Basic immunology from the dermatologic point of view

Basic Immunology from the
Dermatologic point of view
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The Immune System
• Protection from foreign
macromolecules or invading organisms
(viruses, bacteria, protozoa or even larger
parasites).
• Autoimmunity
immune responses against our own
proteins.
• Tumor immunity.
Against our own aberrant cells.

SKIN AS AN ORGAN OF
PROTECTION
• Our first line of defense against foreign
organisms are barrier tissues (skin and
mucous membranes).
• The skin represent a major barrier
against the outside environment, being
constantly exposed to microbial
mechanical and physical insults.
• The skin protection is not only
mechanical.

SKIN AS A PART OF THE
IMMUNE SYSTEM
• It uses the immune system for protection.
• Has the capacity to generate an immune
response through the SALT (skin
associated lymphoid tissues).

TYPES OF THE IMMUNE
REACTION
• There are two types of immune reaction to
invadors.
• A rapid more primitive reaction called the
innate immunity.
• A later highly specific more developed
adaptive immune system.
• Both types of the immune response can
be generated in the skin

Immune system
• Innate immunity:
Composed of heriditary components that provide an
immediate "first-line" of defense to continuously
protect against pathogens.
• Adaptive (acquired) immunity:
DEFENCE MECHANISMS USED BY THE HOST
IMMEDIATELY AFTER ENCOUNTERING A FOREIGN LIGAND
The body can develop a specific immunity Humoral or
cellular to target particular pathogens.
This response takes days to develop, and so is not
effective at preventing an initial invasion, but it will
normally prevent any subsequent infection, and also aids
in clearing up longer-lasting infections.

Innate immunity
• This is the immunity one is born with.
• It is the only form of immunity in
primitive organisms.

Innate immunity
• The first line of defense
- It discriminates between self and non-self
.
- Distinguish between pathogenic and
non-pathogenic microbes.
- It plays an important role in triggering the
adaptive immune response.

The major functions of innate
immune system include:
• The identification and removal of foreign
substances present in organs, tissues, the
blood and lymph, by specialized cells.
• Recruiting immune cells to sites of
infection, through the production of
chemical factors, including cytokines.
• Activation of the complement cascade
• Activation of the adaptive immune system
through antigen presentation.

Innate immune responses
• Immediately or within several hours after
exposure to the stimulus.
• Stop the early spread of infection.
• Provide the necessary stimulus for long-lasting
adaptive immunity, which is specific
to the pathogen.

Mediated through
I. Cells of the innate immune system
- Phagocytic cells (neutrophils, monocytes, and macrophages.
-- Cells that release inflammatory .mediators
(basophils, mast cells, and eosinophils).
-Dendritic cells.
- Natural killer cells (NK cells) and the gamma
delta Tcells
II. cytokines, chemokines and
polyreactive antibodies.
III. Anti microbial peptides.
IV. Complement activation.
V.Inflammation

INNATE IMMUNITY ADAPTIVE IMMUNITY
Trigger PAMP Specific antigens
Action Min-hours Days to weeks
Receptors PRR as TLR TCR,BCR
Memory No Yes
Communications Cytokines and chemokines
Effectors Complement
Antigen presentation
Phagocytosis
Complement
Antibodies
Cytotoxicity

Components of innate immunity include:
-Anatomical and mechanical barriers.
-Pattern recognition receptorsPRR
that recognize PAMP.
-Antigen-nonspecific defense chemicals.
-The alternative complement pathways.
- Phagocytosis.
- Inflammation.
- fever.
Prevent most pathogensand environmental toxins from harming the host.
The skin and epithelial linings.
Epidermis impedes microbial organisms, irritants, toxins,
Absorbs and blocks solar and ionizing radiation
inhibits water loss
St corneum FFA prevent colonization by bacteria as S aureus.
Antimicrobial peptides: defensin HBD-1,2&3
cathelicidins
Activated by microbial surface without antibody formation
Keratinocyte cytokines: IL-1,6,8,10&TNFalpha

Anti microbial peptides
• Secreted by the human epithelia including
the epidermis (Keratinocytes) to exhibit
the capacity of an innate chemical
defense.
• Antiliukoproteases.
• Dramcidin (SWEAT GLANDS)
• Human B defensin 1-4.
• Lysosyme, Psoriasin (Sebocytes),
RNase7,LL-37/hCAP18 (urogenital tract).

