2. CONTENTS:
INTRODUCTION
SCOPE AND HISTORY OF IMMUNOLOGY
CLASSIFICATION
DEVELOPMENT
CELLS OF IMMUNE SYSTEM
IMMUNITY AND INFECTIOUS DISEASES
IMMUNIZATION
CELLULAR IMMUNOLOGY
MOLDECULAR IMMUNOLOGY
HYPERSENSITIVITY REACTION
AUTOIMMUNITY
TRANSPLANTATION
VACCINES AND IMMUNITY
CANCER AND IMMUNE SYSTEM
DIAGNOSTIC IMMUNOLOGY
TRENDS IN IMMUNOLOGY
CONCLUSION
REFERENCES
3. INTRODUCTION
The term ‘immunity’ has traditionally referred to the
resistance exhibited by the host towards injury caused
by microorganisms and their products.
Infection and immunity involve interaction between
the host and the infecting micro-organism.
4. IMMUNE SYSTEM (FUNCTIONALLY)
RECOGNITION RESPONSE
Local and Foreign molecule Recruits variety of cells and molecules
Effector response to eliminate or to neutralize the
organism
LATER EXPOSURE
Memory response
Rapid and heightened immune reaction
Eliminate the pathogen and prevent disease
6. • It is the resistance which individual possesses by birth.
• It is by virtue of his genetic and constitutional makeup. It does not
depend on prior contact with foreign antigen.
INNATE IMMUNITY:
7. FACTORS INFLUENCING THE LEVEL OF
INNATE IMMUNITY
AGE
HORMONAL INFLUENCES
ENDOCRINE DISORDERS
Diabetes mellitus,
Hypothyroidism,
Adrenal dysfunctions
Diabetes - level of carbohydrates
Corticosteroids - Depress host’s Resistance
NUTRITION
-Immune responses are reduced in malnutrition
11. The resistance acquired by an individual during life is known as acquired
immunity. It is of two types, active and passive.
A. Active Immunity
Active immunity is subdivided into two types : Natural and Artificial.
ACQUIRED IMMUNITY:
12. Humoral immunity
It is antibody mediated immunity.
It depends on the synthesis of
antibodies by plasma cells.
These cells produce specific circulating
antibody which combines specifically
with the antigens and modify their
activity. This modified activity may be in
the form of lysis of antigen molecules;
their toxin may be neutralised, or in the
form of removal of antigen by
Cell mediated
immunity
It depends on T-lymphocytes developed
against certain antigens.
Antibody synthesis also occurs in
response to these antigens, but their role
is limited.
Important in resistance to chronic
bacterial infections , organisms can
multiply and survive in phagolysosome
16. Generated - thymus
T cells have two major subtypes:
T- LYMPHOCYTE:
T helper cells Abbreviated as TH cells
Carry CD4 molecule on their surface and hence are also called
CD4+ cells. CD4+ cells in circulation are about twice the
number of CD8+ cells (CD4+/CD8 ratio 2:1)
T suppressor cells
Suppress immune reactions but are cytotoxic and actually
destroy the invading antigen; hence are also termed as cytotoxic
T lymphocytes (CTL). These cells carry CD8 molecule on their
surface and hence are also called CD8+ cells.
17. T Helper cells; Depending upon the type of cytokines elaborated, these TH cells are further of two subclasses:
TH 1 and TH 2.
TH 1 cells elaborate IL-2 and interferon (IFN) [PROINFLAMMATORY]
TH 2 cells elaborate IL-4, IL-5, IL-6, and IL-10.[ANTI-INFLAMMATORY]
CD4+ cells are predominantly involved in cell-mediated reactions to viral infections (e.g. in HIV), tissue
transplant reactions and tumour lysis.
T suppressor cells ; CD8+ cells in circulation are about half the number of CD4+ cells.
Compared to CD4+ cells which act by elaboration of cytokines, CD8+ cells are directly cytotoxic to the antigen.
CD8+ cells are particularly involved in destroying cells infected with viruses, foreign cells and tumour cells.
T CELL PROLIFERATION THUS
GENERATE LARGE NO. OF ANTIGEN
SPECIFIC CELLS EFFECTOR CELLS
MEMORY CELLS
ACTIVATED T
CELLS
SECRETES
CYTOKINES
LIKE IL-2
18. HUMAN IMMUNODEFICIENCY VIRUS:
AIDS is a retroviral disease caused by the human immunodeficiency virus (HIV).
