Adaptive Immune System Chapter 16
Overview of Adaptive Immunity
• Adaptive immunity is the body’s ability to recognize and defend itself against distinct invaders and their products
• Five attributes of adaptive immunity– 1. _______________
• Any adaptive response acts against only one particular molecule shape and not others.
– Specific pathogens
– 2. _______________• Activation of adaptive cells only in response to specific
pathogens
Five attributes of adaptive immunity continued..
• 3. _____________– Once induced cells of the adaptive system proliferate
(expand) to form many generations of nearly identical cells (clones).
• 4. _____________________________– The adaptive system does not act against normal
body cells.• 5. __________________________
– An adaptive immune response has memory which allows a quick response if you encounter the pathogen again
Innate vs. adaptive
• Innate– Nonspecific response
• A fever is a fever whether triggered by a cold virus or Ebola
– Always ready and fast acting
• Born with these systems
• Adaptive– Specific immune
response to a pathogen• If you have a cold virus
antibodies are produced specifically for that virus
– Slower– Not born with an
adaptive system• Antibodies can be
transferred through breast milk
Types of Acquired Immunity• Specific immunity acquired during an
individual’s life– _________________
• – Distinguished as either active or passive
• Active- normal exposure and response to pathogen• Passive immunity
– Receive antibodies from another individual» Newborns respond slowly to antigen» IgG crosses the placenta providing protection– IgA in breast milk-
– ____________________•
Dual Nature of Adaptive Immunity
• T and B cells develop from stem cells in red bone marrow Stem cells develop in bone marrow
Red bone marrow of adults
Differentiate to B cells in adult red bone marrow
Thymus
Differentiate to T cells in thymus
Migrate to lymphoid tissue such as
spleen, but especially lymph
nodes
Dual Nature of Adaptive Immunity
• Two types of adaptive immune responses–
•
–
•
Where does the Adaptive Immune response take place?
– The Tissues and Organs of the Lymphatic System
• Act as a surveillance system that screens the tissues of the body for foreign antigens
• Composed of lymphatic vessels and lymphatic cells, tissues, and organs
The Nature of Antigens
•
• Include various bacterial components as well as proteins of viruses, fungi, and protozoa
• Food and dust can also contain antigenic particles
Types of antigens•
• – Toxins and other secretions– Components of cell walls, membranes, flagella
• • – Endogenous antigens are not accessible to immune
cells– Immune cells will respond if the endogenous antigen
is incorporated into the bodies cells cytoplasmic membranes (external display)
• – – Derived from normal cell processes
Extracellularmicrobes
Exogenousantigens
Endogenousantigens
Intracellularvirus
Virallyinfectedcell
Autoantigens(normal cell antigens)
Normal(uninfected)cell
The Nature of Antibodies
• Globular proteins called immunoglobulin's• Secreted by _____________________• Antibodies (Ab) interact with________________
_______________
Binding sites
antigenic determinants on antigen
Antibody A
Antigens:componentsof cell wall
Antibody B
Bacterial cell
Epitopes (antigenic determinants).
Antibodies
• Classes of antibodies– ____–first antibody produced– ____–most common (80% of serum antibodies) and
longest-lasting antibody– ____– associated with body secretions, provides nursing newborns
some protection against foreign antigens, newborn receives antibodies against antigens that have infected their mothers
– _____–involved in response to parasitic infections and allergies
– _____–exact function is not known
Humoral Response
• The introducing the players:– Extra cellular antigen– B cells
• BCRs
– T helper cells (T-dependent humoral immunity only)• CD4
– MHC class II proteins– Exogenous antigen processing– Cytokines (chemical signalling)
B Cells and Antibodies
• Arise and mature in the red bone marrow – Found primarily in the spleen and lymph
nodes– Small percentage of B cells circulates in the
blood–
B Cells and Antibodies
• The process leads to the secretion of antibodies starts when B cells are exposed to extracellular antigens.