Selectivity of antimicrobial
peptides
• antimicrobial peptides preferentially
interact with the bacterial cell to the
mammalian cells ie Selective
• the cationic property: bacterial
membranes is more negatively charged
than mammalian cells.
• The cholesterol in mammalian cells
protect them from attack by the
antimicrobial peptides.

Induction and Actions
• Induced by bacterial and proinflammatory
products or cytokines as well as toll like
receptor stimulation.
• Broad spectrum anti bacterial and variable anti
fungal and antivrial activities.
• Disrupting membranes, interfering with
metabolism, and targeting cytoplasmic
components
• Attract immature dendritic cells and memory T
cells via CCR6 role in adaptive immunity

IDENTIFICATION OF THE
INVADOR
• On the organism:
Pathogen associated molecular patterns
(PAMPS),
• On the effector cells:
Pattern recognition receptors
(PRP).

PATHOGEN-ASSOCIATED MOLECULAR
PATTERNS PAMPS
• Innate immunity does not recognize
every possible antigen.
• It is designed to recognize a few highly
conserved structures present in many
different microorganisms.
PATHOGEN-ASSOCIATED MOLECULAR
PATTERNS ( PAMPS)

PATHOGEN-ASSOCIATED MOLECULAR PATTERNS
PAMPS (CONT)
1. Must be shared by large groups of pathogens and
thus must represent general patterns rather then
specific structures.
2. Must be conserved products of microbial
metabolism which are not subject to antigenic
variability.
3. pathogens cannot "change" them because they are
essential for the survival or pathogenicity of the
microorganisms. Any attempts to change them
could be lethal to the microbe or render it
nonpathogenic.
4. The recognized structures must be absolutely
distinct from self-antigens. The major consequence
of this requirement is the ability of the innate
immune system to discriminate between self and
non-self.

PAMPS
In all, the innate immune system is thought to recognize
approximately 103 molecular patterns.These include:
Cell wall constituents or nucleic acids
a. Lipopolysaccharide (LPS) from the gram-negative cell
wall.
b. Peptidoglycan found abundantly in the gram-positive cell
wall and to a lesser degree in the gram-negative cell wall .
c. Lipoteichoic acids found in the gram-positive cell wall.
d.Lipoarabinomannum (LAM) in mycobacterial wall
e. Mannose-rich glycans (common in microbial
glycoproteins and glycolipids but rare in those of
humans).
f. Flagellin found in bacterial flagella.
g. Pilin from bacterial pili.

PAMPS (CONT)
g. Bacterial and viral nucleic acid. Bacterial and viral
genomes contain a high frequency of unmethylated
cytosine-guanine dinucleotide sequences (a cytosine
lacking a methyl or CH3 group and located adjacent to a
guanine). Mammalian DNA has a low frequency of
cytosine-guanine dinucleotides and most are methylated.
h. N-formylmethionine, an amino acid common to
bacterial proteins.
i. Double-stranded RNA unique to most viruses.
j. Lipoteichoic acids, glycolipids, and zymosan from
yeast cell walls.
k. phosphorylcholine and other lipids common to
microbial membranes.

Pattern-recognition Receptors
(PRR)
To recognize these microbial
molecules, various body defense cells
have on their surface a variety of
receptors called
Pattern-recognition Receptors
capable of binding specifically to
PAMPS

Pattern Recognition Receptors
• The cornerstone of the innate immune
system is comprised of germline-encoded
receptors (not specific recognition of individual
pathogens, but rather a coarse-grain encoding of the
species).
• These PRRs are activated upon
recognition of “Pathogen-Associated
Molecular Patterns” or PAMPs.

CLASSIFICATION
I. Cell surface PRR two functionally different
classes :
• 1. Endocytic pattern-recognition
receptors.
• 2. Signaling pattern-recognition
receptors
II. Secreted PRR

ENDOCYTIC PATTERN-RECOGNITION
RECEPTORS
Found on the surface of
phagocytes and promote the
attachment of microorganisms to
phagocytes and their subsequent
engulfment and destruction.

