The document provides a history of immunology and an overview of the immune system and its components. It discusses the innate and adaptive immune responses, the types of white blood cells and lymphocytes, immune organs and their functions, and B lymphocytes. The immune system is made up of complex interactions between physical barriers, cells, tissues and cell products that work together to defend the body against pathogens and foreign substances.

1. INTRODUCTION TO IMMUNE
SYSTEM AND INFLAMMATORY
RESPONSE
1

2. 2
IMMUNE SYSTEM

3. HISTORY OFIMMUNOLOGY
•1862 Ernst Haeckel, Recognition of phagocytosis
•1877 Paul Erlich, recognition of mast cells
•1879 Louis Pasteur, Attenuated chicken cholera vaccine
development
•1883 Elie Metchnikoff Cellular theory of vaccination
•1885 Louis Pasteur, Rabies vaccination development
•1888 Pierre Roux & Alexandre Yersin, Bacterial toxins
•1888 George Nuttall, Bactericidal action of blood
•1891 Robert Koch, Delayed type hypersensitivity
•1894 Richard Pfeiffer, Bacteriolysis
bacteriolysis
•1900 Paul Erlich, Antibody formation theory
•1901 Karl Landsteiner, A, B and O blood groupings
•1901-8 Carl Jensen & Leo Loeb, Transplantable tumors
•1902 Paul Portier & Charles Richet, Anaphylaxis
•1903 Almroth Wright & Stewart Douglas, Opsonization reactions
•1906 Clemens von Pirquet, coined the word allergy
blood groups
•1910 Peyton Rous, Viral immunology theory
•1914 Clarence Little, Genetics theory of tumor transplantation
•1915-20 Leonell Strong & Clarence Little, Inbred mouse strains
•1917 Karl Landsteiner, Haptens
•1921 Carl Prausnitz & Heinz Kustner, Cutaneous reactions
•1924 L Aschoff, Reticuloendothelial system
•1926 Lloyd Felton & GH Bailey, Isolation of pure antibody
preparation
•1934-8 John Marrack, Antigen-antibody binding hypothesis
•1936 Peter Gorer, Identification of the H-2 antigen in mice
•1940 Karl Lansteiner & Alexander Weiner, Identification of
the Rh antigens
•1941 Albert Coons, Immunofluorescence technique
•1942 Jules Freund & Katherine McDermott, Adjuvants
•1942 Karl Landsteiner & Merill Chase, Cellular transfer of
sensitivity in guinea pigs (anaphylaxis)
•1944 Peter Medwar, Immunological hypothesis of allograft
•1948 Astrid Fagraeus, Demonstration of antibody
production in plasma B cells
•1948 George Snell, Congenic mouse lines
•1949 Macfarlane Burnet & Frank Fenner, Immunological
tolerance hypothesis
•1950 Richard Gershon and K Kondo, Discovery of
suppressor T cells
•1952 Ogden and Bruton, discovery of agammagobulinemia
(antibody immunodeficiency)
•1953 Morton Simonsen and WJ Dempster, Graft-versus-
host reaction
•1953 James Riley & Geoffrey West, Discovery of histamine
•1907 Svante Arrhenius, coined the term immunochemistry in mastcells
•1910 Emil von Dungern, & Ludwik Hirszfeld, Inheritance of ABO •1953 Rupert Billingham, Leslie Brent, Peter Medwar, &
Milan Hasek, Immunological tolerance hypothesis
•1955-1959 Niels Jerne, David Talmage, Macfarlane
Burnet, Clonal selection theory
•1957 Ernest Witebsky et al., Induction of autoimmunity in
animals
•1957 Alick Isaacs & Jean Lindemann, Discovery of
interferon (cytokine)
•1958-62 Jean Dausset et al., Human leukocyte antigens
•1959-62 Rodney Porter et al., Discovery of antibody
structure
•1959 James Gowans, Lymphocyte circulation
•1961-62 Jaques Miller et al., Discovery of thymus
involvement in cellular immunity
•1961-62 Noel Warner et al., Distinction of cellular and
humoral immune responses
•1963 Jaques Oudin et al., antibody idiotypes
•1964-8 Anthony Davis et al., T and B cell cooperation in
immune response
rejection •1965 Thomas Tomasi et al., Secretory immunoglobulin
antibodies
•1967 Kimishige Ishizaka et al., Identification of IgE as the
reaginic antibody
•1971 Donald Bailey, Recombinent inbred mouse strains
•1974 Rolf Zinkernagel & Peter Doherty, MHC restriction
•1975 Kohler and Milstein, Monoclonal
antibodies used in genetic analysis
•1984 Robert Good, Failed treatment of severe combined
immunodeficiency (SCID, David the bubble boy) by bone
marrow grafting. 1985 Tonegawa, Hood et al., Identification
of immunoglobulin genes
•1985-7 Leroy Hood et al., Identification of genes for the T
cell receptor
•1990 Yamamoto et al., Molecular differences between the
genes for blood groups O and A and between those for A
and B
•1990 NIH team, Gene therapy for SCID using cultured T
cells.
•1993 NIH team, Treatment of SCID using genetically altered
umbilical cord cells.
•1985-onwards Rapid identification of genes for immune
cells, antibodies, cytokines and other immunological
structures.
•1975 Kohler and Milstein
Monoclonal antibodies used
in genetic analysis
6
•1798 Edward Jenner
Smallpox vaccination
3

