Immune Response and Immunity

Envr 133
Mark D. Sobsey
 Antigens
Any foreign substance that elicits an immune
response when introduced into the tissues of a
susceptible animal and capable of combining
with the specific antibodies formed.
Generally high molecular weight
Typically, proteins or polysaccharides.
Polypeptides, lipids, nucleic acids and many
other materials also can also function as
antigens
Microbes are antigenic and they contain and
produce many antigens
Antigens have specific sites that bind to antibodies
called epitopes
 Immunity and Immune Response

Made up of two cellular systems:

Humoral or circulating antibody
system
B cells
Cell mediated immunity
T cells
 Immunity and Immune Response

Immune system identifies antigens

(foreign proteins or polysaccharides)
Components of microbes or their partially
degraded byproducts and
Other foreign proteins and polysaccharides
(including nucleic acids)
Host (human or animal) antigens not made
by the individual are also antigens
Result: in graft, transplant rejection
 The Immune System
Human immune system begins to develop in the embryo.
Starts with hematopoietic (from Greek, "blood-making")
stem cells.
Stem cells differentiate into major cells in the immune
system
granulocytes, monocytes, and lymphocytes
Stems cells also differentiate into cells in the blood that are
not involved in immune function, such as erythrocytes (red
blood cells) and megakaryocytes (for blood clotting).
Stem cells continue to be produced and differentiate
throughout ones lifetime.
Components of Human Immune System
The Immune System
Immunity and the Immune Response System
Immunity and the Immune Response System
Clonal Selection of B Cells is Due to Antigenic Stimulation
Classes of Antibodies (Immunoghlobulins)
Humoral Immune Response to Antigen
 Humoral Immune Response to Antigen
First exposure to antigen "A:
begin to make low levels of antibody in about a week
Second exposure to antigen "A:
produces a much faster response, and
several orders of magnitude higher levels of antibody.
Ability of antibody to bind antigen also increases
dramatically in the secondary response.
Injecting a new antigen "B with "A"
Elicits only a primary response
Shows that a memory or prior exposure is required for
the accelerated response.
Humoral or B-Cell Mediated Immune Response
Produces secreted antibodies (proteins)
Bind to antigens and identify the antigen complex
for destruction.
Antibodies act on antigens in the serum and
lymph
B-cell produced antibodies may be
attached to B-cell membranes or
Free in the serum and lymph.
Each B lymphocyte makes a unique antibody
molecule (immunoglobulin or Ig)
Over a million different B lymphocytes are
produced in each individual
So, each individual can recognize more than a
million different antigens
Immuoglobulin G (IgG)
Immunoglobulin and Reaction with Antigen

IgG antibody molecule

Composed of 2 copies of 2 different proteins
Two copies of a heavy chain
>400 amino acids long
Two copies of a light chain -
>200 amino acids long
each IgG antibody molecule can bind 2
antigens at one time
A single antibody molecule can bind to 2 antigens
(e.g., viruses, bacateria or other particle), which
leads to clumping
Effect of Antigen Size on Humoral Immunity
 Fate of Antigen-Antibody Complexes
Ag-Ab complexes engulfed into the B-cell and partially
digested
Antigen is displayed on the B-cell surface by a special
receptor protein (MHC II) fo recognition by helper T-cells
B-cell is activated by the helper T-cell to divide and
produce secreted antibodies
Abs circulate in the serum and lymph
Some B-cells become memory cells to produce antibody at
a low rate for a long time (long term immunity)
They respond quickly when the antigen is encountered
again
the response is regulated by a class of T-cells called
suppressor T-cells
 Cell-Mediated Immunity and T Cells
T cell receptors are cell surface receptors that
bind nonself substances on the surface of other
cells
Major histocompatibility complex (MHC)
proteins protrude from the surfaces of most
cells in mammals
They help to distinguish self from nonself
They coordinate interactions among lymphocytes
and macrophages
Cytokines are soluble signal proteins released
by T cells
They bind and alter the behavior of their target cells
 Cell Mediated Immune System: T lymphocytes
T-cells mature in the thymus (thus the name T-cell)
Act on antigens appearing on the surface of individual
cells.
Over a million different kinds of T-cells
Each produces a different receptor in the cell membrane
Each receptor is composed of 1 molecule each of two
different proteins
Each receptor binds a specific antigen but has only one
binding site
Receptor only recognizes antigens which are "presented"
to it within another membrane protein of the MHC type
(major histocompatibility complex)
Recognizes specific antigens bound to the antigen-
presenting structures on the surface of the presenting cell.
Recognizes antigens presented by B-cells, macrophages,
or any other cell type
 T Cells and their Functions
Have a specific receptor for a fragment of antigen
Cytotoxic T-cells:
Contain a surface protein called CD8
Destroy pathogen infected cells, cancer cells, and
foreign cells (transplanted organs)
Helper T-cells:
Contain a surface protein called CD4
Regulate both cellular and humoral immune systems
This regulation reduces autoimmunity.
 Autoimmune disease

