This document provides an overview of key concepts in immunology. It defines terms like immunity, antigen, antibody, and discusses the historical perspectives on immunity. It describes the two arms of the immune system - innate and adaptive immunity. The innate system provides immediate non-specific defense mechanisms while the adaptive system mounts an antigen-specific response. It also summarizes the cells and tissues involved in both systems along with their functions.

2. BASIC TERMINOLOGY
• IMMUNITY-A state of protection from the disease comes
from the latin term IMMUNIS meaning “exempt”.
• ANTIGEN-Any substances foreign to the body that elicits
an immune response when introduced into the tissues of
a susceptible animal and capable of combining with the
specific antibodies formed.
• ANTIBODY-an immunoglobulin,(specialized immune
protein) produced because of the introduction of an
antigen into the body, and which possesses the
remarkable ability to combine with the vary antigen that
triggered it’s production.
 Functionally, an immune response can be divided into two
related activities- Recognition
Response

3. HISTORICAL PERSPECTIVE
• 430 BC-The great historian
Thucydides wrote-
“only those who had recovered
from the plague could nurse the sick
because they would not contract the
disease a second time.”
• 1500 AD-The first recorded attempts
to induce immunity deliberately were
performed by the Chinese and Turks
by the technique called “variolation”.
• 1798 AD-Edward Jenner inoculated an
eight-year-old boy with fluid from a
cowpox pustule and later intentionally
infected the child with smallpox. As
predicted, the child did not develop
smallpox.

4. HISTORICAL PERSPECTIVE

5. IMMUNITY INVOLVES BOTH CELLULAR AND HUMORAL COMPONENTS
• 1883AD- Elie Metchnikoff demonstrated that
certain white blood cells, which he termed
phagocytes, were able to ingest (phagocytose)
microorganisms and other foreign material
contribute to the immune state of an animal.
• 1890AD- Von Behring(NP-1901) and Kitasato
demonstrated that serum (the liquid, non cellular
component of coagulated blood) from animals
previously immunized to diphtheria could
transfer the immune state to unimmunized
animals.
• In 1930s, Elvin Kabat , a fraction of serum first
called as gamma-globulin (now immunoglobulin)
was shown to be responsible for all these
activities. The active molecules in the
immunoglobulin fraction are called antibodies.

6. IMMUNITY INVOLVES BOTH CELLULAR AND HUMORAL
COMPONENTS
• In 1940s-Merrill Chase succeeded in transferring
immunity against the tuberculosis organism by
transferring white blood cells between guinea pigs.
• In 1950s- Lymphocyte was identified as the cell
responsible for both cellular and humoral immunity.
• Bruce Glick (Mississippi State University) indicated
that there were two types of lymphocytes: T
lymphocytes derived from the thymus mediated
cellular immunity, and B lymphocytes from the bursa
of Fabricius (an outgrowth of the cloaca in birds) and
bone marrow in mammals were involved in humoral
immunity both were necessary for the immune
response.

7. TWO ARMS OF THE IMMUNE SYSTEM: INNATE IMMUNITY
& ADAPTIVE IMMUNITY
 INNATE IMMUNITY-
• Found in all animals and plants.
• In vertebrates, innate immunity is a first response to infections and
also serves as the foundation of adaptive immunity.
• Responds quickly(within hours).
• Limited, broad and fixed specificity.
• Encoded in the germline and evolutionarily more primitive.
 ADAPTIVE IMMUNITY-
• Not found in all members of a species.
• Provides second and more comprehensive line of defense.
• Shows property of antigenic specificity, diversity, immunologic
memory and self/non self recognition.
• Respond takes days to appear.
• Adapts to improve during the course of immune response getting
more rapid and effective with each subsequent exposure.

