PHYSI O L O G Y O F C O L O R

VISI O N & SEEIN G

A d ju n c t. Prof. S a k c h a i V o n g kittirux
Dir e c t or of Th a m m a s a t Ey e C e nt e r
• htt ps:/ / w w w .sli d e sh a r e .n e t / m a z33 / c olo ur-visio n-p p t-b y-dr-m a zh a r

• htt ps:/ / w w w .sli d e sh a r e .n e t / m e d i c m e sirm a nsur a h / p h o t o tr a nsd u c tio n-visu a l-

p a th w a y-m m p-m a r c h-10

htt ps:/ / w w w .sli d e sh a r e .n e t / DrS a m a rth Mishr a / c olo ur-

visio n-64616934
 VISU AL PR O C ESS

light source

object

eye
• In 1672, Sir Is a a c N e w t o n us e d a prism t o
s e p a r a t e d a yli g ht int o s e v e n prin c i p l e c olors
• It is th e fu n d a m e nt a l d is c o v e ry th a t w hit e li g ht is
a mixtur e o f li g hts o f m a n y d iff e r e nt
w a v e l e n g ths, a s s e e n in a r a in b o w
 PHYSI C S O F LI G HT

In
a. mansion
WN , .
of ,

• Hu m a n e y e c a n p e r c e iv e a b o ut 150 c olors in th e
e l e c tro m a g n e ti c sp e c tru m o f a w a v e l e n g th b e t w e e n 380-780 n m
 6

• O b j e c ts r e fl e c t d iff er e nt w a v e l e n g ths o f li g ht a n d giv e ris e t o

th e p e r c e p tio n o f c olor
• O b j e c t th a t r e fl e c ts a ll w a v e l e n g ths o f li g ht is w hit e
• O b j e c t th a t a bsorbs a ll w a v e l e n g ths, a n d d o e s n o t r e fl e c t
th e m , is b l a c k
• A n a p p l e a p p e a rs r e d b e c a us e
it a bsorbs a ll w a v e l e n g ths e x c e p t r e d

meets laser
' Apple Absdrp ndsm.net
rings ,
'

. .

Univ fun ,
room - evil r
,
media I whew arty '
un Nantou donut
 blots

• Th e r e a r e 2 ty p e s of p h o t or e c e p t ors of r e tin a : ro ds a n d c o n e s
• E a c h r e tin a h a s 120 millio n ro ds, a n d 6-7 millio ns c o n e c e lls Rod > cone
• Ro ds a r e r e sp o nsi b l e f or p e ri p h e r a l a n d ni g ht visio n
• C o n e s a r e r e sp o nsi b l e f or c e ntr a l a n d c olor visio n
• S e e in g c olor is a fu n c tio n of c o n e c e lls, w hi c h a r e stim ul a t e d b y r e sp o nsiv e w a v e l e n g ths within
th e visi b l e sp e c tru m
Fovea at un Red Isi
'
at cone
R O D A N D C O NE PH O T O RE C EPT O RS
 R O D PH O T O RE C EPT O RS
• 120 millio ns/ e a c h r e tin a
• N o ro d in c e ntr a l 0.25 m m . o f f o v e a
• M e d i a t e visio n a t lo w illu min a tio n l e v e ls
(s c o t o p i c ) Urian Not'll Is Too
→ ,
Rod oarfish of
→

• D e c r e a s e n u m b e r with a g e
• C riti c a l fli c k e r thr e sh ol d 20 Hz
Rod dads man u
,

Hos win → Cone pinions ri

 C O NE PH O T O RE C EPT O RS

• 6-7 millio ns/ e a c h r e tin a

• Hig h e st d e nsity a t m a c ul a
• St a b l e n u m b e rs,
n o r e l a tio nshi p t o a g e
• M e d i a t e b e st visio n a t d a ylig ht l e v e ls
(p h o t o p i c )
R e sp o nsi b l e f or g o o d visu a l a c uity a n d
c olor p e r c e p tio n
C riti c a l fli c k e r thr e sh ol d 55-60 Hz

IN
'

Cone do doom
way
 R O DS A N D C O NES T O G ETHER

• N o ro d in c e ntr a l 0.25 m m o f f o v e a , p e a k b e t w e e n 5-
7 m m fro m f o v e a l c e nt e r
• C o n e h a s hig h e st d e nsity a t m a c ul a
 C O NE PH O T O RE C EPT O RS

Red
C o n e c e lls d e vi d e d int o 3 ty p e s a c c ord in g t o th e ir
p ig m e nt green
Sh ort w a v e l e n g th-se nsitiv e c o n es (S c o n es, blu e c o n es)
blue
C o nt a in a p i g m e nt c a ll e d c y a n olo b e
M a xim a lly s e nsitiv e t o li g ht o f w a v e l e n g th 440-450 n m
Mid dl e w a v e l e n g th-se nsitiv e c o n es (M c o n es, gr e e n c o n es)
C o nt a in a p i g m e nt c a ll e d c hlorolo b e
M a xim a lly s e nsitiv e t o li g ht o f w a v e l e n g th 535-555 n m
• Lo n g w a v e l e n gth-se nsitiv e c o n es (L c o n es, re d c o n es)
C o nt a in a pig m e nt c a ll e d erythrolo b e
M a xim a lly se nsitiv e to lig ht of w a v e l e n gth 570-590 n m
 PH O T O RE C EPT O RS

Ro d 507 n m → Elutes Universe

SWS c o n e (B- c o n e ) 445 n m

MWS c o n e ( G - c o n e ) 543 n m
LWS c o n e (R- c o n e ) 566 n m
 C O NE PH O T O RE C EPT O RS

• C o n e p o p ul a tio n c o nsist of
• 60 % r e d c o n e s
• 30% gr e e n c o n e s
• 10% b lu e c o n e s
 VISU AL PR O C ESS
Lig ht p a ss thro u g h c orn e a / A C /l e ns/ vitr e o us
A bsorp tio n b y th e ro d / c o n e p h o t or e c e p t ors
R e tin a l n e ur a l c ir c uit
H orizo nt a l c e lls, A m a c rin e c e lls
Bi p ol a r c e lls
G a n glio n c e lls
O p ti c n e rv e
Hig h e r visu a l c e nt e rs
L G B ( p a rv o c e llul a r p ortio n)
C ort e x
-
RPE
blats
photo .RO I
NFL ← gg ← bipolar ←
( 280 n Not cell
gg cell )
 VISU AL PR O C ESS
Lig ht p a ss thro u g h c orn e a / A C /l e ns/ vitr e o us
A bsorp tio n b y th e ro d / c o n e p h o t or e c e p t ors
R e tin a l n e ur a l c ir c uit 1 Pigmented cells

H orizo nt a l c e lls, A m a c rin e c e lls

Bi p ol a r c e lls
G a n glio n c e lls
O p ti c n e rv e
Hig h e r visu a l c e nt e rs
L G B ( p a rv o c e llul a r p ortio n)
C ort e x
 Lesion rewind LGB →
rig
optic atrophy
VISU AL PR O C ESS laws, runts on LGBT : rin sight
Optic h .
Nuts

Lig ht p a ss thro u g h c orn e a / A C /l e ns/ vitr e o us

A bsorp tio n b y th e ro d / c o n e p h o t or e c e p t ors
R e tin a l n e ur a l c ir c uit
H orizo nt a l c e lls, A m a c rin e c e lls
Bi p ol a r c e lls
G a n glio n c e lls
O p ti c n e rv e optic tract 2
→

Hig h e r visu a l c e nt e rs
L G B ( p a rv o c e llul a r p ortio n)
C ort e x
I

vision)
C central
Broca area ( tip of occipital lobe ,
1.7.

