Acquired Immunity: Humoral & Cell-Med.• Distinction of Humoral versus Cell-Mediated Acquired Immunity

• Antigens and Antigenic Determinants: Non-self and MHC proteins

• Cell Types of the Humoral Response and How they Develop

• B and T cell receptors and immunglobulins (antibodies)

• Antibody Structure and Classes

• Activation of B cells and Clonal Selection

• Immunity and Secondary Response Time, Vaccines

• Antibody Actions

• Passive and Active Immunity

• Monoclonal Antibodies

• Players in the Cell Mediated (Adaptive) Response

• Activation of Cytotoxic T and B cells via TH cells

• Other T cells and their function

• Tissue grafting

• Immune disorders: Allergies

• Immune disorders: Immunodeficiency

Secondary Response (Immunity)

Figure 12.13

Types of Vaccines Live, attenuated vaccines: passed through unnatural host or a

related non-virulent virus

• Benefits: Strong immune response, provide extended response

• Potential Problems: Underattenuation, mutation back to virulent form

Inactivated/dead “whole” microbial vaccines

• Benefits: Moderately immune response, less chance of causing disease

• Potential problems: incomplete inactivation

Subunit vaccines: pieces of outer layer of microbes, often produced through biotechnology

• Benefits: No chance of causing disease, safer

• Problems: Weaker immune response

Subunit Vaccines Made of Microbial Parts

Vaccine Production: Coinfecting With Two Strains

Acquired Immunity: Humoral Response• Distinction of Humoral versus Cell-Mediated Acquired Immunity

• Antigens and Antigenic Determinants: Non-self and MHC proteins

• Cell Types of the Humoral Response and How they Develop

• B and T cell receptors and immunglobulins (antibodies)

• Antibody Structure and Classes

• Activation of B cells and Clonal Selection

• Immunity and Secondary Response Time

• Antibody Actions

• Passive and Active Immunity

• Monoclonal Antibodies

• Players in the Cell Mediated Response

• Activation of Cytotoxic T and B cells via TH cells

• Other T cells and their function

• Tissue grafting

• Immune disorders: Allergies

• Immune disorders: Immunodeficiency

Results of Antibody Binding to Antigen• Agglutination (coralling of the invader)

• Precipitation (removal of soluble antigens from blood and lymph)

• Neutralization (blocking antigen's activity and binding)

• Opsonization (faciliating macrophage phagocytosis)

• Tagging, complement fixation, and transmembrane channel formation (lysis of pathogen)

Agglutination Precipitation (soluble antigens)

Transmembrane channel

formation and lysis

Antibody Function movie

Active vs Passive Immunity Active Immunity

• Your B cells encounter antigens and produce antibodies

• Active immunity can be naturally or artificially acquired (e.g via vaccination)

Passive Immunity

• Antibodies are obtained from someone else

o Conferred naturally from a mother to her fetus

o Conferred artificially from immune serum or gamma globulin - e.g. snake antitoxin

• Immunological memory does not occur

• Protection provided by “borrowed antibodies”

Monoclonal Antibodies Antibodies prepared for clinical

testing or diagnostic services

Produced from descendents of a single cell line

Examples of uses for monoclonal antibodies

• Diagnosis of pregnancy

• Treatment after exposure to hepatitis and rabies

• HIV/AIDS detection in ELISA Assays

• Identifying microbes by using fluorescent-tagged antibodies against known organisms

Monoclonal Antibodies Can Be Used To Deliver Cell Poisons

E.g. Rutuxin-mab for non-Hodgkin’s lymphoma tags B cells, causing apoptosis, NK cell, or complement lysis

Acquired Immunity: Humoral Response• Distinction of Humoral versus Cell-Mediated Acquired Immunity

• Antigens and Antigenic Determinants: Non-self and MHC proteins

• Cell Types of the Humoral Response and How they Develop

• B and T cell receptors and immunglobulins (antibodies)

• Antibody Structure and Classes

• Activation of B cells and Clonal Selection

• Immunity and Secondary Response Time

• Antibody Actions

• Passive and Active Immunity

• Monoclonal Antibodies

• Players in the Cell Mediated Response

• Activation of Cytotoxic T and B cells via TH cells

• Other T cells and their function

• Tissue grafting

• Immune disorders: Allergies

• Immune disorders: Immunodeficiency

Cellular (Cell-Mediated) Immune Response

1. Antigens must be presented by macrophages, dendritic cells, or B cells to a T helper (TH) cell (called “antigen presentation”)

2. T cells must recognize non-self antigen and self MHC proteins (double recognition)

3. After antigen binding, clones form as with B cells, but different classes of cells are produced

Cell-Mediated (Adaptive) Response

Types of T Cells Cytotoxic T (Tc) cells - CD8+

• Specialize in killing infected cells

• Insert a toxic chemical (perforin)

Helper T (TH) cells - CD4+ Recruit other cells to fight the invaders

• Interact directly with B cells

A few members of each clone are memory cells

Helper t cells animation

Cytotoxic t cells animation

Recognition Proteins Found on T cellsCD8: special membrane glycoprotein found

on cytotoxic T (TC) cells only

• CD8 glycoprotein, therefore T cells designated as CD8+

• Function

o Bind to class I MHC molecules on almost every body cell to identify “self” from “non-self” but to kill “bad” self-cells

CD4: different membrane glycoprotein found on TH, monocytes, macrophages, dendritic cells

• CD4 glycoprotein, therefore Tcells designated as CD4+

• Function

o Bind to and recognize class II MHC molecules on dendritic cells, macrophages, or B cells to verify they have a security force name tag”.