4. Microbes are ubiquitous in nature, extraordinarily diverse,
rapidly evolve to exploit opportunities to infect hosts and to
evade their immune systems. 4

5. Immunology
Immunology- nobel prizes
Since 1901 there have been 19 Nobel Prizes
for immunology-related research.
5

6. The body’s defense against disease
causing organisms,
malfunctioning cells, and foreign
particles
6
6

7. The Latin term “IMMUNIS” means
EXEMPT, referring to protection
against foreign agents.
7
Definition: -
The integrated body systemof organs, tissues, cells & cell products that
differentiates self from non – self & neutralizes potentially pathogenic
organisms.
(The American Heritage Stedman'sMedical Dictionary)
7

8. The importance of immune system
 The immune system is clearly essential for survival.
 It constantly defends the body against bacteria, viruses, and other
foreign substances it encounters.
 Distinguishes Self From Non-self: Ability to recognize almost
limitless numbers of foreign cells and non-self substances,
distinguishing them from self molecules that are native to the body.
8

9. 9
 Homeostasis: Destruction of abnormal or dead cells (e.g. dead red or
white blood cells, antigen-antibody complex) and molecules that
periodically develop in the body.
 Defense against the growth of tumor cells : kills the growth of
tumor cells
The importance of immune system

10. A functional system – NOT an organ system
Complex system includes:
 Skin – physical barrier
 Lining of mucus membranes – physical barrier
 Secretions – tears, mucus etc - antimicrobial
 Blood cells and vasculature – WBCs
 Bone marrow
 Liver – makes complement proteins
 Lymphatic system and lymphoid organs
 Most tissues – have resident immune cells
10

11. Immune Response Antigen
 Antigen – “any substance when introduced into the body
stimulates the
production of an antibody”
 Bacteria, fungus, parasite
 Viral particles
 Other foreign material
 Pathogen – an Antigen which causes disease
11

12. Immune Response Antibodies
 Antibody – “a Y-shaped protein, found on the surface of B-
Cells or free in the blood, that neutralize antigen by binding
specifically to it”
Also known as an Immunoglobulin
Antigen
12

13. Overview of the Immune System
Immune System
Innate
(Nonspecific)
1o line of defense
Adaptive
(Specific)
2o line of defense
Interactions between the two systems
13
Types of Immunity

