The immune system protects the body from infection through two main arms: innate and adaptive immunity. The immune response requires the participation of antigen presenting cells, T cells, and B cells. When exposed to an antigen, B cells produce antibodies and T cells help activate other immune cells. Memory cells are formed and lead to a stronger secondary response upon reexposure to the same antigen. Cytokines help regulate the immune response through communication between immune cells.

1. Immune Response
BY DR. RAKESH PRASAD SAH
ASSISTANT PROFESSOR MICROBIOLOGY

2. The Immune System
 The key is
Our ability to produce more than 108 distinct
antibodies and more than 1012 T-cell receptors
We are constrantly exposed to an incredible diversity of
bacteria, viruses and parasites
How does the immune system protect us?

3. The immune system has 2 arms
Innate Immunity
Adaptive Immunity

4. The Immune system is the Third line of
Defense Against Infection

6. Immune response
 It is a specific reactivity induced in a host by an antigenic stimulus. In infectious
diseases, immune response is mainly concerned with protection against invading
microbe.
 But it also includes reaction against any antigen- living or non-living.
 Effects of immune response are generally beneficial.
 But in some sensitized persons, it can give to rise to hypersensitivity reactions,
and also rise to some disease (autoimmune disease)

7. Immune response
 Immune response needs participation of
1. Ag presenting cells – macrophages , dendritic cells
2. T cells
3. B cells
 Immune response also depends on type of antigen-
1. T cell dependent antigens (proteins, RBC)- Require T cell participation.
2. T cell independent antigens (Polysaccharides)-Do not require T cell participation

8. Immune response

14. Difference
Primary response Secondary reaponse
1 . Slow, sluggish, short lived. 1. Prompt, powerful prolonged.
2. Long lag phase 2. Short/negligible lag phase. Memory cells raect
immediately.
3. Low titre of Ab 3. High titre of Ab
4. IgM Ab produced (5-6 days) initially & last (4-
6weeks) for short time.
IgG Ab produced (2 weeks after infection) later &
lasts longer.
4. Same IgM & IgG response.
IgG response is however much more pronounced,
may be about 10 times than primary.

25. T Cells Only Recognises Antigen Associated With MHC
Molecules On Cell Surfaces
T cell recognize with the help of T cell receptor

26. Central Role of Helper T Cells

27. Central Role of Helper T Cells

28. Humoral Response to Antigens
Macrophage engulfs and degrades bacterium.
It displays peptide antigen complexed with a
class II MHC molecule. A helper T cell that
recognizes the complex is activated with the
aid of cytokines secreted from the macrophage,
forming a clone of activated helper T cells.

29. Humoral Response to Antigens
B cell that has taken up and degraded the same
bacterium displays class II MHC–peptide
antigen complex. Activated helper TH bearing
receptors specific for the displayed antigen
binds to B cell. Interaction, with the aid of
cytokines from TH cell, activates the B cell.

30. Humoral Response to Antigens
The activated B cell proliferates
and differentiates into memory
B cells and antibody-secreting
plasma cells. Secreted antibodies
are specific for same bacterial
antigen that initiated response.

32. Antigen (1st exposure)
Humoral (antibody-mediated) immune response
Engulfed by
APC
Helper T cell
B cell
Plasma cells Memory B cells
Antigen (2nd exposure)
Memory
Cytotoxic T cells
Active
Cytotoxic T cells
Cytotoxic T cell
Secreted
antibodies
Cell-mediated immune response
Memory
Helper T cells
Defend against intracellular pathogens
and cancer by binding to and lysing the
infected cells or cancer cells
Defend against extracellular pathogens by binding to antigens,
thereby neutralizing pathogens or making them better targets
for phagocytes and complement proteins
Stimulus
Give rise to

35. Theories of Antibody Formation
1.Instructive Theories
I. Direct template theory
II. Indirect template theory
2.Selective Theories
I. Side chain theory
II. Natural selection theory
III. Clonal slection theory

36. Factors influencing antibody production

37. 7. Adjuvants – Enhance Immunogenicity of an Ag. Enhance Ab production & cellular immunity.
Cause slow release of Ag for deposit, resulting in both primary & secondary immune response.
Alum, Al hydroxide, Al phosphate are commonly used as adjuvants in vaccines
8. immuno-suppressive agents – inhibit immune response. X rays, alklating agents,
corticosteroids, antimetabolites, anti lymphocyte serum.
 During microbial infections, different Abs are produced against different Ag of pathogen by
different clones of B cells. For serological diagnosis of diseases, highly purified Abs
produced by a single clone of B cells against a single Ag are necessary . These are called
Monoclonal antibody

38. Monoclonal Antibodies
 Monoclonal antibodies (mAb) are antibodies
produced by a single clone of antibody forming
cells, and these abs are produced against a
single antigen or single antigenic determinant
site.
 Kohler and Milstein first devised hybridoma
technique for production of monoclonal antibodies.
They were awarded Noble prize in 1984 for their
work.

39. Technique
 Myeloma cells – are malignant cells with capacity to multiply indefinitely .
 Splenic cells – these are T cells with capacity to form antibodies against
given antigen for limited period.
Hybridoma cells have capacity to produce the required specific antibodies
for a long time.