↳ para central -
18 99
,
 VISU AL PR O C ESS
Lig ht p a ss thro u g h c orn e a / A C /l e ns/ vitr e o us
A bsorp tio n b y th e ro d / c o n e p h o t or e c e p t ors
R e tin a l n e ur a l c ir c uit
H orizo nt a l c e lls, A m a c rin e c e lls
Bi p ol a r c e lls
G a n glio n c e lls
O p ti c n e rv e
Hig h e r visu a l c e nt e rs
L G B ( p a rv o c e llul a r p ortio n)
C ort e x
Uno Vu with Mr n' v
Vis oh on n on Ibm r Tin
,

rig
gu In
'
s m no
Cen
 VISU AL PR O C ESS
Lig ht p a ss thro u g h c orn e a / A C /l e ns/ vitr e o us
A bsorp tio n b y th e ro d / c o n e p h o t or e c e p t ors
R e tin a l n e ur a l c ir c uit
H orizo nt a l c e lls, A m a c rin e c e lls
Bi p ol a r c e lls
G a n glio n c e lls
O p ti c n e rv e
Hig h e r visu a l c e nt e rs
L G B ( p a rv o c e llul a r p ortio n)
C ort e x
 P ARA METERS O F C O L O R
Airman I
S : Saturation

H : Hue -

-
foils

B : Brightness
↳ loionnwnwru window
" n'few
I

n°1 air a = Bright Wow

 C O NE PH O T O RE C EPT O RS

C o n e c e lls d e vi d e d int o 3 ty p e s a c c ord in g t o th e ir

p ig m e nt
Sh ort w a v e l e n g th-se nsitiv e c o n es (S c o n es, blu e c o n es)
C o nt a in a p i g m e nt c a ll e d c y a n olo b e
M a xim a lly s e nsitiv e t o li g ht o f w a v e l e n g th 440-450 n m
Mid dl e w a v e l e n g th-se nsitiv e c o n es (M c o n es, gr e e n c o n es)
C o nt a in a p i g m e nt c a ll e d c hlorolo b e
M a xim a lly s e nsitiv e t o li g ht o f w a v e l e n g th 535-555 n m
• Lo n g w a v e l e n gth-se nsitiv e c o n es (L c o n es, re d c o n es)
C o nt a in a pig m e nt c a ll e d erythrolo b e
M a xim a lly se nsitiv e to lig ht of w a v e l e n gth 570-590 n m
• A c q uir e d or
• C o n g e nit a l c olor visio n d e fi c i e n c i es
• A lm ost a lw a ys XR r e d-gr e e n d e f e c t
- C a us e d b y d e f e c ts in X
c hro m oso m e
• It a ff e c ts a b o ut 8% o f m a l e s a n d 0.5% o f f e m a l e s
• จ ก 65 ล้ นคน ช ย 32 ล้ น * 8% = 2,560,000 + หญง 33 ล้ น * 0.5% =
165,000 รวม 2,725,000 คน
 TYPE O F C O L O R VISI O N DEFI C IEN C Y
n i
Anomalous trichromat
Protanomaly 1% 11ns
O
Has all 3 primary color sensations but one of them is abnormal

bath
Deuteranomaly 5%
Tritanomaly 0.0001% ninjas
honesty
-

going =
obvious
,

4 Dichromat Nahi
Lack O
one of the 3 cone pigment
Protanopia 1% -

no pia a
Tutu mold
Deuteranopia 1%
Tritanopia 0.001%
3) Monochromat (Achromatopsia) → 1430 Cone
'

Finn I 1450am Rod

Rod monochromat
Cone monochromat SI .

nystagmus
 Protanomaly
Wutai it .

• Th e mil d e st f orm o f r e d-gr e e n d e fi c i e n c y

• I efe ed o a ed eak
• R e d c olor is s e e n m or e w e a kly b o th in s a tur a tio n a n d
bri g htn e ss
• R e d , or a n g e , y e llo w , y e llo w-gr e e n a p p e a r shift e d t o w a rds
gr e e n a n d a p p e a r p a l e r th a n n orm a l
• Y e llo w t o gr e e n c olors m a y b e c o nfus e d
• Th e r e d n e ss c o m p o n e nt in viol e t c olor is w e a k e n e d , a n d
th e r e f or e o nly th e b lu e c o m p o n e nt is s e e n
N O RM AL C O L O R VISI O N PR O TA N O M ALY

Fans In
 Deuteranomaly
whist .

• Gre e n w e a k
• M ost c o m m o n ty p e
• C a n n o t d is c rimin a t e r e d , or a n g e , y e llo w , gr e e n r e gio n
o f th e sp e c tru m , a p p e a r shift e d t o w a rds r e d
• R e d a n d gr e e n a r e p e r c e iv e d a s a n in d istin c t gr a yish
sh a d e
• Diffi c ult t o d istin g uish viol e t fro m b lu e
N O RM AL C O L O R VISI O N
DEUTERA N O M ALY
• Ph ysi c i a n : A n e sth e tist, O p hth a lm olo gist,
O p t o m e trist, Surg e o n
• B a c t e riolo gist, D e ntist, Ph a rm a c ist a ssist a nt
• A ir f orc e s, n a v y, a rm y, c ivil a vi a tio n
• El e c tri c a l w ork
• Poli c e

28
 C O L O R VISI O N TESTIN G
• Ty p e s o f c olor visio n t e stin g :
• Ps e u d oiso c hro m a ti c p l a t e s (PIP)
• Ishih a r a t e st
• H-R-R (H a rd y, R a n d , Rittl e r) t e st
• Hu e d is c rimin a tio n t e st ( Arr a n g e m e nt t e st)
• F a rnsw orth P a n e l D-15 t e st
• F a rnsw orth-M u ns e ll 100 Hu e t e st
• L a nth o n y D e s a tur a t e d D-15 t e st
• L a nt e rn t e st
• A n o m a los c o p e
29
 Color Vision Sensitivity / Ease of Administration
Test Quantification
Ishihara Extremely sensitive / Nil Difficult for children
HRR Miss very mild R-G / Good classification Excellent for all ages

