Basic Immunology in Obstetric

and Gynecology

dr. Leri Septiani, SpOG, PhD

 Objectives
• The Players -- T-cells and B-cells
• Immunoglobulins
• Antigen Recognition
• Phagocytosis
• Mediators and Complement
• Immunization
• Hypersensitivity Reactions
• Transplant Immunology Basics
 Immunology

• Conceptually challenging
• Complex series of reactions triggered by
immunogens
• Compartmentalize to simplify, but actual
events at molecular and cellular level are
“boundary-less” and only partially
understood
• More we learn the less we know
 Introduction

• Innate vs Adaptive immunity

• Self vs non-self vs altered self
• Three phases of immune response:
– Cognitive phase
– Activation phase
– Effector phase
• Primary and Secondary responses
• Lymphoid organs: primary/secondary
• Humoral and Cell-mediated responses
 Types of immunity

• Innate (natural) immunity

– Phagocytes etc.
– Early, rapid responses, but limited & ‘non-specifc’

• Adaptive (acquired) immunity

– Lymphocytes (B & T cells)
– Take time but powerful - ‘specificity + memory’
Types of Immunity
 Innate Immunity
• Four types of defensive barriers:
– Anatomic
– Physiologic
– Phagocytic
– Inflammatory
Innate Immunity
Electron micrograph of rod-shaped Escherichia coli bacteria adhering to surface
of epithelial cells of the urinary tract
N. Sharon and H. Lis, 1993, Sci. Am. 268(1):85; photograph courtesy of K. Fujita
 Electronmicrograph of macrophage (pink) attacking Escherichia coli (green). The bacteria
are phagocytized as described in part b and breakdown products secreted. The monocyte
(purple) has been recruited to the vicinity of the encounter by soluble factors secreted by
the macrophage. The red sphere is an erythrocyte
Phagocytic Barrier
Inflammatory Barrier
 Adaptive Immunity
Characteristics:
– Antigenic specificity
– Diversity
– Immunologic memory
– Self/nonself recognition
 ANTIGEN
• Substance  host  immune response
(immunogen)
• Substance which reacts with antibodies or sensitisized Tcell
CMI
Ag immunogen IR Humoral:
Tdep/indept

Antigen ~ good immunogen

1. High molecular weight
2. Chemical complexity/structural diversity
3. Structural rigidity
4. Stability & solubility (biodegradability)
5. Foreigness
 Antigen Recognition
• B cells can recognise antigens via their surface
Ig molecules
• T cells can only recognise AG in association
with a Major Histocompatibility Complex
(MHC) molecule.
 The Adaptive Immune System Requires Cooperation
Between Lymphocytes and Antigen-Presenting Cells

• Humoral immune responses

– B cells and antibodies

• Cell mediated immune responses

– Cytotoxic T cell (Tc)
– Helper T cells (TH)
 B Lymphocytes
• Within bone marrow
• Expresses a unique antigen-binding receptor
(antibody)
Antibody

• Antibodies are
glycoproteins that consist of
two identical heavy
polypeptide chains and two
identical light polypeptide
chains.
• Antigen-antibody:
• Memory B cells
• Effector B cells (Plasma
cells)
 T Lymphocytes
• T cells migrate to the thymus gland to mature
• T cell comes to express a unique antigen-
binding molecule,called the T-cell receptor
• T-cell receptors can recognize only antigen
that is bound to cell-membrane proteins
called major histocompatibility complex
(MHC) molecules
Distinctive membrane molecules on
lymphocytes
 T-cells
• T helper (TH) and T cytotoxic (TC) cells
• T helper and T cytotoxic cells can be
distinguished from one another by the
presence of either CD4or CD8membrane
glycoproteins on their surfaces
 Antigen Presenting Cells
• Both the humoral and cell-mediated branches
of the immune system requires cytokines
produced by TH cells
• To ensure carefully regulated activation of TH
cells, they can recognize only antigen that is
displayed together with class MHC II
molecules on the surface of antigen-
presenting cells (APCs)
 T vs B Cells
T cells B cells ______________

Ag receptor TCR related to Ig BCR is membrane-bound Ig

but not Ig

Ag recognition in context of MHC can recognize Ag alone

on APC or accessory cells

Functional Th (helper) and subsets of B cells not

subsets Tc (cytolytic) different in function

Secrete Cytokines Ig (as Ab) and cytokines

Surface CD4 and CD8 Ig (among many others)

markers (among others)