It is characterized by infection and depletion of CD4+ T lymphocytes, and by profound immunosuppression
leading to opportunistic infections, secondary neoplasms, and neurologic manifestations.
Increasing susceptibility to
opportunistic infections and
neoplasms.
CD4 T cells-decreased lymphokine
secretion (IL-2 and INTERF-G)
Decreased response to soluble antigens
CD8 t cells-decreased cytotoxic
response.
Decreasing a host’s ability to fend off
intracellular organisms.
NK cells have a decreased ability to kill
tumor cells.
Lab investigations:
i) Antibody tests:
a) ELISA
b) Western blot
ii) Direct detection of HIV
a) p24 antigen capture assay
b) HIV RNA assay
c) NA-PCR
d) Culture of HIV
2. TESTS FOR DEFECTS IN IMMUNITY
i) CD4+ T cell count: Fall
ii) CD8+ cell count: Increased
iii) Ratio of CD4+ T cell/CD8+ T cell count:
Reversed
iv) Lymphopenia
v) Hypergammaglobulinaemia
vi) Increased -2 microglobulin level
vii) Platelet count: Thrombocytopenia
19. Develop from immature precursors in the bone
marrow.
Constitute 10-20% of the circulating peripheral
lymphocytes.
Also seen in the lymph nodes (superficial cortex),
spleen (white pulp), tonsils, and extra lymphatic
organs (eg. Git).
Recognizes antigen via the b-cell antigen receptor
complex.
B LYMPHOCYTES
20. CYTOKINES:
•A collection of polypeptides used for communications between cells
•Play role similar to hormones
Hormones usually act at a distance.
Cytokines act locally.
•Differ from growth factors that are produced constitutively, while cytokine production is carefully
regulated
•Play an important role in both innate and adaptive immunity
•Interleukins (1-18)
•Interferons (a,b,g)
•These are produced by cells as part of normal cellular activity and/or the result of environmental trigger
to Bind to receptors on cells; Trigger signal transduction pathways and Initiate synthesis of new proteins.
21. Redundancy
More than one
cytokine can do the
same thing (IFNa/b
and IFN)
Pleiotropy
Act on more than
one cell type
(INFa/b)
Synergy
Two or more
cytokines cooperate
to produce an effect
that is different or
greater than the
combined effect of
the two cytokines
when functioning
separately (IL-12
and IL-8)
Antagonism
Two or more
cytokines work
against each other
(IL-4 and IL-12)
CYTOKINE ACTIONS:
22. EARLY MEDIATORS
IL-12, IL-15, 1l-18, IFN-g (from NK cells), IL-10
Proinflammatory mediators
Produced by cell associated with innate immunity
(macrophages, NK, etc.)
Mediate direct effects
Promote inflammation.
Shape downstream responses
LATE MEDIATORS
• IL-2, IL-4, IL-5, IFN-g, TNF, IL-6, IL-10
• Produced by cells of the adaptive immune
response (T and B cells)
• Direct effects
• More immunoregulatory functions
23. CYTOKINE CROSS-REGULATION
•In a given immune response, either TH1 or TH2 response dominates
•Cytokines of one response tend to down-regulate the other type of response
•Example: TH1 cells secrete IFN-g, which inhibits proliferation of TH2 subset
24. CYTOKINE-RELATED DISEASES
Bacterial septic shock
Blood pressure drops, clots form, hypoglycemia ensues, patient dies
TNF induces IL-1 which induces IL-6 and IL-8
Bacterial toxic shock and related diseases
Superantigens
Lymphoid and myeloid cancers
Some cancer cells secrete cytokines
Chagas’ disease
Trypanosoma cruzi infection results in sever immune suppression
Depression of IL-2 receptor production
25. Viral replication is
blocked in uninfected cells
Degrade viral nucleic acid
produce antiviral proteins that prevent
translation of viral mRNA
INTERFERONS
26. THERAPEUTIC USES OF CYTOKINES
Modulation of TH activation
Interfere with receptor function
Soluble T-cell receptor
Anti-IL-2R
Interleukin analogs which bind receptor, but do not
trigger activation (ties up receptor)
Toxins conjugated to cytokines which kill activated T-cells
Administration of cytokines to enhance immunity (side
effects/ short half lives)
Allergies
27. ♠The end result of b-cell activation –
differentiation into
antibody-secreting cells, called plasma cells.