40. Preparation of Monoclonal Antibodies

42. Uses of monoclonal antibodies
 1.Used in serological reactions which require high degree of specificity eg.-
ELISA, Radio immuno assay, Immunofluorescence, Immunochromatography
 Monoclonal antibodies are widely used for diagnosis of bacterial, viral,
parasitic diseases (e.g. HIV infection, Hepatitis B infection, Auto disease
etc).
 2.Tests for tissue transplantation- tissue typing.
 3.Tests for vaccines and their industrial production.

43. Cellular Immune Response (CMI)

44. Induction of CMI
 Antigenic stimulus
 Develops best following infection with intracellular parasite
 Only T-cell dependant antigens lead to CMI
 Killed vaccines or non living antigens do not induce CMI (unless
combined with Fruend type adjuvant)
 T-cell bears specific receptor on its surface
 T cells recognize antigens only when presented with MHC
molecules
 • Helper T-cells
 • Cytotoxic T-cells

47. Central Role of Helper T Cells

48. Central Role of Helper T Cells

49. Cytotoxic T Cells Lyse Infected Cells
Specific cytotoxic T cell binds to
Class I MHC–antigen complex on
target cell via TCR with the aid of
CD8.

50. Cytotoxic T Cells Lyse Infected Cells
Activated T cell releases perforin,
which forms pores in the target cell
membrane. Proteolytic enzymes
(granzymes), enter the target cell.

51. Cytotoxic T Cells Lyse Infected Cells
Apoptosis occurs, leading to fragmentation
of the nucleus and eventual cell death.
Cytotoxic T cell can attack other target cells.

53. Antigen (1st exposure)
Humoral (antibody-mediated) immune response
Engulfed by
APC
Helper T cell
B cell
Plasma cells Memory B cells
Antigen (2nd exposure)
Memory
Cytotoxic T cells
Active
Cytotoxic T cells
Cytotoxic T cell
Secreted
antibodies
Cell-mediated immune response
Memory
Helper T cells
Defend against intracellular pathogens
and cancer by binding to and lysing the
infected cells or cancer cells
Defend against extracellular pathogens by binding to antigens,
thereby neutralizing pathogens or making them better targets
for phagocytes and complement proteins
Stimulus
Give rise to

56. CYTOKINES
 Cytokines are low molecular weight regulatory proteins or glycoproteins
 secreted by white blood cells and various other cells in the body in response to a
number of stimuli.
 These proteins assist in regulating the development of immune effector cells
 And some cytokines possess direct effector functions of their own.

57. Nomenclature
 Interleukins - that act as mediators between leukocytes. The vast majority of
these are produced by T-helper cells.
 Lymphokines - produced by lymphocytes.
 Monokines - produced exclusively by monocytes & macrophages.
 Interferons - involved in antiviral responses.
 Colony Stimulating Factors - support the growth of cells blood cell .
 Chemokines - mediate chemoattraction (chemotaxis) between cells.

58. Properties

59. Cytokines belong to four families
• Falls in 4 families
i. Hematopoietin family
ii. Interferon family
iii. Interleukin family
iv. Tumor necrosis factor family
• All have molecular mass less than 30kDa

61. Cytokines and their Functions

62. Cytokines and their Functions

63. Detection of CMI
A) In vivo test –
Skin test – for delayed hypersensitivity. E.g tuberculin test.Intra
dermal injection of 0.1 ml of tuberculin (tuberculoprotein)
Erythema & induration at site of inj.after 48-72 hrs.
Indicate prior sensitization (exposure) or current infection.

64. B ) In vitro tests –
 Lymphocyte transformation test- Sensitized T cells are cultured . On
contact with specific antigen- undergo blast transformation.
 Macrophage /leucocyte migration inhibition test –
1. Capillary tube containing macrophages
2. Incubate in culture medium chamber
3. Macro/leucocytes migrate & form lacy, fan like pattern
4. Sensiitized leucocytes
Corresponding Ag mixed in culture medium.
Result – Inhibition of migration of macrophages/leucocytes
Detection of T cells by Immunofluorescence Technique

65. Immunological Tolerance
 State in which contact with an antigen specifically abolishes capacity to mount an
immune response against that particular Ag when it is administered subsequently.
 Types
 Natural Tolerance  non-responsiveness to self antigens. Any Ag
immunological system during embryonic life  recoginised as self Ag 
would not provoke an immune response in the mature animal.
 Acquired Tolerance  arises when a potential Ag  state of
unresponsiveness to itself. (for it to be maintained, the Ag must persists or be
repeatedly administered.)

66. Mechanism of Tolerance
 Clonal Deletion  In embryonic life clones of B and T lymphocytes that recognise
self antigens are selectively deleted.
 Clonal Anergy  Clones of B and T lymphocytes that recognise self Ag that might
be present but they can not activated.
 Supression  Clones of B and T lymphocytes expressing receptors that
recognise self Ag are preseved. Ag recognition  capable of activation. Might be
inhibited through active supression.
 Other Mechanisms  Access of Ag to immunocompetent cells is interfered
(afferent block) or Ab synthesized is neutralized or destroyed (efferent block)