14. A TYPICAL IMMUNE RESPONSE
INNATE IMMUNITY
Rapid responses to a
broad range of microbes
ACQUIRED IMMUNITY
Slower responses to
specific microbes
External defenses Internal defenses
Skin
Mucous membranes
Secretions
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response
(antibodies)
Cell-mediated response
(cytotoxic lymphocytes)
Invading
microbes
(pathogens)
Complement
14
“possessed at birth, possessed as an essential
characteristic”
“Acquired after birth in
response to
pathogens”

15. Bacteria Viruses
Physical
barriers
Cilia
Innate response
Mucous membranes
Cytokines
Antimicrobial secretions
Macrophages
Macrophages
present antigens
Acquired response
Cellular response
Cytotoxic T cells
Humoral response
Memory B cells
Plasma cells
35
15

16. Innate immunity vs Adaptive Immunity
No memory
• No time lag
• Not antigen specific
• A lag period
• Antigen specific
• Development
of memory
Innate Immunity
(first line of defense)
Adaptive Immunity
(second line of defense)
16

17. Stem Cells—Progenitors of cells involved in the
immune response
Stem cells are found in the bone marrow of the host
Cytokines cause stem cells to develop into immune cells
Stem cells develop into two classes of leukocytes:
1. Monocytes phagocytic cells which develop from a myeloid
precursor
2. Specialized lymphocytes that are involved in antibody production
and cell mediated killing of pathogens these develop from a
lymphoid precursor
B-cells—produce antibodies AND continue to differentiate
and mature in the bone marrow
T-cells—mediate killing and differentiate and mature in
the thymus.
17

18. Development of Immune Cells involved
in the immune response
18

19. QuickTime™ TIFF(LZW)d areneededto QuickTime™ and aTIFF (LZW) decompressorare needed to see this picture.
Most
blood cells
act to fight
infection.
Adaptive
immunity
Innate
immunity
Blood Cells
Lineages 19

20. Types of White Blood Cells
 There are 5 different types of WBCs
 Neutrophils (60%)
 kill bacteria
 Eosinophils (2%)
 Allergic response
 Parasite killing
 Basophils (1%)
 – Allergic reactions
 Monocytes (4%)
 Become macrophages
 Lymphocytes (33%)
 Direct the immune system
20

21.  Two types of lymphocytes
 T-Cells (Thymus derived)
1. Natural Killer Cells (Innate Immunity)
2. CD4+ T-Cells (helper cells)
3. CD8+ T-Cells (cytotoxic cells)
 B-Cells (Bone Marrow derived)
1. Memory B Cells: Memory for Secondary immune response
against same antigen
2. Plasma Cells: Produce Antibody
Cells Of Immune System 21

22. The Immune Organs
And Their Function
 The Central Lymphoid Organs:
1. Bone Marrow
2. Thymus
Function : Provide the environment for
immune cell production and maturation.
 The Peripheral Lymphoid Organs:
1. Lymph Nodes
2. Spleen
3. Tonsils
4. Appendix
5. Peyer’s Patches in the intestine
6. Mucosa-associated lymphoid tissues in
the respiratory, gastrointestinal, and
reproductive systems.
Function : Trap and process antigen and
promote its interaction with mature immune
cells.
22

23. 23

24. B Lymphocytes
 B Lymphocytes:-
B cells, mature in Bone Marrow
In periphery they express a unique surface antibody
Plasma cells: Differentiated B cell, short lifespan, antibody factory
Memory B cell:
Long life span
Secondary immune response against same pathogen.
24

25. 25
B Lymphocytes

26.  B cells are formed in the bone marrow. B cells have particular sites
(receptors) on their surface where antigens can attach.
 B cells are the major cells involved in the creation of antibodies that
circulate in blood plasma and lymph, known as humoral immunity.
 In mammals there are five types of antibody IgA, IgD, IgE, IgG, and IgM,
differing in biological properties.
 Each has evolved to handle different kinds of antigens.
 Upon activation, B cells produce antibodies, each of which recognizes a
unique antigen, and neutralize specific pathogens.
26
B Lymphocytes

