The immune system functions to eliminate non-self molecules like microbes, cancer cells, and transplanted tissues. It contains central organs like the bone marrow and thymus that produce immune cells, secondary lymphoid tissues that develop these cells, and soluble factors like cytokines. The innate immune system provides non-specific defenses like physical barriers and phagocytes. The adaptive immune system mounts specific responses through B cells and antibodies or T cells. Antibodies mediate humoral immunity against pathogens.

1. Immune System
 Dr.S.Sethupathy,
 RMMC,
 AU.

3. Function of immune system
To eliminate non-self
molecules
and cells such as microbes,
cancer cells, transplant tissues
and foreign substances.

4. Salient features
1. Recognition of self from
non- self or foreign substances.
2.Specificity of the reactions.
3.Memory of the response

5. Epitope
 Any substance that invokes an immunological
response is an antigen or immunogen.
 The immune response is selective against specific
spatial configurations on the antigen, the antigenic
determinant or epitopes.
 An epitope is the part of an antigen that is recognized
by specifically by antibodies, B cells, or T cells.

7. Components of the I.System
1 Central organs
 a. Bone marrow – pluripotent stem cells- precursor of
leukocytes
 b. Thymus
2.Secondary lymphoid tissues –
a. trap antigens and present to lymphoid cells
b. develop precursor immune cells
 Lymph nodes
 Spleen
 GALT
 MALT

8. 3. The cells of the I.S
a. Lymphoid cells
b. Myeloid cells
Lymphoid cells and Myeloid cells develop in the Bone
marrow
Lymphoid cells to B cells in B.M
Lymphoid cells to T cells in Thymus
Myeloid cells are neutrophils, basophils, eosinophils
and monocytes.
4. Soluble factors
Acute phase proteins, cytokines, complement system

10. Types of immune response
 1.Innate immunity
 Non-specific
 From birth
 Exposure to antigen not needed
 Cells - Neutrophils, basophils, eosinophils,
macrophages and natural killer (NK) cells
 2. Adaptive immunity
 Specific
 Previous exposure required
 Memory developed

19. Components of immunity
 Humoral immunity
 Mediated by immunoglobulins produced by B- cells.
 Ig is involved in protection against microbial
infections ,
 in hyper sensitivity
 in autoimmune reactions.

21. Components of innate Immunity
 1.Physical barriers - skin, mucous membrane of
respiratory tract, G.I tract, flushing effects of saliva ,
tears, urine.
 They prevent entry of microbes.
 2.Chemical factors - HCl in gastric juice, lysozyme in
tears and saliva.
 They destroy microbes.

22.  3.Cells
 Natural killer cells (NK) kill malignant or virus
infected cells.
 Neutrophils kill bacteria by phagocytosis.
 Eosinophils are involved in allergic response.
 Basophils are involved in release of inflammatory
mediators and allergic response.
 Macrophages are involved in antigen presentation,
phagocytosis and secretion of cytokines.

23. NK cells
 Release perforins proteins that form holes in the
plasma membrane of the cell to be killed.
 Sodium diffuses in, then water osmoses inward,
causing the cell to swell and burst (cytolysis).
 In nucleated cells, this influx of ions may trigger
apoptosis
 Can also release granzymes that can enter the cell and
trigger apoptosis.

26. Dendritic cells
 Dendritic cells (DCs)- antigen-presenting cells, immune system.
 Their main function is to process antigen material and present it
on the cell surface to the T cells of the immune system.
 They act between the innate and the adaptive immune systems.
 Present in the skin ( Langerhans cell), the inner lining of the
nose, lungs, stomach and intestines.
 They are in immature state in the blood.
 Once activated, they migrate to the lymph nodes where they
interact with T cells and B cells to initiate adaptive immune
response.
 At certain development stages -w branched projections
 Dendritic cells are derived from hematopoietic bone marrow
progenitor cells.

29. Phagocytosis
 Phagocytes engulf the pathogenic organisms.
 Neutrophils, Eosinophils, Monocytes and
macrophages present in tissues.
 Neutrophils are the major phagocytic cells during
acute infection.

