Immunology is the study of the immune system and is a very important branch of the medical and biological sciences. The immune system protects us from infection through

1. IMMUNE
RESPONSE
Lecture 7

2. Learning Objectives
 After reading and studying this chapter, you should be
able to:
 ♦ Differentiate between primary and secondary
humoral immune responses.
 ♦ Discuss monoclonal antibodies—principle, technique
and applications.
 ♦ Describe the following: Cytokines; immunological
tolerance.

3. Definition
• The immune response is the specific reactivity
induced in a host by an antigenic stimulus.
• For the generation of immune response,
antigen must interact with and activate a
number of different cells.
• In addition, these cells must interact with each
other.
• It is generally equated with protection against

4. Conti………
 But the immune response has a much wider
scope and includes reactions against any antigen,
living or nonliving.
 It may lead to consequences that are beneficial,
indifferent or injurious to the host.
 The state of specific nonreactivity (tolerance)
induced by certain types of antigenic stimuli is also
included in it.

5. Type of Immune Response
• The immune response can be divided into two
types— the humoral (antibody mediated) and the
cellular (cell mediated) types. The generation and
control of immune responses are a consequence of a
complex series of antigen-mediated interactions
between various cell types.
• The two are usually developed together, though at
times one or the other may be predominant or

6. Conti…….
 They usually act in conjunction but may sometimes act in
opposition.
 a. Antibody Mediated Immunity (AMI)
 1. Provides primary defense against most extracellular
bacterial pathogens
 2. Helps in defense against viruses that infect through the
respiratory or intestinal tracts
 3. Prevents recurrence of virus infections

7. Conti……..
 4. It also participates in the pathogenesis of immediate
(types 1, 2 and 3) hypersensitivity and certain
autoimmune diseases.
 b. Cell-Mediated Immunity (CMI)
 i. Protects against fungi, viruses and facultative
intracellular bacterial pathogens like Mycobacterium
tuberculosis, Mycobacterium leprae, Brucella and
Salmonella, and parasites like Leishmania and

8. Conti………
 ii. It also participates in the rejection of
homografts and graft-versus-host reaction.
 iii. It mediates the pathogenesis of delayed
(type 4) hypersensitivity and certain
autoimmune diseases.
 iv. It provides immunological surveillance and
immunity against cancer.

9. Humoral Immunity
• Synthesis of Antibody
• On exposure to antigen, antibody production
follows a characteristic pattern (Fig. 18.1). The
production of antibodies consists of three steps:
 1. Lag Phase
 A lag phase, the immediate stage following
antigenic stimulus during which no antibody is

10. Fig. 18.1: Primary immune response. An antigenic stimulus;
1. Latent period; 2. Log phase (rise in titer of serum
antibody);
3. Steady state of antibody titer; 4. Decline of antibody titer

11. Conti……
 This is the time taken for the interactions
described above to take place and antibody to
reach a level that can be measured.
 2. Log Phase
 A log phase in which there is steady rise in the
titer of antibodies. There is an exponential rise in
the antibody level or titer.

12. Conti…….
• 3. A Plateau or Steady State
 This log phase is followed by a plateau with a
constant level of antibody when there is equilibrium
between antibody synthesis and catabolism.
 4. The Phase of Decline
 The amount of antibody then declines due to the
clearing of antigen-antibody complexes and the

13. Conti………
 , i.e. the catabolism exceeds the production and the titer
falls (Fig 18.1).
 Primary and Secondary Responses
 The kinetics and other characteristics of the humoral
response differ considerably depending on whether the
humoral response results from activation of naive
lymphocytes (primary response) or memory
lymphocytes (secondary response).

14. Conti………
• The kinetics and other characteristics of the
humoral response differ considerably depending
on whether the humoral response results from
activation of naive lymphocytes (primary response)
or memory lymphocytes (secondary response).
• a. Primary Humoral Response
 The first contact of an exogenous antigen with an
individual generates a primary humoral response,

15. Conti……….
• characterized by the production of antibody-
secreting plasma cells and memory B cells.
• The kinetics of the primary response, as
measured by serum antibody level, depend on
the nature of the antigen, the route of antigen
administration, the presence or absence of
adjuvants, and the species or strain being
immunized.

16. Conti…….
• When first introduced, the antigen selects the cells
that can react with it. In all cases, however, a
primary response to antigen is characterized by a
lag phase, during which naive B cells undergo
clonal selection, subsequent clonal expansion,
and differentiation into memory cells or plasma
cells.
• The duration of the lag phase varies with the

17. Conti……
• During a primary humoral response, IgM is
secreted initially, often followed by a switch to
an increasing proportion of IgG.
• Depending on the persistence of the antigen, a
primary response can last for various periods,
from only a few days to several weeks.