Signaling pattern-recognition
receptors
• Binding of microbial molecules to the
receptor promotes the synthesis and
secretion of intracellular regulatory
molecules such as cytokines that is crucial
to initiating innate immunity and adaptive
immunity.
• Toll-like receptors and
• CD14.
• NOD (nucleotide-binding oligomerization
domain proteins)

Toll-like receptors
• A series of Signaling pattern-recognition
receptors known as
toll-like receptors (TLRs) play a
major role in innate immunity and
the induction of adaptive immunity.

THE TOLL
• Mamalian TLRs owe their name to a
closely related receptor called Toll, first
identified in Drosophila in 1988.
• TOLL: german word of fantastical or
strange.
• They recognize and bind to PAMPS
(conserved molecular components
associated with microorganisms)

TLRs
• TLRs belong to the IL-1 receptor family.
• Defined by the presence of extracellular
leucine-rich repeats and an intracellular
Toll/interleukin-1 receptor domain.
• Linked to a signaling pathway that involves
the IL-1-receptor kinase and NF- B.

Toll like receptors
Upon binding of the extracellular ligand
recognition domain to specific PAMPs,
changes in the intracellular domain result
in initiation of signaling events leading to
• Inflammatory responses and/or
• Release of antimicrobial agents.

Toll-Like Receptors Responding to Lipopolysaccharide
(LPS)
from the Gram-Negative Cell Wall

CD14
• CD14 is found on monocytes, macrophages,
and neutrophils.
• promotes the ability of TLR-4 to respond to LPS
and peptidoglycan. Which causes secretion of
proinflammatory cytokines such as IL-1, IL-6, IL-
8, TNF-alpha.
• These cytokines then bind to cytokine receptors
on target cells and initiate inflammation and
activate both the complement pathways and the
coagulation pathway

NOD (nucleotide-binding
oligomerization domain) proteins
• NOD1 and NOD2
• allow intracellular recognition of
peptidoglycan components released during
growth or phagocytosis ( muramyl dipeptide)
• Binding of the muramyl dipetides to NOD1 or
NOD2 leads to the activation of genes coding
for proinflammatory cytokines.

Secreted pattern recognition
receptors
• Secreted pattern-recognition receptors.
These bind to microbial cell walls and enable
them to be recognized by the complement
pathways and phagocytes.
• Eg mannan-binding lectin is synthesized by the
liver and released into the bloodstream. MBL
recognizes carbohydrate patterns, found on the
surface of a large number of pathogenic micro-organisms,
including bacteria, viruses, protozoa
and fungi.

Signaling pathways
- NF-kB pathway
It is not known whether TLRs can productively couple to
the IL-1R signaling machinery or whether a parallel set
of proteins is used.
- A number of specific molecules are known to be
involved.
• adaptor molecules such as the myeloid differentiation
factor 88 MyD88,
• Toll/IL-1R (TIR) domain containing adaptor protein
(TIRAP), and TIR domain-containing adapter inducing
interferon (TRIF). and TRAFs (TNF receptor associated
factors).
• Other key signaling proteins include IL-1 receptor
associated kinases (IRAKs) such as IRAK1, 2, and 4,
transforming growth factor kinase (TAK-1), IkB kinases
(IKKs),

MEMBERS OF THE TRLs FAMILY
• The first characterized member of the mammalian
family of TLRs was TLR4 which was shown to trigger
the pro-inflammatory NF-kB pathway upon binding
to LPS with the assistance of CD14 molecule.
• The completion of the human genome project led to
the identification of numerous putative TLRs in the
genome.
• These TLRs differ from each other in ligand
specificities, expression patterns, and target genes
they induce.
• Different combinations of TLRs appear in different
cell types.
• Seem to appear in pairs.

