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IMMUNOLOGY

ADAPTIVE AND INNATE IMMUNITY


ADAPTIVE IMMUNITY
- highly specific for a certain pathogen
- response improves with each successive encounters
- remembers and prevents an infectious agent that had already been
encountered
- 2 key features are specificity and memory.

INNATE IMMUNITY
- Non-specific
- Same response after repeated exposure
- Has no memory

CELLS OF THE IMMUNE SYSTEM


- All cells of the immune system arise from pluripotent stem cells
through two main line of differentiation: 1) the lymphoid lineage
(produces lymphocytes); 2) the myeloid lineage (produces
phagocytes and other cells)
I. PHAGOCYTIC CELLS/ PHAGOCYTES/ ANTIGEN-PRESENTING
CELLS (APC)
- monocytes, macrophages, PMNs
- engulfs pathogens, internalizes them and destroys them
within the cell
- uses non-specific recognition systems
- mediate innate immunity
- considered the first cellular line of defense

II.

A. MONONUCLEAR CELLS/ MONOCYTES


- Derived from the bone marrow stem cells
- Function is to engulf particles, internalize them and
destroy them
- Effective in presenting antigens to T
lymphocytes
- Long-lived phagocytic cells
B. PMNS( POLYMORPHONUCLEAR SEGMENTERS)/
NEUTROPHIL
- Constitutes the majority of blood leukocytes
- Short-lived phagocytic cells (after internalizing
and destroying pathogens, they die)
LYMPHOCYTES
- Central cells in adaptive immunity. Produced at a rate of
10^9 per day.

The adult constitutes about 10^12 lymphoid cells, and the


lymphoid tissue as a whole is about 2% of the total body
weight.
Can recognize individual pathogens whether inside or
outside of host cells
Specific immune recognition
Derived from the bone marrow stem cells, although the T
lymphocytes develop further in the thymus (the bone
marrow and thymus are considered the primary
lymphoid organs.)

CD MARKER/ CLUSTER OF DIFFERENTIATION


- Refers to groups of monoclonal antibodies, each cluster
binding specifically to a particular cell marker
- Depends on computer analysis of monoclonal antibodies
produced mainly in mice against human leukocyte
antigens.
- Example is CD45 also known as the common leukocyte
antigen
A. B CELLS (B = BURSA, bursa of fabricius in chickens)
- CD MARKER:
CD19 main marker to identify B cells.
CD20 main marker to identify B cells.
CD21 also known as CR2, which is the
complement receptor for C3d. Commonly found
in B cells. Associated with homing of cells.
CD22 main marker to identify B cells.
CD35 also known as CR1, which is the
complement receptor for C3b. Commonly found
in B cells. Associated with homing of cells.
CD32 Fc receptors for exogenous IgG, which
play a role in negative signalling to B cells.
CD72 ligand of CD5 in T cells.
- Represents 5-15% of circulating lymphoid pool, and
are classically defined by the presence of surface
immunoglobulins, seen with fluorochrome-labelled
antibodies specific for the immunoglobulins resulting
in a ring-like pattern (when cold) or cap-like (when
warm) pattern.
- The main immunoglobulin seen on their surface are
IgM and IgD
- Specifically recognizes a particular antigen using a
receptor molecule on its surface
- Develops in the fetal liver or adult bone marrow.

B cells are occasionally seen with a developing


rough endoplasmic reticulum.
- Combats extracellular pathogens by release of
antibodies, that bind to a particular target molecule
called antigen
- Divide and differentiate into plasma cells, which
produce large amounts of receptor molecule in
soluble form which are also otherwise known as
antibodies
ANTIBODIES large glycoproteins found in
blood and tissue fluid that function primarily to
bind to antigens, to initiate an immune
response against that specific antigen. It can
also act to activate other parts of the immune
system. It is produced by plasma cells.
B. T LYMPOCYTES( T = THYMUS, where they develop)
- CD MARKER:
CD1 maturation marker for T cells, only
found in cells developing in the thymus,
and is not present in circulating T cells
CD2 ability of T cells to bind to sheep
erythrocytes also known as rosette
formation.
CD3 exclusive for T cells, and is involved
in cell triggering.
CD4 marker for T helper cells
CD5 ligand of CD72 in B cells.
CD8 marker for T cytotoxic cells or T
suppressor cells
CD25 activation marker for T cells, also
known as the T cell growth factor receptor or
IL2 receptor.
- Involved in the control of B lymphocyte development
and production
- T helper and T cytotoxic cells are smaller, nongranular and with high N:C ratio. They also carry a
structure called a Gall Body, which consists of a
cluster of primary lysozymes, seen in
cytochemistry.
- Interacts with phagocytic cells and helps them
destroy pathogens
- Recognizes infected cells by viruses and destroys
them
- Uses the TCR( T CELL RECEPTOR) to recognize
antigens.

