IMMUNITY
Dra. Dacula
Aug. 16, 2018
Outline
I. Evolution of immune system
II. Infectious Agents and Immune Response
III. Immunogens and Antigens
A. Major defense
B. White Blood Cell
C. The myeloid progenitor
D. The lymphoid progenitor
E. The peripheral lymphoid organs
IV. Pathogens
V. Principles of innate and adaptive immunity
A. Mechanisms of innate
B. Types of Immune response
C. Innate immune system
D. Complement system
E. Humoral Immunity
VI. Antibodies/Immunoglobulins
A. Classifications of Antibodies/Immunoglobulins
VII. Cell mediated immunity
VIII. T-cell receptor for antigen
IX. Types and functions of effector T-cells
X. Major HIstocompatibility complex
XI . Human Leukocyte Antigen
a. Human MHC on Chromosoe 6: HLA
B. MHC Class 1
C. MHC class 2
XII. Hypersensitivity
A. Type i
B. Type II
C. Type III
D. Type IV
XIII. Failures of immune regulations
A. Primary immunodeficiencies
B. Complement System
XIV. Autoimmune disease
A. Etiology and Pathogenesis
B. Chain leading to autoimmune disease
C. Infections associated with immune
[ESTELLA,
disease NISERIO, SO, YU]
2 1
Evolution of Immune System
 Different type of microorganism exist and the immune
system developed different type of response to obtain
protection against each pathogen
 It is important to know immunology because this is how
you will know how humans will combat pathogenic
microorganisms
Infectious Agents and Immune Response
 There are different kinds of microorganisms that exists
and there are different components in the immune
system that produces a response against each
pathogens.
 Microorganisms are generally divided into four. It can
be a parasite, fungi, virus, or a bacteria. And our
immune system deals with this different pathogens
depending on the microorganisms. For example, the
viruses, they have to go inside the cell to replicate. Or
the bacteria kahit na extracellular sila they can still
multiply but that is where your antibodies generally
work along with your APC.
 Infectious Agents:
o Bacteria
o Virus
o Fungi
o Parasites
 Immune Response
o T-response
o B-response
o Phagocytosis
IMMUNOGENS AND ANTIGENS
 Any substance that induces an immune response,
generally proteins are immunogenic rather than
carbohydrates kasi bacteria do have proteins and
carbohydrates in their cell walls so sometimes the
lipopolysaccharides itself are immunogenic and is
capable of reacting with the product of response,
referred to as antibody
 The immune system does not recognize a whole
organism but only part of it, kung ano yung pinakalabas
nya such as coats, capsules, cell walls, flagella,
fimbriae and sometimes they release toxins
 Vaccines are said to be an example of an immunogenic
antigen kasi when you are given a vaccine, it’s like
mimicking the infectious agents.
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TWO MAJOR DEFENSES
 The immune system is generally divided into different
responses
Innate Immunity or Innate Immune Response:
o It is called innate kasi present na sya at birth
palang
 All mechanisms of defense which are always present
and ready to block all type of pathogens or damaging
agents. It is not specific (take note that this is the major
difference between an innate response compare to
adaptive response kasi pag innate, itatry nya lahat
icontain at iingest) and does not induce immunological
memory
o The innate primarily includes the phagocytes..
yung mga nageengulf. They are the ones that
initiate immune response
Acquired (or adaptive) immunity or acquired immune
response:
 It is a specific response against each particular
pathogens raised by each individual as a consequence
of infection or vaccination. . It is usually results in
immunological memory which allows a long lasting
protection from reinfection by the same pathogen.
 For example, once you had a chickenpox,
pwede na kayong di mahawa kasi you are
already immune with that virus. And also
because viruses have only one serotype. It is
because yung time na nainfect kayo ng
chickenpox nagdevelop na ng certain
antibodies and immune cells against that virus
so pag naexpose kayo again on the same
virus, macocontain na yung virus, di na sya
makakapagmultiply and di na sya
makakapagcause ng disease.
 In the concept of vaccines, kaya importante
ang acquired immune response kasi ang
ginagawa natin, parang tinitrick yung immune
system natin. We give an antigen, it could be
the virulence factor of a certain bacteria na
iiinject sainyo and we trigger the immune
response. Our immune system will then work
on the antigen and create a specific antibody
and create an immune response
 Given the vaccines, we also check the level of
antibodies para malaman natin if we could say
na you are already protected from a certain
pathogen
o in order for us para maging specific ang response
and kill a certain pathogen, it needs the action of
the adaptive immune response which generally
comprises of your T and B cells.
WHITE BLOOD CELL
 The white blood cells of the immune system derive
from precursors in the bone marrow.
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 The white blood cells are primarily the major actors of
our immune system
 RBCs are not part of the immune system so they can
be infected. They are the factor in your
histocompatibility complex.
 Majority of the cells that are involved in the immune
system are from lymphoid progenitors
o These are the mononuclear cells such as yung
macrophage, phagocytes, and lymphocytes
 Lymphocytes can differentiate and it could be a
B cell or a T cell
 The granulocyte progenitors will become your
neutrophils, eosinophils, basophils, monocytes, and
immature dendritic cells
o Each of these granulocyte has their own function
THE MYELOID PROGENITOR
Macrophage
 Phagocytosis and activation of bacterial mechanisms
 Antigen Presentation
o They serve as antigen presenters kase ineengulf
nila yung microorganism or antigen or immunogen
then they help release proteins sa extracellular
membrane so they become recognized as
infected cell. Then they present it to an antibody.
 They came from a monocyte then when activated
becomes phagocytes
Dendritic Cell
 Antigen uptake in peripheral sites
 Antigen presentation in lymph nodes
o They are said to be the major antigen presenting
cells. Para silang mga sentinel cells within the
outer layer of the body particularly in the skin
shempre doon una pumapasok yung mga bacteria
or yung pathogens. It uptakes the antigen in the
peripheral sites. It presents the antigens in the
lymphnodes. And in the lymph nodes you have
there the B cells and T cells so napprocess na
yung antigen.
Neutrophil
 Phagocytosis and activation of bacterial mechanisms
Eosinophil
 Killing of anti-body coated parasites
 Also involved in allergic reactions
Basophil
 Unknown
 Less known ang kanilang actions
Mast Cell
 Release of granules containing histamine and other
active agents
 Involved in hypersensitivity reactions
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the antigen.
THE LYMPHOID PROGENITOR
 Lymphocytes: B and T cells SUMMARY: CELLS INVOLVED IN THE IMMUNE
 Majority are involved in adaptive immunity RESPONSE
 If hindi pa sila activated, magkakaichura yung mga
cells but when it becomes activated lumalaki yung Fig. 2 :Cells involved in the immune response
kanilang cell membranes.
 Yung B cells nagiging plasma cells while the Tcells,
THE PATHOGENS
marami pa siyang subtypes.
 The immune system protects against four classes of
Natural Killer (NK) Cell
pathogens
 Releases lytic granules that kill some virus-infected
cells
o Ang action nila ay more on sa viruses

THE PERIPHERAL LYMPHOID ORGANS

 The peripheral lymphoid organs are specialized to trap
antigen, to allow the initiation of adaptive immune
responses, and to provide signals that sustain
recirculating lymphocytes.
 Kung saan yung site of infection lets say sa skin, kung
ano yung pinakamalapit na lymph node, ayun yung
magrerelease ng mas maraming B cells
o Kaya if you have rhinitis or sinusitis, you can feel
yung lymph notes nyo sa submandibular kasi
that’s the nearest lymph nodes.
 Take note of the parts of the lymph nodes where T
cells and B cells are produced.
o Most T cells are present in the paracortical area
o Germinal centers are the ones where the B cells
are generally placed and also in the lymphoid
follicles
o In the medullary cords, you will see the
macrophages in the plasma cells
 Also remember that in the lymph nodes, nagcocollect
sila. And each lymph nodes, merong afferent and
efferent lymphatic vessels where lymphoid cells are
released.
 Aside from the lymph nodes, spleen is also part of your
lymphoid system.
o This is where the RBCs are deposited.
o Graveyard of lysed RBCs
 In the mucosa area particularly in the intestines you
have the GALT and the MALT.
o They act in the immune response in the GI tract.
They are the ones that traps the immunogen or
o It can be an extracellular bacteria, parasite, or
fungi or an intracellular bacteria or parasite.
o Viruses are generally intracellular
 Why is it important to know whether intracellular or
extracellular yung pathogen? It is because iba yung
processing ng antigen.
o Example, the viruses, once it infects the cell,
generally, the immune response will not recognize
it intracellularly. What happens instead is that
when they process the proteins or antigens
intracellularly, the main histocompatibility complex
will now function in a way that it will release the
antigen into its cell membrane hence the immune
response will know that this cell is infected
 Bacteria on the other hand, extracellular sila
o Immediately they can be recognized by your
phagocytes.
o It can also be opsonized by antibodies and
presented as pathogen
 Knowing whether extracellular or intracellular ang
pathogen is important para malaman natin kug anong
klaseng immune response ang magcocombat sakanila.