♠Secreted antibodies enter mucosal
secretions and the blood and
are able to find, neutralize, and eliminate antigens
28. NATURAL KILLER CELLS
10% to 15% of the peripheral blood lymphocytes
do not bear T-cell receptors or cell surface immunoglobulins
Morphologically, larger than small lymphocytes, and they contain
abundant azurophilic granules
Innate ability to kill a variety of tumor cells, virally infected cells
without previous sensitization.
Two cell surface molecules, CDI6 and CD56, are widely used to
identify NK cells
29. MONONUCLEAR PHAGOCYTES:
Monocyte
Enlarge 5-15 times
intracellular organelles
increase in number and complexity,
cells acquire increased phagocytic ability,
increased secretion of many soluble factors
Most powerful activator of macrophages is
interferon-gamma secreted by activated TH
cells.
Activated macrophages
Greater phagocytic activity,
Inflammatory mediators secretion,
Ability to activate T-cells.
30. Process the antigens and present peptide fragments to T cells.
induction and in the effector phase of immune responses.
important in the effector phase of humoral immunity. macrophages
phagocytose microbes that are opsonized (coated) by IgG or C3b
Cell-mediated immunity, such as the delayed hypersensitivity
reaction.
MACROPHAGES
31. 60% of WBC population.
multilobed nucleus
granular cytoplasm and are also called
polymorphoneutrophils (PMN).
Hematopoiesis in bone marrow.
Blood stream; circulate for 7-10 hrs before migrating
into tissues.
Lifespan of few days.
PMN are first to arrive at a site of inflammation by
extravasation
Neutrophils like macrophages are phagocytes and
phagocytosis is almost similar to that of macrophages.
32. resemble neutrophils
but their phagocytic activity is significantly less
the defense activity is specially enhances in parasitic
infestations.
these are non-phagocytic granulocytes
function by releasing pharmacologically active substances
from their cytoplasmic granule.
these agents induces certain allergic responses.
33. Released from the bone marrow as undifferentiated precursor
cells
do not differentiate until they enter the tissues (skin,
connective tissue, mucosal epithelium, etc.)
Morphology and function similar to circulating basophils
Mast cells bear Fc receptors for IgE and contain large
numbers of cytoplasmic granules(HISTAMINE)
play a very important role in the allergic response.
34. DENDRITIC CELLS
Located— under epithelia, the
common site of entry of
microbes and foreign antigens,
and in the interstitia of all
tissues, where antigens may be
produced.
Receptors for capturing and
responding to microbes (and
other antigens), including
tlrs and mannose receptors.
Express high levels of mhc
class ii molecules as well as
the costimulatory molecules
They are ideally located to
present antigens to
recirculating t cells.
cells express the same
chemokine receptor as do
naive t cells and are thus
recruited to the t-cell zones
of lymphoid organs
35. Typical APCs express both class-I and class II MHC:
Dendritic cells
Macrophages
B cells
Tissue-specific APCs:
Langerhans cells (skin)
Kupffer cells (liver)
Microglial cells (CNS)
ANTIGEN-PRESENTING CELLS (APC)
37. DETERMINANTS OF ANTIGENICITY:
Size
Chemical Nature
Susceptibility To Tissue Enzymes
Foreignness
• Large molecular
size highly
antigenic
• Low molecular
size less or non-
antigenic
• Proteins and
polysaccharides
highly antigenic.
• Lipids and
nucleic acids less
antigenic.
Metabolized
and are susceptible
to the action of
tissue enzymes.
Only antigens that
are foreign to the
individual (non self)
induce
an immune
response.
38. The same or closely related antigens present in
different tissues of more than one species are
known as heterophile antigens.
Antibodies to these antigens produced by one
species cross react with antigens of other
species.
Forssman antigen
Paul-Bunnell test
HETEROPHILE SPECIFICITY OF ANTIGENS:
39. Synthesized by Plasma cells and some extent by
lymphocytes.
So all the antibodies are immunoglobulins, but all
immunoglobulins may not be antibodies.