Self immunity
Some examples:
rheumatic fever
rheumatoid arthritis
ulcerative colitis
myasthenia gravis
Lyme disease (microbial etiology)
Guillan-Barre syndrome (microbial etiology)
Reiters syndrome or reactive arthritis (microbial etiology)
Insulin dependent diabetes mellitus (IDDM) (microbial etiology?)
Interactions of the Components of The
Immune Response
T-cells, B-cells, and macrophages use MHC-II
receptors for presentation;
All other cells use MCH-I
(responsible for most of tissue graft rejection)
When a T-cell is presented with an antigen:
its receptor binds to the antigen and
it is stimulated to divide and produce helper T-cells
activate B-cells with bound antigen
suppressor T-cells
regulate the overall response
Cytotoxic "killer" T-cells
kill cells with antigen bound in MHC-I
 Role of Immunity in Infections
Localized Infections:
Immunity to infection is usually short-term and transient
Mucosal (secretory or IgA) immunity in the gut or
respiratory tract wanes over time
Proof of concept: live, oral rotavirus vaccine:
immunity declines over time and reinfection with wild
type rotaviruses occurs
Repeated localized (e.g., gastrointestinal) re-infection is
possible. Examples:
Viruses: rotaviruses, noroviruses, adenoviruses and some
enteroviruses.
Salmonella spp, Shigella spp., Campylobacter spp, and E. coli spp.
cause localized infections
Giardia lamblia and Cryptosporidium parvum
 Role of Immunity in Infections:
Generalized/Systemic/Disseminated Infections
Immunity against generalized/systemic/disseminated
infection is usually lifelong, unless immune system is
severely compromised
Localized (e.g., gastrointestinal) re-infection is possible
Hepatitis A and E and many enteroviruses are viruses
causing systemic/generalized/disseminated infections
Salmonella typhi is a bacterium causing systemic infection
Typically, immunity against severe illness is long-term and
probably lifelong
Proof of concept: live, oral poliovirus vaccine and poliomyelitis
eradication; susceptibles are newborns and infants
Antigenic changes in microbes may overcome long-term
immunity and increase risks of re-infection or illness
Role of Selection of New Microbial Strains in
Susceptibility to Infection and Illness
Antigenic changes in microbes overcome immunity,
increasing risks of re-infection or illness
Antigenically different strains of microbes appear and are
selected for over time and space
Constant selection of new strains (by antigenic shift and drift)
Partly driven by herd immunity and genetic recombination,
reassortment , bacterial conjugation, bacteriophage infection
and point mutations
Antigenic Shift:
Major change in virus genetic composition by gene substitution
or replacement (e.g., reassortment)
Antigenic Drift:
Minor changes in virus genetic composition, often by mutation
involving specific codons in existing genes (point mutations)
A single point mutation can greatly alter microbial
virulence