Adaptive Immune System Chapter 16

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