins made in response to an ag; can bind to that ag. Other names: __________________, _________________ Serology: Study of reactions between abs and ags in vitro. Antiserum: Blood-derived fluid containing abs. Complement:

Serum Proteins Fig 17.19

The Nature of Antigens Antigens and antigenic Determinants Antibodies recognize and react with parts of antigens known as antigenic determinants or epitopes Fig 17.1

Hapten Definition: Small molecule not antigenic by itself. Becomes antigenic when bound to “carrier molecule” Fig 17.2 Some drugs, esp. (?) _________________________

The Nature of Antibodies Immunoglobulin Structure: 4 polypeptide chains (2 heavy and 2 light) Variable regions Constant regions Fig 17.3 Fig 17.3

5 Immunoglobulin Classes: G, M, A, E, D Monomers (bivalent) 80% of serum abs Protect fetus and newborns (how?) _______________________ Activate complement Act as opsonins (_____________________) Neutralize toxins and viruses; Half-life = 23 days IgG

IgM Pentamer aggregates (too big to move freely) 5-10% of serum abs Good at causing clumping of ags (= ______________) 1st ab produced in response to infection Half-life = 5 days (short! – good for use in diagnostics!)

IgA Dimer aggregates Most abundant in body, especially in secretions (?) Mucosal protection  prevents ___________

IgD IgE Monomers Mostly on surface of virgin B cells  initiate immune response Monomers Produced by B cells, but bind to mast cells and basophils  Degranulation (?) when IgE binds to ag Useful in parasitic infections (e.g.:________) Annoying in allergies

B cells and Humoral Immunity Effective against free or extracellular antigens, such as _____________ B cell receptors (mostly IgM and IgD) After clonal selection  clonal expansion leading to Plasma cells (effector cell for antibody production) and Memory cells

Clonal Selection and Clonal Expansion Fig 17.5 Mastering: Humoral Immunity – Clonal Selection and Expansion

Response to T – dependent antigens B cells require help of T cells for most protein antigens (T-dependent ags) B cells internalize antigen and present it to T-helper cell in combination with MHC class II molecules If T cell recognizes antigen it activates B cell  clonal expansion  plasma cells and memory cells Fig 17.4

Response to T – Independent Antigens No T-helper cells involved Polysaccharides (bacterial capsules) and LPS Weak response with no memory cells Young children react poorly Fig 17.6

Antigen—Antibody Binding & its Results Affinity: __________of bond between ag and ab. Specificity: Ab recognizes a specific epitope. Agglutination and precipitation Opsonization Neutralization (to immobilize and prevent adherence) Complement activation ADCC: Antibody-Dependent Cell-mediated Cytotoxicity via NK cells and eosinophils  Protective outcome: Disposal of antigen

5 Protective outcomes of ag-ab binding The Results of ag-ab Binding Review next slide ADCC The Results of ag-ab Binding Fig 17.7

T Cells and Cellular Immunity Compare to Fig 17.10 T cells have specific TCR on surface. TCR does not recognize free antigen. Ag must be presented in association with MHC II on an antigen-presenting cell (APC). Antigens are processed by APC and positioned on the surface of the APC.

Fig 17.10 Activation of CD4+T helper cells

Classes of T cells T Helper Cells (TH, CD4+) Activated by APC with MHC-II. Starts to secrete cytokines activating other T cells and B cells Co-stimulatory signal necessary: TLRs T Cytotoxic cells (TC, CD8+)  CTL (= effector cell) when activated) Target cells are self-cells carrying endogenous antigens Activated into cytotoxic T lymphocytes (CTLs) CTLs recognize Ag + MHC I Induce apoptosis in target cell CTL releases perforin and granzymes

Antigen Recognition by T Cells MHC Class I on all nucleated cells Antigen Recognition by T Cells MHC Class II on surface of APCs (Macrophages, B-cells, dendritic cells)

Apoptosis in target cell Mechanism of Action of CTL: Destruction of cells displaying MHC-I-Ag complexes Perforin forms pores in target cell membrane Granzymes enter and trigger Apoptosis in target cell Similar but different from MAC !! Fig. 17.12

APCs Three major types: __________________ Digest antigen Present ag fragments on surface in connection with MHC-II molecule Th-cells recognize ag-MHC-II complex Mastering: T Cell-mediated Immunity – Helper T Cells

Natural Killer (NK) Cells 10 – 15% of circulating lymphocytes Not immunologically specific  part of _______ Kill target cell if MHC-I absent, e.g.: Some transformed cells Some virus infected cells, esp. early infection stage Large extracellular parasites Similar mechanism to CTLs: Pore formation, then apoptosis or lysis Colored SEM; NK cells attacking a cancer cell. (Karolinska Institute)

Immunological Memory Amount of abs in serum is called the antibody titer. 1st contact with an ag  1 response  1st ab? Subsequent contact with same ag  2 response  Rapidly very high antibody titer. Mostly _____. Is immunological memory good for ever? Fig 17.17

Types of Adaptive Immunity Active immunity Protection via introduction of antigen into responsive host, e.g.: Naturally acquired via ___________ or Artificially acquired via ___________

Passive Immunity Protection via transfer of antibodies or immune cells into a non-immune host, e.g.: Naturally acquired: Artificially acquired: injection of immune serum Snake bite Rh+ child with Rh- mother Treatment of infectious diseases (??)

Compare to Fig 17.18

The End Foundation Fig 17.20: Summary of Adaptive Immunity Immunology Micro Flix The End