Farnsworth Only detect moderate to severe anomalous Easy to administer

D-15 trichromats and dichromats / Good
classification
F-M 100 Hue Extremely sensitive / Classify by error Tedious to administer
scoring
Anomaloscope Very by anomaly (R-G) quotient Good
 ISHIH ARA TEST
• D e si g n e d b y Dr. Shin o b u Ishih a r a (1879-1963).
Th e t e st w a s first p u b lish e d in 1917
• E a c h p l a t e is m a d e o f m a n y d iff e r e nt siz e d
d o ts o f sli g htly d iff er e nt c olors. Within th e d o t
p a tt e rn is a n u m b e r, a n d d iff e r e nti a t e d b y
c olor
• A full t est c o nsists o f 38 p l a t e s, b ut th e
e xist e n c e o f a c olor d e fi c i e n c y is usu a lly
c l e a r a ft e r n o m or e th a n 4 p l a t e s
 Kidwai n von IN
a .

guars
• Ishih a r a t e st is s c r e e nin g t e st f or r e d -gr e e n a n o m a li e s o nly
• D o n o t d istin g uish c o n g e nit a l fro m a c q uir e d d e f e c t
• D o n o t gr a d e th e d e gr e e o f c olor a n o m a ly
• Sh o ul d b e vi e w e d u n d e r a ft ern o o n d a yli g ht
• Vi e win g d ist a n c e is 75 c m or 30 in c h es
• With pro p e r r e fr a c tiv e c orr e c tio n
• Vi e win g tim e f or e a c h p l a t e sh o ul d b e n o m or e th a n 4
s e c o n ds

32
33
 11/10/18

Outline; The normal immune response

• Organs and cells of immune system
• Types of immunity
Basic Concepts in Immunology – Innate immunity vs. Adaptive immunity
• Innate immunity
– Components, triggers, leukocytes activation, phagocytosis, complement
activation, cytokine
• Adaptive immunity
Wantanee Sittivarakul, MD
– Humoral immunity
Ocular Immunology and inflammation Unit
– Cell-mediated immunity
Department of Ophthalmology, Faculty of Medicine,
• How the immune system causes disease
Prince of Songkla University
– hypersensitivity and autoimmunity

Basic science course ราชวิทยาลัยจักษุแพทย์แห่งประเทศไทย 15/11/2018

What does immune system do? The Players (principal cells) of Immune
System
• The most important physiologic function of immune • Sentinel cells in tissues
system(IS) is to prevent infections and to eradicate – Dendritic cells, macrophages, mast cells
established infections • Circulating phagocytes and granulocytes
• Promote normal function of (tissue cleanup, wound – Neutrophils, monocytes, eosinophils, basophils
repair) • Lymphocytes: cells which can recognize particular pathogens
• It removes abnormal cells including malignant ones (but also can cause allergies and autoimmune diseases)
– B lymphocytes: antibodies
• But the immune system can also cause disease when it
– T lymphocytes: cell-mediated immunity
is not doing the right thing (allergies, autoimmunity,
– NK cells, innate lymphoid cells, etc.
transplant rejection, etc.)
• Tissue cells (epithelial cells, endothelial cells, etc.)

1
 11/10/18

Immune sentinel cells in the tissues: dendritic cells Inflammatory mediators are
made in response to
detection of infection or
injury

Inflammatory mediators:
Green= dendritic cells -Lipids (prostaglandins, etc.)
Blue= nuclei of all cells -Proteins
TNF
Others
(cytokines/chemokines)
Langerhans cells (epidermal dendritic cells) in the skin
W J M ullholland et al. J. Invest. Dermatol. 126: 1541, 2006.

Cytokines Cytokines and Inflammation

• Cytokines : soluble protein mediators secreted by

immune cells (mostly) and act on other cells (“cyto”) to • Pro-inflammatory cytokines are many, but especially
regulate their activity (“kine”) important: TNF, IL-1, and IL-6

• Name of a cytokine often doesn't reflect its most • TNF and IL-1 signal to endothelial cells to make them:

important function (example: TNF stands for tumor – Leaky to fluid (influx of plasma; containing antibodies,
necrosis factor ) complement components, etc.)

• Many cytokines are called interleukins (IL-1, IL-2, etc.) – Sticky for leukocytes, leading to influx of leukocytes
• Cytokines that direct migration of cells are called • IL-6 promotes adaptive immune responses; systemic
chemotactic cytokines or chemokines effects

2
 11/10/18

Anatomy and cells of immune system Myeloid Lymphoid

Bone marrow

– Bone marrow is the source of precursor cells that

ultimately give rise to cell component of immune
system
– Pluripotent hemopoietic stem cell differentiated
to Circulation

• Erythrocytes
• Platelets
• Granulocyte/monocyte (myeloid) lineage Tissue

• Lymphocyte (lymphoid) lineage

Innate Adaptive
immunity immunity
Peakman, Mark, MBBS PhD FRCPath, Basic and Clinical Immunology, 1, 1-9
Copyright © 2009 First Edition © 1997, Elsevier Limited. Second Edition © 2009, Elsevier Limited. All rights reserved.

I. Granulocyte; 3 types I. Granulocyte; 3 types

1) Neutrophils 2) Eosinophils 3) Basophils (blood) and mast cells (tissue)
• 90-95% of granulocyte • 3–5% of granulocytes
– 1% of granulocyte
• Major phagocytes • Role in parasitic infection
• The first cell type to and allergic response – Mast cells express high affinity to
respond to most infection; – Major basic protein (MBP) Fc receptor to IgE
• Toxic to parasite
acute infection
• induce histamine release – Major effector cells in IgE mediated reaction
• Efficient phagocytes; from mast cell
– Kill microbes by release of • Allergy, hypersensitivity; vernal conjunctivitis
granules and cytokines

3
 11/10/18

II. Monocytes and macrophages III. Dendritic cells (DCs)

• Mononuclear phagocytes system • Mononuclear phagocytes system
• They are major phagocytes
• Important bridge between innate and adaptive IR
– Monocyte; circulating form
– Macrophage; tissue form • Professional (most efficient) antigen presenting cells (APCs)
• alveolar macrophages in the lung,
• Kupffer cells in the liver, that capture foreign substances and display to lymphocytes
• osteoclasts in bone
• microglial cells in the brain, retina • Epidermal Langerhan cells (LCs)
• Macrophages respond more slowly than neutrophils, reaction – Subset of DCs
of chronic inflammation
– 3-8% of cells in human epithelium included in conjunctiva and limbus
• Macrophages also help in repair damaged tissue
– Act as APCs
• Epithelioid cells and giant cells represent terminal
differentiation of activated macrophages

Myeloid Lymphoid
IV. Lymphocytes
Bone marrow

• Make up 25–35% of total white cells

• Main subtypes;
Ø B cells

Ø T cells; 2 main types à helper T cells (Th) and cytotoxic T cells (CTL)
Circulation
Ø Non-T non- B cells (natural killer cells)

• Each subset of lymphocytes are differentiated by specific surface

markers
Tissue
Ø Method of monoclonal antibodies can identify these markers
Ø Markers are name according to standardized Cluster of differentiation (CD)
Innate Adaptive
immunity immunity nomenclature
Peakman, Mark, MBBS PhD FRCPath, Basic and Clinical Immunology, 1, 1-9
Copyright © 2009 First Edition © 1997, Elsevier Limited. Second Edition © 2009, Elsevier Limited. All rights reserved.