30. 4.Soluble factors
 Acute phase proteins play a role in inflammatory
response and defense against microbes.
 Cytokines play a role in inflammatory response and
apoptosis.
 Complement proteins are involved in killing microbes,
allergic response, stimulation of inflammatory
response and attraction of phagocytes.

31. Immune response
 Active immunity
 It is acquired through direct interaction of immune
system with antigens by infection or vaccination.
 2.Passive immunity
 It is the immunity acquired by the administration of
antibodies or immune cells.

32. Cytokines
 Cytokines are the molecules involved in immune
response.
 Example : Interferons (IFN),
 Interleukins (IL-1 to 18),
 Transforming growth factor (TGF alpha and TGF
beta),
 Chemokines
 Colony stimulating factor(CSF).

33.  Interferons alpha, beta, gamma help the cells
overcome viral infection.
 Tumour necrosis factor(TNF) by moncytes and
macrophages.
 TNF alpha induces IL-1 production. It is cytotoxic to
tumor cells. It also induces IFN secretion.
 Transforming growth factor alpha and beta modulate
immune response.
 Colony stimulating factors -Granlocyte –monocyte
CSF (GM-CSF),granulocyte CSF(G-CSF), monocyte
CSF (M-CSF) are involved growth and differentiation
of hemopoietic and immune cells.

34. Interferons
 Interferons (IFNs) are released by dying, virus-
infected lymphocyte or other cell .
 Interferons "call in" other immune cells (NK cells
and macrophages) that destroy virus-infected cells
and prevent spread of viral infection
 Interferons also "interfere" with viral replication.
 Interferons are paracrine agents, regulating nearby
cells

35. Chemotaxis
 Chemical attractants are released from damaged tissue
cells and immune system cells to "call over" immune
cells to the site of injury.
 Neutrophils reach the site of infection as a response
to C5a, C3 complements, leukotrienes, and
chemokines.
 Neutrophils - engulf and digest microbes by the
lysozymal enzymes- oxidant independent killing.
 Using superoxide, the killing of microbes is called
oxidant dependent killing.

36. Chemokines
 Chemokines are the recent cytokines
 Cause chemotaxis.
 They cause chemotaxis of T- cells,
monocytes, NK cells, mast cells and
eosinophils.
 They play an important role in phagocytosis
and inflammatory response.

37. Less ROS
 Chronic granulomatous disease- defect in NADPH
oxidase in neutrophils – less ROS
 Leukocyte fails to adhere to endothelium due to defect
in adhesion molecule.
 Myeloperoxidase deficiency results in impaired
production of hypo chlorite ion.
 Chediak-Higashi disease is due to defective fusion of
phagosome with lysosome.

38. Clinical applications
 Interferon gamma is used treating for chronic
granulomatous disease , leukemia ,chronic active
hepatitis C.
 G-CSF is used for neutropenia.
 IL-2 is used in renal carcinoma.

39. Cell mediated immunity
 It is mediated by T- cells.

 Major defense against cancer cells and cells infected with
microbes.
 Involved in transplant rejection
 Delayed hypersensitivity reactions
 Help in proliferation and differentiation of B- lymphocytes
by presenting antigens to them.

42. Acute phase proteins
 Plasma proteins whose concentrations increase (positive
acute-phase proteins) or decrease (negative acute-phase
proteins) in response to inflammation.
 The acute-phase reaction or acute-phase response.
 In response to injury, local inflammatory cells (neutrophil
granulocytes and macrophages) secrete a number of
cytokines
 The interleukins IL-1, IL-6 andIL-8, and TNF-α.
 The liver produce a large number of acute-phase reactants.
 Certain proteins are reduced - "negative" acute-phase
reactants.

43. C-reactive protein(CRP)
 Coating of C- reactive protein to bacteria -
opsonization , complement activation and
phagocytosis.
 Serum level is lesser than 1 mg/dl .
 High sensitive CRP is a risk marker for coronary heart
disease.
 CRP is elevated in inflammatory conditions.