Different TLRs
• 1. TLRs found on cell surfaces:
a. TLR-1/TLR-2 pairs bind uniquely bacterial lipopeptides and
glycosylphosphatidylinositol (GPI)-anchored proteins in parasites;
b. TLR-2/TLR-6 pairs bind lipoteichoic acid from gram-positive cell
walls and zymosan from fungi;
c. TLR-2 plays a role in binding peptidoglycan fragments
(glycopeptides);
d. TLR-4/TLR-4 pairs bind lipopolysaccharide from gram-negative
cell walls;
e. TLR-5* binds bacterial flagellin;
• 2. TLRs found in the membranes of the
endosomes used to degrade pathogens:
• a. TLR-3* binds double-stranded viral RNA;
b. TLR-7* binds uracil-rich single-stranded viral RNA such as in
HIV;
c. TLR-8* binds single-stranded viral RNA;
d. TLR-9* binds unmethylated cytosine-guanine dinucleotide
sequences (CpG DNA) found in bacterial and viral genomes.

TLRs are found both on the surface and
within the phagolysosomes of phagocytes.

PAMPs Binding to TLRs on Macrophage

The TLRs found in the membranes of the phagosomes
Recognizing Viral Double-Stranded RNA after phagocytosis

ROLE IN INNATE IMMUNITY
• The binding of a microbial molecule to its TLR transmits
a signal to the cell's nucleus inducing the expression of
genes coding for the synthesis of cytokines.
• Many of the TLRs, especially those that bind to bacterial
and fungal cell wall components stimulate
IL -1, TNF-alpha, and IL-8. trigerring innate immune
defenses such as inflammation, fever, and phagocytosis
in order to provide an immediate response against the
invading microorganism.
• Most of the TLRs that bind to viral components trigger
the synthesis of interferons that block viral replication
within infected host cells.
• Cytokines such as interleukin-6 (IL-6) that promotes B-lymphocyte
activity and interleukin-12 that promotes T-lymphocyte
activity are also produced.

Role in adaptive immunity
• TLRs trigger various secondary signals needed
for
- humoral immunity (the production of antibodies).
-cell-mediated immunity (the production of
cytotoxic T-lymphocytes and additional cytokines).
• Without innate immune responses there could be
no adaptive immunity.

Imiquimod Activates I
the
Toll-Like Receptor 7
cell lysis & release
of bioactive IL1-a
IL1 IL18 TLRs TNF
NF-kB
cytokines (IL1, TNF-a)
IL-12, IFN-g, chemokines,
& ‘danger’ signals

T-independent (TI) antigens
and humoral immunity:
1) These antigens activate B-lymphocytes by binding to
their specific toll-like receptors rather than to B-cell
receptors.
2) allow B-lymphocytes to mount an antibody without
the requirement of interaction with T-lymphocytes.
3)TI antigens are PAMPS such as lipopolysaccharide
(LPS) and bacterial nucleic acid.
4)Antibody molecules generated against TI antigens
are often called "natural antibodies" because they are
always being made against bacteria present in the
body. IgM isotype and do not give rise to a memory
response.

The Complement system
• a biochamical cascade of the immune
system that helps, or “complements”, the
ability of antibodies to clear pathogens or
mark them for destruction by other cells.
• The cascade is composed of many plasma
proteins, synthesized in the liver.

• Activated by three pathways:
1) Classical: antigen antibody complex.
2) Alternative pathway: polysaccharides of
microbial cell walls.
3) Lectin pathway: by the binding of the
microbial carbohydrates with mannose
binding lectin.
• Innate immune response uses 2 and 3
• Activation of C3 and starts the cascade.

• The proteins work together to:
-trigger the recruitment of inflammatory cells,
-"tag" pathogens for destruction by other cells,
and enhances phagocytosis.
- Disrupt the plasma membrane of an infected
cell.
• Rrid the body of neutralized antigen-antibody
complexes.
• Normal cells are less sussceptible to
desruction by complement .

Cytokines
• Substances secreted by various cell types to
interact with other cells to produce ceratain
actions.
• Interlukins (interaction between WBCs),
interferons (antiviral activities)
• colony stimulating factors induce
differentiation and proliferation of
hematopoeitic progenitor cells.
• Chemokines,(Inflammatory and lymphoid)
chemoattraction ability.