4
 11/10/18

IV. Lymphocytes; B lymphocyte IV. Lymphocytes; T lymphocytes

• B lymphocytes; Bone marrow-derived • Mature in thymus
• Involved in cell-mediated immunity of adaptive IR
– Generate and mature in bone marrow
– Combat microbes that live inside cells (where they are inaccessible to
antibodies)
• Involved in humoral adaptive immunity; Antibody production
• Subpopulation;
– Bind and eliminate extracellular microbes
– T helper cells; express CD4+
• Primary role à recognition of antigens through surface • help B cells to make high quality Ab and help macrophages to kill ingested
microbes
receptors (membrane-bound immunoglobulins)
– Cytotoxic T cells; express CD8+
• Kill infected host cells à eliminate reservoir of infection
• Mature B cell express IgM and IgD on surface
– Regulatory T cells; control IR, prevent inappropriate response

IV. Lymphocytes; Natural killer cell (NK cell), Major cell types involved in immune and
inflammatory responses
• Lack antigen receptor (TCR or mIg) so they differ from both Cell type Principal functions
T and B cells
T lymphocyte - Help for B cells and macrophages (Th cells)
• Named based on their ability to kills target cells without - Killing of infected and tumor cells (CTL)
B lymphocyte Antibody production
the need for sensitization (previous exposure)
• Act as non specific cytotoxic cells Dendritic cells Capture and display of foreign (eg.microbial) antigens

• Role ; virus-infected cells and tumor cells Macrophages - Phagocytosis and killing of microbes
- Antigen capture and display
• NK cells are a major source of IFN-γ, which augments the - Tissue repair
Neutrophils Phagocytosis and killing of microbes
microbicidal functions of macrophage

5
 11/10/18

Principal cells of immune system

Organs of the immune system
• Primary (central) lymphoid organs
– the sites of development and maturation of the
lymphocytes
• bone marrow and thymus
• Secondary (peripheral) lymphoid organs
– Trap antigen and initiate immune response
• lymph nodes
• spleen,
• mucosal associated lymphoid tissue[MALT, included conjunctival
associated lymphoid tissue(CALT)]

innate adaptive

Concept of innate and adaptive immunity

• Defense against microbes consists of 2 types of reaction (innate vs. adaptive)

• Innate immunity; mediated by cells and proteins that are always present
and ready to fight against microbe

• Innate immune response is able to prevent and control many infections but

some microbes have evolved to overcome innate defenses so we have to

call in the more powerful mechanism of adaptive immunity

• Adaptive immunity is normally silent, and response (adapt) to microbes by

becoming active, expanding, generating potent mechanisms for eliminating

microbes

6
 11/10/18

Types of immunity
1. Innate (natural or native) immunity
• Mediates initial protection against infection

2. Adaptive (specific or acquired) immunity

• Develops more slowly, mediates later but more effective against
infection
• Consists of lymphocytes and their products
2.1 Humoral immunity; B lymphocyte
Principal mechanisms of innate and adaptive immunity
2.2 Cell- mediated immunity; T lymphocyte

Basic Im m unology: Functions and D isorders of the Im m une System , Chapter 1, 1-25
Copyright © 2016 Copyright © 2016 by Elsevier Inc. All rights reserved.

Comparative features of immunity

Innate immunity; overview
Innate immunity Adaptive immunity
• Present at birth • Stimulated by exposure to organism
• Preprogrammed reaction; present at birth, ready to recognize
• Immediate response • Slower response microbes
• Limited receptors; recognize • Variability of receptors, can recognize • Comprised of;
general classes of pathogens millions (10 7-109) of different 1) Epithelial barriers to the environment (i.e., skin, mucosa) with
(bacteria, viruses, fungi, parasite) but molecular structures of microbes
cannot make fine distinction antimicrobial protein and peptide (chemical barrier)
• Has memory (memory cells)
• No memory • lactoferrin in saliva, tear
• Increases in intensity with re-
• Does not change in intensity with • Lysozyme in keratinocytes, hair bulb cells
exposure
number of exposures • Acid pH of stomach
• Components; lymphocytes and their
• Components; 2) Phagocytic leukocytes; neutrophils, macrophages,
products
– Epithelial, chemical barriers
– Cells; phagocytes (neutrophil, – Humoral response: B cell 3) A specialized cell type; NK cell
macrophage), DC, NK cell – Cell mediated response; T cell 4) Circulating plasma proteins; complement system
– Circulating plasma proteins
(complement)

7
 11/10/18

Response to Infection; Inflammation

• Resident cells (DC, macrophage) in tissue recognized
characteristic features of infectious agent
• They secrete proteins (cytokine) that act on neighboring
Response to infection; Inflammation cells/blood vv. endothelium
• Endotheliums put adhesion molecules on their surface à
circulating immune cells adhere and move into site of
infection
• Blood vessels also allow fluid from blood to enter into site of
infection providing soluble components eg. antibodies

Migration and activation of leukocytes to sites of infection Migration and activation of leukocytes
1 2 3
• Leukocytes interact with the vessel wall, using several leukocyte
surface molecules and receptors on endothelial cells.
• Require specialized adhesion; 3 groups
Ø selectin

Ø integrin

Ø Ig superfamily; ICAM-1, ICAM-2

TNF and IL-1 • 3 basic steps of activation and migration

I. Rolling; mediated by selectins

II. Adhesion; firm adhesion by integrins, Ig superfamily

III. Trans-migration; to site of infection

Abbas, Abul K., MBBS, Basic Immunology: Functions and Disorders of the Immune System, Chapter 2, 27-53
Copyright © 2016 Copyright © 2016 by Elsevier Inc. All rights reserved.

8
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Phagocytosis and Killing of Microbes by Activated

Killing of Microbes by Activated Phagocytes Phagocytes

• Phagocytic vesicles fuse with lysosomes à

“phagolysosomes”

• Phagocytosed microbes are killed by the action of

“microbicidal molecules” in phagolysosomes
– Oxygen dependent pathway; using superoxide dismutase,
MPO à ROS,NO
– Oxygen independent pathway; using lysosyme
Abbas, Abul K., M BBS, Cellular and M olecular Im m unology, Chapter 4, 51-86
Copyright © 2015 Copyright © 2015, 2012, 2007, 2005, 2003, 2000, 1997, 1994, 1991 by Saunders, an im print of Elsevier Inc.