Has the ability to release cytokines


CATEGORIES OF T CELLS:
1. T HELPER CELL (CD4+ CELLS)
- Positively influence the response of
T and B cells
- Helper cell function which is
CD29+
- 2 TYPES OF T HELPER CELL:
a) TH1 mediate several
functions related to
cytotoxicity and local
inflammatory reactions.
These are important in
combating intracellular
pathogens. It produces IL2
and IFN gamma.
b) TH2 more effective in
stimulating B cells to
proliferate and produce
antibodies., and function
therefore to protect against
free living microorganisms.
2. T CYTOTOXIC CELL (CD8+ CELLS)
3. TCR-1+ T CELLS
- Minor subpopulation of T cells that
are found in mucosal surfaces.
C. LARGE GRANULAR LYMPHOCYTES (LGLs)/ NK CELL
(NATURAL KILLER)
- CD MARKER:
CD7 found in almost all of NK cells.
CD16 monoclonal antibodies used to identify
NK cells, also involved in the activation of NK
pathway.
CD56 definitive marker of NK cells.
- Accounts for 15% of blood lymphocytes, and can be
negatively defined as lymphocytes having no
conventional surface antigen.
- Recognizes surface changes in tumour cells and
virally infected cells
- Can be distinguished from the T and B cells, by their
ability, in vitro, to lyse tumour cell lines without
prior sensitization.
- Uses a non-specific recognition system
- Does not express antigen receptors
- Has the ability, ANTIBODY-DEPENDENT CELLULAR
CYTOTOXICITY (ADCC).

It is neither a T lymphocyte nor B lymphocyte.

LYMPHOCYTE ACTIVATION
- Both T and B cells utilize a GTP-dependent component (or G-protein)
to induce signalling reactions. These G-proteins stimulate
phosphatidylinositol metabolism, at the same time a number of
surface receptors for cytokines such as IL2 are produced.
III.

OTHER IMPORTANT CELLS OF THE IMMUNE SYSTEM


A. EOSINOPHILS (EOSIN = RED = ACIDOPHILIC)
- Has the ability to engage and damage extracellular
parasites
B. AUXILLARY CELLS
- Involved in the development of immune response by
the production and release of mediators
a) Mast Cells cells that lie close to the blood
vessels in all tissues. It functions in
hypersensitivity reactions
b) Basophils cells in the blood circulation that
function similarly to the mast cells
c) Platelets attracts leukocytes to site of injury

SOLUBLE MEDIATORS OF IMMUNITY


I.
ACUTE PHASE PROTEINS
- Proteins produced by the liver that are increased
rapidly during infection
A. CRP/ C-REACTIVE PROTEIN
- Name comes from the ability to bind with the C
protein of pneumococci
II.
COMPLEMENT
- CD MARKER:
CD21 also known as CR2, which is the
complement receptor for C3d. Commonly found
in B cells.
CD35 also known as CR1, which is the
complement receptor for C3b. Commonly found
in B cells
- Group of 20 serum proteins that control inflammation
Generates the following effects:
1. Opsonization
2. Chemotaxis
3. Increased blood flow and permeability of
capillaries

4. Damages plasma membranes of cells,


gram (-) bacteria, and enveloped viruses
2 MAJOR PATHWAYS OF COMPLEMENT
ACTIVATION:
1. CLASSICAL PATHWAY initiated by
antigen-antibody reaction
2. ALTERNATIVE PATHWAY initiated by
certain microorganisms
III.

