Immunity

Immune System
Role of lymphocytes
 Immune System
• Resistance of the body against infections
• Immunology is the study of the physiological defenses
by which the body (the host) recognizes itself from
nonself (foreign matter).
• →Foreign matter, both living and nonliving, is destroyed
or rendered harmless.
 Immune System
• Protect against infection by pathogens —viruses, and
microbes including bacteria, fungi, and eukaryotic parasites
• Isolate or remove foreign substances
• Destroy cancer cells that arise in the body (immune
surveillance)

Consists of a diverse collection of cells found in the blood and

lymph and in tissues and organs throughout the body.
 Immunity Classified into Two Categories

Effective Immediately Improves

Type of Has
Specificity After Exposure to After
Immunity Memory
Microbe Exposure
Innate Nonspecific Yes—acts within No No
minutes
Adaptive Highly specific No—requires several Yes Yes
days before becoming
effective
 Cytokines
• Collective term for the protein messengers secreted by the cells of the immune
system

• Cytokines link the components of the immune system together.

• The chemical communication network that allows different immune system cells
to “talk” to one another
E.g.:
• I n t e r l e u k i n s (ILs)
• Interferons ( I F N s )
• Colony s t i m u l a t i n g factors ( C S F s )
• Tumor necrosis factors, T N F α a n d T N F β ,
• Chemokines
 Innate Immunity
• Inherent in all individuals
• Non-specific
• Innate immune responses include
• Defenses at the body surfaces
• Response to injury or infection known as inflammation
• Immune Cells
• Family of antiviral proteins called interferons.
Innate immunity:
Defenses at Body
Surfaces
• Though not immune
responses
• First lines of defense against
pathogens are the barriers
offered by surfaces exposed
to the external environment
Innate immunity: Defenses at Body Surfaces

• Intact Skin acts as barrier to microbes and viruses

• GIT
• HCl kills ingested bacteria,
• Bacterial flora prevents growth of pathogenic organisms
• Ciliated epithelium in Respiratory tract
• Mucus traps foreign particles
• Reflex mechanisms like sneezing, coughing & Vomiting
Innate immunity: Defenses at Body Surfaces

• The various skin glands, salivary glands, and lacrimal (tear)

glands secrete antimicrobial chemicals. E.g.:
• Lysozyme(destroys bacterial cell walls)
• Lactoferrin
Innate Immunity: Inflammation
• Inflammation is the local response to infection or injury.
• Functions of inflammation
• To destroy or inactivate foreign invaders
• To set the stage for tissue repair

• Can be elicited by other injuries—cold, heat, and trauma.

• Also seen in adaptive immune responses
Innate Immunity: Inflammation
• Key mediators : Cells that function as phagocytes.
• Chemical mediators(Histamine , Chemokines)
Innate Immunity: Inflammation
• Signs & symptoms:
• Pain (dolor)
• Local Swelling (tumor)
• Reddish (rubor)
• Warm (calor)
• Loss of normal function
Innate Immunity
• W B C and Macrophages – phagocytosis
• Natural killer lymphocytes
• The complement complex
• Interferon
 Interferons
• Two families called type I and type II interferons.
• The type I interferons
• several proteins that nonspecifically inhibit viral
replication inside host cells.
• also play a role in the killing of tumor cells
• role in generating fever during an infection
Interferons
Complement system
• A group of sequentially reacting plasma proteins.
• >30
• “complemented” the effect of Antibodies
Complement activation pathways
Membrane Attack Complex
Functions of complement
Acquired or Adaptive immunity

• Selective

• Specific

• Delayed

• Forms : Antibodies and/or activated lymphocytes

Origin of Thymic (T) and Bursal (B) lymphocytes
 Acquired or Adaptive immunity
Two types of acquired immunity
• 1. Cell-mediated immunity or T-cell immunity
• 2. Humoral immunity or B-cell immunity

• Both types of acquired immunity are initiated by

antigens
 Antigen (Immunogen)
An antigen is a substance that can evoke an immune response
when introduced into an immunocompetent host and react with
the antibody produced from that immune response.

