Acquired Immunity: Humoral & Cell-Med.

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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
Antibody
Function
movie
Precipitation
(soluble antigens)
Transmembrane
channel formation
and lysis
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)
Cytotoxic t cells animation
 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
Recognition Proteins Found on T cells
CD8: 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
• 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)
Hey buddy, my patch of
skin is damaged! Can I
have your autograft?
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
Life Cycle of Human Immunodeficiency Virus
Diseases of AIDS
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
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