• B cells carry immunoglobulin's on surface of cell– Called B cell receptors (BCRs)
• Each B lymphocyte has multiple copies of the same B cell receptor
• Each B cell generates a single BCR– ~500,000 identical copies per cell
– Billions of different BCR’s in a human
Figure 16.4 B cell receptor (BCR)
Heavy chain
Light chain
Epitope
Antigen-bindingsites
Variable region
Cytoplasmicmembrane ofB lymphocyte
Transmembraneportion of BCR
B cell receptor(BCR) Cytoplasm
T Cells• T cells mature in the thymus
– Have T cell receptors (TCRs) on their cytoplasmic membrane• TCRs do not recognize epitopes directly• TCRs only bind epitopes associated with a MHC protein• Have either CD 4 or CD 8 protein (to recognize MHC)
– T Helper lymphocyte•
– T helper cells require ______________________ _____________________
– Major histocompatibility antigens are proteins found in the membranes of most cells of vertebrate animals
–
The Roles of the Major Histocompatibility Complex (MHC)
The Roles of the Major Histocompatibility Complex (MHC)
• Antigens bind to MHC molecules• Two classes of MHC proteins
• _______________Found on every nucleated cell • _______________Found only on B cells and
antigen presenting cells (APC)Antigen-binding grooves
Cytoplasmicmembrane
Class I MHCon every nucleatedcell
Class II MHCon B cell or otherantigen-presentingcell (APC)
Antigen Presenting Cells (APC) and Antigen Processing
– Digest antigen– Display antigen fragments on APC surface with
MHC– Exogenous Antigen processing
• Antigen presenting cells internalize the antigen and digest the in the phagolysosome
• A vesicle containing MHC II fuses with the phagolysosome and the antigens can bind to its complementary MHC II molecule
Role of CD4
• T helper cells recognize antigens presented with their ______and _____protein on T helper recognizes _____________
• T helpers become activated when antigen is presented on a MHC II and matches its ______
Exogenous Processing
B cell
Antigen
Costimulatory molecule, (required to activate T cells that have not previously encountered antigen)
Microorganism carrying antigens
Antigen fragment (short peptides)
TH cell receptor (TCR)
Complex of MHC class II molecule
and antigen fragment
A receptor (TCR) on the surface of the T helper cell (TH cell) binds to the MHC–antigen complex. The APC is stimulated to secrete a costimulatory molecule. These two signals activate the TH cell, which produces cytokines.
The cytokines cause the TH cell to become activated.
Cytokines
T helper cell
An APC encounters, in this case a B cell, and ingests a microorganism. The antigen is enzymatically processed into short peptides, which combine with MHC class II molecules and are displayed on the surface of the APC.
Humoral Immune Responses
• Two types– ________________humoral immunity– ________________humoral immunity
T-dependent humoral immunity
• T-dependent– – Antigen is presented with __________to TH cell
– TH cell produces _________that activate the B cell
– Once B cell is activated the B cell undergoes _____ _____________________
– B cells differentiate into:• •
The process
Clonal selection and differentiation of B cells.Stem cell
B cells
Antigen
Some B cells proliferate into long-lived memory cells, which at a later date can be stimulated to become antibody-producing plasma cells. See Figure 17.17.
Memory cells
B cell III complexes with its specific antigen and proliferates.
Other B cells proliferate into antibody-producing plasma cells.
Plasma cells
Plasma cells secrete antibodies into circulation.
Antigens in circulation now attached to circulating antibodies
Cardiovascular system
I II III IV
Stem cells differentiate into mature B cells, each bearing surface immunoglobulins against a specific antigen.