To enhance efficacy of phagocytosis Soluble factors in innate immunity

• Soluble immune components (complements and Ab) can bind to microbes
and allow phagocytes to eat them voraciously • Complement system;
• Using Fc receptors and complement receptors on phagocytes
– Several plasma proteins that work together

Opsonised
– Serves the following functions;
bacterium binds • Opsonize microbes; C3b
to neutrophil
• Promote the recruitment of phagocytes to the site of infection;
C3a,C4a,C5a (chemotaxis)
• Promote lysis of cell membrane by membrane attack complex
(MAC);C6-C9

– The first step in activation of the complement system is

Opsonization recognition of molecules on microbial surfaces
Peakman, Mark, MBBS PhD FRCPath, Basic and Clinical Immunology, 3, 23-34
Copyright © 2009 First Edition © 1997, Elsevier Limited. Second Edition © 2009, Elsevier Limited. All rights reserved.

9
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Complement; 3 pathways 3 different pathways of complement activation

• Both innate and adaptive immunity can initiate

complement activation pathways Innate

1) Classic pathway; Ag-Ab(IgM,IgG) complex (adaptive

immunity) Adaptive

2) Alternate pathway; cell wall component of bacteria

(innate immunity) Innat
e

3) Lectin pathway; mannose binding lectin (MBL) on

microbes cell wall chemoattraction chemoattraction C6-C9

Abbas, Abul K., MBBS, Cellular and Molecular Immunology, Chapter 4, 51-86
Copyright © 2015 Copyright © 2015, 2012, 2007, 2005, 2003, 2000, 1997, 1994, 1991 by Saunders, an imprint of Elsevier Inc.

Overview of humoral and cell mediated

immunity

• Microbes may be present in the lumens of GI tracts, free in

circulation and tissues, and hiding inside host cells
Adaptive immunity; – Immune system has to detect and eliminate microbes in all these
locations
most powerful of our immunity I. Humoral immunity is mediated by antibodies (Ab) (from B
cells)
– Ab is secreted into mucosal lumens, blood, interstitial fluids
– Ab combats microbes at all these locations (extracellular microbes
which are accessible to Ab)

10
 11/10/18

Overview of humoral and cell mediated

How lymphocytes recognize antigens
immunity
• The immune system recognizes and directs responses against an
II. Cell mediated immunity is mediated by T cells enormous number of antigens by generating a large number of
– Effective against intracellular microbes lymphocytes, each with a single antigen receptor
• Different type of T cells work in different way to eliminate – Antigen receptors of T and B cells are generated by DNA rearrangements in each developing cells

intracellular microbes • There are about 1012 lymphocytes in an adult

• It is estimated that these are able to recognized 107-109 different
• Helper T cells act on macrophages that have ingested microbes antigens produced by microbes
Introduction to Immunology I. The normal immune response Abul K. Abbas, MD
and activate macrophages to kill these microbes • The frequency of antigen responsive lymphocytes is only about 1 in
• Cytotoxic T cells recognize microbes hiding in cytoplasm of 10,000 to 1 in 100,000 (the challenge for lymphocytes7!!) 9
estimated that these are able to recognize at least 10 – 10 different antigens. Thus, only a
infected cells (viruses), and kill the infected cells Lymphocytes
– few thousandmust be able to express
lymphocytes locate microbes that
identical enter anywhere
antigen receptorsinand
the recognize the same
antigen.
body The molecular mechanisms responsible for the production of this enormous and
diverse collection of antigen receptors are beyond our scope, and will be discussed in I-3.

The antigen receptors of B cells are membrane-bound antibodies (also called

immunoglobulins, or Ig). Antibodies are Y-shaped structures. The tops of the Y recognize
the antigen and, in B cells, the “tail”Introduction
of the Y toanchors
ImmunologytheI. molecule
The normal immune
in the response
plasma membrane. Abul K. A
Antibodies are able to recognize whole microbes and macromolecules as well as small
chemicals. These could be in the circulation (e.g.
estimated a bacterial
that these are abletoxin) or attached
to recognize at least to
107cells
– 109 (e.g.
different antige
a microbial cell wall component). few thousand lymphocytes express identical antigen receptors and recog
antigen. The molecular mechanisms responsible for the production of this
The antigen receptors of T cells arediverse collection
structurally of antigen
similar receptors are but
to antibodies, beyond our scope,
T cell and will be disc
receptors
(or TCRs) recognize only small peptidesThe that are receptors
antigen displayedofonBspecialized peptide-display antibodie
cells are membrane-bound
molecules. These peptide display molecules are orcalled
immunoglobulins, MHC (major
Ig). Antibodies histocompatibility
are Y-shaped structures. The tops of t
complex) molecules, because they were discovered
the antigen and, in Bincells,
the the
context
“tail” of of
the graft acceptance
Y anchors or in the plas
the molecule
rejection (tissue compatibility); humanAntibodies are able are
MHC molecules to recognize
called HLA whole(for
microbes
humanand macromolecules a
leukocyte
antigens, because they were detected chemicals. These could be
by antibodies in the against
made circulation leukocytes).
(e.g. a bacterial HLA
toxin) or attach
a microbial cell wall component).
molecules pick up peptides from intracellular microbes and display these peptides for
recognition by T cells; this is how T The
cellsantigen
sensereceptors
the presence of are
of T cells microbes inside
structurally similarinfected
to antibodies, but
cells. (or TCRs) recognize only small peptides that are displayed on specialized
molecules. These peptide display molecules are called MHC (major h
Although the immune system is capable complex) ofmolecules, because
recognizing they were
millions discovered
of foreign in the context
antigens, it of graf
rejection (tissue compatibility); human MHC molecules are called HLA (for h
normally does not react against one’santigens,
own (self) antigenic
because substances.
they were As antibodies
detected by we shall made
see inagainst le
the next lecture, this is because lymphocytes
molecules pick thatuphappen
peptides tofromexpress receptors
intracellular microbesforand
self
display the
antigens are killed or shut off when recognition
they recognize these
by T cells; this antigens.
is how T cellsThis phenomenon
sense the presence is
of microbes
cells.
called self-tolerance, implying that we “tolerate” our own antigens; the breakdown of this
process results in autoimmune diseases.
Although the immune system is capable of recognizing millions of fore
normally does not react against one’s own (self) antigenic substances. As
the next lecture, this is because lymphocytes that happen to express re
E. Steps in immune responses antigens are killed or shut off when they recognize these antigens. This