18. Conti…….
• b. Secondary Humoral Response (Fig. 18.2)
• On subsequent exposure, the responding cells, i.e. memory
cells, are at a different level of activation and are present at
an increased frequency.
• Therefore, there is a shorter lag before antibody can be
detected: the main isotype is IgG.
• Activation of memory cells by antigen results in a secondary
antibody response that can be distinguished from the primary
response in several ways.

19. Conti……..
• The secondary response has a shorter lag
period, reaches a greater magnitude, lasts
longer and is also characterized by secretion
of antibody with a higher affinity for the
antigen, and isotypes other than IgM
predominate.
• The level of antibody produced is 10 or more
times greater than during the primary

20. Conti…….
• Priming dose and booster doses: A single
injection of an antigen helps more in sensitizing
or priming the immunocompetent cells
producing the particular antibody than in the
actual elaboration of high levels of antibody.
Only by subsequent injections of the antigen,
effective levels of antibody are usually induced.

21. Conti……..
• The first injection is known as the ‘priming’
dose and subsequent injections as ‘booster’
doses. With live vaccines, a single dose is
sufficient as multiplication of the organism in the
body provides a continuing antigenic stimulus
that acts as both the priming and booster dose.

22. Conti………
 Negative phase: If the same animal is subsequently
exposed to the same antigen already carrying the
specific antibody in circulation, a temporary fall in the
level of circulating antibody occurs due to the
combination of the antigen with the pre-existing
antibody.
 This is known as the ‘negative phase’. It is followed
by an increase in the titer of the antibody exceeding

23. Fig. 18.2: Effect of repeated antigenic stimulus. A, B, C antigenic stimuli; 1.
Primary immune response; 2. Secondary immune response; 3. Negative
phase; 4. High level of antibody following booster injection

24. Fate of Antigen in Tissues
• The manner in which an antigen is dealt within the
body depends on factors such as the physical
and chemical nature of the antigen, its dose
and route of entry, and whether the antigenic
stimulus is primary or secondary.
 Physical and chemical nature of the antigen:
Particulate antigens are removed from circulation
in two phases.

25. Conti……..
 The first is the nonimmune phase during which the
antigen is engulfed by the phagocytic cells, broken
down and eliminated.
 The phase of immune elimination begins with the
appearance of the specific antibody, during which
antigen-antibody complexes are formed and are
rapidly phagocytosed, resulting in an accelerated
disappearance of the antigen from circulation.

26. Conti…….
• Soluble antigens: Three phases can be recognized with
soluble antigens: Equilibration, metabolism and
immune elimination. The phase of equilibration
consists of diffusion of the antigen to the extravascular
spaces.
• During the metabolic phase, the level of the antigen falls
due to catabolic decay. During the phase of immune
elimination, there is rapid elimination of the antigen with
the formation of antigen-antibody complexes.

27. Conti………
• Such complexes can cause tissue damage and
may be responsible for ‘immune complex
diseases’ such as serum sickness.
 Route of entry: Antigens introduced
intravenously are rapidly localized in the spleen,
liver, bone marrow, kidneys and lungs. They are
broken down by the reticuloendothelial cells and
excreted in the urine,

28. Conti………
• about 70-80 percent being thus eliminated
within one or two days.
• In contrast, antigens introduced subcutaneously
are mainly localized in the draining lymph
nodes, only small amounts being found in the
spleen.

29. Conti……..
• Speed of elimination: The speed of elimination of
an antigen is related to the speed at which it is
metabolized. Protein antigens are generally
eliminated within days or weeks, whereas
polysaccharides which are metabolized slowly,
persist for months or years.
• Pneumococcal polysaccharide, for instance, may
persist up to 20 years in human beings, following a

30. Production of Antibodies
• The majority of antigens will stimulate B cells
only if they have the assistance of T
lymphocyte helper (TH) cells. Antigens can be
divided into two categories based on their
apparent need for TH cells for the induction of
antibody synthesis
• (1) those that require Th cells, referred To as T-
dependent antigens (TD-antigens) such as

31. Conti…….
• and (2) those that do not require TH cells, called
T-independent antigens (TI-antigens) such as
polysaccharides and other structurally simple
molecules with repeating epitopes.
• Immune response to an antigen is brought
about by three types of cells - antigen
processing cells (APC-principally
macrophages and dendritic cells), T cells and B

32. Conti………
1. Antigen Processing and Presentation
• For successful development of antibody response to a T-
dependent antigen, the antigen must be associated with
MHC class II molecules on the surface of an antigen-
presenting cell (APC).
• APC can ingest antigen, degrade it and present it to T
cells. T cell is able to recognise only when the processed
antigen is presented on the surface of APC, in association