When Ag- Become (proliferating) Become lymphoblasts, then

activated lymphoblasts become plasma cells

Costimulation Yes No
required?
 B - cells

 Comprise 5 - 15 % of the circulating

lymphoid pool
 Specific Ag-receptor : surface Ig
 Ag-receptor complex (Ig/CD79a, Ig/CD79b)
 Other B-cell markers, i.e. CD19, CD20, CD22,
C3bR
 B-cell receptor

• Before contact with antigen, the B-cell does

not secrete any antibodies. However they do
make B-cell receptors.
• The B-cell receptor is an IgM or IgD antibody
with a membrane spanning domain on the
end of the constant region of the heavy chain.
• The B-cell receptor is associated with two
other membrane proteins which function in
signal transduction (Ig and Ig)
 Contact (activation) with antigen

• When a B-cell comes in contact with it’s

specific antigen:
– It is first trapped in the T-cell areas where the
receive signals for differentiation by TH cells.
– Some B-cells immediately develop into plasma
cells that secrete IgM (stage 4).
– Some B-cells enter the B-cell area, and proliferate
to form a germinal center (now the follicle is
termed a secondary lymphoid follicle)
 Differentiation into plasma cells

• Within the germinal center, B-cells divide,

undergo somatic hypermutation and isotype
switching.
• Those B-cells which produce the highest
affinity continue to proliferate and
differentiate into plasma cells (affinity
maturation) and secrete other classes of
antibody (IgG, IgA, IgE)
 T cells

• T cells display TCR as their antigen recognition

protein
• When stimulated they become Cytotoxic or
Helper T cells
• Secrete cytokines that recruit other cells of
the IS
• TCR’s only recognise short peptides.
 T cell receptor structure

• The T-cell receptor is also associated with

other proteins which function in signal
transduction
– CD3 complex
  (zeta)
• T-cells also have co-receptors. Each T-cell has
either a CD4 or CD8 co-receptor. These
distinguish subtypes of T cells.

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 Antigen Processing and Presentation

• CD8+ T-cells
– are cytotoxic T-cells (Tc) – they kill cells that are infected
with virus (intracellular antigen)
– CD8 / T-cell receptors only bind to antigens displayed on
MHC class I.
• CD4+ T-cells
– Are helper T cells (TH) – they are involved in stimulating
other immune cells by secreting cytokines.
– CD4 / T-cell receptors only bind to antigens displayed on
MHC class II.

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 Antigen Processing and Presentation

• T-cell receptors must bind to processed antigen

fragments that is displayed by the host’s cells rather
than native antigen.
• Antigens are displayed on membrane glycoproteins
called “MHC” (major histocompatability complex)
• There are two kinds of MHC:
– Class 1- displays antigens of intracellular source
– Class II-displays antigens of extracellular source

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 Antigen Processing and Presentation

• The CD4+ T helper cells are further divided

into two subclasses:
– Th1 – activates tissue macrophages to
phagocytose and kill extracellular pathogens and
secrete cytokines
– Th2 – stimulates B-cells to differentiate into
plasma cells and secrete antibody
• Clinical note – CD4 is the receptor the HIV
virus uses to gain access to T-cells

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Antigen Processing and Presentation

– CD8+ cytotoxic T cell + virus infected cell 

activated Tc cell  dead virus infected cell
– CD4+ TH1 cell + macrophage  activated
macrophage  cytokine release and pathogen
killing.
– CD4+ TH2 cell + B cell  activated B (plasma) cell
 antibody release.

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 Antigen Processing and Presentation

• Fragmentation of protein into peptides

• Association of peptide with an MHC molecule
• Transport to cell surface for expression
• Different cellular pathways for association of
peptide with MHC class I and class II
molecules
 Antigen processing

• MHC I
– Virus particles, indigenous protein are digested in
proteosomes
– Antigenic fragments are attached to newly formed
MHC I
– MHC / antigen is displayed on MHC I on the
surface of the cell
• MHC I can be displayed on any nucleated cell
of the body.

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 Antigen Processing
• MHC II
– Extracellular antigen (free protein, bacteria or free virus) is
engulfed by macrophage
– Phagosome fuses with lysosome where the antigen is
digested
– Antigen fragment is attached to MHC II and displayed on
the cell surface.
• MHC II is found on “antigen presenting cells” such as
macrophages and dendritic cells, and even B cells.