44. Alpha1 antitrypsin
 It is synthesized in liver.
 It is active against proteases such as trypsin,
chymotrypsin.
 Deficiency - chronic obstructive pulmonary disease.
 Its level is increased in bacterial infections.
 Normal serum level – 0.2-0.4 mg/dl.

45. Ceruloplasmin
 It is a copper containing alpha2- globulin - by liver.
 It has ferroxidase activity.
 It facilitates iron storage by ferritin and inhibits
microbe iron uptake.
 Normal serum level is 15-60 mg/dl .
 Decreased in Wilson’s disease, malnutrition,
Nephrotic syndrome, liver diseases and Menkey’s
syndrome.
 Increased in cancer, inflammatory conditions.

46. Haptoglobin binds
hemoglobin and inhibits iron
uptake by microbes.
Ferritin stores iron and inhibits
microbial iron uptake.

47. Fibrinogen
 It is a clotting factor present in blood .
 Coagulation factors trap invading microbes in blood
clots.
 Some cause chemotaxis.
 Normal plasma level is 200-450 mg/dl.
 Elevated fibrinogen level is a risk factor for CAD.
 Decreased fibrinogen level -in disseminated intra
vascular coagulation (DIC).

48. Complement proteins
 A group of about 20 different plasma proteins
 C1, C2, C3, and so on
 Activated in a cascade of chemical reactions triggered
by innate or adaptive mechanisms
 Can act directly, as do perforins
 Form MACs (membrane attack complexes) that poke
holes in the outer membrane
 Complement can act indirectly as a chemotactic agent
or regulating immune cells in some other way

50. Complement proteins
 They are involved in opsonization, lysis and
clumping of target cells and chemotaxis.
 C1 to C9 are involved in immune response.
 It is synthesized in liver and macrophages.

51.  Antibody opsonization is the process by which a
pathogen is marked for ingestion and destruction by a
phagocyte.
 Opsonization involves the binding of an opsonin, e.g.,
antibody, to an epitope on an antigen.
 After opsonin binds to the membrane, phagocytes are
attracted to the pathogen.
 Fab portion of the antibody binds to the antigen
 Fc portion of the antibody binds to an Fc receptor on
the phagocyte, facilitating phagocytosis.

52. Classical pathway
 Classical activation pathway starts from
activation of C1 followed by C4 and C2 and
the finally active C3.
 Active C3 activates C5.
 Active C5 causes activation of membrane
attack complex (MAC) composed of
C7,C8.C9.
 This MAC causes cell lysis.

55. Alternate pathway
In alternate activation pathway, C1,
C4, C2 is bypassed .
Activation of C3 occurs by binding
of C3 to bacterial endotoxin.

56. Lectin pathway
 Similar in structure to the classical complement
pathway
 After activation, it proceeds through the action of C4
and C2 further down the cascade.
 In contrast to the classical complement pathway, the
lectin pathway does not recognize antibody bound to
its target.
 The lectin pathway starts with mannose-binding
lectin or ficolin binding to certain sugars -bacteria.

58. Role of complements
Opsonization of microbes
Chemotaxis
Anaphylactic reactions
Cell lysis
Clearance of immune complex and
apoptotic cells

59. Clinical applications
 Serum complement levels are increased in
inflammatory conditions.
 Serum C3 is decreased in glomerulonephritis
 Its level is used to monitor the disease course.
 Complement deficiency is associated with serious
infections.
 Inhibitors of complement systems such as factor 1,
C1 esterase inhibitor control the level of
complements.

61. Humoral immunity
 The cells originated from bone marrow and processed
by the Bursa of fabricus in Avians are called B- cells.
 In humans Bursa equivalent organs are Gut associated
Peyer’s patches and lung associated lymphoid
organs.
 Immunoglobulins are secreted by plasma cells
belonging to B- lymphocytes.
 B- cells mediate the humoral immunity.

62. Plasma cells
 The binding of microbial antigen to appropriate
IgM type of receptor on B- lymphocytes results in
the conversion of them to plasma cells
 They secrete a selective population or clone of
immunoglobulins.
 T4 helper , T cells secrete interleukins which
mediate conversion of B- lymphocytes to plasma
cells.
 Memory B- cells are able to keep in memory of the
previous exposure to antigens.