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 Generally there’s vasodilation and therefore, a

lot of cells will go into that area and help in
containing the immunogen.
 This vascular permeability helps cells to
migrate and contain the antigen.

 Activation of specialized antigen-presenting cells is a

necessary first step for induction of adaptive immunity

Figure3: Kinetics of immune response

PRINCIPLES OF INNATE AND ADAPTIVE IMMUNITY

o These dendritic cells talaga yung mga nasa
 There is an interplay between the innate and adaptive peripheral area
immune responses. Majority they overlap with the B  APCs (antigen presenting cells) or immature
and T cells because they act as presenting cells dendritic cells usually reside at the peripheral
 In the adaptive immune response you have there the B tissues.
cells that later on will release antibodies and the T cells  Once there is an antigen, it migrates into the
which later on differentiates into helper T cell or upper lymphatic vessels to the regional lymph
cytotoxic T cells nodes. Then it goes into the cortex of the
 NKT cells (or natural killer T cells) sometimes can act lymph nodes then activates the B lymphocytes
as innate immune response and sometimes pwede din and later on will release antibodies.
sya doon sa adaptive.
 Lymphocytes activated by antigen give rise to clones of
antigen-specific cells that mediate adaptive immunity
o That’s why ang adaptive immune response natin
ay very specific
 Lymphocytes will differentiate
 Sometimes, they can release lymphocytes but
recognize itself as self antigen but at the end,
meron tayong selection mechanism that makes
them release specific plan para sa antigen.

 Most infectious agents induce inflammatory responses

by activating innate immunity.
o Example are the bacteria triggers the
macrophages to release the cytokines and the
chemokines
 These are actually part of the inflammatory
response
 Once there is an inflammation, you know the
cardinal signs of inflammation: redness,
swelling, warmth, pain, loss of function

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 Nonspecific cells are removed before it is
released in the circulation
Postulates of clonal selection hypothesis
Each Lymphocyte bears a single type of receptor
with a unique specificity
Interaction between a foreign molecule and a
lymphocyte receptor capable of binding that
molecule with high affinity leads to lymphocyte
activation
The differentiated effector cells derived from an
activated lymphocyte will bear receptors of
identical specificity to those of the parental cell
from which that lymphocyte was derived
Lymphocytes bearing receptors specific for
ubiquitous self molecules are deleted at an early
stage in lymphoid cell development and are
therefore absent from the repertoire of mature
lymphocytes
 Each developing lymphocyte generates a unique
antigen receptor by rearranging its receptor genes
o Genes are rearranged so that it can respond to a
specific antigen
Inherited gene segments ▼
Unique combination of segments becomes joined
by somatic gene rearrangement ▼
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Chains pair to give a unique receptor for each
lymphocyte
 Lymphocytes proliferate in response to antigen in
peripheral lymphoid organs, generating effector cells
and immunological memory
o Effector cells are the activated cells that combats
the antigen
o Effector or activated b cells may mas coarse na
granules.
Mechanisms of Innate Immunity
Microbial Sensors
 3 Major Groups of Microbial Sensors:
o TLR (toll-like receptors)
 Best known and best studied microbial sensor
 Family of served pattern recognitions receptors
(PRRs)
o PRR initiates intracellular signalling
 Transmitted via a pathway which features
several different types of enzymes as well as
adaptor proteins that act as scaffolding for
these enzymes and allow them to carry out
their catalytic activities
 End result: activation of nuclear transcription
factors and new gene transcription that
supports the effector functions of the leukocyte
 These recognize pathogen-associated
molecular patterns (PAMPs)
 Recognition of microbial patterns leads to rapid
& robust inflammatory response
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o NLR (nod-like receptors)
 Located in the cytoplasm
 Activate the nuclear factor kappa light chain-
enhancer og activated B cells (NF-kB)
o RIG-1-like helicases & MDA-5
 Sensors of viral ssRNA (postitive sense single-
stranded RNA)
 Triggers the producton of type 1 IFNs
(interferons), IFNs are inhibitors of viral
replication
Cellular Components and Phagocytes
Phagocytic cells can participate in:
Chemotaxis
Migration
Ingestion
Microbial Killing
Natural Killer Cells
 Natural killer cells are large granular lymphocytes
morphologically related to T cells
 Make up to 10-15% of blood leukocytes
 NK cells express two types of receptors
 1. Lectin-like NK cell receptors – these bind
proteins, not carbohydrates
 2. Killer immunoglobulin-like receptors – these
recognize the major histocpatibility complex
(MHC) class I molecules
Complement System
Inflammatory Mediators
 Cytokines are soluble mediators responding to an
inflammatory response caused by injury
 These include cytokines, prostaglandins and
leukotrienes
 Interferons are substances secreted by virus-infected
cells that triggers neighboring cells into producing
substances that allow it to resist viral infection, and
replication (your antiviral state)
 Interferons also induce infected cells to
produce receptors that make them easier to be
targeted by cytotoxic cells
TYPES OF IMMUNE RESPONSE
PRIMARY RESPONSE
 When an animal or human is injected with an antigen
(first contact with the antigen)
 Rise in detectable antibody in serum within several
days depending on the route, dose, nature of injection
of antigen a long LAG PERIOD occurs before antibody
is detected
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o This comes from the innate response
 In general, IgM antibodies appear earlier than IgG in
primary response
o IgM type is the initial antibody that will act on the
antigen
 IgM declines more rapidly than IgG because IgM and
IgA are normally catabolized more rapidly than IgG
SECONDARY RESPONSE
 When an animal is re-injected with the same antigen
weeks or even years after the primary antibody levels
have subsided
 More rapidly antibody response, with short and no lag
period, to a higher level and for a longer period than in
the primary response
 Based on the persistence of a substantial number of
antigen-sensitive MEMORY CELLS after initial contact
with the antigen
 During the secondary response, IgM antibody
production may be similar to that in the primary
response, whereas IgG antibody production is usually
greater
 Figure: Kinetics of Immune Response
o Since meron ka nang memory cells, the primary
antibody that will rise would be the IgG rather than
IgM
 Given na same antigen sa secondary response IgG
ang magaact. Pero pag panibago, IgM.
 Kinetics of Immune system shows us what cell in the
immune system tends to act upon exposure to an
antigen. We’ll see the time after infection and what
type of immune response
 In the innate immune response, let’s say we have
microorganism..
o Epithelium barrier is a part of the first line of
defense. Skin is the largest defense against any
antigen
o Once the microbe breached the barrier, may
second line na agad, you have there the
phagocytes and also the complement along with
the NK cells but in the later time of infection.
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“complements”, the ability of antibodies to clear

So it goes like, pagkaintroduce ng antigen, haharapin sya pathogens in the body
ng first line of defense (or innate immunity)   Kaya nga sila tinawag na “complement” kasi
they help the action of the antibody to clear the
complement  NK Cells
pathogen.
 Since the inflammatory cascade is activated, the o Activation of the complement system may result
immune response will now function. in:
o Now you have there the B lymphocytes exposed  Opsonization – the enhancement of
there and becomes activated then it releases phagocytosis
antibody.  Chemotaxis – attraction of phagocytes to the
o The T helper cells or cytotoxic T cells will be sites where the pathogen is
present on the later part  Lysis of bacteria and other foreign cells
 Palagi, on the first hours of infection si innate then sa  Inflammation
later part si adaptive.
 When you are injected with vaccines, kelangan mo EPITHELIAL BARRIER
muna magkaroon ng antibodies. Usually it takes two
weeks.