27. B-cell response to antigens
 The response has two stages:
 Primary immune response:
 When B cells first encounter an antigen, the antigen attaches to
a receptor, stimulating the B cells.
 Some B cells change into memory cells, which remember that
specific antigen, and others change into plasma cells. Helper T cells
help B cells in this process.
 Plasma cells produce antibodies that are specific to the antigen
that stimulated their production. After the first encounter with an
antigen, production of enough of the specific antibody takes several
days. Thus, the primary immune response is slow.
 Secondary immune response
 Whenever B cells encounter the same antigen again, memory B
cells very rapidly recognize the antigen, multiply, change into
plasma cells, and produce antibodies. This response is quick and
very effective.
27

28. Primary and secondary phases of the humoral
immune response to the same antigen
28

29. T Lymphocytes Cells
 T cells, mature in Thymus (CD4, CD8)
 Two Major subsets, TH (CD4) and TC (CD8)
 Third type TS not as clear
 Mature T cell expresses TCR
 TCR cannot recognize antigen on its own
 MHC I (all nucleated cells) or MHC II (APCs) is required
 TH cells secrete cytokines
 TC less cytokines, more cytotoxic (virus and tumor
survailance)
29

30.  T cells are maturated in the thymus.
 T-cell training in Thymus: learn how to distinguish self from nonself.
 Only the T cells that ignore self antigen molecules are allowed to
mature and leave the thymus. Without this training process, T cells could
attack the body's cells and tissues.
 Mature T cells are stored in secondary lymphoid organs (lymph nodes,
spleen, tonsils, appendix, and Peyer's patches in the small intestine).
 Circulate in the bloodstream and the lymphatic system. After they first
encounter a foreign or abnormal cell, they are activated and search for
those particular cells.
30T Lymphocytes Cells

31.  Helper T (CD4) cells :
• help other immune cells.
• help B cells produce antibodies against foreign antigens.
• help activate killer T cells to kill foreign or abnormal cells or
• help activate macrophages enabling them to ingest foreign or abnormal
cells more efficiently.
Th1 responses are more effective against intracellular pathogens
(viruses and bacteria that are inside host cells), while Th2 responses
are more effective against extracellular bacteria, parasites and
toxins
31T Lymphocytes Cells

32. Th1 cells :
• Th1 response is characterized by the production of interferon –
gamma
• activated by signals from intracellular bacteria and viruses
• secrete IL-2, IL-12, IFN gamma, TNF-beta
• activate macrophages, amplifying their cytokine secretion capacity and
potential for presentation of antigens
• induces B-cells to make opsonizing (coating) antibodies, and leads to
cell mediated immunity.
• activate synthesis of IgG but not IgE
32T Lymphocytes Cells

33. Th2 cells:
• Th2 response is characterized by the release of interleukin 4
• secrete IL-4, IL-5, IL-6, IL-10
• activate the synthesis of IgE
• stimulate proliferation and activation of eosinophils
• stimulated by allergens or parasite components
• which results in the activation of B-cells to make neutralizing
(killing) antibodies, leading to humoral immunity.
33T Lymphocytes Cells

34. The central role of Thelper cells (CD4)
34

35.  Killer (cytotoxic) T cells (CD8) :
 Kills particular foreign or abnormal (for example infected) cells.
 Kill by making holes in their cell membrane and injecting enzymes into
the cells or by binding with certain sites on their surface called death
receptors.
 Suppressor (regulatory) T cells :
 Produce substances that help end the immune response or
 Sometimes prevent certain harmful responses from occurring.
Sometimes T cells—for reasons that are not completely understood - do not
distinguish self from nonself. This malfunction can result in an autoimmune
disorder, in which the body attacks its own tissues.
35T Lymphocytes Cells