Glycoproteins
Each molecule consists of two pairs of polypeptide chains
Smaller chain – ‘Light’ chain , molecular weight 25000
Larger ones – ‘Heavy’ chain , molecular weight 50000
H chain is attached to L chain by a disulphide bond
ANTIBODIES (IMMUNOGLOBULIN)
40. FUNCTIONS OF ANTIBODIES Activates B
lymphocytes
Antigen binds
to antibody
Antigen
binding
site
Bacterial
toxins
Activates antibody-
dependent cellular
activity
Acts as
opsonins
Causes antigen clumping
and inactivation of
bacterial toxins
Triggers mast cell
degranulation
Memory
cells
Plasma
cells
NK cell or eosinophil
Antibody
Secrete
antibodies
Activates
complement
Enhanced
phagocytosis
1
2
3
4
5
6
41. TYPES OF ANTIBODY (Ab) REACTIONS
NEUTRALIZATION = When the antigen is a soluble toxin, the addition of an Ab against it will
usually render the toxin INEFFECTIVE (nontoxic), that is it NEUTRALIZES it. Such neutralized
toxins are called TOXOIDS and can be used as vaccines.
PRECIPITATION = under the proper conditions a soluble antigen can be precipitated in the
presence of its Ab because of the antigen-antibody net-work that forms gels large enough to
form masses that SETTLE OUT (precipitate) on their own.
AGGLUTINATION = When the antigen is a large PARTICLE, like a whole bacterium or a RBC, the
addition of its Ab will form an Ab-antigen net work that causes the particles to CLUMP IN
LARGE MASSES like milk coagulating when it spoils.
42. • Discovered at the end of the 19th century as a heat-labile component of serum that augmented (or
‘complemented’) its bactericidal properties.
• Now known to comprise some 16 plasma proteins, together constituting nearly 10% of the total
serum proteins, and forming one of the major immune defence systems of the body.
Functions:
the triggering and amplification of inflammatory reactions;
attraction of phagocytes by chemotaxis
clearance of immune complexes
cellular activation
direct microbial killing; and an important role in the development of antibody responses
THE COMPLEMENT SYSTEM
45. COMPLEMENT SYSTEM AND INFLAMMATION
Efficient, rapid, and occurring in synchrony with the initiation of an inflammatory reaction, the
activation of complement is a prerequisite for its involvement in regulation of inflammatory
processes.
soluble components of complement are present not only in the circulation but also in body fluids and
tissues, ready to engage in defense reactions triggered by exogenous (eg, infectious agents) or
endogenous (eg, ischemia, autoimmunity) stimuli that could cause cell injury
For example, in infection induced by Leishmania, approximately 90% of promastigotes are lysed by
complement in just 2.5 minutes after contact with human blood. Therefore, complement effectors
generated as a result of this activation can participate in the earliest events of an inflammatory
reaction.
C5a activates the lipoxygenase pathway of arachidonic acid metabolism in neutrophils and monocytes, leading to an
acceleration of eicosanoid production by these cells.
Mast cells and neutrophils that are activated by complement anaphylatoxins release mediators that cause vasodilation
and extravasation of fluid.
C5a and C3a stimulate the production of cytokines.
The interactions between the complement system and proinflammatory cytokines are reciprocal. Several reports have
suggested that proinflammatory cytokines enhance the expression of anaphylatoxin receptors in inflammatory cells.
46. HEREDITARY ANGIOEDEMA
Hereditary angioedema (HAE) is a rare disorder,
characterized by intermittent attacks of swelling in any
part of the body, without the presence of hives.
Presents in the first 2 decades of life.
Commonly associated with a deficiency in functional
C1 esterase inhibitor (C1-INH) activity.
C1-INH levels may be decreased or normal, with an
accompanied decrease in functionality.
Early diagnosis of the disease can lead to the
development of an individualized treatment plan to
assist with prevention and management of angiodema
attacks.
47. PHAGOCYTOSIS
Bacterium becomes attached to membrane
evaginations called pseudopodia
Bacterium is ingested, forming phagosome
Phagosome fuses with lysosome
Lysosome enzymes digest captured material
Digestion products are released from the
cell
48. Macrophages
Ingest and digest
•whole antigen
molecule,
•pathogens,
•insoluble particles,
•cellular debris, and
•activated clotting
factors
PHAGOCYTOSIS
49. O2 dependent
Activated Macrophages
reactive O2 intermediators
(ROIs), and
reactive N2 intermediators
(RNIs).