E.g. : protein coats of viruses, specific proteins on foreign cells,

transplanted cells, and toxins

Ability of lymphocytes to distinguish one antigen from another

confers specificity upon the immune responses
 Acquired immunity

• Key to acquired immunity is the ability of

lymphocytes to

• Produce Antibodies (in the case of B cells) or

• Cell-surface receptors (in the case of T cells)

• That are specific towards a particular Antigen

 Acquired immunity
• T-lymphocytes
• Helper cells, Cytotoxic cells, Suppressor cells, Memory cells
• B-lymphocytes
• Plasma Cells, Antibodies, Memory Cells
• Antigen-presenting cells
• Non-specific cells – Activated Macrophages, Natural Killer
cells
• Complement system
• Cytokines
 B-Lymphocytes
• Mediate humoral immunity

• Derived from pluripotent hemopoietic stem cells

• Preprocessed in bone marrow – B-Cells (Bursa of Fabricius)

• Activated by antigens
 B-Lymphocytes

In response to antigenic stimulation:

• → differentiate into large secretory Plasma cells →

synthesize and secrete Antibodies

• B cells present antigen to helper T cells

B-Lymphocytes
 Antibodies
• Immunoglobulins
• Gamma globulins
• Proteins that recognize and bind to a particular antigen with
high specificity
• Formed as a response to exposure to the antigen
• One pathogen may have several antigenic determinant sites,
to which different antibodies may bind
Immunoglobulin
structure

Each antibody has at

least two identical
sites that bind antigen
 Immunoglobulins (Ig)

There are five major classes of immunoglobulins,

determined by the amino acid sequences in the heavy
chains and a portion of the light chains.
 Immunoglobulins (Ig)
Immunoglobulin Function
IgG (most abundant)
Complement activation; Cross Placenta
IgA Localized protection in external secretions
(breast milk, tears, intestinal secretions,
etc)
IgM (abundant during primary response)
Complement activation
IgD Antigen recognition by B cells
IgE releases histamine from basophils and
mast cells
 Immunoglobulins

B-cell receptors and plasma cell antibodies constitute

the family of proteins known as immunoglobulins.
 B-cell receptors
• Each B cell always displays on its plasma membrane, copies of the
particular antibody its plasma cell progeny can produce.
• This surface protein (glycoprotein) acts as the receptor for the
antigen specific to it.
• The receptors themselves, even though they are identical to the
antibodies to be secreted by the plasma cell derived from the
activated B cell, are technically not antibodies because only
secreted immunoglobulins are called antibodies
 B-cell receptors
B-cell receptors can bind antigen whether the antigen is
a molecule dissolved in the extracellular fluid or is
present on the surface of a foreign cell.
 B-cell receptors
• Any given B cell or clone of identical B cells possesses
unique immunoglobulin receptors—that is, receptors
with unique antigen-binding sites.
Mechanisms on
Antibody Action
• Precipitation of soluble
antigens
• Agglutination of foreign cells
• Neutralization
• Opsonization
• Enhanced phagocytosis
• Complement activation
leading to cell lysis
Direct enhancement of phagocytosis by antibody.
The antibody links the phagocyte to the bacterium
Activation of classical complement pathway by binding of antibody to bacterial antigen.
C1 is activated by its binding to the Fc portion of the antibody.
The membrane attack complex (MAC) is then generated, along with C3b, which acts as
an opsonin by binding the bacteria to a phagocyte
 T- Lymphocytes

• Cell-mediated immunity
• Derived from pluripotent hematopoietic stem cells
• Precursors of T-cells migrate to Thymus gland
• Preprocessed in the thymus – hence termed T-cells
• Defense against: - Bacteria & viruses that are inside host
cells & are inaccessible to antibodies.
 T-Cell Receptors

• T-cell receptors for antigens are two chained proteins that,

like immunoglobulins, have variable regions that differ from
one T-cell clone to another.

• T-cell receptors remain embedded in the T-cell membrane

and are not secreted like antibodies.
 T-Cell Receptors

The T-cell receptor cannot combine with antigen unless the

antigen is first complexed with certain of the body’s own
plasma membrane proteins.

The T-cell receptor then combines with the entire complex of

antigen and body (self) protein
 T-Cell Receptors

The self plasma membrane proteins that must be

complexed with the antigen in order for T-cell
recognition to occur are known collectively as the
major histocompatibility complex (MHC).
Major histocompatibility complex (MHC)

• The major histocompatibility complex (MHC) is a region of

DNA that encodes a group of molecules that recognize
antigen.

• The human MHC, found on human chromosome 6, is known

as human leukocyte antigen (HLA).
Major histocompatibility complex (MHC)

• MHC molecules are membrane proteins on APCs that display

peptide antigens for recognition by T lymphocytes

• Class I molecules are expressed on all nucleated cells

• Class II molecules are expressed mainly on dendritic cells,
macrophages, and B lymphocytes.
 T Helper Cells

• Recognize antigen on the surface of Antigen Presenting Cells

• Induce formation of cytotoxic T cells
• Stimulate B cells to produce antibodies.
• Activate macrophages
• Cytokines secreted by Helper T cells also act as inflammatory
mediators.
Antigen Presentation to T Cells

Presentation to Helper T Cells (CD4)

• Helper T cells require class II MHC proteins to function.