How lymphocytes recognize antigens 4 Steps in adaptive IR

All adaptive immune responses follow called self-tolerance,
essentially the sameimplying that weof“tolerate”
sequence
process results in autoimmune diseases.
reactionsour(Fig.
own antigens;
1). the bre

1 2 3 E. Steps in4 immune responses

Fig. 1. Steps in an
• Upon infection, T cells and B cells whose antigen receptors All adaptive immune responses follow essentially the same sequence of reac
adaptive immune
response. The
recognize molecules of infectious agent multiply many times kinetics are Fig. 1
approximate, and
to expand their number (clonal expansion), some fight for reflect a response to
adapt
respo
a typical acute kinetic
infection, others are reserved as “memory” cells infection. appro
reflec
– Expanded number of memory cellsà stronger defense upon second a typic
infecti
infection

4 4

11
 11/10/18

Humoral immunity
How B cell recognize antigens?
Adaptive immunity; Humoral immunity
• Naive B lymphocytes express two classes of membrane-bound
antibodies (IgM and IgD), that function as receptors for Ag
• These naive B cells are activated by antigen binding to membrane Ig
• Often, B cells are helped by “helper T lymphocytes” (protein antigens)
these B cells take longer to make antibodies but make higher quality
Ab (bind more strongly, class switching), some of these B cells turn
into memory B cells that go to bone marrow and last a very long
time (years)

Antibodies u Components; 2 heavy chains Phases of humoral immune responses

and 2 light chains
u Heavy chains have 5 varieties;
3
u IgM, IgG (G1-4), IgA(A1-2),
1 2
IgE, IgD
u Variable region vs. Constant
region

Abbas, Abul K., MBBS, Basic Immunology: Functions and Disorders of the Immune System, Chapter 7, 147-168
Copyright © 2016 Copyright © 2016 by Elsevier Inc. All rights reserved

12
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Different antibody isotypes perform different functions

Heavy-Chain Isotype (Class) switching
• Specific cytokines by helper T cell stimulate and regulate
activated B lymphocytes to produce Abs of different heavy-
chain classes
– IFN-γ from Th1 induces switch from IgM to IgG1 àenhance
phagocytosis (opsonize) by binding to Fc receptor of phagocytes
– IL-4 from Th2 induces switch from IgM to IgE àkill parasite via
eosinophil
• Different antibody isotypes perform different functions
– To broaden the functional capabilities of humoral immune responses

Abbas, Abul K., MBBS, Basic Immunology: Functions and Disorders of the Immune System, Chapter 7, 147-168
Copyright © 2016 Copyright © 2016 by Elsevier Inc. All rights reserved.

Effector Mechanisms of Humoral Immunity

Effector Mechanisms of Humoral Immunity
1

• Antibodies can be directly protective or can

2
promote immune protective mechanism via
other cells or molecules
• Mechanisms of antibodies; 3

i. Direct neutralization
ii. Opsonization
iii. Antibody dependent cell cytotoxicity (ADCC)
iv. Activation of complement (classic pathway) 4

Abbas, Abul K., MBBS, Basic Immunology: Functions and Disorders of the Immune System, Chapter 8, 169-189
Copyright © 2016 Copyright © 2016 by Elsevier Inc. All rights reserved.

13
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Clinical application Monoclonal antibodies

• Local antibody production within a tissue (aqueous • We can take a single B cell that makes a desired
or vitreous) antibody, immortalized it, and use this antibody as a
• Measurement by Goldman-Witmer (GW) coefficient therapeutic. This is called a “monoclonal antibody”
– Titer of specific Ab in aqueous/ total Ab in Aq because it all derives from one original B cell (or
Titer of specific Ab in serum/ total Ab in serum clone of B cells)
• Used in infectious uveitis; Fuch uveitis, herpetic • Several monoclonal Ab therapies have been
uveitis, ocular toxoplasmosis introduced each year.
– Most of these are used for treating cancers or for
suppressing immune responses

Monoclonal Antibodies used in therapies

Monoclonal Ab Target Disease Adaptive immunity;

Infliximab
Adalimumab
TNF Rheumatoid arthritis,
Ankylosing spondylitis,
Cell-mediated immunity
Golimumab noninfectious uveitis
Certolizumab

Ranibizumab VEGF AMD

Rituximab CD20 Non-Hodgkin’s lymphoma

OKT3 CD3 Graft rejection

Trastuzumab HER2 Breast cancer

14
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Cell-mediated immunity Cell-mediated immunity; CD4+ vs. CD8+

T cells responses are tailored according to type of infection
How T cell recognize antigens?
• T lymphocytes recognize small piece of proteins (peptide) • They work in different ways to eliminate intracellular
associated with our own cells (MHC molecules, HLA molecules
in human) microbes
– Using “T cell antigen receptor” (TCR) which is like an • CD4+ act on macrophages that have ingested microbes into
antibody, but always on the surface of T cell, never
secreted phagocytic vesicle and activate macrophages to kill these
– Using antigen presenting cells (APCs) to process and microbes
present peptide antigen
• CD8+ recognize microbes hiding in cytoplasm of infected cells
• T cell receptors have “dual restriction”
1) For specific peptide Ag (e.g virus), and kill the infected cells
2) For MHC molecules

Peptides are presented to T cells bound to MHC Processing and Presentation of Protein Antigens by APCs
molecules (MHC restriction)
Dual restriction
of T cell
Class I MHC Class II MHC

MHC = major histocompatibility complex, collection of genes that make up

MHC locus locate on short arm of chromosome 6 Protein antigen in phagosomes à class II MHC pathway
Protein antigen in cytosol (cytoplasm) à class I MHC pathway
HLA= human leukocyte antigen
Abbas, Abul K., MBBS; Lichtman,. Published January 1, 2016. Pages 55-78. © 2016.

15
 11/10/18

MHC molecules are membrane proteins on APCs that Genes of the major histocompatibility complex (MHC) locus.
Schematic maps show the human MHC, called the human leukocyte antigen
display peptide antigens for recognition by T lymphocytes (HLA) complex

• MHC class I molecules (HLA-A,-B, and-C) serve as the antigen

presenting platform for CD8+ T lymphocytes
– Class I APCs are best for processing peptide antigens that have been
synthesized by the host cell itself e.g. Tumor peptides or viral peptides
– Class I molecules are present on all nucleated cells

• MHC class II molecules (HLA-DR,-DP, and-DQ) serve as the

antigen presenting platform for CD4+ T lymphocytes
– Macrophages, DCs, B lymphocytes are class II APCs
– Class II APCs are best for processing extracellular protein antigens that
have been endocytosed from external environment (bacteria, fungus)

Abbas, Abul K., MBBS, Basic Immunology: Functions and Disorders of the Immune System, Chapter 3, 55-78
Copyright © 2016 Copyright © 2016 by Elsevier Inc. All rights reserved.