INNATE IMMUNE SYSTEM

 Epithelial barrier (Mechanical, Chemical,
Microbiological)
o Mechanical, diba ang skin intact sya, so walang
makakapasok na antigens
o Chemical, because meron kang lysozymes which
can act as barrier
o Microbiological, kasi meron tayong microflora
which actually helps in the maintainance of the pH
of the skin.
Our skin has a normal bacterial flora (or microflora) which
serves as our protection. Hindi lahat ng bacteria ay bad
 Once the bacteria adheres in the epithelium, there’s a
or kadiri. Normal ito and kasama sya talaga sa line of
normal microflora in the area, there are chemical
defense ng body natin. factors and some phagocytes and they will act on the
 Cytokines and chemokines antigen
 Complement  Only when there is local infection where bacteria
1st Line of Defense penetrates the epithelium, the pathogen can enter the
cells but that area palang, you already have
 Skin
antimicrobial proteins and peptides, phagocytes. It can
 Respiratory system
help in the activation of your complement. Then the
 Digestive system dendritic cells in the peripheral area will bring it to the
 Conjunctive lymph nodes
 Genitourinary system
CYTOKINES
2nd Line of Defense
 Transferrin
o Protein produced by the liver
o Like lactoferrin, it acts by binding with iron to
deprive the pathogens of this much needed
nutrient
 One of the main source of nutrient ng bacteria
ang IRON. Kaya nga sa bacterial culure
gumagamit tayo ng blood agar kasi diba sa
blood maraming iron.

 Complement system
o Biochemical cascade composed of a group of
proteins called C1 to C9 that helps, or

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 Activated macrophage secretes a range of cytokines,
like interleukin 1, tumor necrosis factor alpha,
interleukin 6, 8, and 12
o Each of these interleukins will have an effect on
the inflammatory responses
 IL-1, TNF-alpha, and IL-6 will cause systemic
effects like fever.
 For chemotaxis, macrophage releases IL-8
which enhances migration of cells into the site
of infection
CHEMOKINES
No need to memorize these chemokines according to
Doc.
 There are a lot of chemokines that helps in the
inflammatory response.
o Major effects nila eh yung it mobilizes neutrophils,
it can result to angiogenesis, immunostimulant, B
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cell development. It may also have a role in the
allergic reactions
COMPLEMENT SYSTEM

 It is a cascade of protein labeled as C1 to C9
depending on the pathway.
 Generally, you have three pathways of complement
activation
o Classical Pathway
o MB-Lectin Pathway
o Alternative Pathway
 Each of the pathway has its own activating mechanism
o Classical pathway  antigen-antibody complex in
the pathogen surface
 Example, you have a bacteria and the antibody
recognizes the bacteria and attaches itself to it
and it will activate your complement
o MB-Lectin Pathway  Lectin
 The lectin present in the pathogenic surface
can immediately activate the complement
o Alternative pathway  pathogen surface itself
 Particularly, the properdin factors
 Upon activation, it results into recruitment of
inflammatory cells, opsonization of pathogen, and
eventually at the end of the cascade, it creates a
membrane attack complex which leads to the lysis of
the cells, hence killing the pathogen.
Nomenclature of Complement System
 Classical Complement Pathway and the membrane-
 attack complex are designated by the letter C followed
by a number.
 Nomenclature:
o Letter C
o Numbers 1-9
o a – smaller fragment
o b – bigger fragment
 b fragments are enzymatic
 Exception: C2a (larger and enzymatic)
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o Several complement components must associate

to form an active complex
 C4b2a3b
o Alternative pathway uses factors B,F,D,H,I
 I – discovered later / updated

o Ex. C4 is cleaved to C4b, the large fragment of C4

that binds covalently to the surface of the
pathogen, and C4a, a small fragment with weak
pro-inflammatory
 Pag naactivate sila, they cleave into “a” or “b”.
b is the larger fragment and a is the smaller.

Steps
1. C1q can bind to Fc of antigen specific abs in close
proximity
2. C1r is activated and activates C1s
3. C1s cleaves serum C4a and C4b
4. C4b attached to pathogenic surface proteins then
binds C2
5. C2 is cleaved by C1s
6. C2a is bound to C4b forming C4bC2a
o C4bC2a - classical C3 convertase
7. C3 convertase cleaves C3 causing C3b to bind to C3
convertase becoming
o C4bC2aC3b – Classical C5 convertase
 Alternative pathway components are designated by
different capital letters
 The pathogen surface itself activates this pathway.
o It is designated as Factor B and D
o Cleavage products:
 b- larger fragment
 a-smaller fragment
o Ex. The large fragment of B is called Bb and the
small fragment is Ba
 Mannose-binding lectin pathway
o First enzymes to be activated are known as the
mannan-binding lectin-associated serine
proteases MASP-1 and MASP-2
o The rest is the same as the classical pathway
 The binding of MBL to a pathogen results in the
formation of a tricomplex of MBL with two serine
proteases (MASP-1 and MASP-2).
 In classical pathway, you have the antigen and
antibody complex on the surface of the pathogen then
it activates the C1q, C1r, C1s.
 All of these pathways will converge to the C3
convertase
 C3 convertase cleaves the C3,
o it releases the C3a molecule that serves as
inflammatory mediators or phagocyte
enhancement
o C3b on the other hand will bind into the
complement receptor of the phagocyte to
opsonize the pathogen and removes the immune
complexes
o Terminal complement components of the C5 can
also bind to C3b along with the other
complements, the 6789 which is known as the
membrane attack complex.
o Yung membrane attack complex andun sya sa
sya sa membrane ng pathogen and it creates a
pore within the membrane. Hence shempre may
butas, mala-lyse na yung pathogen
Regulation of the complement system
 C1-inhibitor proteins – binds to and inactivates
the serine protease activity of C1r and C1s,
causing them to dissociate from C1q
 Factor I – cleaves C3b and C4b, thereby
reducing the amount of C5 convertase available
 Factor H – enhance the effect of Factor I on C3b

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 Factor P (properdin) – protects C3b and CD59

stabilizes the C3 convertase of the alternative
pathway
 Proteins have the ability to accelerate the decay
of the complement proteins
 Decay-accelerating factor (expressed on blood
and endothelial cells) that can act to accelerate
dissociation of the C3 convertases of all three
pathways.
 Remember, within the complement system, may
regulatory proteins because otherwise, if continuously
syang activated, magrerelease sya ng smaller
fragments which are proinflammatory mediators so pag
maraming smaller fragment, maraming inflammation,
masama yun sa host kasi mataas mashado ang
inflammatory response.
Proteins of Classical pathway of complement
activation

Functional protein classes in the Complement

System
Binding to antigen-antibody C1q
complexes and pathogen
surfaces
Binding to mannose on MBL
bacteria
C1r
C1s
C2b
Activating Enzymes Bb
D
MASP-1
MASP-2
Membrane-binding proteins C4b
and opsinins C3b

