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Title: Microbiology Chapter 16
Description: Grand Valley State University, BMS 212 class notes. These notes follow the book: Microbiology with Diseases by Taxonomy, 4th Edition Author - Robert W. Bauman Ph.D.

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16 – Adaptive Immunity
Overview

1
...

a
...
Any particular adaptive immune response acts against only one
particular molecular shape
...

b
...
Cells of adaptive immunity activate only in response to specific
pathogens
...
Clonality
...

d
...
Several mechanisms help ensure that immune
responses do not attack the normal body itself
...
Memory
...

2
...

a
...
T Lymphocytes
3
...

a
...

b
...

Elements of Adaptive Immunity

1
...

a
...

b
...

c
...

2
...

a
...

b
...

i
...


3
...

a
...

b
...

Essentially, lymph nodes are sites to facilitate interactions among immune cells and
material in the lymph arriving from throughout the body
...
The spleen removes bacteria, viruses, toxins, and other foreign matter from the
blood
...

d
...

i
...

ii
...

4
...

a
...
These are the villains in the story
...
The ability for an antigen to provoke a response are a molecule’s shape, size, and
complexity
...
The body recognizes antigens by the three-dimensional shapes of regions called
epitopes, which are also known as antigenic determinants
...
The most effective antigens are large foreign macromolecules, such as proteins and
glycoproteins
...
Small
molecules usually make poor antigens by themselves, unless bound to larger
molecules
...
Complex molecules make better antigens than simple ones because they have more
epitopes
...
In contrast, glycoproteins have more distinct shapes and subunits
...
Distinguish among exogenous antigens, endogenous antigens, and autoantigens
...
Exogenous antigens include toxins and other secretions and components of
microbial cell walls, membranes, flagella, and pili
...

b
...
The immune system cannot look inside the cell so immune
response only occurs when these antigens are incorporated into the cell’s
membranes, leading to their external display
...
Autoantigens are antigenic molecules derived from normal cellular processes
...
Describe the characteristic of B lymphocytes that gives them specificity
...
Specificity comes from membrane proteins called B cell receptors (BCR), which is a
type of immunoglobulin that is rooted in a B-cell membrane
...
A simple immunoglobulin contains two identical longer chains called heavy chains
and two identical shorter light chains arranged like a ‘Y’, connected via disulfide
bonds
...

c
...


d
...

e
...

a
...
If a pathogen has differing
epitopes, then differing BCRs can attach to each specific epitope
...
Once a BCR is activated by an epitope, the B-cell is triggered to cellular division
...
Each offspring (known as plasma cells) secrete identical free immunoglobulin,
known as antibodies
...
Describe the basic structure of an immunoglobulin molecule
...
Antibodies are free immunoglobulins, thus they are not attached to a membrane
...
The antigen-binding sites of antibodies from a given plasma cell are identical to one
another and to the antigen-binding sites of that cell’s BCR
...
Thus, antibodies carry the same specificity for an epitope as the BCR of the
activated B cell
...
As in the figure, the anti-binding sites belong in the Fab region, then there is the
hinge region, and the stem belongs to the Fc region
...
There are 5 types of Fc regions, designated by the Greek letters mu, gamma, alpha,
epsilon, and delta
...

8
...

a
...
This begins the classical complement pathway, which releases
inflammatory mediators
...
Attachment triggers the release of inflammatory
chemicals, as seen in allergies
...
Neutralization
IgA antibodies can neutralize a toxin by binding to a critical portion of the toxin so
that it can no longer harm the body
...

c
...

Neutrophils and macrophages have receptors for the stems of IgG molecules
...

d
...

e
...
Numerous antibodies can aggregate antigens together
...
Agglutination may hinder the activity of pathogenic organisms and

f
...

Antibody-Dependent Cellular Cytoxicity (ADCC)
Antibodies often coat a target cell by binding to epitopes all over the target’s
surface
...
NK
lymphocytes lyse target cells with proteins called perforin and granzyme
...


9
...

a
...
Most IgM is secreted during the initial stages of immune response
...
A secreted IgM is a pentamer, which means it consists of 5 basic units linked
together in circular fashion via disulfide bonds and a short polypeptide
joining (J) chain
...
IgM is efficient in complement activation, but can also be involved in
neutralization and agglutination
...
IgG (γ)
i
...

ii
...
It plays a role in complement
activation, opsonization, neutralization, and ADCC
...
IgG are so small they can leave blood vessels to enter extracellular spaces
and bind to pathogens before they reach the circulatory systems
...
IgG are also the only antibody that can cross the placenta to protect child
...
IgA (α)
i
...

ii
...