8. CLASSIFICATION OF IMMUNITY

9. CELLS OF IMMUNE SYSTEM

10. COMPONENTS OF INNATE IMMUNITY & THEIR FUNCTIONS

11. CHEMICAL MEDIATORS OF INNATE IMMUNITY
• Peptides and proteins function in innate defense by attacking
pathogens or impeding their reproduction.
• Lysozyme-hydrolytic enzyme found in mucous secretions, tears
cleaves peptidoglycan layer of the bacterial cell wall.
• Interferon- proteins secreted by virus-infected cells, provide innate
defense, interfering with viruses and helping activate macrophages.
• Complement system-About 30 proteins make up the complement
system, which causes lysis of invading cells and helps trigger
inflammation.
• Collectins- these surfactant proteins may kill certain bacteria directly
by disrupting their lipid membranes or, alternatively, by aggregating
the bacteria to enhance their susceptibility to phagocytosis.

12. TOLL-LIKE RECEPTOR(TLR)
 Pattern recognition by toll-like receptors(TLR)-
• Pathogens entering the mammalian body are
subjected to phagocytosis by binding with the
receptors(TLR) of phagocytic cells.
• TLR has the capacity of “pattern recognition”,
the ability to recognize certain unique types of
molecules that are never found in multicelular
organisms known as pathogen associated
molecular pattern(PAMP).
• Lysozyme, complement system or cell
associated TLR has the ability of “pattern
recognition”.
• Ex-TLR-2 can recognize the
lipopolysaccharide(LPS) found in gram –ve
bacteria and elicits a variety of molecules in the
inflammatory response upon exposure.
• TLR-5 recognizes protein flagellin found in
flagellated bacteria.
• TLR-3 recognizes double stranded RNA.

13. PHAGOCYTIC BARRIER
• Another important innate defense
mechanism is the ingestion of
extracellular particulate material
by phagocytosis.
• Most phagocytosis is conducted
by specialized cells, such as-
• blood monocytes,
• Neutrophils
• tissue macrophages.
• Most cell types are capable of
receptor-mediated endocytosis, in
which extracellular molecules are
internalized after binding by
specific cellular receptors, and
pinocytosis, the process by which
cells take up fluid from the
surrounding medium along with
any molecules contained in it.

14. INFLAMMATORY BARRIER/ RESPONSE
• Tissue damage caused by a wound or by an invading pathogenic
microorganism induces a complex sequence of events collectively
known as the inflammatory response.
• In the first century AD, the Roman physician Celsus described the
“four cardinal signs of inflammation” as rubor (redness), tumor
(swelling), calor (heat), and dolor (pain). In the second century AD,
another physician,
• Galen, added a fifth sign: functio laesa (loss of function).
• The cardinal signs of inflammation reflect the three major events of
an inflammatory response-
• Vasodilation- Causing erythema, increase in tissue temperature.
• ↑capillary permeability-Causing exudation &edema.
• Influx of phagocytes- By margination, dipedesis and chemotaxis.
• As phagocytic cells release lytic enzymes, a fluid rich in white blood
cells, dead pathogens, and cell debris from damaged tissues is
formed called Pus.

15. CHEMICAL MEDIATORS OF INFLAMMATORY RESPONSE
 ACUTE-PHASE PROTEINS-They are various serum proteins whose
concentration increase dramatically in tissue-damaging infections.
eg-
• C-reactive protein(C-RP)- binds with C-polysaccharide cell wall
component of variety of bacteria and fungi and activates
complement system.
• Histamine- Released from the mast cells, a type of connective
tissue, causing vasodilatation & ↑permeability.
• Kinins- Small peptides present in blood plasma, activated by tissue
injury causing vasodilation & ↑capillary permeability. A particular
kinin, bradykinin stimulate the pain receptors of skin.
• Fibrin-Main component of the clotting system, wall off the injured
area and prevent the spread of infection.

16. SCHEMATIC DIAGRAM EVENTS OF INFLAMMATORY
RESPONSE

17. ADAPTIVE IMMUNITY
• Capable of recognizing & selectively eliminating foreign antigens.
• Shows four characteristic attributes-
 Antigenic specificity-can distinguish between two protein molecules that
differ in only a single amino acid.
 Diversity-allows to identify billions of unique structures on foreign antigens.
 Immunologic memory-second encounter with the same antigen induces
more rapid & effective response due to which it can confer life long
immunity to many infections after an initial encounter.
 Self/nonself recognition- Responds only to nonself molecules.
• Phagocytic cells of the innate immunity is intimately involved in activating
the specific immune response. conversely, various soluble factors
produced by adaptive immunity augment the activity of these phagocytic
cells.