Respiratory burst of cell
Activation of membrane bound oxidases
Oxygen Superoxide ion
catalyses
Hydroxyl radicals H2O2
Toxic to pathogens
Secrete Cytokines,
Activate TH cells,
RNIs
NO synthatase
PHAGOCYTOSIS
50. Activated macrophages
lysosomes and various other
hydrolyzing enzymes
defensins which are cytotoxic enzymes,
can kill a variety of bacteria including
staphylococci, streptococci, E. coli,
Psuedomonas species etc
The tumor necrosis factor is also secreted
by the activated macrophages which has a
variety of effects including cytotoxic to
tumor cells.
Kill pathogens
O2 independent
PHAGOCYTOSIS
52. MHC or HLA complex –located on short arm of chromosome 6
They code for 3 different classes of proteins:
1 class I protein that determines histocompatibility and the
acceptance and rejection of allografts
2 class II protein regulate immune response
3 class III protein that include some component of immune system
Antigen
The Major Histocompatibility Complex (MHC)
HLA class I antigens
found on all nucleated cells.
Principle antigens involved in graft rejection and cell mediated cytolysis
HLA class II antigens
Found only in cells of immune system
Macrophages, dendritic cells, Activated T cells
HLA class III antigens
Heterogenous
Take part in formation of C3 convertase and tumor necrosis factor
53. GRAFT VERSUS HOST DISEASE:
Multisystem Disorders due to immune reaction caused by transplanted cells from a non-identical donor
(the graft) that recognize recipient cells (the host) as foreign, thus disease is caused in the recipient organs.
PATHOPHYSIOLOGY OF GVHD:
•Effector cells(Donor T cells)
• Proinflammatory Cytokines(IL1,
IL2, TNF, IFN)
• Target Host tissues (Skin, Liver,
Intestines)
Allogenic recognition &
•Autologous dysrecognition
CLASSIFICATION:
• Classic acute GVHD
• Persistent, recurrent, late
onset acute GVHD
• Classic chronic GVHD
• Overlap syndrome “Acute
on Chronic GVHD”
CLINICAL MANIFESTATIONS:
• Diarrhea
• skin lesions
• Jaundice
• spleen enlargement, and
• death.
Epithelial cells of the skin and gastrointestinal tract
often become necrotic, causing the skin and intestinal
lining to be sloughed.
54. 1.The afferent phase: activation of APC
(antigen presenting cells)
2.The efferent phase: activation,
proliferation, differentiation and migration
of effector cells
3.The effector phase: target tissue
destruction
PATHOPHYSIOLOGY:
55. MANAGEMENT:
Grade 1 GVHD Management
A. Topical steroids are the most commonly used skin-
directed therapy for acute GVHD.
B. Antihistamines may be used as supportive therapy
for patients with pruritus.
C. In Resistant grade 1 aGVHD, Topical Tacrolimus may
be useful.
D. Optimizing prophylactic agents When acute GVHD
of any grade develops, to ensure a therapeutic level.
For those no longer receiving prophylaxis, the prior
prophylactic agent should be restarted again.
GRADE 2-4 GVHD
• A. First Line of Treatment: Corticosteroids
• Second Line of Treatment:
• Given in Patients who fail to respond To steroids
1. Mycophenolate mofetil (MMF)
2. Etanercept “ Anti TNF Antibodies”
3. Pentostatin
4. Sirolimus
5. Basiliximab
6. Extracorporeal Photopheresis.
56. HYPERSENSITIVITY
Hypersensitivity is defined as an exaggerated or inappropriate state of normal immune response
with onset of adverse effects on the body.
These lesions are termed as hyper sensitivity reactions or immunologic tissue injury, of which 4
types are described: type I, II, III and IV.
Depending upon the rapidity, duration and type hypersensitivity reactions are grouped into:
1. Immediate type of hypersensitivity reactions include type I, II and III.
2. Delayed type includes Type IV reaction.
58. ANAPHYLAXIS:
Allergic reactions may be triggered by a
variety of factors including drugs (e.g.
penicillin), foods (e.g. shellfish), insect
stings and chemicals.
Wide spectrum of severity ranging from
a harmless skin rash (urticaria), to
potentially fatal airway obstruction
(laryngeal oedema) and full-blown
anaphylaxis (hypotension,
bronchospasm).
59. PATHOPHYSIOLOGY:
The clinical manifestations of allergy result from an antigen-antibody
reaction. Such reactions are a part of the body’s defense mechanisms (i.e.,
immune system), described in the following section to provide a better
understanding of the processes involved in allergy.