1
...

a
...

iii
...
Protects the body from infections in the gastrointestinal,
respiratory, urinary, and reproductive tracts
...
IgA provides newborns some protection against foreign antigens
because mammary glands secrete IgA into milk
...
IgE (ε)
i
...

ii
...

1
...

iii
...


e
...
They are not secreted by any B cells
...
Scientist do not know the function or importance yet
...
Describe the importance of the thymus to the development of T lymphocytes
...
T-cells originate in the red bone marrow
...

b
...

11
...

a
...

b
...
Variable regions grant each TCR a specific antigen-binding site
...
However, unlike BCRs, TCRs only bind to epitopes associated with the MHC
protein
...
T-cells typically directly attack intracellular pathogens or cancer cells
...

12
...

a
...
This type is distinguished with the presence of CD8 glycoproteins and its
own unique TCR for every cell
...
CD stands for cluster of differentiation
...
The number reflects the order of discovery
...
These cells directly kills other cells infected with viruses, intracellular
pathogens, and abnormal cancerous cells with Perforin and granzyme
...
Helper T Lymphocyte (also known as Th or CD4 cell)
i
...

ii
...

1
...

2
...

c
...
This type expresses CD4 and CD25 glycoproteins
...
This type represses adaptive immunity and prevent autoimmune diseases
...
Scientists still not sure about the method of function but they do secrete
cytokines
...
Describe apoptosis and its role in lymphocyte editing by clonal deletion
...
We know that B-cells and T-cells variable region are randomly generated
...
Thus, it’s not surprising B-cells or T-cells could complement normal body
cells
...
To avoid autoimmune disease, the body eliminates self-reactive
lymphocytes via clonal deletion
...
Clonal deletion simply means the killing of a cell so it does not
produce offspring or clones
...
Lymphocytes that react with autoantigens (normal cell antigens), undergo a
process called apoptosis (programmed cell suicide)
...
In humans, clonal deletion of T-cells occurs in the thymus and for B-cells in
the bone marrow
...
Compare and contrast clonal deletion of T cells and clonal deletion of B cells
...
As T-cells mature in the thymus, they are exposed to all sorts of epitopes of natural
proteins in the body
...

b
...
Those T cells that do not recognize the body’s MHC protein undergo
apoptosis
...

ii
...

iii
...

iv
...

c
...

i
...
Vice versa
...
However, useless B cells are either inactivated, have their BCR changed, or
undergo apoptosis
...
Consider this figures below for understanding purposes
...


T-CELL FIGURE
-------------------------------------------------------------------------------------------------------------

B-CELL FIGURE

15
...
Specifically, know what the following do: IL2, IL-4, IL-12, IFN-γ, and TNF
...
Cytokines are soluble regulatory proteins that act as intercellular messages when
released For example, cytotoxic T cells do not respond to antigens unless they are
first signaled by cytokines
...
Interleukins (ILs) signal among leukocytes, though cells other than leukocytes may
also use interleukins
...
Immunologists named interleukins sequentially as they were discovered
...
IL-2 signals a Cytotoxic T Lymphocyte to start cloning
...
IL-4 signals a B cell to differentiate into plasma cell (not sure what book is
saying)
...
IL-12 signals a Helper T cell to differentiate into a Th1 cell
...
Interferons (IFNs) are proteins which inhibit the spread of viral infections (as
discussed in Chapter 15), and may also act as cytokines
...

d
...
The body can
control the progression of an adaptive immune response by limiting the production
of growth factors
...
Tumor necrosis factor (TNF) are macrophages secreted by T cells to kill tumor cells
and to regulate immune responses and inflammation
...
Chemokines are chemotactic cytokines
...

Preparation for an Adaptive Immune Response

1
...

a
...

b
...
They go around and bind to
epitopes to aid T-cells in recognizing epitopes
...

i
...

c
...

d
...