Peptide mediators of C5a

inflammation C3a Figure: Proteins of the classical pathway of complement
C4a activation
C5b Proteins of Alternative Pathway of complement
C6 activation
Membrane-attack proteins C7 Native Active Function
C8 Component Fragment
C9 C3 C3B Binds to pathogen surface,
CR1 binds B for cleavage by D,
CR2 C3b, Bb is C3 convertase
Complement receptions CR3 and C3b2Bb is C5
CR4 convertase
C1qR Factor B (B) Ba Small fragment of B,
C1INH unknown function
C4bp Factor B (B) Bb Bb is active enzyme of c3
Complement Regulatory CR1 convertase C3b,Bb and C5
Proteins MCP convertase C3b2Bb
DAF Factor D D Plasma serine protease,
H (D) cleaves B when it is bound
I to C3b to Ba and Bb
P Factor P P Plasma protein with affinity

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(Properdin) for C3b,Bb convertase on

bacterial cells HUMORAL IMMUNITY
 Humor kasi liquid. Usually nasa liquid part sya kaya
humoral immunity
IN SUMMARY: COMPLEMENT SYSTEM  Consists mainly of B cells
Classical Alternative Lectin  Directed primarily against:
o Toxin-induced disease
Activating Immune LPS Mannose  Example is yung Clostridium botulinum.
subs. complexes (bacterial groups on Pathogenic mechanism is yung released upon
(IgG or capsule), microbial toxin. So it’s the function of your antibody to
IgM) IgA cell take up that toxin.
Recognition C1q, C1r, C3, Factor MBP, o Infections in which virulence is related to
Unit C1s B, Factor D MASP-1, polysaccharide capsules
 Ideally, antigens should be protein for it to be
MASP-2
recognized. But most of the bacteria capsules
C3 C4b2a C3bBb C4B2a are made of carbohydrates, hence the function
convertase of the B cells is to bind to the cell membrane of
C5 C4b2a3b C3bBb3b C4b2a3b the antigen so that it can be acted upon by the
Convertase adaptive immunity
MAC C5b6789 C5b6789 C5b6789 o Certain viral infections
End result Cell lysis Cell lysis Cell lysis
ANTIBODIES/IMMUNOGLOBULINS
 React specifically with the antigen that stimulated their
Control proteins of the classical and alternative production
pathways  20% of blood plasma
Name (symbol) Role in the regulation of  produced by plasma B-cells
complement activation  two importance features:
C1 inhibitors (C1INH) Binds to activated C1r, o Specificity – means that each is able to react with
C1s, removing it from C1q only one epitope
o Biologic activity – ability to pass through the
C4-Binding protein Binds C4b displacing placental barrier (primarily the IgG), fixation of the
(C4BP) C2b; cofactor for C4b complement, binding to surface of cells and
cleavage by I among others
Complement receptor 1 Binds C4b displacing  When treated with papain, an Ig is broken into 2
(CR1) C2b, or C3b displacing fragments:
Bb; cofactor for I o 2 Fab (antigen bonding fragment)
 Ag binding
Factor H (H) Binds C3b, displacing Bb;
 Valence = 1
cofactor for I  Specificity determined by Vh and VL
Factor I (I) Serine protease that
cleaves C3b and C4b; o 1 Fc (crystallizable fragment)
aided by H, MCP, C4BP  Effector functions
or CR1
Decay-accelerating factor Membrane protein that
Protective Functions of Antibodies
(DAF) displaces Bb from C3b
and C2b from C4b
Membrane cofactor Membrane protein that  Enhanced Phagocytosis
o Antibodies produce resistance b yopsonizing
protein (MCP) promotes C3b and C4b
(coaing) organisms which make them readil
inactivation by I ingested by phagoctyes
Cd59 (Protectin) Prevents formation of  Virus neutralization
membrane-attack o Antibodies directed against specific viral proteins
complex on autologous or can bind to the virus and block the ability of the
allogenic cells, widely virus to attach toe the cell’s receptor
expressed on membranes o This results in the virus not being able to replicate

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 MICROBIOLOGY
 Neutralization of proteins
 Complement-mediated lysis
o Attachment of antibodies to viral proteins on virus-
infected cells, tumor cells or microbial cells can
activate the complement system, leading to cell
lysis
 Antibody-dependent cell cytotoxicity (ADCC)
o ADCC by eosinophils is an important defense
mechanism against helminthes
o IgE coats the worms and eosinophils attach to the
Fc portion of IgE triggering eosinophil
degranulation
Antibodies can participate in host defense in three
main ways
 They act by neutralization, opsonization,
complement activation
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 In Neutralization, let’s say you have bacterial toxins.
You also have cells with receptor for toxins, supposedly
the toxins will bind to them but since you have
antibodies, it will then bind to the toxins and present
them to the macrophage. The macrophage will then
process it intracellularly for lysis.
 Opsonization let’s say for example, we have bacteria in
the extracellular space, it opsonizes this bacteria and
then by that, the effector part will have a receptor in the
macrophage. It will then bind to the macrophage for
ingestion and lysis of the bacteria
 When the antigen and antibody binds together, it will
activate the complement system. It will create a
mebrane attack complex and will soon produce a pore
which will lead to the lysis of the bacterial pathogen
Classifications of Antibodies/Immunoglobulins
IgG
 2 Light chain and 2 Heavy chains
 most abundant Ig in the serum (75%) and
extravascular spaces
o marami ang IgG sa circulation
 has the longest half life
 provides the longest protection against infection
 Can pass through the placenta kasi maliit lang sya
 Predominant antibody in secondary immunity
IgM
 5 Heavy chain and 5 Light chain
 Marami if you have primary infection
 Has extra domain and J chain
 Has 10 antigen binding sites
 The most efficient Ig in agglutination, complement
fixation and other Ab reactions
 Largest Ig; macroglobulin
 First Ig that is produced in the primary response
 Important defense against bacteria and viruses kasi
they help in the opsonization of pathogen
 Presence serum of IgM may be useful in diagnosis of
certain infectious diseases
IgA
 Monomer in serum; dimer in external secretion with J
chain and secretory component
 Main Ig in external secretions (sweat, saliva, milk,
urine, tears, mucosal surfaces of the respiratory,
intestinal and genital tracts)
 Prevents attachment of microorganisms to mucous
membranes
o In some bacteria for example ang
Staphylococcus, it has an IgA protease. Same
with Streptococcus, it also has IgA kaya
or nakakapagcolonize sila sa mucosal surfaces
 Provides local protection kasi andun sila mismo sa
mucosal area
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 MICROBIOLOGY [IMMUNITY] [TRANS #2]

IgD
 Monomer with tail piece
 Serves as antigen receptor on B cells
o Ito yung mismong nakaattach sa B cells
 No biologic activity at the present time
 Does not bind to complements
 Present in small amount in the serum

IgE
 Monomer with extra domain
 The least in concentration in the serum under normal
conditions
 Also known as reaginic antibody
Reagin:
an antibody found in the blood of individuals having a g
enetic predisposition to allergies.)
 Increased level in the serum in times of hypersensitivity
reactions and parasitic infection Figure: Development of T cells

 Figure: Summary of different immunoglobulins

CELL-MEDIATED IMMUNITY Figure: T-cell development in the Thymus

 Refers to a wide range of functions carried out directly  T cells came from the thymus
by T-cells or products of these cells (CD4+, CD8+) o In the cortex, T cells differentiate to become a
other than antibody CD8 or a CD4 committed cell. Though positive
selection, they go into the medulla to become
 Important in:
activated.
o Protection against infections caused by intra-
cellular organisms
o Transplant rejection T-CELL RECEPTOR (TCR) FOR ANTIGEN
o Tumor elimination  TCR is a transmembrane heterodimeric protein
 You have an antigen ingested by a macrophage. The containing two disulfide-linked chains
macrophage can present this antigen and activate the  Two different classes:
T helper cells. Once activated it becomes a non o Alpha-BETA (a and B)
specific cell but it can soon be a memory T cells.  Majority of T-cells
 Once the antigen is displayed, it activates immature  Surface markers – CD4 or CD8
cyto\toxic T cells to become mature and kill intracellular o Gamma-delta (y and ó)
antigens and part of them will lead to the creation of  Primarily located in the epithelial linings of the
memory cytotoxic T cell reproductive and GI tracts

