Adaptive Immunity

Chapter 24.1-24.3, 24.5-6

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 Chapter Overview
! Overview of adaptive immunity
! Antibody structure, diversity, and
synthesis
! Cytotoxic T-cells kill infected cells
! Complement as part of adaptive immunity
! Gut mucosal immunity and the
microbiome
! Immunization
! Hypersensitivity and autoimmunity
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 Introduction
! Our immune system’s memory relies on special
lymphocytes in the circulation called memory B cells
and T cells.
- These form during an infection and “remember” it
for years.
- Armed with this “knowledge,” the lymphocytes
circulate throughout the body like tiny sentries, ready
to detect and quickly respond to a second attack.

! From birth, the immune system is able to adapt and

recognize billions of possible foreign antigens.

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 24.1 Overview of Adaptive Immunity
! The immune system has both nonadaptive and adaptive mechanisms.
- Nonadaptive (innate) immune mechanisms are present from birth.
- Adaptive immunity develops as the need arises.

! Two types of adaptive immunity are recognized:

1. Humoral immunity

- Mediated by B cells (B lymphocytes)

- Produce antibodies that directly target antigens of invaders

2. Cell-mediated immunity

- Involves T cells (T lymphocytes)

- Control antibody production and can directly kill infected host cells
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Antibody-Dependent versus Cell-
Mediated Immunity – 1
! What triggers an immune response, and how long
does it take?
- Adaptive immunity develops over a 3- to 4-day
period after exposure to an invading microbe.
- The immune system does not recognize the
whole microbe, but innumerable tiny pieces of
it.
- Each small segment of an antigen that
elicits an immune response is called an
epitope or an antigenic determinant.

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Antibody-Dependent versus Cell-
Mediated Immunity – 2

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 Antibody-Dependent versus Cell-
Mediated Immunity – 3
! The immune response to a microbe is really a composite of
thousands of B-cell responses to different epitopes.

- The response to each individual epitope is clonal.

- It gives rise to a population of cells that originate

from a single B cell.

- Thus, each clone of B cells will target a unique

epitope.

! The humoral immune response requires several cell types

and cell-to-cell interactions.
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Cell-Cell Interactions Involved in
Making Antibody

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 Immunogenicity
! Immunogenicity measures the
effectiveness by which an antigen elicits an
immune response.
! Proteins are the most effective antigens.
- Form more diverse chemical forms and
maintain their tertiary structures
! Antigen-presenting cells
- Degrade pathogen proteins
- Attach antigens to major histocompatibility
complex (MHC) for presentation
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 Immunological Specificity – 1
! Immunological specificity means that an
antibody made to one epitope will not bind to
other epitopes.
- However, cross-binding to similar epitopes can
happen.
- For example, the antibody to the cowpox virus will
bind to a similar epitope on the smallpox virus.
- This technique is used in vaccination.
! Most vaccinations today involve administering
crippled (live, attenuated) strains of the
pathogenic microbe or inactivated microbial
toxins.

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 Immunological Specificity – 2

Smallpox and coxpox look alike at the

microscopic level.

More importantly, at the protein level,

the two viruses are similar enough in
structure that an antibody raised
against one can recognize the other.

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Immunological Specificity – 3

Disease Vaccine Vaccination recommended for:

Chickenpox Attenuated strain (will still replicate) Children 12 to 18 months
Hepatitis A Inactivated virus (will not replicate) Children 12 months
Hepatitis B Viral antigen Newborns
Influenza Inactivated virus or antigen Everyone, after 6 months old, yearly
Measles, mumps, Attenuated viruses: MMR combined Children 12 months
rubella (MMR) vaccine
Polio Inactivated (injection, Salk) Children 2 to 3 months
Rabies Inactivated virus Persons in contact with wild animals
Yellow fever Attenuated virus Military personnel

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 Immunological Specificity – 4
Disease Vaccine Vaccination recommended for:
Anthrax Bacillus anthracis, toxin components; Agricultural and veterinary
unencapsulated strain personnel; key health care workers
Cholera Killed Vibrio cholerae, toxin components Travelers to endemic areas
Diphtheria Toxoid (inactivated toxin) Children 2 to 3 months
Lyme disease Borrelia burgdorferi, lipoproteins OspA Canines; human vaccine
and OspC surface antigens discontinued
Meningitis caused by Haemophilus Bacterial capsular polysaccharide Children under 5 years
influenza type b (Hib)
Meningococcal disease Neisseria meningitides, bacterial capsular Children greater than 2 years;
polysaccharides adults greater than 50 years
Pertussis Acellular Bordetella pertussis Children 2 to 3 months
Pneumococcal pneumonia Streptococcus pneumoniae, bacterial Children; adults greater than 50
capsular polysaccharides years
Tetanus Toxoid Children 2 to 3 months
Tuberculosis (Mycobacterium Attenuated Mycobacterium bovis [BCG Exposed individuals
tuberculosis) (Calmette-Guerin) vaccine]
Typhoid fever Killed Salmonella Typhi Individuals in endemic areas
Typhus Killed Rickettsia prowazekii Medical personnel in endemic areas;
scientists; discontinued

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 Immunological Specificity – 5
! Cross-protection will work only if two proteins critical to
the pathogenesis of the two different microorganisms
share key antigenic determinants.
- No cross-protection occurs if these determinants differ
significantly.