Introduction to Immunology I. The normal immune response Abul K. Abbas, MD

Phases of T Cell Responses Effector mechanism of CD4+ T cells Naïve CD4+

T cell

Each subsets of helper T cell

I. Microbes enter through epithelium, produce different sets of
are captured by resident APCs, cytokine and perform different
transported to LN function
II. T cells recognized peptide antigen Subset Th1 Th2 Th17
and costimulatory molecules on
Cytokines
APC in LN (second signal) IFN-gamma IL-4, IL-5, IL-13 IL-17, IL-22
produced
III. Activation of naive T cells Immunological - Help B cell for IgE - Recruitment
- Macrophage activation
Fig. 2. Subsets of helper T cells. Note that all the subsets arise from naïve CD4+ cells;
- Secretion of cytokines (eg. IL-2) reaction
whichtriggered - Help B cell
subset is dominant for IgG
depends on the nature ofprodution
the intial activation. of neutrophils,
- Clonal expansion - Activation of mast monocytes
production
CD8+ T cells differentiate into CTLs that kill host cells harboring cytoplasmic microbes (e.g.
cells and eosinophil
- Differentiation of naïve T cells into viruses) and thus eradicate the infection. CTLs are the effector cells of the CD8 + lineage.
Host defense Intracellular microbes Helminthic parasites; Extracellular
Effector T cells H. Immunological memory
against (bacteria, fungus)
The initial lymphocyte activation generates not i.e.
onlyocular toxocariasis
effector bacteria
cells but also a fungi
small population
- Development of memory T cells of antigen-specific lymphocytes that have the capacity to live for a long time, lying in wait for
Rolethe
in disease Autoimmune
antigen to return. disease;cells are
These long-lived Allergies, asthma cells, because
called memory Inflammatory
they ensure
IV. Migration of T cells to sites of that the immune system remembers what microbes it may have encountered. The number
uveitis (SO, VKH, Sarcoid), diseases
of memory cells increases with age (again reflecting our exposure to microbes) – almost all
infection circulating T cellsgraft
in arejection,
newborn are naïve cells, whereas as many as half in an adult are
memory cells. phlyctenulosis
Memory cells respond more rapidly and powerfully than do naïve
Abbas, Abul K., MBBS, Basic Immunology: Copyright © 2016 Copyright © 2016 by Elsevier Inc. All rights reserved. lymphocytes; this is why the response to repeat exposures to a microbe (“secondary
responses”) are more effective that the response to the first exposure (“primary response”).
A goal of vaccination is to stimulate strong memory responses (and long-lived plasma cells).

Now that we have summarized the principal components of the immune system and how
they react against foreign antigens, in the next lecture we will highlight some of the ways
that the immune system can attack the host and cause injury.

16
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Effector mechanisms of Th1 and Th2 cells

Th1 cells
Effector mechanism of CD8+ T cells
Th2 cells

• Differentiate into
“cytotoxic T
lymphocyte”
• killing tumor or viral
Introduction to Immunology I. The normal immune response Abul K. Abbas, MD
infected cells through
release of granules
that these are able to recognize at least 107 – 109 different antigens. Thus, only a
protein(granzymes,
estimated
few thousand lymphocytes express identical antigen receptors and recognize the same
perforin)
antigen. The cell lysis mechanisms responsible for the production of this enormous and
àmolecular
diverse collection of antigen receptors are beyond our scope, and will be discussed in I-3.

The antigen receptors of B cells are membrane-bound antibodies (also called

immunoglobulins, or Ig). Antibodies are
Abbas, Abul K., MBBS,Y-shaped structures.
Basic Immunology: Functions and Disorders of the ImmuneThe tops
System, Chapter of the Y recognize
6, 129-146
Copyright © 2016 Copyright © 2016 by Elsevier Inc. All rights reserved
Abbas, Abul K., MBBS, Basic Immunology: Functions and Disorders of the Immune System, Chapter 6, 129-146
Copyright © 2016 Copyright © 2016 by Elsevier Inc. All rights reserved the antigen and, in B cells, the “tail” of the Y anchors the molecule in the plasma membrane.
Antibodies are able to recognize whole Introduction microbes
to Immunology and I.macromolecules
The normal immune response as well as small Abul K. A
chemicals. These could be in the circulation (e.g. a bacterial toxin) or attached to cells (e.g.
a microbial cell wall component). 7 9
estimated that these are able to recognize at least 10 – 10 different antige
few thousand lymphocytes express identical antigen receptors and recog
The antigen receptors of T cells are structurally similar to
antigen. The molecular antibodies,
mechanisms but T cell
responsible receptors
for the production of this
(or TCRs) recognize only small peptides thatcollection
diverse are displayed
of antigen on specialized
receptors are beyond peptide-display
our scope, and will be disc
molecules. These peptide display molecules are called MHC (major histocompatibility
The antigen receptors of B cells are membrane-bound antibodie
complex) molecules, because they were discovered or
immunoglobulins, in Ig).
theAntibodies
context are of Y-shaped
graft acceptance or tops of t
structures. The
rejection (tissue compatibility); human MHC molecules
the antigen and, in Bare called
cells, HLA
the “tail” (for
of the humanthe
Y anchors leukocyte
molecule in the plas
antigens, because they were detected by antibodies
Antibodies are able to made
recognize against leukocytes).
whole microbes HLA
and macromolecules a
chemicals. These
molecules pick up peptides from intracellular could be
microbes andin the circulation
display (e.g. apeptides
these bacterial toxin)
for or attach
a microbial cell wall component).
recognition by T cells; this is how T cells sense the presence of microbes inside infected
cells. The antigen receptors of T cells are structurally similar to antibodies, but
(or TCRs) recognize only small peptides that are displayed on specialized
Although the immune system is capable molecules. These peptide
of recognizing display of
millions molecules
foreignareantigens,
called MHCit (major h
complex) molecules, because they were discovered in the context of graf
normally does not react against one’s own (self) antigenic substances. As we shall see in
rejection (tissue compatibility); human MHC molecules are called HLA (for h
the next lecture, this is because lymphocytes that happen
antigens, because they were to express
detected by receptors
antibodies for selfagainst le
made
antigens are killed or shut off when they recognize
molecules pick upthese
peptidesantigens. This phenomenon
from intracellular microbes and is display the
recognition by T cells; this is how T cells sense
called self-tolerance, implying that we “tolerate” our own antigens; the breakdown of this the presence of microbes
cells.
process results in autoimmune diseases.
Although the immune system is capable of recognizing millions of fore
normally does not react against one’s own (self) antigenic substances. As
E. Steps in immune responses the next lecture, this is because lymphocytes that happen to express re

Decline of immune responses and Phases of adaptive IR

All adaptive immune responses follow antigens are killed or shut off when they recognize these antigens. This
essentially the same sequence of reactions (Fig. 1).
called self-tolerance, implying that we “tolerate” our own antigens; the bre

immunological memory
process results in autoimmune diseases.