33. Conti………
to the T cell carrying the receptor (TCR) for the
epitope.
 The antigen has to be presented complexed with
MHC Class II in the case of CD4 (Helper T/TH)
cells, and for CD8 (cytotoxic T/Tc) cells with
MHC Class I molecules.
 B cells, which possess surface Ig and MHC Class II
molecules, can also present antigens to T cells,

34. Conti……….
• The activated TH cell forms interleukin-2 and other
cytokines such as interleukin-4, IL-5 and IL-6
required for B cell activation. These interleukin-4
(formerly known as B cell stimulatory factor I), IL-5
(B-cell growth factor, BCGF) and IL-6 (formerly called B-
cell stimulatory factor, BCSF-2) activate B cells which
have combined with their respective antigens to clonally
proliferate and differentiate into antibody-secreting
plasma cells.

35. Conti……..
• B cells carry surface receptors which consist of
IgM or other immunoglobulin classes. A plasma
cell secretes an antibody of a single specificity of
a single antibody class (IgM, IgG or any other
single class) depending upon these receptors,.
• However, primary antibody response is
characterized by the initial production of IgM, and
later switching over to form IgG.

36. Conti……..
• Class switching is influenced by different
combinations of lyniphokines produced by
helper T (TH) cells.
• Under the direction of cytokines produced by
effector T-helper (TH) cells, some B cells
become programmed to produce antibodies
other than IgM. Following antigenic stimulus, not
all B lymphocytes are converted into plasma

37. Conti……
• A small proportion of activated B cells
become long lived memory cells which
produce a secondary type of response to
subsequent contact with the antigen.
• During secondary antigenic stimulus, the
increased antibody response is due to the
memory cells induced by the primary contact
with the antigen.

38. Conti…….
• Cytotoxic T (CD8/Tc) cells are activated when they
contact antigens presented along with MHC Class I
molecules. Again, these cells require two signals
to be activated
• (1) antigen fragment in association with MHC
class1is the first signals;
• (2) co-stimulatory signal IL2, which is secreted
by activated TH cells is the second signal.

39. Conti……
• On contact with a target cell carrying the antigen
on its surface, the activated Tc cells release
cytotoxins that destroy the target, which may be
virus infected or tumour cells. Some Tc cells also
become memory cells.

40. Monoclonal Antibodies
 Monoclonal Antibodies
 When a clone of lymphocytes or plasma
cells undergoes selective proliferation, as
in multiple myeloma, antibodies with a
single antigenic specificity accumulate.

41. Conti……
• Such antibodies produced by a single clone and
directed against a single antigenic determinant
are called monoclonal antibodies, e.g. plasma
cell tumor (myeloma). In myeloma, antibodies
are produced by a single clone of plasma cells
directed against a single antigenic determinant
and hence the antibodies are homogeneous
and monoclonal.

42. Conti…….
• Uses of Monoclonal Antibody
• 1. They are routinely used in the typing of tissue.
 2. Use in the identification and epidemiological
study of infectious microorganisms.
 3. Use in the identification of tumor and other
surface antigens.
 4. Use in the classification of leukemias. ( is a
cancer of the blood or bone marrow)

43. Conti…..
• 6. Anticipated future uses:
 i. Passive immunizations against infectious
agents and toxic drugs.
 ii. Tissue and organ graft protection.
 iii. Stimulation of tumor rejection and
elimination.
 iv. Manipulation of the immune response.

44. Conti……
 v. Preparation of more specific and sensitive
diagnostic procedures.
 vi. Delivery of antitumor agents (immunotoxins)
to tumor cells.

45. Factors Influencing Antibody Production
1. Genetic Factors
• The immune response is under genetic
control. Level of immune response to a
partcular antigen is controlled by the MHC
class II molecules.
• Response in different individuals to same
antigen varies due to genetic factor.

46. Conti………
• Persons capable of responding to a particular
antigen are called responder and those who
cannot respond are termed nonresponder. The
Ir (immune response) genes control this
property.
2. Nutritional Status
• Malnutrition affects host susceptibility to certain
microorganisms, especially bacteria.

47. Conti……..
 Examples:
 i. Protein calorie malnutrition suppresses both
humoral and cellular immune responses, the
latter more severely.
 ii. Deficiences of amino acids and vitamins:
Deficiences of amino acids have been shown to
cause a decrease in antibody synthesis.

48. Conti……….
3. Route of Administration
 There is better humoral immune response
following parenteral administration of antigen than
oral or nasal routes.
 Large particulate antigens, such as bacteria or
erythrocytes, are more effective when injected into
tissues.

49. Conti……….
• The route of administration may also influence
the type of antibody produced.
• Oral or nasal route is most sui for IgA
production, and inhalation of pollen antigens
induce IgE production, whereas the same
antigens given parenterally lead to IgG
antibodies.