- Infection with one strain of rhinovirus will not immunize the victim
against a second strain.

- Sequence differences between strains of rhinovirus are larger

than sequence differences between smallpox and cowpox.

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 Immunological Specificity – 6
! How do neutralizing antibodies work?
! Block a key step in the viral life cycle, usually viral entry.

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 24.2 Antibody Structure,
Diversity, and Synthesis
! Antibodies, also called immunoglobulins, are
members of the larger immunoglobulin
superfamily of proteins.
- Made by the body in response to an antigen,
antibodies are the keys to immunological specificity.
! Antibody immunoglobulins individually circulate
through blood, ignoring all antigens except those
for which they were designed.

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 Antibody Structure – 1
! An antibody is a Y-shaped structure made
up of four polypeptides:
- Two large heavy chains and two smaller light
chains, connected by disulfide bonds

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 Antibodies Have Constant and
Variable Regions
! An antibody has:
- Constant regions: highly conserved amino acids
- Denoted CH and CL, for heavy and light chains
- Variable regions: highly different amino acids
- Denoted VH and VL, for heavy and light chains, respectively
- Form the antigen-binding site

! Functional parts of the antibody can be separated following

certain protease treatments.

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 Constant and Variable
Regions in Antibody Structure

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 Classes of Antibodies
! Heavy chains and light chains come in different
types, which differ in their own constant regions.
- There are five different types of heavy chains:
- Alpha (α), mu (μ), gamma (γ), delta (δ), and epsilon
(ε)
- But only two types of light chains:
- Kappa (κ) and lambda (λ)
! There are five classes of antibodies, which are
defined by the type of heavy chain they possess:
- IgG, IgM, IgA, IgD, and IgE

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 Primary and Secondary
Antibody Responses – 1
! Primary antibody response
- Via disease or vaccination
- Antibodies appear in serum after several days.
- B cells that bind antigen make antibodies.
- IgM, then IgG (isotype switching)
- Some B cells become memory cells.
! Secondary antibody response
- Via a second exposure to pathogen or booster
dose
- Antibodies appear in blood within hours.
- A much bigger response, with mostly IgG

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Primary and Secondary
Antibody Responses – 2

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 B Cells Differentiate into Plasma
Cells by Clonal Selection
! Each B cell circulating throughout the body or ensconced
in a lymphoid organ is programmed to synthesize an
antibody that reacts with a single epitope.
! In a process called clonal selection, an invading antigen
will inadvertently select which B-cell clone will proliferate to
large numbers.
- When a B cell contacts its cognate antigen, it is
stimulated to proliferate and differentiate into plasma
cells (which secrete antibodies) and memory cells.

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Clonal Selection

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Steps in Antibody Formation

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 Concept Check 24.1
! The _______ is the part of an antigen that
is capable of eliciting an immune response.
a) antibody
b) variable region
c) light chain
d) B cell
e) epitope

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 Concept Check 24.2 – 2
! In immunology, the term “clonal selection” best refers to
a) multiple types of cells needed to generate an antigenic-
specific response.
b) ability of one B cell to produce multiple isotypes of
antibodies.
c) ability of specific lymphocyte subsets to proliferate upon
exposure to a specific epitope.
d) ability of memory cells to induce a quick secondary
antibody response.
e) process of opsonizing antigen for rapid phagocytic
degradation.

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 24.3 T Cells Link Antibody and
Cellular Immune Systems
! T cells develop in the thymus and contain surface
antigens different from those of B cells.
! They can be divided into two broad groups:
̵ 1. Helper T cells (TH cells)
- We will not discuss
̵ 2. Cytotoxic T cells (TC cells)
- Display the surface antigen CD8
- Destroy bacteria and infected host cells

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 The Major Histocompatibility
Complex – 1
! Consists of membrane proteins with variable regions that
can bind antigens

! MHC proteins differ between species and among

individuals within a species.

- They help determine whether a given antigen is

recognized as self or nonself (foreign).

! Two classes are found on cell surfaces

- Class I MHC: found on all nucleated cells

- Class II MHC: found only on antigen-presenting cells

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The Major Histocompatibility
Complex – 2

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 The Major Histocompatibility
Complex – 3
! MHC class I presents intracellular antigens:
- Microbial proteins made in the host cytoplasm are
degraded.
- Peptides are imported into the ER and loaded onto
MHC class I molecules.
! MHC class II presents extracellular antigens:
- Microbial proteins made outside the cell are
endocytosed in an endosome.
- They are then degraded and placed on MHC class II
molecules.