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 MICROBIOLOGY [IMMUNITY] [TRANS #2]

TCRαβ positive T-cells

CD8 Tcells
 CD8 T cells
o Cytotoxic T lymphocytes (CTL)
o MHC class 1-resitricted
o Effector molecules
 Perforim, Granzymes, Granulysin, FasL
 IFN-y, TNF
o Cytotoxic T cell recognizes complex of viral
peptide with MHC class 1 and kills infected cell
 For example, you have a macrophage with
MHC class 1 on the surface. Only the CD8 T
cells can interact with it. This will activate the
macrophage once they bind. It kills the
infected cell
Figure: Types and functions of effector T cells
 CD4 T cells (effector, helper, regulatory)
o Subtypes: Th1 (IFN-y, TNF, IL-2), Th2 (IL04, IL-5,
IL-13), Th17 (il-117), Treg (IL-10)  A. Cell-Mediated Immunity
 T helper cells are MHC class II restricted o Development of T Cells
o Th1 cell recognizes complex of bacterial peptide o T cell receptor for antigen
with MHC class II and activates macrophage
o Helper T cell recognizes complex of antigenic  B. T Cell Effector Functions:
peptide with MHC class II and activates B cell  CD8 (positive cytotoxic T cells)  kills large infected
 Kaya siya tinawag na T helper cell kasi, given cells
yung macrophage, naengulf nya yung o It targets viruses and some intracellular bacteria
pathogen. The macrophage releases the MHC o CD8 T cell releases perforin that helps in
class II molecule binding to the receptor of the Granzyme and Granulysin enter the infected cell
CD4 Th1. The T helper cell helps the  Granulysin - functions to create holes in the
macrophage to become activated and hence target cell membrane and destroy it
lyse the cell intracellularly.  Granzyme - induce programmed cell
death (apoptosis) in the target cell

 CD4 (may apat na subtype)

o Th1  activator of macrophage,
o Th2  activator of B cells
o Th17  enhancer of neutrophil response
o T reg suppress the T cell responses
 Kailangan maactivate si T reg otherwise
continuous ang immune response

Figure: CD4 Tcells

Types and Functions of Effector T cells

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 MICROBIOLOGY [IMMUNITY] [TRANS #2]

Note: all of these four are CD4 T helper cells

T cells are needed to control intracellular pathogens

 Virus infected cell  Cytotoxic cell kills infected cell
o Example, the macrophage is infected with virus. It
exposes the antigen with MHC class I. then it
activates the cytotoxic T cells

Figure: the nomenclature of functions of well-defined T-

cell cytokines

 T cell also have cytokines. There are a lot of T cell

cytokines. Sometimes they enhance the growth of the
T cells.
 These cytokines also have a role in the T cells and B
cells.

MAJOR HISTOCOMPATIBILITY COMPLEX (MHC)

 Highly polymorphic genes encoding the CHONS’s
(proteins) that regulate the immune response
Figure: Virus infected C to Cytotoxic kills infected cell
 It came from the HLA.
 Infected macrophage  activated infected macrophage
o Example, T helper cells naman. Activating the HUMAN LEUKOCYTE ANTIGENS (HLA)
macrophage to kill the antigen intracellularly.  MHC Gene products
 Found on short arm of Chromosome 6
 Function: immune regulation

Molecular products of Human MHC on chromosome

6: HLA
 Class I Gene Products:
o HLA-A, HLA-B, HLA-C
 Class II gene products:
o HLA-DP, HLA-DQ, HLA-DR

Intracellular compartments: Cytosol and Intracellular

vesicles
Figure: Infected macrophage to Activated infected
 Infectious agents can replicate in either of two distinct
macrophage
intracellular compartments: cytosol and intracellular
vesicles
 Viruses and certain bacteria replicate in the cytosol or
in the contiguous nuclear compartment whereas many
pathogenic bacteria and some eukaryotic parasites
replicate in the endosomes and lysosomes that form
part of the vesicular system
o Majority of viruses and some bacteria such as
Mycobacterium tuberculosis are intracellular. The
rest of the bacteria are extracellular

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 MICROBIOLOGY [IMMUNITY] [TRANS #2]

 The MHC molecule will have an effect on intracellular  Toxins and extracellular pathogens are processed by B
pathogen cells and are also processed by MHC class II that
 T cells usually have MHC Class I and II activates both in order to kill the pathogen or eliminate
 B cells have MHC Class I and II the toxins
 RBCs do not have MHC molecules
Cytosolic Intravesicular Extracellular
pathogens pathogens pathogens
MHC CLASS 1 PROCESSING
and toxins
Degraded in Cytosol Endocystic Endocystic
vesicles (low vesicles (low
ph) ph)
Peptide bind MHC Class I MHC class II MHC class II
to
Presented to CDB T cells CD4 T cells CD4 T cells
Effect on Cell death Activation to Activation of B
presenting kill cells to
cell intravesicular secrete Ig to
bacteria and eliminate
parasites extracellular
bacteria/toxins

HUMAN MHC SUMMARY

Figure1: MHC class 1
 The major difference between MHC Class I and Class
II is when the microorganism is present in the MHC CLASS I MHC CLASS II
cytoplasm or in the intracellular membrane Gene products HLA-A, B, C HLA-DP, DQ,DR
o Pag nasa cytoplasm ang antigen, it is processed Tissue All nucleated B-lymphocytes,
by MHC Class I molecule.
distribution cells; platelets macrophages,
o Pero pag nasa intracellular vesicle sya gaya ng
pag nasa loob sya ng macrophage, it is processed dendritic cells,
by MHC Class II. Langerhan cells,
activated T cells,
MHC CLASS 2 PROCESSING Activated
endothelial cells
Recognized by Cytotoxic T cell Helper T cells
(CDB8+) (CD4+)
Peptides bound Endogenously Exogenously
synthesized processed
Function Elimination of Presentation of
abnormal host foreign antigen to
cells by helper T cells
Cytotoxic T cells
B2 Invariant chain
macroglobulin

Figure: MHC class 2  Remember na in MHC Class I important ang beta 2

microglobulin
 Pag yung antigen nasa intracellular vesicle,
magpaprocess na ang MHC II. Anong T helper cell
ang magaactivate sa macrophage? Th1. Activating
this macrophage will kill the pathogen inside.
 Cytosolic pathogens are degraded in the cytosol and
the peptide usually bind to MHC Class I presented to
CD8 T cells and leads to cell death
 Intravesicular pathogens present in the macrophages is
processed by MHC Class II.