2
...
g
...

a
...

b
...

c
...
Contrast endogenous antigen processing with exogenous antigen processing
...
Endogenous antigen processing
i
...

ii
...

iii
...

iv
...

v
...

b
...
Only antigen-presenting cells (APCs), usually dendritic cells, process
exogenous antigens
...
First, a dendritic cell phagocytizes an invading pathogen and catabolizes the
pathogen’s molecules, producing peptide epitopes
...
Another vesicle, already containing MHC class II molecules in its membrane,
fuses with the phagolysosome
...
MHC II molecules bind complementary epitopes
...
The vesicle then fuses with the cytoplasmic membrane, leaving MHC II–
epitope complexes on the cell’s surface
...
Any empty MHC II molecules are not stable on a cell’s surface so
they degrade
...
Describe a cell-mediated immune response
...
The body uses cell-mediated immune responses primarily to fight intracellular
pathogens and abnormal body cells
...
The body induces cell-mediated immune responses only against specific
endogenous antigens
...
Compare and contrast the two pathways of cytotoxic T cell action
...
The Perforin-Granzyme Cytotoxic Pathway
i
...

ii
...

iii
...

iv
...

b
...
This pathway involves an integral glycoprotein called CD95 that is present in
the membranes of many body cells
...
Activated Tc cells insert the CD95L receptor into CD95
...
This then activates enzymes in the infected cell that trigger apoptosis, killing
the target cells
...
This pathway does not involve the travel of enzymes from Tc cells
...
Describe the establishment of memory T cells
...
Some activated T cells become memory T cells, which may persist for months or
years in lymphoid tissues
...
If a memory T cell subsequently contacts an epitope–MHC I protein complex
matching its TCR, it responds immediately and produces cytotoxic T cell clones that
recognize the offending epitope
...
These cells need fewer regulatory signals and become functional immediately and
effectively
...
An enhanced cell-mediated immune response upon subsequent exposure to the
same antigen is called a memory response
...
Contrast T-dependent and T-independent antigens in terms of size and repetition of subunits
...
T-independent antigens have many identical, repeating epitopes
...
These antigens can induce an antibody immune response without a helper T
cell
...
T-dependent antigens lack the numerous, repetitive, and identical epitopes and the
large size of T-independent antigens
...
This type of response requires assistance from helper T cells
...
Describe the steps and effect of clonal selection
...
Antigen presentation for Th activation and cloning
i
...

ii
...

iii
...

iv
...
This induces the Th cell to
produce a clone
...
Differentiation of helper T cells into Th2 cells
i
...

c
...
The repertoire of B cells and newly formed Th2 cells survey one another
...

3
...

a
...
The first secrete antibodies with binding sites identical to one another
...
However, as the plasma cell clones replicate, the cells slightly modify their
antigen-binding-site genes in hopes their antibodies have a slightly better fit
into the epitope
...
Plasma cells are usually short lived due to high metabolism
...
A small percentage of the cells produced during B cell cloning do not secrete
antibodies but survive as memory B cells, that is, long-lived cells with BCRs
complementary to the specific epitope that once triggered their production
...
In contrast to plasma cells, memory cells retain their BCRs and surviving for
more than 20 years, ready to initiate antibody production if the same
epitope is encountered again
...
Contrast the primary and secondary immune response
...
Primary response is the first response to an antigen, which is slow to develop and of
limited effectiveness
...
Secondary immune response is when an antigen is encountered for a second time
activating memory cells producing a rapid and strong immune response
...
Contrast active vs
...
artificially acquired
immunity
...
Artificial acquired passive immunity
i
...

1
...

b
...
Achieved by deliberately injecting someone with antigens in vaccine to
provoke and active response, this is the process of immunization such as
giving hepatitis B virus vaccine or smallpox or polio vaccine/oral form
...
Naturally acquired active immunity
i
...

1
...

d
...
The passing of maternal IgG to the fetus and the transmission of secretory
IgA in milk to a baby
...
IgG transferred across the placenta or
IgA transferred through the breast milk to the Newborn
This is simply a review
...
This is not new information
...

 The “stage” is the tissues and organs of the lymphatic system
 “Cast of characters”
o Antigens with their epitopes are the “villains
...

 The dialogue consists of cytokines
...

o Bad actors are those T cells and B cells that recognize autoantigens and have been
eliminated
Title: Microbiology Chapter 16
Description: Grand Valley State University, BMS 212 class notes. These notes follow the book: Microbiology with Diseases by Taxonomy, 4th Edition Author - Robert W. Bauman Ph.D.