For acute, immediate allergy or for anaphylaxis to occur, three conditions
must be met:
1. An antigen-induced stimulation of the immune system with specific
immunoglobulin E (IgE) antibody formation
2. A latent period after the initial antigenic exposure for sensitization of
mast cells and basophils
3. Subsequent reexposure to that specific antigen
60. EITIOLOGY FOR PERIOPERATIVE ANAPHYLAXIS:
Muscle relaxants
Latex
Antibiotics: Penicillin, cephalosporins, and
other-lactam antibiotics
Plasma volume expanders (colloids)
Intravenous drugs used for anesthetic induction
Benzodiazepines
Povidone-iodine
Chlorhexidine
Nonsteroidal anti-inflammatory drugs
Local Anaesthesia
61. RING J, MESSMER K. INCIDENCE AND SEVERITY OF ANAPHYLACTOID REACTIONS TO COLLOID
VOLUME SUBSTITUTES. LANCET 1977;1(8009):466–9.
62.
63.
64. TYPE II: ANTIBODY-MEDIATED (CYTOTOXIC) REACTION
Type II or cytotoxic reaction is defined as reaction by humoral
antibodies that attack cell surface antigens on the specific cells
and tissues and cause lysis of target cells.
65. TRANSFUSION REACTIONS DUE TO ABO INCOMPATIBILITY
Transfusion reactions are the adverse reactions in the body, which occur due to
transfusion error that involves transfusion of incompatible (mismatched) blood.
In mismatched transfusion, the transfusion reactions occur between donor’s RBC
and recipient’s plasma.
So, if the donor’s plasma contains agglutinins against recipient’s RBC,
agglutination does not occur because these antibodies are diluted in the
recipient’s blood.
But, if recipient’s plasma contains agglutinins against donor’s RBCs, the immune
system launches a response against the new blood cells.
Donor RBCs are agglutinated resulting in transfusion reactions.
66. TRANSFUSION REACTIONS DUE TO RH INCOMPATIBILITY
When a Rh negative person receives Rh positive blood for the first time, he
is not affected much, since the reactions do not occur immediately.
But, the Rh antibodies develop within one month.
The transfused RBCs, which are still present in the recipient’s blood, are
agglutinated.
These agglutinated cells are lysed by macrophages.
So, a delayed transfusion reaction occurs.
But, it is usually mild and does not affect the recipient.
However, antibodies developed in the recipient remain in the body forever.
So, when this person receives Rh positive blood for the second time, the
donor RBCs are agglutinated and severe transfusion reactions occur
immediately
67. HEMOLYTIC DISEASE OF FETUS AND NEWBORN – ERYTHROBLASTOSIS FETALIS
Œ
Haemolytic disease of newborn results from the passageof IgG
antibodies from the maternal circulation across the placenta into the
circulation of the foetal red cells.
It could be due to incompatibility of Rh or ABO groups.
Œ
Ultimately due to excessive hemolysis severe complications develop,
viz.
1. Severe anemia
2. Hydrops fetalis
3. Kernicterus.
Prevention or treatment for erythroblastosis fetalis
i. If mother is found to be Rh negative and fetus is Rh positive, anti D
(antibody against D antigen) should be administered to the mother
at 28th and 34th weeks of gestation, as prophylactic measure.
ii. If the baby is born with erythroblastosis fetalis, the treatment is
given by means of exchange transfusion. Rh negative blood is
transfused into the infant, replacing infant’s own Rh positive blood.
68. TYPE III: IMMUNE COMPLEX MEDIATED (ARTHUS) REACTION
Type III reactions result from deposition of antigen-antibody complexes on tissues, which is followed by
activation of the complement system and inflammatory reaction, resulting in cell injury.
The onset of type III reaction takes place about 6 hours after exposure to the antigen.
69. RHEUMATOID ARTHRITIS
Rheumatoid arthritis is a chronic disease of unknown aetiology.
But there is evidence to indicate that it may be a hypersensitivity
reaction to bacterial toxins, specifically streptococci.
Involvement of the TMJ may occur concomitantly with the other
joint lesions or may arise subsequently.