36. 36

37. Antigen Presenting Cells
 Number of Cells capable of Antigen Presentation
 Dendritic Cell (DC) are professional APC
 Macrophages, B cells
 Besides Antigen :They Provide Co-stimulation
 APCs are a safeguard against autoimmunity
37

38. APC INTERACTING WITH T CELL
38

39. Immune sentinel cells in the tissues:
Dendritic cells
Langerhans cells (epidermal dendritic cells) in the skin
WJ Mullholland et al. J. Invest. Dermatol. 126: 1541, 2006.
Green= dendritic cells
Blue= nuclei of all cells
39

40. NK cells
 The NK cell is a nonspecific effector cell that can kill
tumor cells and virus-infected cells.
 They are called natural killer cells because, unlike T
cytotoxic cells, they do not need to recognize a specific
antigen before being activated.
 NK cells kill after contact with a target cell. The NK cell
is programmed automatically to kill foreign cells.
 Programmed killing is inhibited if the NK cell membrane
molecules contact MHC self-molecules on normal host
cells.
 The mechanism of NK cytotoxicity depends on production
of pore-forming proteins (i.e., NK perforins), enzymes,
and toxic cytokines.
40

41. Major Histocompatibility Complex (MHC)
 Genetic Complex With Multiple Loci
 MHC I - TC
 MHC II - TH
 MHC I+2-microglobulin
 3 classes A, B, C (human)
 2 classes K and D (mouse)
 MHC II
 3 classes DP, DQ, DR (human)
 2 classes IA, IE (mouse)
 Highly Polymorphic in Humans
41

42. Processing and Presentation of Antigens
 First Protein Antigens Must Be Broken Down
 Form Complexes With MHC I or II
 Exogenous Antigens
 Antigens Processed Through Endocytic Pathway
 Binding of Ags To MHC II
 Expression of MHC II+Ag On Surface
 CD4 T Cells Recognize Ag Through Class II MHC
 Endogenous Antigens
 Antigens Processed Through Cytosolic Pathway
 Produced Within Cell, Ex. Virus Ag, Cancer Ag
 MHC I Molecules Bind Ag in ER
 CD8 T Cells Recognize Ag Thru MHC I
42

43. Class I MHC proteins
and cytotoxic T cells
(Tc)
Class I pathway is useful in destroying
cells that have been infected by viruses or
have been transformed by tumors
1. Protein antigens manufactured in the cell
by viruses or tumors are degraded in the
cytoplasm and transported to the
endoplasmic reticulum
2. The processed antigens bind to Class I
MHCs and are transported to the cell
surface
3. Together this complex interacts with the
TCR of a Tc cell, the binding of the
complex with the TCR is strengthened
by a CD8 coreceptor
43

44. Class I MHC proteins and cytotoxic T cells (Tc)
The cell-cell interaction between
the infected cell and the Tc
cell is mediated by the
MHC/antigen complex and TCR
The Tc cell produces cytotoxic
proteins perforins—produce holes
or pores in the target cell and
granzymes enter the virus infected
cell causing apoptosis or
programmed cell death
The cytotoxic proteins only affect
those cells to which the Tc cell has
specifically interacted
44

45. Class II MHC
proteins and helper
T cells (TH)
The Class II proteins and antigen
are expressed on B cells, APCs
and macrophages
1. The APC takes up an external foreign
protein via phagocytosis or endocytosis
2. Class II proteins are produced in the
endoplasmic reticulum and assembled
with a blocking protein (Ii) or invarient
chain
3. The Class II proteins enter the
phagolysosome where the Ii is degraded
and the partially processed antigen
binds to the class II molecule
4. The complex is translocated to the
surface of the APC where it interacts
with the TCR of a T helper cell
45

46. Class II MHC proteins and helper T cells (TH)
Specialized TH cell involved in
the inflammatory response
Cell-cell interaction mediated
by the TCR and the class II
MHC-antigen complex activates
The TH cell which produces
cytokines
TNF-alpha (tumor necrosis factor)
IFN-gamma (interferon)
GM-CSF (granulocyte-monocyte
colony stimulating factor)
These cytokines further stimulate
macrophages to increase phagocytic
activity and to in turn produce
cytokines that promote inflammation
46