CYTOKINES
- Molecules involved in the signalling between cells
A. INTERFERONS (IFN)
- Considered the first line of resistance to many
viruses.
- Determines how effective tissue cells interact with
lymphocytes
- Induces a state of anti-viral resistance in
uninfected cells
- Important in limiting certain viral infactions
3 CATEGORIES OF INTERFERONS:
1. IFN ALPHA
2. IFN BETA
3. IFN GAMMA
*Both IFN ALPHA and BETA are produced
by virally infected cells
B. INTERLEUKINS (IL)
- Produced mainly by T lymphocytes, some by
mononuclear cells
- Most are involved in directing cells to divide and
differentiate
C. COLONY STIMULATING FACTORS (CSFs)
- Direct division and differentiation of bone marrow
stem cells
- The balance of the different CSFs partly determines
the proportion of different cell types which will be
produced
D. TUMOR NECROSIS FACTOR (TNF ALPHA and TNF
BETA) and TRANSFORMING GROWTH FACTOR (TGF
BETA)
- Important in mediating inflammation and cytotoxic
reactions
E. ANTIBODIES
- Serum molecules produced by plasma cells
- Soluble form of B cell antigen receptor
PARTS:

1. Fab part of the antibody where the


antigen can be bound
2. Fc part that interacts with the cells of
the immune system
N.B. Phagocytes can recognize antigens using either an activated (C3b) or
antibody that act as opsonins, but phagocytosis is more effective if both are
present.
Antigen
any molecule which can be specifically recognized by adaptive
elements
PARTS OF AN ANTIGEN:
1. EPITOPE Part of the antigen where the antibody binds
to.
CLONAL SELECTION
- Each lymphocyte is capable of recognizing only one particular antigen
- A specific antigen selects for the specific clones of its own antigenbinding cells
IMMUNE EFFECTOR MECHANISMS
A. Antibody Binding
- Antibodies bind to the outer membrane of some
rhinoviruses (those that cause common colds) can
prevent viral paricles from binding to host cells
B. Activation of Complement by Antibody
- Antibodies in circulation can activate the classical
complement pathway in order to cause lysis to
foreign antigens
C. Antibodies act as Opsonins
- Opsonins are antibodies/ complement that can coat a
pathogen and make phagocytosis more effective
D. Phagocytosis
- Phagocytic cells proceed to engulf antigen-carrying
microbe by extending their pseudopodia around it.
the microbe is then internalized in a phagosome and
reactive oxygen intermediates (ROIs) produced by
monocytes are toxic to bacteria, or neutrophils can
secrete transferrin which chelates iron and prevents
bacteria from acquiring this vital nutrient, or finally
granules from lysosomes can fuse with the
phagosome, pouring digestive enzymes into the
phagolysosome, digesting its contents.
E. Cytotoxic Reactions

Directed against whole cells which are too large for


phagocytosis
Attacking cells direct their granules towards the
target cell, in contrast to phagocytosis where it is
directed against the phagosome.
T cells contain molecules called perforins which can
punch holes in the outer membrane of the target
Some cytotoxic cells can signal to the target to selfdestruct by fragmentation of DNA or otherwise
known as Apoptosis.

INFLAMMATION
- Manifestation of infection, wherein the body concentrates immune
products toward the site of infection.
MAJOR EVENTS THAT OCCUR DURING INFLAMMATION;
1. Increased blood supply to site of infection
2. Increased capillary permeability due to the retraction of
endothelial cells. This permits larger molecules to escape
from capillaries and allows soluble mediators to reach the
site of infection
3. Leukocytes migrate out of the capillaries into surrounding
tissues (diapedesis).
DEFENSES AGAINST EXTRACELLULAR AND INTRACELLULAR
PATHOGENS
- In dealing with extracellular pathogens, the immune system aims to
destroy the pathogen itself, or neutralize its products.
- In intracellular pathogens, there are two options. Either the T cells can
destroy the infected cell (cytotoxicity) or they can activate the cell to
deal with the pathogen itself.
VACCINATION
- PRINCIPLE: based on the two key elements of adaptive immunity,
namely specificity and memory.
- The aim in vaccine development is to alter a pathogen or its toxins in
such a way that they become innocuous without losing their
antigenicity.
IMMUNOPATHOLOGY
- The immune system itself is the cause of disease or other undesirable
consequences.
3 WAYS OF IMMUNOPATHOLOGY
1. Mistaken recognition of self antigens/
AUTOIMMUNITY
- The body reacts to not only foreign pathogens but also to
host cells

2. An ineffective immune response/


IMMUNODEFICIENCY
- Defective immune elements, unable to fight infection
3. An overactive immune response/ HYPERSENSITIVITY
- The immune response causes more damage than the
pathogen itself.