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 MICROBIOLOGY
Involvement of the different effector T cells in the
immune responses to different classes of pathogens:
Phases of Immune Response
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Figure: Phases of immune response
Characteristics of immunological memory
 Important in vaccination kasi pag navaccinate kayo,
kailangan magcreate ng memory otherwise, walang
effect yung vaccine. Yan yung tinitignan, kung may
antibodies na naproduce upon immunization
Figure: Characteristics of Immunological memory
HYPERSENSITIVITY
 Nagkakaroon tayo ng hypersensitivity reaction because
sometimes our regulatory cells are not properly
working. Or sometimes the mediators itself like mga
eosinophils dami nilang pwedeng irerelease na
histamines or other inflammatory mediator. This is now
called as the hypersensitivity reactions when there is
inappropriate or excensonated immune response
harmful to the coombs. So the reactions are typically
for after a second contact with a specific antigen. The
first contact is a necessary preliminary event that is
sensitization. So generally, we have four types of
hypersensitivity reactions.
 Antibody-mediated
 CD4 T lymphocytes recognize the pathogens bound to
class II MHC molecules on antigen-presetnign cells
(APCs)
o Type I: Immediate Hypersensitivity
(Allergy/Anaphylaxis)
o Type II: Antibody Mediated Cytotoxic
o Type III: Immune Complex Hypersensitivity
 T cell-mediated or late type hypersensitivity reaction
o Type IV: Cell Mediated (Delayed) Hypersensitivity
Mnemonics: ACID
A - naphlaxis
C - ytotoxic
I – mmune Complex
D – elayed Type
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 MICROBIOLOGY [IMMUNITY]
Type 1 – IgE mediated
Type 2 – IgG mediated
Type 3 – Immune complex mediated
Type 4 – Cell Mediated
Figure: the coombs and gell classification of
hypersensitivity
 In type 1 you have a mast cell that is hyperreacting
there is mast cell degranulation and releases the
different mediators. So, you have your allergen and
meron siyang receptors in its cell membrane and when
it interacts with another allergen it reacts
hyperreactively.
 In type 2 is when the antibodiy particularly IgG
mediated type of hypersensistivity reaction happens so
there is we say that cell surface antigen and antibody
binds to it it leads to cytotoxic reaction after that
sometimes it leads to a lot of release of inflammatory
mediators same as to when a complement is activated.
The lysis itself it can also release other mediators that
lead to reactions. Sa type 2, IgG mediated siya it is
where the allergen binds with IgG.
 Sa type 3 naman binded na silang dalawa and then the
immune complex system deposited into the tissues so
here’s a complex of antibody and antigen and it
deposits into the tissue membrane hence creating a
hypersensitivity reaction that’s why ang best example
glomerular nephritis post streptococcal infection
 Sa Type 4, cell mediated it involves your t cells that
reacting to an antigen and then delayed type best
example is mantoux test or PPD it is a screening test
for tuberculosis it is a form of delayed type
hypersensitivity reaction and then later on you will see
wheal formation in patients previously exposed with
PTB.
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Type 1 Hypersensitivity
 Manifests itself in tissue reactions occurring within
seconds after the antigen combines with the matching
antibody
 Systemic anaphylaxis
 Local Reaction
 Antigen induces the formation of IgE antibody, which
binds firmly by its Fc portion to a receptor
 Second contact of the individual with the same antigen
results in the antigen’s fixation to cell bound IgE
 Cross-linking of IgE molecules, and release of
pharmacologically active mediators from cell within
seconds to minutes
 For example initially when you have second exposure
to the allergens the IgE now binds to your mast cells
then your mast cells will release this inflammatory
mediators so in patients asthma eczema anaphylaxis
Mediators
 Histamine
o Is one of the primary mediators of type 1 reaction
o Histamine exists in a performed state in platelets
and in granules of mast cells, basophils, and
eosinophils
o Causes vasodilation, increased capillary
permeability, and smooth muscle contraction so
for patients with asthma attack they have difficulty
of breathing because of Bronchospasm.
 Prostaglandins and Leukotrienes
o Derived from arachidonic acid via the
cyclooxygenase pathway
o Prostaglandins: leads to bronchoconstriction
Pagnagrelease si histamine at si prostaglandin
hirap na huminga ung patient kasi may
bronchospasm na may bronchoconstriction pa.
o Leukotrienes: Increased permeability of capillaries
o That’s why sometimes with type 1 hypersensitivity
reaction are emergency cases kasi they have
difficulty of breathing that could lead to respiratory
compromised that will eventually lead to death.
o Leukotrienese C4 & D4 are vasodilators
 Treatment aims to reserve the action of mediators kasi
yung reaction is secondary to the release of mediators
by
o Maintaining the airway
o Providing artificial ventilation if necessary
o Supporting cardiac function
 One or more of the following may be given: epinephrine
for emergency cases give epinephrine kasi ano
reaction ni epinephrine it leads to bronchodilation and
the patient could breath normally, antihistamines and
corticosteroids.
 Atopic hypersensitivity disorders exhibits a strong
familial predisposition and are associated with elevated
IgE levels
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 Antigens are typically environmental o Eg. Antibody binds to the thyroid-stimulating

o Respiratory allergy to pollens, ragweed, or house hormone (TSH) receptor and by stimulating the
dust thyroid to release more hormones causing
o Foods (eg, intestinal allergy to shellfish) hyperthyroidism
 Common clinical manifestations include hay fever,
asthma, eczema and uticaria elevated reddish macular Type III Hypersensitivity
rashes.  When you have an immune complex that means there
are already antibody attached to your antigen and then
Type II Hypersensitivity can deposits into the tissue membrane. Since meron
 Involves the binding of IgG antibodies to cell surface ka ulit antibody antigen reaction then it can cause to
antigens or extracellular matrix molecules activate the complement.
 Antibody directed at cell surface antigens remember  When antibody combines with its specific antigen,
pag may antibody antigen interaction eventually it can immune complexes are formed
activate complement (or other effectors) to damage the  Normally, they are promptly removed but occasionally
cells. Best example is the ABO incompatibility kasi they persist and are deposited in tissues, resulting in
magkaiba ung kanilang blood type. Red blood cell niyo several disorders
may antigen. Pagnatransfuse ng ibang blood type sa
iyo magrereject. Kung anong blood type mo un ung Three categories of immune diseases
antigen mo. Let’s say blood type A you have A antigen
Cause Antigen Site of complex
and you have anti – B. if you were transfused with B
positive blood the antibody will react to the B positive deposition
blood hence you create ABO transfusion reaction. Persistent Microbial Infected organ (s),
 The result may be complement-mediated lysis, as infection antigen kidney
occurs in hemolytic anemias, ABO transfusion Autoimmunity Self antigen Kidney, joint,
reactions, and Rh hemolytic disease often seen on Rh arteries, skin
negative babies or Rh positive mom usually happens in Inhaled Mold, plant or lung
the second pregnancy kasi sa first pregnancy Rh
antigen animal antigen
positive si mommy tpos na expose si mommy ng Rh
negative na baby nagcrecreate sya ng anti - D. Pag Rh
negative ulit si baby meron na siyang anti D now  Wherever immune complexes are deposited:
pupunta si anti-D na IgG mediated pwede siyang o They activate the complement system, and
pumunta ng placenta. Hence, it will lead to Rh macrophages and neutrophils are attracted to the
hemolytic disease of the newborn. site
 Drugs such as penicillin can attach to surface proteins o Cause inflammation and tissue injury
on RBC and initiate antibody formation that’s why ung  Arthus Reaction
mga drug na may hypersensitivity reactions are type 2 o Typically elicited in the skin when a low dose of an
 Such autoimmune antibodies may combine with the antigen is injected and immune complexes form
cell surface, with resulting hemolysis locally
o IgG antibodies are involved, and the resulting
activation of complement – activation of mast cells
Good Pasture syndrome and neutrophils – enhanced vascular permeability
o Occurs in about 12 hours para siyang pinalaking
o For example you have patient with streptococcal
urticaria
infection and that circulating streptococcus
nagkaroon ng antistrep then once the patient that
is infected results in severe damage in the Systemic Immune Complex
membrane can activate the complement so  Acute Post-Streptococcal Glomerulonephritis
pagnaactivate na ung complement nakaattach sya o Onset occurs several weeks after a group A-
dun sa cell membrane pati ung normal tissue hemolytic streptococcal infection kasi sometimes
pwedeng malyse nung complement. nagcicirculate pa yan eventually they will be
o Antibody forms against basement membranes of deposited sa glomerular basement membrane and
kidney and lungs, resulting to severe damage to then activation of the complement that’s why pag
the membranes through activity of complement- meron post strep g we also measure the level of
attracted leukocytes C3 kasi component also that eventually will lead to
Grave’s disease the activation of the rest of the component.
o Lumpy deposits of immunoglobulin and
o Antibodies to cell surface receptors alter function
complement component C3 are seen along
without cell injury