18. COMPONENTS OF ADAPTIVE IMMUNITY-CELL MEDIATED & HUMORAL
IMMUNITY
• HUMORAL IMMUNITY-
Mediated by B-lymphocyes.
• B-lymphocyte is synthesized
and matured within bone-
marrow where they expresses
a unique antigen binding
glycoprotein, membrane bound
receptor called “antibody
molecule.”(Ab)
• Amino terminal ends of the
pairs of heavy and light chains
form a cleft with in which
antigen(Ag) binds.

19. FATE OF ANTIGEN-ANTIBODY COMPLEX
• Ag-Ab complexes is then engulfed by
phagocytic cells and partially digested.
• Antigen is displayed on the B-cell
surface by a special receptor protein
(MHC II) for recognition by helper T-
cells(TH).
• B-cell is activated by the helper T-cell to
divide rapidly and differentiate into-
Effector B-cell also known as plasma
cells- produce secreted antibodies that
circulate in the serum and lymph.
 Some B-cells become memory cells-
• produce antibody at a low rate for a
long time (long term immunity as it has
longer life span)
– They respond quickly when the
antigen is encountered again
– the response is regulated by a
class of T-cells called suppressor T-
cells

20. HUMORAL IMMUNE RESPONSE

21. CELL MEDIATED IMMUNITY
• Mediated by T-Lymphocyte which
arises in the bone marrow and
mature within the thymus gland to
express a unique antigen-binding
molecule called T-cell receptor.
• T cell receptors are cell membrane
receptors that bind nonself
substances presented on the
surface of antigen presenting cell
bound with major histocompatibility
complex(MHC) molecules.
• Unlike antibodies, T-cells can
recognize antigens only when it is
presented along with MHC on the
membrane of the APC.
• After binding T-cell activation takes
place.

22. CELL MEDIATED IMMUNITY
• There are two well-defined subpopulations of T-cells.
 Memory T-cells
 Effector T-cells - Helper T-cells (TH) and
- Cytotoxic T-cells (TC)
• Helper T-cells:
• Contain a surface glycoprotein called CD4 on their surface.
• Recognizes and interacts with an antigen-MHC class II molecule complex.
• Secretes various growth factors known as “cytokines” which activates B-cells,
TC cells, macrophages and various other cells that participate in immune
response.
• Regulate both cellular and humoral immune systems.
• Cytotoxic T-cells:
• Contain a surface glycoprotein called CD8 on their surface.
• Activated by TH- derived cytokines and recognizes antigen-MHC class I
molecule complex.
• proliferates and differentiates into cytotoxic T-lymphocytes (CTL).
• Destroy virus infected cells, cancer cells, and foreign cells (transplanted organs)
by secreting “PERFORIN” and GRANZYME.

24. GENERATION OF DIVERSITY IN ANTIGEN RECEPTORS OF B
AND T LYMPHOCYTES
• Antigenic specificity is determined by the membrane-bound antigen-
binding receptor(antibody)on B-cells and antigen-binding T-cell
receptor(TCR) expressed on T-cells.
• As the B cells and T cells matures, random rearrangement of a series
of gene segments occure that encode the antigen binding receptors.
• Random rearrangement of antigen encoding genes can capable of
generating on the order of 10⁹ and 10¹² unique antigenic specificities in
B and T cell receptors respectively.
• This enormous diversity then goes through a “selection process” which
eliminate any B cell and T-cell with self-reactive receptors(negative
selection).
• This selection process ensures that self-reactive antibodies (auto-
antibodies) are not produced.
• Any derangements in the selection process leads to the formation of
auto-antibodies which is the basis of various autoimmune diseases.