Summary of B Cell Activation

B cells can be activated directly by antigen or from a TH cell activated by an antigen-presenting macrophage

Summary of the Immune Response

Acquired Immunity: Humoral Response• Distinction of Humoral versus Cell-Mediated Acquired Immunity

• Antigens and Antigenic Determinants: Non-self and MHC proteins

• Cell Types of the Humoral Response and How they Develop

• B and T cell receptors and immunglobulins (antibodies)

• Antibody Structure and Classes

• Activation of B cells and Clonal Selection

• Immunity and Secondary Response Time

• Antibody Actions

• Passive and Active Immunity

• Monoclonal Antibodies

• Players in the Cell Mediated Response

• Activation of Cytotoxic T and B cells via TH cells

• Other T cells and their function

• Tissue grafting

• Immune disorders: Allergies

• Immune disorders: Immunodeficiency

Organ Transplants and Rejection Major types of grafts

• Autografts – tissue transplanted from one site to another on the same person

Hey buddy, my patch of skin is damaged! Can I have your autograft?

• Isografts – tissue grafts from an identical person (identical twin)

• Allografts – tissue taken from an unrelated person (sometimes successful)

• Xenografts – tissue taken from a different animal species (rarely successful)

Allergies (Hypersensitivity) Abnormal, vigorous immune responses

Type I -IgE antibodies bind to mast cells

• Immediate hypersensitivity

o B cells exposed to foreign antigen and IgE antibodies are made

o Reaction triggered by release of histamine from IgE binding to mast cells

o Reactions begin within seconds of contact with allergen

o Anaphylactic shock – dangerous, systemic response

• Delayed hypersensitivity

o Triggered by the release of lymphokines from activated helper T cells

o Symptoms usually appear 1–3 days after contact with antigen

o E.g. reaction to poison ivy, contact dermatitis

Type II - complement lyses antibody-tagged cells

• Immediate reactions, life threatening

o E.g. Transfusions, hemolytic disease of newborns

Acquired Immunity: Humoral Response• Distinction of Humoral versus Cell-Mediated Acquired Immunity

• Antigens and Antigenic Determinants: Non-self and MHC proteins

• Cell Types of the Humoral Response and How they Develop

• B and T cell receptors and immunglobulins (antibodies)

• Antibody Structure and Classes

• Activation of B cells and Clonal Selection

• Immunity and Secondary Response Time

• Antibody Actions

• Passive and Active Immunity

• Monoclonal Antibodies

• Players in the Cell Mediated Response

• Activation of Cytotoxic T and B cells via TH cells

• Other T cells and their function

• Tissue grafting

• Immune disorders: Allergies

• Immune disorders: Immunodeficiency

Disorders of Immunity: Immunodeficiencies Autoimmune Diseases (antibodies attack own tissues)

• Multiple sclerosis – Schwann cells and oligodendrocytes forming myelin sheaths are destroyed, slowing communication, esp. muscles

• Myasthenia gravis – antibodies blocking acetylcholine receptors on post-synaptic side of neuromuscular junction; muscle weakness

• Juvenile diabetes – destroys pancreatic beta cells that produce insulin

• Rheumatoid arthritis – destroys joints by attacking tissues and causing inflammation

• Systemic lupus erythematosus (SLE) – affects kidney, heart, lung and skin

• Glomerulonephritis – impairment of renal function

• Grave’s disease - antibodies bind to TSH receptors on thyroid follicular cells, stimulating overproduction of thyroxine

Inefficient lymphocyte programming (e.g. T cells that escaped "education")

Appearance of self-proteins in the circulation that have not been exposed to the immune system (eggs, sperm, eye lens)

Cross-reaction of antibodies produced against foreign antigens with self-antigens

• Rheumatic fever - Anti-streptococcal antibodies also attack myocardium and joints; --> arthritis, congestive heart failure

Acquired Immune Deficiency Syndrome (AIDS)

HIV and Acquired Immunodeficiency Syndrome

Titers of TH cells and blood viruses

Diseases of AIDSLife Cycle of Human Immunodeficiency Virus

Acquired Immunity: Humoral Response• Distinction of Humoral versus Cell-Mediated Acquired Immunity

• Antigens and Antigenic Determinants: Non-self and MHC proteins

• Cell Types of the Humoral Response and How they Develop

• B and T cell receptors and immunglobulins (antibodies)

• Antibody Structure and Classes

• Activation of B cells and Clonal Selection

• Immunity and Secondary Response Time

• Antibody Actions

• Passive and Active Immunity

• Monoclonal Antibodies

• Players in the Cell Mediated Response

• Activation of Cytotoxic T and B cells via TH cells

• Other T cells and their function

• Tissue grafting

• Immune disorders: Allergies

• Immune disorders: Immunodeficiency

Activation of T and B Cells Through TH cells

MHC "self"

identifying

protein