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 MICROBIOLOGY [IMMUNITY]
glomerular basement membranes suggesting
antigen-antibody complexes
o Inflammatory process damages the kidney
Type IV Hypersensitivity
 Cell-mediated hypersensitivity is a function not of
antibody but of specifically sensitized T lymphocytes
that activate macrophages to cause an inflammatory
response
 Here is an example of tuberculin skin test. So you call
this method of measuring this induration as the ball
point method. Again when reading the result of the
PPD you measure the induration not the erythema.
 Contact Hypersensitivity – sa mga hikaw initially hindi
pa magkakaroon ng reaction then you wear again
leads to eczematous reaction. So eczema can be type
1 or 4 pag immediately type 1 pag delayed type 4
 Tuberculin Type hypersensitivity – Local induration if
the patient has previously exposed to tuberculosis lalo
na sa children primary infection usually what you see in
children but previously you can see nagcrecreate na
sila ng antibodies against sa PPD when you do skin
test that actually represents secondary exposure pag
nilagyan niyo na ng protein antigen they will react to it
and create a local induration dun sa site of injection we
measure the induration not the erythema kasi
sometimes may erythema may induration. Mas malaki
ung erythema sometimes. It is the induration that we
measure during tuberculin skin test.
 Granulomas – sa mga patients with pulmonary
tuberculosis it takes almost a month or sa mga may
leprosy you see persistent antigen or antibody
complexes or non immunoglobulin stimuli as an
antigen.
Contact Hypersensitivity
o Occurs after sensitization with simple chemicals,
plant materials
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o , topically applied drugs, some cosmetics, soaps
and other substances
o Small molecules enter the skin and then, acting as
haptens, attach to body proteins to serve as
complete antigen
o When the skin again comes in contact with the
offending agent, the sensitized person develops
erythema, itching, vesication, eczema, or necrosis
of skin within 12-48 hours
o Patch testing on a small area of skin can
sometimes identify the offending antigen
o Subsequent avoidance of the material will prevent
recurrences
Tuberculin Type Hypersensitivity
o When a small amount of tuberculin is injected into
the epidermis of a patient previously exposed to
Mycobacterium tuberculosis, there is little
immediate reaction
o Good example of Delayed-type Hypersensitivity
o Gradually, however, induration and redness
develop and reach a peak in 24-72 hours that’s
why we measure the PPD reaction or mantoux
test after 48 – 72 hours kasi nga delayed type ung
reaction na ineexpect natin.
o A positive skin test indicated that the person has
been infected with the agent but does not imply
the presence of current disease kung we are
trying to diagnose tuberculosis this is one of the
criteria we still have to look for other criteria like
the signs and symptoms before we diagnose
tuberculosis.
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Figure: Types of hypersensitivity there are intracellular and extracelluar pathogens. This
summarizes the humoral and cell mediated immunity
What type of Hypersensitivity? and actually what is important is that you know
 SLE - Type 3 pagdeficient si B cell ang nagdodominate extracellular
 Allergic Rhinitis - Type 1 pathogen, pag intracellular pathogens naman T cells
nagdodominate kasi you need the cell mediated
 Multiple Sclerosis – Type 3
immunity.
 Hashimoto’s thyroiditis – Type 3
Normal and Deficient immune response
 PPD – Type 4
 Hemolytic Anemia – Type 2
 Eczema – Type 1 or 4
FAILURES OF IMMUNE REGULATION:
IMMUNODEFICIENCY
AUTOIMMUNE DISEASE

 Grafted organs - That’s why ung mga transplanted

patients are in the state of immunocompromised. Kasi
they have to accept the grafted organs.

PRIMARY IMMUNODEFICIENCIES
 Primary immunodeficiency kapag ang deficiency is
secondary to the cells that are reactive to the antigen.
Deficient ka ng B cells, deficient ka ng phagocytes,
deficient ka ng T cells that’s primary immunodeficiency.
However, patient is for example undergoing
Figure: Cells involved in immune response chemotherapy nababawasan din ung kanyang immune
cells that’s what you call secondary immunodeficiency.
Pagprimary dun sa cell na may deficiency.

 Phagocyte cell function

 Complement protein
 B-cell development/function
 T-cell development/ function
 Combined B and T cell deficiency

Figure: Humoral and Cellular Immune system

 So you have the B cells, T cells that react depending

on the type of antigen or allergen and the pathogens

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Figure: Common infections associated with COMPLEMENT SYSTEM

immunodeficiency
Classical Alternative Lectin
Activating Immune LPS Mannose
PHAGOCYTE DEFICIENCY
subs. complexes (bacterial groups on
(IgG or capsule), microbial
IgM) IgA cell
Recognition C1q, C1r, C3, Factor MBP,
Unit C1s B, Factor D MASP-1,
MASP-2
C3 C4b2a C3bBb C4B2a
convertase
C5 C4b2a3b C3bBb3b C4b2a3b
Convertase
MAC C5b6789 C5b6789 C5b6789
End result Cell lysis Cell lysis Cell lysis

 Chronic granulomatous disease kulang lang ng

granules that enhances lysis of engulfed pathogens
kaya pagwala ka nung granules na yun kahit na engulf
sya hindi mamamatay ung pathogen. Hence, it results
to recurrent infections particularly with catalase mga
staph catalase positive bacteria and fungi.
 Chediak-hegashi syndrome NK – Natural Killer (refer to
table)
 Leukocyte-adhesion deficiency hindi makapunta sa site
ung leukocyte.
 Glucose-6-phosphate dehydrogenase deficiency
 Myeloperoxidase deficiency
 Lahat yan kulang sila ng granule within the phagocytes
kaya it leads to proliferation of bacterial pathogen kaya
hindi nila malyse kulang sa enzyme or kulang sa
granule enzymes.
Figure: Clinical Syndromes Associated with Inherited
Deficiencies of Complement Components
 Diba sabi natin dapat may regulatory complements
pagdeficient ng C1 inhibitor it can lead to hereditary
angioedema deficiency in C1, C2, C4 can lead to
immune complex diseases. C3 deficiency can lead to
recurrent bacterial infections. Property D, B, P
deficiency can lead to recurrent neisserial infections
and the membrane attack complex proteins C5 to C9
deficiency can lead to recurrent neisserial infections.
Kasi ang Neisseria is with capsule kailangan mo talaga
ng complement to lyse ang kanyang cell membrane.

 If you have B cell deficiency, wala kayong antibodies

therefore walang magoopsonized. Anong function ng
antibodies? For opsonization and also complement
activity. Pag B cells deficiency lang intact pa din ang T
cells function it can result to recurrent pyogenic
infection with dose of extracellular pathogen.