63. Plasma cells

64. Immunoglobulins
 Antibodies
 Two identical heavy and light chains –four
polypeptides
 IgA = α heavy chain
 IgM = µ heavy chain
 IgG = γ heavy chain
 IgD = δ heavy chain
 IgE = ε heavy chain

70.  IgD, IgE, IgG –
monomers
 IgA – Dimer
 Pentamer- IgM

71.  Both heavy and light chains have a carboxyl
terminal constant region
 Amino terminal variable region.
 Heavy chains also contain a hinge region.
 Variable regions of heavy and light chains
have variable amino acid sequences
 within them hyper variable regions that act
as antigen binding site.
 It is unique to each immunoglobulin.

72. Hinge region allows movement of the
two antigen binding sites.
Constant regions are involved in
biological functions
CH2 of IgG and CH4 of IgM bind to
complement C1.
The carboxy terminal of
immunoglobulins (FC region) binds FC
receptors on immune cells.

73. Role of antibodies
 Antibodies neutralize microbial toxins and inhibit
microbes.
 Opsonization of microbes by antibody promotes
phagocytes through FC receptor of phagocytes.
 Activation of complement promotes lysis of
microbes.
 Antibody presents target cells to cytotoxic cells
through its interaction with Fc receptors on
cytotoxic cells.

74. IgG
 IgG- 75% of total serum immunoglobulins.
 It activates complement system
 It has antimicrobial activity.
 It can cross the placenta and protects the fetus.
 Normal serum level = 0.8-1.5 gm/dl
 Increased serum IgG - infections, cirrhosis of liver,
auto immune diseases. Monoclonal IgG is increased in
multiple myeloma.
 Decreased serum level in immune deficiency
diseases, Hodgkin’s disease, lymphoid neoplasia.

75. IgA
 IgA -as a monomer or dimer.
 Secretary IgA - dimer with a joining peptide called J
chain. IgA1 is in serum and IgA2 is in secretions.
 Against viral and bacterial injections by blocking them
across the mucosal cells
 Normal serum level : 0.1 to 0.3 gm/dl
 Increased serum IgA level -in liver diseases,
infections, autoimmune diseases.
 It is decreased in immune deficiency disorders.

76. IgM
 IgM- pentamer , J chain, the primary immune response.
 It is effective against parasitic and viral infections.
 It is mainly present in the intravascular compartment.
 It does not cross the placenta .
 Antibodies against blood group antigens - IgM.
 Normal serum level is 50 – 200 mg/dl
 Increased serum level - in autoimmune diseases,
infections, Waldenstrom’s macroglobulinemia, liver
diseases, infections, and autoimmune diseases.
 It is decreased in immune deficiency diseases.

77. IgD
 It is a monomer.
 The function is not known.
 Serum level is 1-4 mg/dl.
 It is increased in infections , cirrhosis of liver,
autoimmune diseases and monoclonal IgD is
increased in multiple myeloma.

78. IgE
 It is a monomer and involved in allergic reactions.
 It binds to Fc receptors present in mast cells and
basophils.
 It mediates immune response against parasitic
infections.
 Serum level is 0-380 IU/mL.
 Its serum level is increased in allergic conditions and
parasitic infections.

79. Clinical applications
Hypogammaglobulinemia, Immune
deficiency disorders
 1.Decreased synthesis of Ig
 2. Loss of Ig through urine in Nephrotic
syndrome ,through feces in protein losing
enteropathy, through the skin in burns.

80. Hypergammaglobulinemia
 It can be polyclonal or monoclonal.
 Polyclonal Increase in Infections, chronic liver
diseases, autoimmune diseases and sarcoidosis.
 Monoclonal increase in multiple myeloma,
Waldenstrom’s macroglobulinemia,
 cryoglobulinemia,
 benign monoclonal gammapathy,
 heavy chain disease.