Radiographically, joints may be irregular, articular surfaces
become flat, and subcortical pseudocysts and osteophytes may be
present
70. TYPE IV: DELAYED HYPERSENSITIVITY(T CELL-MEDIATED) REACTION:
Type IV or delayed hypersensitivity reaction is tissue injury by T cell-mediated immune
response without formation of antibodies (contrary to type I, II and III) but is instead a
slow and prolonged response.
The reaction occurs about 24 hours after exposure to antigen and the effect is prolonged
which may last up to 14 days.
71. STEVEN JOHNSON SYNDROME
SJS is a type IV hypersensitivity reaction in which a drug or its
metabolite stimulates cytotoxic T cells (i.e. CD8+ T cells) and T
helper cells (i.e. CD4+ T cells) to initiate autoimmune reactions that
attack self tissues
The immune reaction can be triggered by drugs or infections
Individuals may have variations in their efficiency
to absorb, distribute to tissues, metabolize, or excrete (this
combination is termed ADME) a drug.
73. LICHEN PLANUS
Oral lichen planus (OLP) is a common mucocutaneous disease.
The condition can affect either the skin or mucosa or both.
Oral lichen planus is a T cell-mediated autoimmune disease in which
cytotoxic CDS+ T-cells trigger the apoptosis of oral epithelial cells.
It can cause bilateral white striations, papules, or plaques on the
buccal mucosa, tongue, and gingivae.
The involvement of the oral mucous membrane is so frequent and
accompanies or precedes the appearance of lesions on the skin and
genital mucous membrane.
TREATMENT: symptomatic relief, topical corticosteroids.
74. MIKULICZ SYNDROME
• Mikulicz disease is a chronic condition characterized by the abnormal
enlargement of salivary and lacrimal glands. The tonsils and other glands in the
soft tissue of the face and neck may also be involved.
• The exact cause of Mikulicz disease is not known, although it is suspected to
be an autoimmune disorder. The symptoms of Mikulicz disease may occur due
to the excessive accumulation of lymphocytes into involved glands.
75. SJOGREN’S SYNDROME
Sjogren syndrome is a condition, consisting of a triad of
keratoconjunctivitis sicca, xerostomia and rheumatoid arthritis.
Sjogren syndrome have been found to be associated with the HLA
system, specifically HLA-DR3 and HLA-B8, which are associated
with the primary form of the disease, and HLA-DRw52
76. SYSTEMIC LUPUS ERYTHEMATOSUS:
•Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibodies, immune
complex formation, and immune dysregulation resulting in damage to essentially any organ, including kidney,
skin, blood cells, and CNS.
•Patients with SLE produce autoantibodies against DNA, other nuclear antigens, ribosomes, platelets,
erythrocytes, leukocytes, and other tissue-specific antigens. Thus, the resulting immune complexes result in
widespread tissue damage.
•FEATURES: butterfly malar rash, photosensitivity, fibrinoid thickening of glomerular capillaries, localized
telangiectasis
77. VACCINES
A state of immunity can be induced by passive or active immunization
a) Short-term passive immunization is induced by transfer of preformed antibodies.
b) Infection or inoculation achieves long-term active immunization.
■ Three types of vaccines are currently used in humans: attenuated (avirulent)
microorganisms, inactivated (killed) microorganisms,or purified macromolecules.
80. IMMUNOMODULATORS:
These are natural or synthetic substances that help regulate or normalize the
immune system.
They correct immune systems out of balance,
Immunomodulators may be further classified into immunostimulants and
immunosuppressants.
81. CANCER AND THE IMMUNE SYSTEM
CANCER INDUCTION
Proto-oncogenes-encode proteins involved in control of
normal cellular growth.
proto-oncongenes oncogenes
Tumor suppressors - inhibit cell proliferation.
Inactivation of these results in unregulated proliferation.
Regulators of apoptosis- bcl-2, an anti-apoptosis gene
Chromosome translocation-Defects in any of these can lead
to uncontrolled cell growth
82. IMMUNE RESPONSE TO
TUMORS:
• -Cell-mediated response appears to
play the major role:
• - Tumors reduce MHC Class I
expression
• The recognition of tumor cells by NK
cells is not MHC restricted.
• Activated macrophages ~ regression
• (lytic enzymes, ROI, RNI, TNF-
alpha)
• Tumors can evade immune response
• Anti-tumor antibody can block T cell
responses (enhance tumor growth)
• The antibody binds to tumor-specific antigens
and masks the antigens from cytotoxic T
cells.