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 Antigen Presenting Cells
• Macrophages, B lymphocytes, and dendritic
cells
• Properties:
– express class II MHC molecules on their
membranes
– are able to deliver a co-stimulatory signal that is
necessary for TH-cell activation.
 Antigen processing by APC

• The immune response starts with an antigen

approaching a cell of the immune system,
here a macrophage. antigen

macrophage
 Antigen engulfed in vesicle

The macrophage
engulfs the antigen
by phagocytosis.
Lysosome
containing
enzymes
The vesicle containing an antigen
fuses with a lysosome. The
enzymes in the lysozome break
down the antigen into fragments.
This is antigen processing.

antigen processing
 enzymes and
Inside the macrophage, proteins combining

the processed antigens

combine with special
class II MHC proteins.
These proteins can move
to the cell surface
Class II
membrane. MHC proteins
 Processed antigen/
The antigen/MHC protein MHC protein complex

complex is displayed on the

immune cell surface
membrane. The macrophage
is now known as an antigen
presenting cell. Antigen-presenting cell
The next stage involves a helper T cell (also
know as a T-helper cell) as well as the
macrophage
receptors which bind to specific
antigen/MHC protein complex

T helper cell (TH)

macrophage (antigen-presenting cell)

The receptors on the helper T cell enable it to
bind to the specific antigen-MHC complex of
the antigen presenting cell.

helper T cell

macrophage (antigen-presenting cell)

Antigen Presenting Cells
The binding of the helper T cell with the antigen -
MHC protein complex triggers the macrophage to
release proteins (cytokines) that activate the
helper T cell.
Cytokines from
macrophage
The activated helper T cell now releases its
own cytokines

Cytokines
from helper T
cell
The released cytokines stimulate the helper T
cell to reproduce and form a clone of cells.
Each new cell has the same receptors as the
original helper T cell, so they are specific for
the original antigen.

Clone of helper T cells

 Antigen processing by B cells

• Another phase of the immune response begins with

a B cell. The B cell has membrane bound globular
receptor proteins (called IgM). Some of these are
specific for the same antigen presented earlier by the
antigen presenting cell. IgM receptor

antigen

B cell
 IgM bound to
lysosome
antigen engulfed
The B cell’s receptor by cell

protein (an IgM) binds to

the antigen, and the cell
engulfs the antigen by
endocytosis.
 Fused vesicles containing antigen
and enzymes from lysosome
The vesicle formed inside
the B cell fuses with a
lysosome. This contains
digestive enzymes which
break down the antigen.

B cell
 Processed antigen
Fragments of the
digested antigen
remain after processing
within the vesicle. Class II
MHC
protein
The processed antigen is
attached to Class II MHC
receptors within the B
cell, and is transported to
the membrane.
 Antigen/MHC protein complex

The MHC proteins form a

complex with the antigen
which is displayed on the
surface of the B cell. It has
become another type of
antigen presenting cell
B cell (antigen presenting cell)
A helper T cell from the clone of cells
produced earlier specifically recognises the
antigen presented by the B cell.

Helper T cell clone

Antigen-presenting B cell
The helper T cell cell binds to the antigen/MHC protein
complex displayed by the B cell.
This triggers the release of cytokines from the T cell.
Once the cytokines are released the helper T cell no
longer binds to the B cell.

helper T cell binds to

antigen complex on B cell

Cytokines released by
helper T cell
The cytokines released by the helper T cell
stimulate the B cell to divide and form a clone
of identical cells

B cell clones
The B cells continue to
divide and form two groups
of clones. Some are long – Memory
cell
lived MEMORY cells. Most
are antibody-secreting
PLASMA cells. Plasma cells
have extensive endoplasmic
reticulum and many
ribosomes. Plasma cells
Plasma cells are essentially antibody factories.
They produce and secrete antibodies identical
to those of the surface receptors of the
original parent B cell

antibodies
Like the IgM surface receptors on the parent B cell, the
antibodies can bind to and inactivate the antigens,
forming an antibody-antigen complex. This complex
makes it easier for other white blood cells to engulf the
antigen (phagocytosis).

Antibody-antigen complex
Humoral and Cell Mediated Immune
Response
Complex Antigens Are Degraded (Processed) and Displayed
(Presented) with MHC Molecules on the Cell Surface
Antigen Selection of Lymphocytes Causes Clonal
Expansion
 “Memory” in adaptive immunity

• 1st infection  memory  2nd infection

slow response fast response

pathogen proliferate pathogen killed

disease no disease
symptoms no symptom
Primary and Secondary Response
 Cells, tissues and organs of
the immune system
• Immune cells are bone marrow-derived, & distributed through out
the body
• Primary lymphoid organs:
– Thymus: T cell maturation
– Bone marrow (bursa of Fabricius in birds): B cell maturation
• Secondary lymphoid organs:
– Lymph nodes
– Spleen
– Mucosal lymphoid tissues (lung, gut)

Blood vessels and lymphatic systems connect these

organs,uniting them into a functional whole.
Components of the Immune System

Dendritic cell
(sentinel)
Components of the Immune System
Thank You