81. Multiple myeloma
 It is a plasma cell tumor
 Increase in monoclonal immunoglobulin or Bence
Jones protein.
 In 55% of cases, IgG are overproduced. IgA in 20%
cases, light chain in 20% of cases are overproduced.
Clinical features
 Skeletal pain is seen in the back or thorax.
 Renal failure due to cast formation in renal tubules.
 Anaemia is caused by impaired erythropoiesis
 Bacterial infections are common.

82. Hyperviscosity syndrome
 Excess plasma globulins increase the viscosity
 fatigue, weakness, headache, mucosal bleeding and cardiac
impairment.
 Lab findings M band in EPP. Urine B- Jones positive
 Bone marrow biopsy shows clusters of plasma cells.
 Osteolytic lesions on X-ray serum calcium level high .
 Hyperuricemia .
 Increased serum beta- 2 microglobulin level - multiple
myeloma, rheumatoid arthritis ,HIV infection and renal
failure. It is small and easily filtered by the glomerulus.

83.  Waldenstorm’s macroglobulinemia- anemia ,
lymphadenopathy and IgM monoclonal antibodies.
 Heavy chain disease - rare and the heavy chains is
IgA alpha chain and the clinical features are diarrhea
and malabsorption.
 Cryoglobulinemia is characterized by
cryoglobulins in serum which precipitates at
temperature lower than 37oC.
 They may be polyclonal or IgM monoclonal.
 They are also observed in multiple myelin and
lymphoma.

84. Monoclonal antibodies
 Monoclonal antibodies -Ig produced by a single clone
 Produced by hybridoma technology.
 A specific antibody producing lymphocyte is fused
with immortal myeloma cell with the help of
polyethylene glycol.
 In HAT medium, only fused hybridoma cells will grow
 They are immortal and grown in large number

85. Uses of monoclonal antibodies
 Diagnostic kits
 Therapeutic drug monitoring(TDM)
 Diagnosis of infections diseases such as HIV
 Diagnosis and monitoring tumor markers.
 Diagnosis of auto immune diseases.
 Mouse monoclonal antibodies to lymphocyte surface
antigens have been used to prevent acute kidney
transplant rejection.
 Humanized monoclonal antibodies raised against
HER-2 antigen is used to treat HER-2 positive breast
cancer

86. T -Lymphocytes and Cell mediated
immunity
 Helper T cells (CD4+) :They respond to
antigens presented by Major
histocompatibility complex (MHC) class II
molecules containing cells.
 Cytotoxic cells (CD8+) They interact with
cells containing viral antigens or tumor cell
protein and it requires MHC I molecules on
these cells.

87. Major histocompatibility complex
and HLA system
 Major histocompatibility antigens are also called as human
leukocyte antigens.
 The genes for HLA- chromosome 6
 three classes, class I , II and III.
 MHC class I antigen consists of alpha chain and beta 2
microglobulin chain.
 Class II consists of alpha and beta chain.
 MHC antigens are essential for the recognition self and non
self.
 They are essential for the presentation of antigens to T
lymphocytes.

88. Clinical applications
 Incorrect HLA matching - rejection of transplantation.
 Some HLA antigens are associated with the disease
 Myasthenia gravis ( HLA DR3)
 Anykylosing spondilytis(HLA B27)
 Multiple sclerosis (HLA 37).

89. Disorders of T cells
 Deficiency of T cells:
 Primary deficiency - rare, partial or complete.
 Example. Di George syndrome, severe combined
immune deficiency, Aldrich syndrome.
 Secondary deficiency
 Diabetes mellitus, uremia, malnutrition, cancer
immunosuppressive therapy and AIDS.

90. HIV (AIDS)
 RNA virus. 3 major genes -5'gag-pol-env-3‘.
 Env: envelope protein gp 160. gp160 into gp120 and
gp41.
 gp 120 interacts with CD4 receptor in T cells
 gp41 mediates the fusion of the infected T cells.
 Gag codes for core protein P24, P17, P9 and P7.
 P24 is the major capsid protein,
 P9 is the nucleocapsid proteins
 P17 is a matrix protein.