• Tumors can modulate antigens – “Ag
modulation”
83. 5. Monoclonal antibodies are useful in treating some
tumors
Immunomodulators
4. Cytokine therapy
Augment Immune Responses
to Tumors
Interferons(INF-alpha, beta,
gamma),
-(increase. MHC I, MHC II
expression on tumour cells).
Tumor necrosis factors (TNF-
alpha, beta,)- inhibits tumour
induced vascularization
3. Adjuvants
Any substance which enhances the immunogenicity of an antigen is
called adjuvant
The attenuated strains of Mycobacterium bovis called bacillus
calmette-guerin (BCG) and corynebacterium parvuum
These adjuvants activate macrophages, increasing their
expression of various cytokines, class II MHC molecules, and the
B7 co-stimulatory molecule.
These activated macrophages are better activators of TH cells,
resulting in generalized increases in both humoral and cell-
mediated responses.
2. Enhancement of Antigen Presenting Cells Activity Can Modulate
Tumor Immunity
1. Manipulation of Co-Stimulatory Signals Can Enhance
Immunity
CANCER IMMUNOTHERAPY
84. ELISA
The enzyme-linked immunosorbent assay (ELISA) is a commonly
used analytical biochemistry assay.
The assay uses a solid-phase type of enzyme immunoassay (EIA) to
detect the presence of a ligand (commonly a protein) in a liquid
sample using antibodies directed against the protein to be measured.
The sample with an unknown amount of antigen is immobilized on a
solid support either non-specifically or specifically.
After the antigen is immobilized, the detection antibody is added,
forming a complex with the antigen.
The detection antibody can be covalently linked to an enzyme or can
itself be detected by a secondary antibody that is linked to an enzyme
through bioconjugation.
85. POLYMERASE CHAIN REACTION:
Principle: it is a DNA amplification system that produces a large amount of
DNA in vitro from small amounts of starting material. It amplifies a specific
DNA sequence or gene of interest.
It is used in the early stages of processing DNA for sequencing?, for detecting
the presence or absence of a gene to help identify pathogens ?during infection,
and when generating forensic DNA profiles from tiny samples of DNA.
Procedure: it involves 4 main stages:
1. Denaturation
2. Primer annealing
3. DNA synthesis
4. Detection of amplified product.
87. Roth Karin, Hadrick Werner-Animal and human bite wounds-nature (2015)
Incidence of animal or human bites 200/100000/year
Most commonly by dogs and cats , affecting children more than adults .
Classification of bite wound by Lackman
1. superficial not involving muscle
2. deep injury with muscle
3. deep injury with muscle and tissue loss
4. above+ nerves and vessels
5. the above with bone involvement
Wounds with high risk of infection
Deep contaminated wounds with poor perfusion , wounds on hands ,feet and face involving bones , joints and
tendons.
88. Treatment :
General measures for local treatment
i)Cleaning (1% iodine solution)
ii)Irrigation
iii) debridement of devitalized tissue
iv)primary wound closure
v)limb immobilization
Infection prophylaxis
Immunization : tetanus , rabies
Antibiotic : wounds of high risk of infection
current studies show that primary suturing can be extended to 12 hours / longer and wound infection is no more common after primary suturing can of the bite. It is
contraindicated in deep puncturing wounds with deep inoculation of pathogens.
89. £ The knowledge of essential immunology is essential to understand the ability of an individual to cope-up to the disease
situation and also to modify the immune mechanisms to be effective in cases of immunocompromised statuses.
£ It can be applied for the benefit of patients either in terms of immune enhancement or immune suppression whichever is
beneficial to the patients.
CONCLUSION
90. REFERENCES:
1) Essential Immunology, Ivon Roitt.
2) Basic immunology and its medical approaches (2nd edit). Barette
3) Oral microbiology with basic microbiology and immunology. - William A. Nolte
4) Immunology – Weir
5) Oral microbiology and basic immunology – Newman and Nisergaurd.
6) Immune Defects In Specific Diseases: Oral Maxillofacial Surg Clin N Am 15 (2003) 103–110
7) Immunology and immunohistochemistry-Williams a Curtis
8) Microbiology in dentistry – Frank J. Orland.
9) Immunology – Zamtito
10)Immunology and infectious diseases of head and neck-zambito and clevi.
11)Textbook of microbiology – Ananthanarayan and Paniker.