25. MAJOR HISTOCOMPATIBILITY COMPLEX
• Large genetic complex with multiple loci, each loci encode three major
classes of memebrane bound glycoproteins-MHC class I,II &III.
• Acts as antigen-recognition molecule but do not have the fine specificity for
antigen as that of antibody or TCR.
• Distal regions of different alleles display wide variation in their amino acid
sequences that form a cleft within which antigenic peptides are presented
to T-lymphocytes.
• Different allelic forms of the genes encoding class I and class II MHC
molecules confer different structures on the antigen binding cleft with
different specificity.
• Helper T-cells(TH) recognizes class II MHC molecules while cytotoxic T-
cells(TC) recognizes class I MHC molecules.
• PROMISCUITY- A given MHC molecules can bind to numerous different
peptides and some peptides can bind with several different MHC
molecules.

26. TYPES OF MHC MOLECULES
• MHC is a collection of genes arrayed within a long continuous stretch of
DNA on chromosome 6 in human referred to as Human Leukocyte
antigen(HLA) complex.
• Class I MHC genes-Encode glycoproteins expressed on the surface of
nearly all nucleated cells, presents endogenous peptide antigens to CD8⁺
T-cells.
• Class II MHC genes-Encode glycoproteins expressed predominantly on
APCs, presents exogenous antigens to CD4⁺ T-cells.
• Class III MHC genes-Encode components of immune system and
molecules involved in inflammation.

27. STRUCTURE OF MHC I
• Consists of two polypeptides-
• α-chain (45kDa) and β₂-
microglobulin(12kDa)
• α-chain is organized into three external
domain α1,α2 and α3,transmembrane
hydrophobic domain, short stretch
hydrophillic amino acids and a
cytoplasmic anchor segment.
• β₂-microglobulin doesnot contain a
transmembrane region and non-
covalently bound to α3 domain.
• α1 and α2 domains form a platform of
8 antiparallel β-strands spanned by two
long α-helical regions that form a deep
peptide binding groove.
• α3 domain and β₂-microglobulin are
organized into two β pleated sheath.
α3 domain contains a sequence that
interact with CD8 molecules of TC
cells.

28. STRUCTURE OF MHC II
• Contain two different polypeptide
chains,α-chain(33kDa) and β-
chain(28kDa) associated by non
covalent interactions.
• Two external domains,α₁ and β₁ form
the peptide binding groove for
processed antigen.
• The membrane proximal domains,α₂
and β₂ bear sequences that interact
with CD4 cells of TH cells.
• Forms open ended antigen binding
groove.

29. MECHANISM OF ANTIGEN PROCESSING& PRESENTATION BY CLASS I & II
MHC

30. IMMUNE DYSFUNCTION AND IT’S CONSEQUENCES
• Sometimes the immune system fails to protect the host
adequately or misdirects it’s activities to cause discomfort,
debilitating disease or even death. Most instances of
immune dysfunction fall into three broad categories-
• Hypersensitivity(including allergy)-Inappropriate and over
zealous attacks on common benign but foreign antigens.
• Autoimmune disease-Erroneous targeting of self-proteins
or tissues by immune cells.
• Immune deficiency-Insufficiency of the immune response
to protect against infectious agents.

31. HYPERSENSITIVITY REACTIONS
• Inappropriate and over-active immune response to a common,
innocuous environmental antigens, such as pollen, food, animal dander
etc.
• This type of reactions were first recognized by Charles Richet(NP-1912)
and his colleague Paul portier in 1902 & concluded that anaphylaxis
(anti-protection) is an extreme, rapid and often lethal over-reaction of
the immune response to something it has encountered before.
• There are different types of hypersensitivity reactions
caused by antibody or as a result of T-cell activity.
• Most allergic reactions involves IgE which binds with antigen and induces
release of vasoactive amine that cause irritation, inflammation or
accumulation of cells and fluid at the site.
• Symptoms include- sneezing, wheezing, difficulty in breathing(asthma),
dermatitis or skin eruptions(hives) and in severe cases constriction of
the airways following extreme inflammation.