47. Superantigens
Bacterial
superantigens act by
binding to both the
MHC protein and the
TCR at positions
outside the normal
binding site
superantigens can
interact with large
numbers of cells,
stimulating massive T-
cell activation,
cytokine release and
systemic
inflammation
47

48. Class II MHC proteins, helper T cells
that stimulate antibody producing
cells—the B cells B cells are coated with
antibodies that react with
specific antigens
When the antigen binds to the
antibody, the B cell first acts
as an APC.
The bound antigen is endo
cytosed and complexed with
MHC II and then surface
expressed
The surface expressed complex
interacts with and activates TH
cells that produce the cytokines
interleukin 4 & 5IL4 and 5
stimulates the B cells to produce
identical memory B cells and
Antibody secreting plasma cells
that secrete the
same antibody
48

49. Antibodies
and the
complement
pathway are
involved in
killing cellular
pathogens
49

50. Innate Immunity
 Protection by Skin and Mucous Membranes
 Phagocytic Cells
 Remove debris (garbage men)
 Macrophages, Neutrophils, Monocytes
 Natural Killer Cells
 Lymphocytes that kill virally infected cells and tumours
 Complement System
 “complements antibody in the killing of bacteria”
 A group of >30 proteins found in the blood
50

51. Nonspecific defense system
 The anatomical barriers are very effective in preventing colonization of
tissues by microorganisms.
 However, when there is damage to tissues the anatomical barriers are
breached and infection may occur. Once infectious agents have penetrated
tissues, another innate defense mechanism comes into play, namely acute
inflammation.
 Humoral factors play an important role in inflammation, which is
characterized by edema and the recruitment of phagocytic cells.
51

52. Adaptive Immunity
 Two Components of Adaptive Immune System
 Humoral (humoral mediated immunity)
B-Cells  Plasma Cells  Antibodies
 Cellular (cellular mediated immunity)
CD8+ T-Cells  Direct Cellular Killing
CD4+ T-Cells  Recruitment of other immune cells (inflammatory
response)
52

53. Humoral Mediated Immunity 53

54. Cellular Mediated Immunity
 Via T-Cells
 CD8+ T-Cell
Stimulated  Direct Killing
 CD4+ T-Cell
Th1  Stimulated  Macrophage Activation
Th2  Stimulated  B-Cell Activation
54

55.  Remember B-Cells have direct surface receptors
(immunoglobulins) for antigen!
 T-Cells do not possess these receptors
 Instead, T-Cells need to have antigen presented to them
(like on a silver platter)
 Antigen is presented to T-Cells by … Antigen Presenting
Cells
55Cellular Mediated Immunity

56.  Two Types of Antigen Presenting Cells (APCs)
General
APC
Professional
APC
All Cells B-Cells, Macrophages,
Dendritic Cells
Present antigen found inside the cell Present antigen found outside the cell
Use an MHC class I molecule to
present antigen
Use an MHC class II molecule to
present antigen
Interact with CD8+ T-Cells
 Cellular Killing
Interact with CD4+ T-Cells
T-Cell Help
56Cellular Mediated Immunity

57. General APCs
 All cells in the body are always “cleaning”
themselves
 When they find some “dirt” (viral protein, normal
cellular debris)  Need to make sure it is not
something harmful
 Attach the “dirt” to an MHC-I molecule
 Present this “dirt” to a CD8+ T-Cell
57

58. General APCs &
CD8+ T-Cells
58

59. Professional APCs
 Professional APCs have the ability to take up
(endocytosis) extracellular proteins (self or foreign)
 Break down this protein into peptides and attach it to
an MHC-II molecule
 Present the peptide to a CD4+ T-Cell
59