• Only macrophages, B cells, and dendritic cells express class II
MHC proteins and therefore can function as APCs for helper
T cells.
Sequence of events by which
antigen is processed and
presented to a helper T cell by
a macrophage
Sequence of events by which antigen
is processed and presented to a
helper T cell by a B cell
Activation of
helper T cells
• Requirements:
• Presentation of the antigen bound to a class
II MHC protein on an antigen-presenting cell
(APC);
• Costimulus : binding of matching
nonantigenic proteins in the plasma
membranes of the APC and the helper
T cell
• Secretion by the APC of the cytokines
interleukin 1 (IL-1), tumor necrosis factor-
alpha (tnf-α), and other cytokines, which act
on the helper T cell.
T Helper Cells
 Cytotoxic T Cells
• Recognize antigens on the surface of all cells:
• Kill host cells that are infected with viruses or bacteria.
• Recognize and kill : cancer cells & transplanted tissue.
• Release protein called perforin which forms a pore in target cell,
causing lysis of infected cells.
• Release granzymes (digestive enzymes) – granzymes enter through
perforin-formed pores - induce apoptosis in the infected cell
Presentation to Cytotoxic T Cells (CD8)

• Require class I MHC proteins to function.

• Class I MHC proteins are synthesized by virtually all
nucleated cells, any such cell can act as an APC for a
cytotoxic T cell.
Presentation to
Cytotoxic T Cells (CD8)
Cytotoxic T Cells
 Suppressor or Regulatory T cells

• Inhibit the function of both B cells and cytotoxic T cells.

• Believed to suppress the ability of certain B and cytotoxic T
cells to attack a person’s own proteins.
 NK (natural killer) cells
• Constitute a distinct class of lymphocytes.
• Have several functional similarities to those of cytotoxic T cells.
• Major targets are virus-infected cells and cancer cells
• They attack and kill these target cells directly after binding to them.
• NK cells are not antigen-specific; that is, each NK cell can attack
virus-infected cells or cancer cells without recognizing a specific
antigen.
Antibody-Mediated
Immune Responses:
Defences Against
Bacteria, Extracellular
Viruses, and Toxins
Defences Against Virus-
Infected Cells
and Cancer Cells
Antibody Response After Exposure to Antigen
Antibody Response After Exposure to Antigen

Primary Response:
• After initial exposure to antigen, no antibodies are found in
serum for several days.
• A gradual increase in, first of IgM and then of IgG is
observed.
• Some B cells become long living memory cells.
• Gradual decline of antibodies follows.
Antibody Response After Exposure to Antigen

Secondary Response:
• Subsequent exposure to the same antigen displays a rapid &
more powerful antibody response.
• Increased antibody response is due to the existence of
memory cells, which rapidly produce plasma cells upon
antigen stimulation.
 Induced Immunity
• Immunity may be induced in an individual by infection or
vaccination (active immunity) or conferred on an individual
by transfer of antibodies or lymphocytes from an actively
immunized individual (passive immunity).
 Passive immunity
• A naive individual receives antibodies from another
individual already immune to an infection.
• The recipient acquires the ability to combat the
infection for as long as the transferred antibodies or
cells last.
• Physiologic example : newborns acquiring antibodies
from their mothers through the placenta and breast
milk.
 Active Immunity.
• In active immunity, an individual is exposed to the antigens
of a microbe.
• Dependent upon the presence of memory B and T cells
capable of responding to lower antigen doses.
 Vaccination
• Based on the key elements of adaptive immunity : specificity
and memory.
• Memory cells allow the immune system to mount a much
stronger response on a second encounter with antigen.
Compared with the primary response, the secondary
response is:
• faster to appear
• more effective.
Vaccination

• The aim in vaccine development is to alter a pathogen or its

toxins in such a way that they become innocuous without
losing antigenicity. This is possible because antibodies and T
cells recognize particular parts of antigens (the epitopes),
and not the whole organism or toxin.
Immunopathology
Immunopathology
• Autoimmunity
• Inappropriate reaction to self antigens
• Example: rheumatoid arthritis or pernicious anemia.
• Immunodeficiency
• Ineffective immune response
• Example: Acquired immune deficiency syndrome (AIDS)
• Hypersensitivity
• Overactive immune response
• Sometimes immune reactions are out of all proportion to the damage that
may be caused by a pathogen. The immune system may also mount a reaction
to a harmless antigen, such as a food molecule. E.g hay fever or asthma.
 Acute phase proteins
• A wide variety of molecules are involved in the development of
immune responses, including antibodies, opsonins and complement
system molecules.
• The serum concentration of a number of these proteins increases
rapidly during infection and they are therefore called acute phase
proteins.

• Example : C reactive protein (CRP).

APOPTOSIS
• Programmed cell death
• Apoptosis is a very common process during development and in
adulthood
• E.g.: Apoptosis - removal of the webs between the fingers in fetal life
and regression of duct systems in the course of sexual development in
the fetus.