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COMPLEMENT DEFICIENCY
 C1Sinh  Heriditary Angiodema
 C2  Increased incidence of Connective Tissue d/o
(SLE)
 C1/C4/C2  Opsonization not efficient (LAD)
 C3  Increased susceptibility to pyogenic infection
 C5-C8  Recurrent Neisseria Infection
B-CELLS DEFICIENCY
 Bruton X-linked hypogammaglobulinemia
 Transient Hypogammaglobulinemia of infancy
 Common variable (acquired) hypogammaglobulinemia
 Selective Ig deficiency (dysgammaglobulinemia)
1. Bruton X-linked Hypogammaglobulinemia
 First appear in childhood (>6 months) pagtransient less
than 6 months ung mas common
 Immunologic findings
o Low immunoglobulin: all
o No circulating B cells
o Pre-B cells in the BM
o (N) CMI (cell mediated immunity)
 Primary defect: a block in maturation of the B cell due
to a deficiency of tyrosine kinase
 Tx: monthly IgG replacement, antibiotics for infection
2. Transient Hypogammaglobulinemia of infancy
 Delayed onset of normal IgG synthesis
 Seen in the 5th-6th month of life
 As the patient grows older, usually resolves by 16-30
months of age the patient will now have normal levels
of immunoglobulin
3. Common Variable (acquired)
Hypogammaglobulinemia
 Immunoglobulin levels decrease with time
 First appear in late teens to early 20s
 Associated w/ autoimmunity in the patient or in the
family
 A syndrome that is probably several different disease
 Low immunoglobulins  any class
 Unlike in brutons, B cells are present in the peripheral
blood kasi sa brutons wala talaga bone marrow lang
hindi sya nagmamature.
4. Selective Ig deficiency (dysgammaglobulinemia)
 Several different diseases described
 Pagselective we have IgG or IgM pero Selective IgA
deficiency is the most common
o Repeated sinopulmonary infection,
gastrointestinal disease
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o Many with IgA deficiency have no symptoms
o If both IgA and IgG2 subclass deficiencies, more
likely to have infections
T-CELL DEFICIENCIES
 Px presents with recurrent viral/fungal infections
 B-cell function: compromised by lack to T-cell help
 Major defect: handling intracellular pathogens
 Px’s receiving immunosuppressive drugs for treatment
of allograft may have similar problems with these
organisms
1. Di George syndrome
 Failure of development of third and fourth pouches
o Hypoplasmic thymus kaya walang T cells
o Hypoplastic parathyroid glands kaya mababa ang
calcium
 Clinical features
o Thymic aplasia
o Recurrent viral and fungal infections
o Hypoparathyroidism – hypocalcemic tetany
o Cardiac anomalies
o Facial anomalies (fish mouth and flat face)
2. Chronic mucocutaneous candidiasis
 Severe chronic skin and mucous membrane infections
with the fungal pathogen Candida Albicans
 You will see patients na palaging may oral candida so
kapag patients with AIDS ang kanilang primary
deficiency ay T cell. Pagrecurrent ung kanilang
candiasis check level of T cells and maghistory baka
prone to AIDS or HIV Kung pabalik-balik check niyo
ung kanyang T cells.
COMBINED B AND T CELL DEFICIENCY
 Both B and T cells are deficient, susceptible to
bacterial, viral and fungal infections
 T cell def  prodemonates
1. Adenosine deaminase deficiency (ADA)
 1st
human diseases successfully treated with gene
therapy
 normal RXN: Deoxyadenosin Deoxyinose (non toxic)
 ADA def: Deoxyadenosine  Deoxyadenosine
Phosphate (Toxic for T-cells and precursors)
2. Severe combined immunodeficiency disease
(SCID)
 X-linked and autosomal
 Early infancy (3mths)
 B and T cells: -/N not fnx Normally
 Pneumocystic pneumonia  most common
 Def:
o Class I and II molecules
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 MICROBIOLOGY [IMMUNITY] [TRANS #2]

o T cell receptors
o Cytokine receptors  A person is really susceptible meaning to say, sa
o Signal-transduction genes niya talaga based on family history meron silang
potential for immune diseases. So there is family
history other artificient with exudate HLA 827 you need
3. Wiskott-Aldrich Syndrome (X-linked) that in cell mediated immunity.
 Triad  Trigger comes from the environment can be infection or
o Thrombocytopenia subclinical autoimmunity with immune markers they will
o Eczema have positive serum autoantibodies.
o Immunodeficiency  Then Failure of regulation, that’s when you see clinical
 Inability to mount an IgM response to the capsular autoimmune diseases.
polysaccharide of bacteria, such as pneumococci
SUSCEPTIBILITY –GENETIC FACTORS
4. Ataxia-Telengiectasia  Sa defective genes, it can be in the immunoglobulin, T
 Develops 1-2 years of age cell receptor or Major Histocompatibility Complex
 Sinopulmonary infections  Three main set of genes are related to:
 Autosomal recessive o Immunoglobullines
 Ataxia: uncoordinated muscle movements o T-cell receptors
 Talengiectasia: dilation of small vessels; seen in sclera o Major Histocompatibility Complex (MHC)
of eye  MHC class II allotypes are strongly correlated
with diseases
 Immunodeficiency
 HLA DR2 –strongly correlated with SLE
o Selective IgA deficiency
and MS and negatively with DM Type 1
o Cell-mediated defects – variable
 HLA DR3 – strongly with Sjogren’s,
o Other immunoglobulin – variable
Myasthenia Gravis, SLE, and DM Type 1
 HLA DR4 – rheumatoid arthritis, DM
AUTOIMMUNE DISEASE Type 1, and pemphigus vulgaris
Etiology and Pathogenesis  Most notable MHC class 1 correlation
 Two possible explanations, which are not mutually  HLA b27 – Ankylosing Spondylitis
exclusive, for self-reactivity are:
 1. Similarity between foreign and self molecules that TRIGERRING
are recognized by immune cells, particularly T  Sa Trigger ang best example nito is ung sa rheumatic
lymphocytes, and; heart disease. Kasi ang streptococcus o strep pneumo
 2. Viral or other infections that incite, exaggerate, or ang kanilang virulence factor ay ang M protein. The M
prolong otherwise self-limited immune response protein structure mimics or almost the same with the
myosin of the heart so nagkaroon ng infection si patient
The Chain Leading to Autoimmune Disease nagproduce na sya ng antibodies specific for M protein
it will circulate pagnapunta na yan sa myosin ng heart
irerecognize ng antibody that the myosin is actually an
M protein kaya magaattach na un si antibody kay
myosin eventually the antibody will attach to the tissue
will activate the complement now leading to a reaction
that’s what you call mimicry as part of the triggering
mechanism for autoimmune disease.
 Mimicry
o Human cardiac myosin and group B streptococcal
M protein
 Immune Mechanisms
o Toll-Like Receptors

Figure: Chain Leading to autoimmune disease

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 MICROBIOLOGY [IMMUNITY] [TRANS #2]

 DNA and RNA present in endogenous

complexes kasi each toll like receptors will
have specific reaction to a certain antigen it
can be DNA and RNA. Sometimes, may
abnormality or dun sa cytokines that are
release like interleukin. (such as apoptotic
debris) may contribute to activating
autoreactive B and T cells by triggering
TLR7/8/9 pathways. (Ex. Systemic lupus in
mouse model)
o Cytokines
 Anti-IL12 inhibits transfer of EAE by lymph
node cells activated in vitro by MBP plus CpG
oligo or bacterial DNA)
 IL-12 modulation is potent inducer and remitter
of relapsing autoimmune encephalomyelitis

Infections associated with Immune diseases

 Infections that causes autoimmune diseases dba sabi

natin the second possible explanation it prolongs
normal diseases. Sa EBV pagsa normal person easily
nacocontain sya pero pagsa immunocompromised
patients this now can lead to MS. E coli can also lead
to rheumatoid arthritis. Figure: Examples of autoimmune diseases

 Autoimmune diseases can be presented with organ Sample Questions

specific or systemic. What kind of deficiency?
 For failures of autoimmune regulation it can be Choices for 1-5:
hypersensitivity reaction immunodeficiency or A. B-cell
autoimmune diseases. B. T-cell
C. Complement
D. Combined B and T cell

1. Di George
2. Wiskott-Aldrich syndrome
3. Bruton’s disease
4. recurrent Neisseria
5. ataxia-talengiectasia

TRUE or FALSE
6. Viral infections can trigger an autoimmune response
7. genes for T-cell receptors may render an individual
susceptible for autoimmune disease
8. autoimmune diseases are always systemic in nature
9. Streptococcal infection can lead to Rheumatic
Myocarditis
10. Escherichia coli is associated with Rheumatoid
arthritis
Figure: Infections associated with autoimmune diseases Answers:
1. B.
2. D.
3. A.

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 MICROBIOLOGY [IMMUNITY] [TRANS #2]

4. C.
5. D.
6. True
7. True
8. False
9. True
10. True

References
Doc’s PPT and Audio
Jawetz, Melnick & Adelberg’s Medical Microbiology 27th
Ed
Immunology Overview:
https://www.youtube.com/watch?v=2-57bqFSJ1E
Innate Immunity:
https://www.youtube.com/watch?v=LSYED-7riNY

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APPENDIX

Fig: Common infections associated with

immunodeficiency

Figure: Different types of hypersensitivity

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Figure: Cytokines/chemokines produced by activated

macrophages

Fig: Proteins of the classical pathway of complement

activation

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Figure: Types and function of effector T-cells

Figure: Nomenclature and functions of T-cells

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Fig: Humoral and cellular immune system

Fig: MHC Class I

Fig: MHC Class II

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