60. Professional APCs
CD4+ Th1-Cells
60

61. Professional APC
CD4+ Th2-Cells
61

62. Summary of Adaptive
Immunity
 Humoral
 Antibody Production – B-Cells
 Cellular
 CD8+ T-Cells  MHC-I  Cytotoxic
 MHC-II 
 CD4+ Th2-Cells  MHC-II  Activate B-Cells to
produce Antibody
62

63. What Prevents the Body
from Attacking Itself?
 Two Concepts
 Central Tolerance
 Peripheral Tolerance
63

64. Central Tolerance
 Occurs during lymphocyte (T & B Cells)
maturation in the primary lymphoid organs
(thymus & bone marrow)
 The body presents immature lymphocytes with
self-antigen
 Lymphocytes which react with high affinity to
this self-antigen are deleted (apoptosis)
 Lymphocytes which react with low affinity are
positively selected to mature
64

65. Central Tolerance 65

66. Peripheral Tolerance
 During maturation, lymphocytes cannot be
presented with every self-antigen
 Some antigens are found in low concentrations
in specific locations
 New antigens are formed during life
 Therefore, lymphocytes come in contact
with new antigen
 Particular importance to the cytokine
environment present when lymphocytes
encounter this new antigen
66

67. Cytokines
 Molecules secreted by cells(lymphocytes) and
which affect the function of other cells
 Secreted in response to specific stimulus
 Interleukin is a type of cytokine
67

68. Role of interleukins 68

69. 69
INFLAMMATORY RESPONSE

70.  “Inflame” – to set fire.
 Inflammation is “A dynamic response of vascularised tissue
to injury to a pathogenic.”
 It is a protective response.
 It serves to bring defense & healing mechanisms to the site of
injury.
What is Inflammation? 70

71. Cardinal Signs of Inflammation
 Redness : Hyperaemia.
 Warm : Hyperaemia.
 Pain : Nerve, Chemical
mediators.
 Swelling : Exudation
 Loss of Function: Pain
71

72. Inflammation
• Mediated by a subgroup of leukocytes (white blood cells)
that produce cytokines that lead to fibrin clots at the site
of inflammation.
• The inflammatory response results in redness, swelling, heat
and pain at the site of the infection
• Most important outcome is the immobilization of the
pathogen at the site of inflammation
• Physical manifestations:
Absces :- Localized collection of pus surrounded by a
wall of inflammatory tissue (surface localized)
Boils :- Abscesses located in the deeper layers of the skin
Ulcers :- Localized area of necrosis of the epithelial cells
72

73. How Does It Occur?
 The vascular & cellular responses of inflammation are mediated by
chemical factors (derived from blood plasma or some cells) &
triggered by inflammatory stimulus.
 Tissue injury or death --- > Release mediators
73

75. Inflammation Outcome
Acute
Inflammation
Resolution
Chronic
Inflammation
Abscess
SinusFistula
Fibrosis/Scar
Ulcer
Injury
Fungus
Virus
Cancers
T.B. etc.
< 48 hours >48 hours
Neutrophils
Mononuclear cells:
Macrophages
Lymphocytes
Plasma cells
75

76. Processes occur at the site of
inflammation, due to the release of
chemical mediators :
1. Vascular dilation and increased
blood flow (causing erythema and
warmth).
2. Extravasation and deposition of
plasma fluid and proteins (edema).
3. Leukocyte emigration and
accumulation in the site of injury
(Chemotaxis).
Mechanism of Inflammation
76

77. Pathogen Splinter
Macrophage
Mast cell
Chemical
signals
Capillary
Phagocytic cellRed blood cells
Fluid
Phagocytosis

78. TNF
or dendritic cell
Others
78
 Proteins (cytokines/chemokines)
 Histamine by mast cells - vasodilatation.
 Prostaglandins – Cause pain & fever.
 Bradykinin - Causes pain.
Inflammatory mediators:
synthesized or released and
mediate the changes in
inflammation.