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Processing and Presentation of
Antigens by APCs – 1

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 T-Cell Receptors
! T-cell receptors
(TCRs) are the antigen-
binding molecules
present on the surfaces
of T cells.
! TCRs associate with
CD3 proteins on cell
surface.
- Bind antigens only if
attached to MHC
- Complex transduces
signal into cell, triggering
T-cell proliferation.

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Processing and Presentation of
Antigens by APCs – 2

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 24.6 Immunization – 1
! The adaptive immune response is why
vaccines work.
! Vaccines come in three basic types:
- Killed organisms (hepatitis A vaccine)
- Live, but attenuated, microbes (BCG vaccine for
tuberculosis)
- Purified subunits of an infectious agent (such as
capsular antigens from Streptococcus
pneumoniae and Haemophilus influenzae type b)

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 Recommended Immunization
Schedule for Children and Adolescents
Vaccine Birth 1 2 4 6 9 123months 153to3183 243months 43to363years 113to3123years
month months months months months months
Hepatitis Bb Hep3B Hep3B Hep3B none Hep3B Hep3B Hep3B Hep B Hep B3 Hep B3 Hep B3series:3
series:3 series:3 Catch<up3
Catch<up3 Catch<up3 immunization
immunizati immunizatio
on n
Rotavirus none none Rota Rota Rota none none none none none none
Diphtheria,3 none none D3TaP D3TaP D3TaP none none D3TaP none D3TaP T3dap
tetanus,3
acellular3
pertussisc
Haemophilus, none none Hib Hib Hib none Hib Hib none none none
influenzae,
type3bd
Inactivated3 none none IPV IPV IPV IPV IPV IPV none IPV none
poliovirus
Measles,3 none none none none none none MMR MMR none MMR MMR:3Catch<
mumps,3 up3
rubella immunization
Varicella none none none none none none Varicella Varicella none Varicella none
Meningococc none none none none none none Administer3 Administe Administer3 Administer3 MCV43
al0 to3high<risk3 r3to3high< to3high<risk3 to3high<risk3 Assessment3at3
children risk3 children children age311–123
children years
Pneumococca none none PCV13 PCV13 PCV13 none PCV13 PCV13 PPSV23:3 PPSV23:3 none
l1 Catch<up3 Catch<up3
immunizati immunizatio
on n
Influenza8 none none none none Influenza Influenza Influenza Influenza Influenza Influenza Influenza
(yearly) (yearly) (yearly) (yearly) (yearly) (yearly) (yearly)
Hepatitis3Ah none none none none none none Hep,A,series Hep,A, Hep,A, Hep,A:3 Hep,A,
series series Catch<up3
immunizatio
n
Human none none none none none none none none none none HPV
papillomaviru
s'

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 Herd Immunity
! For infections spread by person-to-person
contact, the risk of disease to an unvaccinated
person can be lowered dramatically even when
only about
two-thirds of the community are vaccinated.
! Vaccinating a large percentage of a community
effectively conveys community (or herd) immunity
by interrupting transmission of the disease.
! However, herd immunity will not lower the risk
that an unvaccinated person will contract tetanus,
which is not spread by person-to-person contact.
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 Herd Immunity Simple Animation

https://www.reddit.com/r/dataisbeautiful/comments/5v72fw/how_herd_immunity_works_oc/ 40
 Herd Immunity Complex Animation

https://www.youtube.com/watch?v=rAGHXMq9ttw 41
 Chapter Summary – 1
! Adaptive immunity is of two types:
- Humoral immunity: mediated by antibody-producing B
cells
- Cell-mediated immunity: involves T cells
! Antigens are molecules that elicit antibody response.
- May contain a number of epitopes
! An antibody is a Y-shaped molecule that has two heavy
and two light chains, each of which has constant and
variable regions.
! The five antibody classes are IgG, IgM, IgA, IgD, and IgE.

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 Chapter Summary – 2
! The secondary antibody response to an antigen is faster, larger, and
longer than the primary response.
- Because of the presence of memory cells
! B cells differentiate into plasma cells by clonal selection.
! T cells link antibody and cellular immune systems.
! Cytotoxic T cells kill cancerous and infected cells
! MHC class I and class II proteins are critical to immune system.
! Vaccines can be made from live, attenuated organisms; killed
organisms; or purified microbe components.

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 Concept Check 24.3 – 1
! Which of the following statements about
MHC class II molecules is true?
a) They are found on all nucleated cells.
b) They present extracellular antigens.
c) Both A and B
d) Neither A nor B

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 Concept Check 24.3 – 2
! Which of the following cells produce
perforins and granzymes?
a) Memory B cells
b) Plasma B cells
c) Cytotoxic T cells
d) Helper T cells
e) Antigen-presenting cells

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 Concept Check 24.6
! Which of the following can be used to make
vaccines?
a) Live, attenuated microorganisms
b) Killed microorganisms
c) Purified components of microorganisms
d) Two of the above
e) All of the above

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