E. Steps in immune responses Fig. 1. Steps in an

All adaptive immune responses follow essentially
adaptivethe same sequence of reac
immune
• Majority of effector lymphocytes induced by pathogen die by response. The
apoptosis after microbe is eliminated kinetics are
approximate, and Fig. 1
– Returning immune system to steady state called “homeostasis” adapt
reflect a response to respo
a typical acute kinetic
• But the initial activation of lymphocytes generate long-lived infection. appro
reflec
memory cells, may survive for years after that infection a typic
infecti
• These memory cells respond faster and more effectively upon the
following infections
• A goal of vaccination is to stimulate strong memory responses with
long-lived plasma cells

4 4

17
 11/10/18

How the immune system causes disease

• There are 3 main situations in which imm responses

are pathologic
i. When self-tolerance fails and immune system begins to
How the immune system causes disease?
attack individual’s own tissues (autoimmune disease)
ii. When imm response becomes excessive or uncontrolled,
either against microbial Ag or normally harmless
environmental Ag (poststreptococcal GN, allergy, asthma)
iii. As part of entirely normal reaction against some microbes
(viral hepatitis)

Hypersensitivity and autoimmunity • Autoimmunity:

– the response of the adaptive immune system to self-antigens that occurs when
mechanisms of self-tolerance fail
• Hypersensitivity diseases – Autoimmunity is one cause of hypersensitivity
– An abnormal or pathologic immune reaction that • The failure of self-tolerance:
is caused by an immune response to repeated
– Normal imm system does not react against self-Ag
exposure to an antigen
– During the generation/maturation of lymphocytes (T and B), the clone of
– Hypersensitivity diseases include lymphocyte that react to self Ag are deleted/inactivated
i. Autoimmune diseases, in which immune responses – Some individuals, this mechanism fails and these lymphocytes survive, become
are directed against self-antigens activated and they attack their own tissues
ii. Diseases that result from uncontrolled or excessive – Why self- tolerance fails is unclear
responses to foreign antigens
• Multifactors; inheritance of susceptibility genes and environmental triggers ( infections
or tissue injury)

18
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4 major types of hypersensitivity

Figure. Hypothesis for how

susceptibility genes and
environmental triggers work
together to cause autoimmune
diseases

1. Immediate (type 1) hypersensitivity: Th2-mediated

4 major types of hypersensitivity diseases

1. Immediate (type I) hypersensitivity • Abnormally strong Th2 responses against environmental antigens that are
essentially ignored by the ~75-80% of the population
2. Antibody-mediated (type II) hypersensitivity
• All the clinical and pathologic manifestations of allergy are the result of

cytokines produced by Th2 cells (IL-4, IL-5)

3. Immune complex-mediated (type III) hypersensitivity
• IL-4 stimulates B cells to produce IgE

4. Cell-mediated (type IV) hypersensitivity – IgE then binds to mast cells and activates mast cells to release many mediators
(histamine, proteases) àvascular and smooth muscle reactions

Note; the effector mechanisms of tissue injury in these diseases are the • IL-5 activates eosinophils which can exacerbate tissue damage
same as the effector mechanisms used by the immune system to combat
and destroy microbes

19
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2. Antibody-mediated (type II) hypersensitivity

Example of Diseases • Antibodies are directed against antigens on the surface of cells or
other tissue components
- Asthma
- Allergic rhinitis • The deposition of the antibody can have a variety of detrimental
- Allergic conjunctivitis effects
- Anaphylaxis – Complement activation (inflammation),
- Vernal keratoconjuctivitis, – Opsonization and phagocytosis if it occurs on the surface of circulating
atopic keratoconjunctivitis cells,
(combined type 1 and type 4) – Functional derangements

Mechanism of Immediate (type 1)

hypersensitivity

3. Immune complex-mediated (type III) hypersensitivity

Example of Diseases • Complexes of antibodies and antigens in circulation deposit in

- Mismatch transfusion reaction the vascular walls of blood vessels leading to inflammation
- Autoimmune hemolytic anemia
- Mucus membrane pemphigoid • Alternatively, the complexes may form “in situ” at locations
- Myasthenia gravis where the antigen or antibody has been initially deposited
• The antigens in these complexes may be exogenous (i.e.
microbial proteins) or endogenous (i.e. nucleoproteins from
Mechanism of type 2 hypersensitivity within the individuals own cells)

20
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3 steps mechanism 4. Cell-mediated (type IV) hypersensitivity

1. 2. 3.
T lymphocytes injure tissues by two principal mechanisms
1. Delayed type hypersensitivity, (DTH) is mediated by CD4+ Th cells (Th-1 and Th-17
cells)
– Th-1 cells secrete large amount of IFN-gamma which is potent stimulator of macrophages,
they come to site of Ag and secrete inflammatory mediator, growth factors à
inflammation and fibrosis à result in fibrosis and granulomatous inflammation
• Th17 cells secrete cytokines that also recruit leukocytes, such as neutrophils,
• Take 24-48 hours to develop after antigen challenge (the classical example is a PPD skin
test)
Example of diseases;
• Th1 and/or Th17 reactions against self-antigens or against persistent microbes are
- Serum sickness
responsible for many chronic disorders (Crohn’s, multiple sclerosis)
- Acute post streptococcal glomerulonephritis
2. Cell mediated cytotoxicity; mediated by CD8+ T cells
- SLE (scleritis, PUK)
• CTL release enzymes that attack target cells à lysis and apoptosis of cells
- Rheumatoid arthritis (scleritis, PUK)
- Systemic vasculitis (ANCA related) • Solid organ transplantation, viral hepatitis (cirrhosis at the end)

Clinical application
• Th1-DTH example of diseases;
– Contact dermatoblepharitis (thimerosal)
– Phlyctenulosis (bacterial Ag)
– Sympathetic ophthalmia, VKH (retinal or uveal autoAg)
– Solid organ transplantation
– Ocular graft versus host disease (GVHD)
– Tuberculin PPD skin test (Tuberculin Ag)

• Th2-DTH
– Toxocara granuloma;
• eosinophilic granuloma as Th-2 cells secrete IL-4 that induces eosinophil infiltration

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Summary; Basic concepts in immunology

• List principal cells and tissues of immune system

– Tissue cells (DCs, macrophages), circulating cells (phagocytes), lymphocytes
• Summarize the main differences between innate and adaptive immunity
• Describe how B and T cells recognize foreign antigens? Thank You For Your Attention
• Describe the process of activation naïve B and T cells, and effector
mechanisms of B and T cells
– Effector mechanism of antibody
– Effector mechanism of T-cell (T-helper vs. cytotoxic T- cell)
• Hypersensitivity and autoimmunity
– The meaning of these 2 terms
– Describe the mechanisms by which antibody and T cells cause tissue injury

22