Cytokines of the innate immune
system
• Mainly cytokines withi nflammatoryand
antivral capacities.
- IL-6,IL-1and TNF alpha and inflammatory
chemokines.
- IFN alpha and IFN beta.

Macrophages
• Expresses PPR to identify organisms.
• Receptors for antibodies and complement that
enhances phagocytosis.
• Destroy the organisms by toxic intracellular molecules
as:superoxide anions, hydroxyl radicals,nitrous oxide,
etc.
• Antigen presenting capacity (much less than
Langerhan’s cells)
• Releases G-CSF, AND GM CSF that stimulate the
devision and release of neutrophils from the bone
marrow.

Neutrophils
• The enter the blood stream to enter the site
of infection through the complex effect of
proinflammatory mediators,adhesion
molecules chemoattractants and
chemokines.
• Phagocytosis is enhanced by coating the
organism by antibodies and complement that
bind to their receptors on the neutrophils
• Phagocytose and kills the organisms by
oxygen (H peroxide and hydroxyl radicals)
dependant or independent mechanisms
(myeloperoxidase or lysosyme).

Eosinophils
• Protective agains parasites.
• Antibodies bind the parasite and then the
eosinophils
• Weak phagocytic activity.
• Release toxic substances to the parasite
as major basic ptn, Eosinophil cataionic
protein, E peroxidase Eneurotoxin,
• Prostaglandins leukotrienes and
cytokines.
• Important in allergic reactions.

Basophil and mast cells
• Basophil in the blood and mast cell in the
tissues.
• Only cutaneous mast cells express
receptors for the anaphylatoxin C5 a so
when activated by binding antigen specific
antibodies only a local reaction occur.
• Palys an important role in immediate allergic
reaction, urticaria and angioedema.
• Mast cells are involved in TLR-mediated
responses against Gram-negative bacteria.

Natural killer cells
• Pattern recognition receptors (TLR 3,9) it
can identify and eliminate infected or
malignant cells.
• Adhere and kill targets coated with IgG as
they carry receptors for it (antibody
dependant cellular cytotoxicity ADCC).
• Activation of killer activating receptors that
recognize the abnormal cells and kills
them by secreting perforin and injecting
granzyme that kills the cells by inducing
apoptosis.

Natural killer cells
• MHC shuts off the killer signals.
• Tumour cells and viral infected cells are
vulnerable.as they sometimes mask MHC
to escape cytotoxic T cells

inflammation
• One of the first responses of the immune
system to infection or irritation.
• Inflammation is stimulated by chemical
factors released by injured cells and cells
of the innate immune syste and serves to
establish a physical barrier against the
spread of infection, and to promote
healing of any damaged tissue following
the clearance of pathogens.[3]

Inflammation
• Chemical factors produced during
inflammation (histamine, bradykinin,
leukotrienes, serotonin and prostaglandin,
sensitize pain receptors, cause
vasodilatation at the scene, and attract
phagocytes, especially neutrophils.[

interactions between the innate and
adaptive immune
• The interactions between the innate and
adaptive immune systems are crucial to
promote proinflammatory reactions against
pathogens and to ensure maintenance of
vital self-tolerance.
• TLRs are expressed on both innate and
adaptive immune cells and are critically
involved in this interplay.
• TLR-stimulated dendritic cells induce
specific T cells to differentiate into TH-1, TH-
2 or T-reg

Adaptive immunity
• Cells of the innate immune system
effectively prevent free growth of bacteria
within the body.
• however, many pathogens have evolved
mechanisms allowing them to evade the
innate immune system and generates a
threshold level of antigen which triggers .
the adaptive immune system include:

Functions of the adaptive
immune system
• the recognition of specific “non-self” antigens
in the presence of “self”, during the process
of antigen presentation.
• the generation of tailored responses to
eliminate specific pathogens.
• the development of immunologic memory in
which each pathogen is “remembered” by a
signature antibody. These memory cells can
be called upon to quickly eliminate a
pathogen on subsequent infections .