79. Macrophages respond to infection by secreting inflammatory
cytokines

80. Cytokines and Inflammation
 Pro-inflammatory cytokines are many, but especially important: TNF, IL-1,
and IL-6
 TNF and IL-1 signal to endothelial cells to make them:
 Leaky to fluid (influx of plasma; containing antibodies, complement
components, etc.)
 Sticky for leukocytes, leading to influx of leukocytes
• IL-6 promotes adaptive immune responses; systemic effects
80

81. Neutrophil chemotaxis
acPGP: N-acetyl Proline-Glycine-Proline – neutrophil chemoattractant
MMP: matrix metalloproteinase

82. Killing of bacteria by neutrophils involves the fusion of
two types of granule and lysosomes with the phagosome

83. Changes in vascular flow
(hemodynamic changes)
 Slowing of the circulation
Outpouring of albumin rich fluid into the extravascular tissues
results in the concentration of RBCs in small vessels and increased
viscosity of blood.
 Leukocyte margination
Neutrophi become oriented at the periphery of vessels and start to
stick.
83

84. Leukocyte recruitment to sites of
inflammation
 Divided into 4 steps
 Margination, rolling, and adhesion to endothelium
 Diapedesis (trans-migration across the endothelium)
 Migration toward a chemotactic stimuli from the
source of tissue injury.
 Phagocytosis
84

85. 85
Leukocyte recruitment to sites of inflammation

86. 86

87. Phagocytosis
3 distinct steps
 Recognition and attachment
 Engulfment
 Killing or degradation
87

88. Phagocytosis and Killing of Microbes
Abbas et al. Fig. 2-17
88

89. Acute inflammation has one of four outcomes:
 Abscess formation
 Progression to chronic inflammation
 Resolution--tissue goes back to normal
 Repair--healing by scarring or fibrosis
89

90. Thank You
90
Meditation is superior to severe
asceticism and the path of knowledge. It
is also superior to selfless service. May
you attain the goal of meditation,

91. Thank You 91

92. Many different antibodies are created by
combinations of gene segments 92

93. Generation of lymphocytes of
many specificities
Clonal deletion to remove self-
reactive lymphocytes
Clonal selection to expand
pathogen-reactive lymphocytes
during an immune response
The Clonal Selection Hypothesis
93

94. 94

95. Antibody responses proceed in two phases
Goodnow et al, Nature Immunol. 2010
95

96. Antibodies bind antigens
Two protein components: heavy
chain and light chain; can come
in 5 varieties of heavy chains:
IgM, IgG, IgA, IgE, IgD
96

97. CD Nomenclature
• Structurally defined leukocyte surface molecule that is expressed on
cells of a particular lineage (“differentiation”) and recognized by a group
(“cluster”) of monoclonal antibodies is called a member of a cluster of
differentiation (CD)
• CD molecules (CD antigens, CD markers) are:
• Identified by numbers
• Used to classify leukocytes into functionally distinct
subpopulations, e.g. helper T cells are CD4+CD8-, CTLs are
CD8+CD4-
• Often involved in leukocyte functions
• Antibodies against various CD molecules are used to:
• Identify and isolate leukocyte subpopulations
• Study functions of leukocytes
• Eliminate particular cell populations
97

98. Innate Lymphoid Cells: Parallels to
T cell subsets
Spits and DiSanto, Nature
Immunology 12: 21-27, 2011
IL-5
98

99. Immune system and chronic inflammation
 Sterile inflammation (tissue injury but no infectious agent
present): innate recognition of tissue damage
 Chronic inflammation: if antigen persists, antigen-
reactive T cells can drive continued inflammation, which
can cause tissue damage (autoimmune diseases and
inflammatory diseases)
 Likely important role of inflammation in pathogenesis of
chronic diseases: atherosclerosis, type 2 diabetes,
probably Alzheimer’s disease, cancer (can be positive or
negative)
99