32. DIFFERENT TYPES OF HYPERSENSITIVITY REACTIONS AND THEIR MECHANISMS

33. SELF TOLERANCE AND BASIS OF AUTOIMMUNITY
• HOW DOES THE IMMUNE SYSTEM DISTINGUISH BETWEEN SELF AND
NONSELF?
• “SELECTION PROCESS” early in the developmental pathways for immune
cells kill or suppress those immune cells that react strongly with self
antigens.
• POSITIVE SELECTION- Prevents the production of T-cells that will not bind
with reasonable affinity with any MHC complex regardless of the peptides
bound.
• NEGATIVE SELECTION- T-cells that bind with high affinity to MHC
complex bound to self peptides expressed on the surface of the antigen
presenting cells(APC) in the thymus undergo apoptosis or suppressed.

34. AUTOIMMUNE DISEASES
• In certain conditions, the immune system malfunctions by losing it’s
sense of self and nonself and mis interprete a self-component as
dangerous causing an immune attack on host tissues. This condition is
called as autoimmunity & is responsible for many chronic debilitating
diseases.
• Both genetic and environmental factors are likely to be involved in most
of the autoimmune diseases.
• Symptoms may differ depending upon the tissues or organs under
attack. Some common diseases are-
• MULTIPLE SCLEROSIS- autoimmune attack on a protein in nerve
sheaths in brain and CNS causing neuromuscular dysfunctions.
• CROHN’S DISEASE- autoimmune attack of intestinal tissues causing
destruction of the gut epithelium & malabsorption.
• RHEUMATIC ARTHRITIS- autoimmune attack on joints of the hands,
feet, arms and legs.
• RHEUMATIC FEVER- production of antibody against streptococcus
infections that cross-reacts with exposed epitopes on the heart muscles.

35. IMMUNODEFICIENCY DISEASES
• If any of the components of innate and adaptive
immunity is defective because of genetic
abnormality or if any immune function is lost
because of damage by chemical physical or
biological agents, host suffers from a condition
known as immunodeficiency.
• primary immunodeficiency-A condition resulting
from a genetic or developmental defect in the
immune system. Most of the is defects are
hereditary & present at birth although it may not
manifest itself until later in life.
• Secondary immunodeficiency, or acquired
immunodeficiency-Loss of immune function and
results from exposure to various agents.

36. PRIMARY IMMUNODEFICIENCY DISEASES

37. ACQUIRED IMMUNODEFICIENCY DISEASE
• Most common acquired
immunodeficiency diseases is
AIDS(acquired
immunodeficiency syndrome)
caused by HIV-1 and HIV-2.
• In 1981,first case of AIDS were
recognized. The causative
agent was discovered and
characterized by efforts in the
laboratories of Luc Montaigner
in Paris and Robert Gallo in
Bethesda.
• Binds to CD4 molecules on the
surface of helper T-cells with
the help of gp120 molecules on
the surface.

38. MECHANISM OF PROLIFERATION OF HIV VIRUS

39. CANCER & IMMUNOLOGY

43. SUMMARY
• Immunity is the state of protection from the diseases.
• Composed of innate and adaptive immunity. Adaptive immunity may be cell
mediated performed by T-lymphocytes and humoral immunity mediated by B-
lymphocytes.
• Chemical mediators, phagocytic barrier and inflammatory response etc. are the
various components of innate immunity for mediating early response against
antigen.
• Cell mediated response, a part of adaptive immunity is responsible for acting
against intracellular of extracellular antigen bound with MHC I & MHC II molecule
on the surface of nucleated cells & APC respectively.
• Humoral immunity, mediated by antibody binds with antigen to causes
precipitation, agglutination or opsonisation of the antigens.
• Immunological dysfunction leads to hypersensitivity reactions, autoimmune
diseases and immune deficiency diseases of immense medical importance.
• Hypersensitivity is the inappropriate and overt immune reactions to a common &
innocuous environmental antigens.
• Positive & Negative selection process is essential to distinguish self from nonself &
derangement of this vital process leads to auto-immune reactions.
• Immune reactions may be primary or secondary.