Adaptive immune system
• The cells of the adaptive immune system
are
• B cells and T cells are the major types of
lymphocytes.
• The process starts by antigen
presentation.
• Adaptive immunity relies on the capacity
of immune cells to distinguish between the
body's own cells and unwanted invaders

Antigen presenting cells ( APC)
With the exception of non-nucleated cells all
cells are capable of presenting antigen
and of activating the adaptive response.
- Some cells are specially equipped to
present antigen, and to prime naive T cells
and are termed professional (APC).
- Dendritic cells and B-cells (and to a lesser
extent macrophages. are equipped with
special receptors that allow for enhanced
activation of T cells.

LNGERHAN’ S CELLS
• Dentritic Cells of the epidermis.
• Expresses CD1, S100 ptn, Vimentin, Birbeck
granules associated molecule (langerin) and
MHC II.
• Derived from the bone marrow from CD34
precursor cells.
• Factors behind Dcs stimulation of either Th1 or
Th2 is still not determined but immature
dendtritic cells induce tolerence through
activation of Treg .

• Resident Langerhan’s cell engulf’s the
exogenous antigen or express the
edogenous one
• Starts emigration to the lymph nodes to
meet the T cells .
• During this trip it develops some changes
to become similar to mature Dendritic cell.

Changes of LCs during migration
- Decrease molecules involved in antigen
uptake as birbeck’s granules,Fc receptors
and those mediating the attachement to
neighboring keratinocytes ( E-Cadherins).
- Increase expression of receptors involved
in tissue homing at the lymph nodes as
CD44. and surface molecules necessary
for antigen presentation and Tcell priming
asCD40,54,58,80,86

• APC to B cells and T cells is not the same.
• B cells can identify the whole antigen by
antibodies on thier surface
• T cells only identify the antigen when
processed into peptides bound to specific
surface molecules on APC.

AP TO T CELLS
• Tceels identify the processed antigen
bound to MHC on the surface of Dendritic
cells.
• CD4 T cells identify antigens bound to
MHC II while Cytotoxic CD8 T cells
identify antigen T cells bound to MHC II
• Exogenous and endogenous antigen
presentation.

TYPES OF AP to T cells
• Exogenous antigens are engulfed by the
APC, processed and presented in
association with MHC II.
• Endogenous antigens (VIRUS AND
TUMOURS) are processed and presented
in association with MHC I

T cells
• T cells develop and mature in the thymus
after migration of the stem cells from the
bone marrow.
• At the thymus only T cells that can
recognize foreign and not self antigen in
the MHC peptide complex get a survival
signal (positive selection) and pass to the
circulation and lymphnodes..
• Those who fail have affinity to self
antigens receive signals for apoptosis
(negative selection) thus no auto attack.
•

Types of T cells
• Immature T cells Express both CD4 and
CD8 molecules.
• Later with the development of the Tcell
receptor, they either express CD4 and
become T helper cell that binds antigens
in MHCII or express CD8 molecule and
becomes T cytotoxic cell that binds
antigens on MHCI.

The T CELL RECEPTOR (TCR)
• It is the part responsible for recognition
of the specific antigen and the further T
cell response.
• TCR are transmembrane molecules that
are mainly of the α/β type while only 10%
are of the γ/δ type in body and skin.

γ/δT cells
• Do not follow the classic way of
antigen recognition may be able od
direct antigen recognition.
• May play a role in innate immunity.
• Increase in the skin in leprosy and
lieshmaniasis.

TCR
• Can recognize a huge number of antigens
encoded by more than 400 genes thet are
modified and rearranged to cover an
endless number of antigens by
recombination activation genes
• Rag-1 Rag-2 .
• when deffective ----combined immune
defficiency.

TCR SIGNALLING
• CD3 is an important part of TCR
responsible for transmission of the signal
to the cell that encodes for the cytokine
needed to stimulate the required response
for that particular antigen.

Costimulatory molecules
• B 7 FAMILY
• CYTOKINES (TNF IL-1 AND IL-6)
• CELL ADHESION MOLECULES ARE
VERY IMPORTANT FOR COMPLETION
OF THE T CELL RESPONSE OTHER
WISE ANERGY AND FAILURE OF T
CELL STIMULATION OCCURS.