T-dependent humoral response worksheet
T-independent humoral immunity
• • When a molecule with ________________
____________________________the BCRs on a B cell– 1. The B cell is activated– 2. undergoes clonal expansion– 3. the clones become plasma cells which secrete
antibodies
T-independent humoral immunityPolysaccharide
(T-independent antigen)
Epitopes
B cell receptors
T-independent humoral response worksheet
Humoral Immune Responses
• Memory B Cells and the Establishment of Immunological Memory– Produced by B cell proliferation but do not secrete
antibodies– Have BCRs complementary to the antigenic
determinant that triggered their production– Long-lived cells that persist in the lymphoid tissue– Initiate antibody production if antigen is
encountered again
Outcomes of Antigen–Antibody Binding
• • • •
•
The results of antigen–antibody binding.PROCTECTIVE
MECHANISM OF BINDING ANTIBODIES TO ANTIGENS
Activation of complementAgglutination
Opsonization Antibody-dependentcell-mediated cytotoxicity
Neutralization
Reduces number of infectious units to be dealt with
Coating antigen with antibody enhances phagocytosis
Phagocyte
Bacteria
Causes inflammation andcell lysis
Bacterium Lysis
Antibodies attached to target cell cause destruction by macrophages, eosinophils, and NK cells
EpitopesEosinophil
Perforin and lytic enzymes
Large target cell (parasite)
Blocks adhesion of bacteria and viruses to mucosa
Bacterium
Virus
Blocks attachment of toxinToxin
Complement
Cell mediated response
• The Players– Intracellular antigen (virally infected cells)– T cytotoxic cells (Tc)
– Cytotoxic T lymphocytes (CTLs) – CD8
– T helper cells– APCs
• Macrophages• Dendritic cells
– MHC class I
T Cells and Cell Mediated Immunity
• T cytotoxic cells (Tc)–
• Have ______________which recognize Endogenous antigen packaged with ___________protein on _____ ________________________________
• Produce perforins and granzyme – Directly kills infected cells
• Tc and CTLs require antigen-presenting cells with MHC class I
Antigen presenting cells (APC)
• Macrophages• Dendritic cells- “scouts” most important!
– Found under surface of skin and mucous membranes
– After acquiring antigen they will migrate to lymph nodes to interact with B and T cells
A dendritic cell.
Antigen Processing
• Endogenous – from pathogens living within a cell the antigen is broken down and packaged inside the cell with MHC I and displayed on the cell surface
Processed antigen
MHC class I
Virus-infected cell (example of endogenous antigen) Virus-infected cell
Processed antigen presented withMHC class I Virus
Virus-infected cell
Cell-Mediated Immune Responses
• See worksheet or next 3 slides explain process
Cell-Mediated Immune ResponsesSteps involved in activation of CTL’s (see worksheet)•Antigen presentation- an APC (usually dendritic cell) presents antigen on a MHC class I protein to Tc cells (T cytotoxic cells)
– The one with matching TCR binds to dendritic cell– CD8 on Tc cell recognizes MHC I
•Helper T cell stimulates Tc cell -A T helper cell will provide a signal to the Tc to undergo differentiation into a CTL and clonal expansion
Steps involved in activation of CTL’s•Differentiation- the signal from the Th cell causes the Tc cell to differentiate into a CTL•Clonal expansion- CTLs reproduce to form memory T cells and CTL clones
•Self-stimulation- the clonal CTLs cells no longer need an APC or helper T cell, they will signal themselves and leave the lymph node ready to attack virally infected cells
Steps involved in activation of CTL’s
•Activated CTLs with their TCRs and CD8 will recognize virally infected cells with endogenous antigen packaged with MHC class I, since viral antigens are presented on the cytoplasmic membrane•CTLs will bind to the infected cell with its TCR and complementary MHC I/antigen complex
– Once bound the CTL kills their target• By activating apoptotic factors
– Perforin and granzymes
Figure 16.15b A cell-mediated immune response: perforin-granzyme cytotoxic pathway
Tc cell
Perforin Granzyme
Perforincomplex (pore)
Inactiveapoptoticenzymes
Granzymes activateapoptotic enzymes
Active apoptoticenzymes induceapoptosis
Virally infected cell
Apoptosis.
Natural Killer (NK) Cells
• Granular leukocytes destroy cells that don’t express MHC I
• Kill virus-infected and tumor cells• Attack parasites
Immunological Memory
• Primary response occurs after initial contact with Ag
• Secondary (memory) response occurs after second exposure
Figure 16.19 The production of primary and secondary humoral immune responses--overview