95.  pol codes for enzymes reverse transcriptase,
integrase and a protease.
 Helper Tcells - interaction of gp120 protein
with CD4 receptor
 Fusion is mediated by gp41.
 The DNA is integrated into host DNA by
integrase.
 Once the T lymphocytes are activated by
antigens or other viruses enhanced protein
synthesis occurs along with enhanced synthesis
of viral proteins
 Replication of virus and lysis of the cell.

96. Complications
 Infection such as viral and fungal infections
 cancer such as Kaposi sarcoma, a neoplasm
of endothelial cell in the mucocutaneous
sites,
 Burkitt’s lymphoma,
 B- cell lymphoma etc.

97. Diagnosis of AIDS
 1.ELISA test for HIV antibodies .It is rapid
but false positive occurs.
 2.Western immunoblot test for HIV
antibodies is the confirmatory test.
 3.Quantitative PCR for detecting Viral RNA
is sensitive ,specific test. It is useful in
detecting the infection at very early stage
and assessing viral load.

98.  Absolute number of CD4+ and CD8+ T
lymphocytes
 CD4+ cells decrease as the disease progresses.
 So CD4+ count is useful to monitor the disease.
 Treatment
 Drugs used to treat HIV are reverse transcriptase
and protease inhibitors
 Example: Zidovidine is a nucleoside inhibitor and
Indinavir is a protease inhibitor.

99. Immunologic mechanisms of
tissue injury
1. Hypersensitivity reactions
 Harmful immune response
 four types. Type I – Anaphylactic reactions,
 Type II -antigen antibody cytotoxic
reactions,
 Type III - immune complex reactions
 Type IV- cell mediated delayed immune
reactions.

100. 2. Autoimmunity
 It is the production of immune response to one’s own
tissues resulting in damage to them.
 Mechanism : dysregulation of immune response or
impairment in self tolerance.
 1. Cross reactivity in the microbial antigens.
 2. Polyclonal activation T lymphocytes by tumor cells or
microbes .
3. Genetic predisposition results in lack of self tolerance
4. Association of with HLA antigens.
example Rheumatoid arthritis - HLA B27 mediators of auto
immune diseases

102. Mediators of autoimmune
diseases
 1.Autoantibodies : Auto antibodies form antigen
antibody complexes and activate complement system
which induces inflammatory response in the affected
tissues. Eg. Systemic lupus erythematosus due to
antinuclear antibody.
 2.Activated T cells : Activated cytotoxic T cells
will target cells. Delayed hypersensitivity helper T cells
(DTH T cells) secrete lymphokines that cause
inflammatory response .

103.  3.Antibody dependent cytotoxic immune
response can cause cell injury.
 Examples for autoimmune diseases ( They can be
systemic or organ specific)
 Rheumatoid arthritis and systemic lupus
erythematosus are systemic.
 Grave’s disease involving thyroid, diabetes mellitus
involving pancreas, perinicious anemia involving
stomach, myasthenia gravis and Guallian Barrie
syndrome involving nervous system are organ specific
diseases.

104. Transplant rejection
 Transplantation is replacement of the diseased tissue or
organ by living, healthy tissues or organs from a donor. The
common transplants are kidney, liver, heart, lung and
pancreas.
 Types Auto graft refers to transfer of one’s own tissue
from one site to another site. Eg. Skin graft.
 Isograft refers to graft from one twin to another twin.
 Allograft is transplantation of tissues between the
genetically dissimilar members of the same species
 Xenograft refers to graft between members of different
species.

106. Transplant rejection
 Rejection of cells or tissues transplanted from are
person to another.
 It may be host versus graft disease or graft versus host
disease.
 In host versus graft disease , antigens on the
transplanted cells are recognized by the host immune
system (MHC molecules).
 Graft versus host disease Ex: Hemopoietic tissues
 Itching, diarrhea,hepatitis are features.

107. Prevention of graft rejection
1.HLA typing - Class II molecules
typing - Identical twins or selected
donors with match are preferred.
2. Immunosuppressive drugs such as
cyclosporine, steroids, azathioprine
can be used.

108. Thank
you