CLONAL EPANSION
• After proper antigen
presentation and costimulation
T cell becomes activated .
• Memory T cells develop

Memory T cells
- Central memory T cells: at the lymphnode,
CD45RO+CD45RA- CCR7+ Have no
effector function. They stimulate dendritic
cells to produce il-12 upon secondary
stimulation and differentiate into ccr7- cells.
- Effector memory Tcells (TEM):
CD45RO+CD45RA- CCR7- develop
receptors to migrate to the inflamed tissues
(e.g CLA in the skin). Have an effector
function.

Skin T cells
• Majority is :
• In the dermis.
• CD4 OR CD8.
• α/β TCR.
• memory phenotype CD45RO+CD45RA-
• Skin homing receptor CLA(cutaneous
lymphocyte associated antigen).

Effector T cell function
• After recognition of the antigen
• CD4: T helper cells(Th):
-activate the immune system to combat the
antigen including both T and B cells.
CD8 T cytotoxic cells(Tc):
Antiviral and anti tumour responses

T helper response
• According to the type of antigen
recognized by the Th cells they secrete
different cytokine patterns that will further
stimulate different parts of the immune
system.
• T0 secretes a wide variety if cytokines
which then develops into Th1 or Th2 with
more restricted type of cytokine secretion.

Th 1 cells
• IL-12 stimulates differnetiation of Th0 into
Th1 which secretes:
• IL-2: stimulates both Th and Tc proliferation.
• IFN GAMMA: activates macrophages and
NK cells and IL-12.
i.e a cell mediated inflammatory response
As in granuloma and autoimmunity.

Th2 cells
• IL-4: Stimulates Bcells to produce IgE and
stimulates furhter Th 2 response and
inhibits TH1 response.
• IL-5: promotes eosinophil growth.
• IL-6:
• IL-10: inhibits TH1 response.
Mediates humoral immunity.

Th1/Th2 decision
• Very important to achieve the required
state if immunity .
• Depends upon the type of antigen
presented and the cytokines it stimulates.
• The Dendritic cells, the toll like receptor,
Dose of antigen,Genetic background of
the host, The APC and its cytokines,The
costimulatory molecules.

Th3 cells
• Transforming growth factor B .
• Helps IgA production.
• Supresses both Th1 and Th2 responses.

Tcytotoxic cells CD8
• Direct killing of the organism or the
abnormal or infected cells.
• TC1 and TC2 in cytokine pattenrs.
• Viral and antitumour activities.

Regulatory T cells (Tregs)
• CD4 + T cells.
• Secretes large amounts of IL-10.
• Suppressor effect on both immune
responses.
• Produced by immature inactive dendritic
cells.
• Impotant for tolerance towards self
antigens and regulating inflammation.

The B lymphocyte
• B cells function to protect the host by
producing antibodies that identify and
neutralize foreign objects like bacteria and
viruses.
• B Cells are the major cells involved in the
creation of humoral immunity.

Antibodies
• Antibodies (or immunoglobulin, Ig), are
large Y-shaped proteins used by the
immune system to identify and neutralize
foreign objects.
• 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.

B cells
• Upon activation, B cells produce
antibodies, each of which recognizes a
unique antigen, and neutralize specific
pathogens.[1]
• Like the T cell receptor, B cells express a
unique B cell receptor (BCR), in this case,
an immobilized antibody molecule. The
BCR recognizes and binds to only one
particular antigen.

Bcell Vs T cell ACTIVATION
• T cells recognize their cognate antigen in
a processed form - as a peptide in the
context of an MHC molecule,[1] while B
cells recognize antigens in their native
form.[
• B- cells receives additional signals from a
helper T cell (predominately Th2 type)), to
further differentiates into an effector cell,
known as a plasma cell]

Plasma cells
• Short lived cells (2-3 days) which secrete
antibodies that bind to antigens, making
them easier targets for phagocytes, and
trigger the complement cascade.[
• About 10% of plasma cells will survive to
become long-lived antigen specific
memory B cells primed to produce specific
antibodies and respond quickly if the
same pathogen re-infects the host; while
the host experiences few, if any,
symptoms.

Basic immunology from the dermatologic point of view

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Basic immunology from the dermatologic point of view