2. Introduction
⢠These are mechanisms that prevent the entrance of
pathogens or destroy them if they enter the tissues
⢠It comprise both the innate and adaptive immune
responses.
⢠Innate Immunity is the first line of defense against
infections.
⢠Acquired immunity occurs after the exposure with an
antigen and is mediated by either antibody or lymphoid
cells
3.
4. Defence strategies
INNATE
⢠Present at birth
⢠Response is antigen-
independent
⢠Limited diversity
⢠Nonspecific defense
⢠No memory
⢠Examples: skin, cough,
⢠gastric pH, fever,
⢠Inflammation,
(phagocytic cells)
⢠There is immediate
maximal response
ACQUIRED/ADAPTIVE
⢠Appears after contact
with antigen
⢠Response is antigen-
dependent
⢠Vast diversity
⢠Specific defense
⢠Memory responses
⢠Examples: Antibody,
⢠cytotoxic lymphocytes,
Helper T Cells.
⢠There is a lag time
between exposure and
maximal response
5. ďThe major functions of the vertebrate innate
immune system include:
⢠Recruiting immune cells to sites of infection,
through the production of chemical factors,
including specialized chemical mediators, called
cytokines.
⢠Activation of the complement cascade to identify
bacteria, activate cells and to promote clearance of
dead cells or antibody complexes.
6. ⢠The identification and removal of foreign
substances present in organs, tissues, the blood
and lymph, by specialized white blood cells.
⢠Activation of the adaptive immune system
through a process known as antigen
presentation.
7. MECHANISMS OF INNATE IMMUNITY
⢠THE SKIN
⢠The skin employs both mechanical and
chemical factors to prevent invasion by
microbes.
⢠1) Mechanical factors
â Tightly packed in tack skin, multilayered,
reinforced with keratin, periodic shedding
â Mucus membrane with mucus that traps particles,
nasal hairs and tracheal cilia, coughing, sneezing
â Lachrymal apparatus that washes the eye
â Saliva washes microbes from teeth
â Cleansing action of urine.
8. ⢠2) chemical factors
â Sebaceous glands produce unsaturated fatty acids
that inhibit the growth of certain microbes
â The low pH (lactic and fatty acids) discourage the
growth of some microbes
â Sudoriferous (sweat) glands produce lysozymes
that lyse bacteria cell wall (also in tears, saliva,
and nasal secretions)
â Hyaluronic acid in loose connective tissue localize
infection
â Gastric juice (pH 1.2 â 3.0) kill bacteria and toxins
10. Cells of the innate immunity
Neutrophils (PMNs):
⢠Polymorphonuclear cells (PMNs) are recruited
to the site of infection by chemotasis where
they phagocytose invading organisms and kill
them intracellularly.
11. ⢠Dendritic cells (DC) are phagocytic cells present
in tissues that are in contact with the external
environment, mainly the skin and the inner
mucosal lining of the nose, lungs, stomach and
intestines.
⢠They are named for their resemblance to
neuronal dendrites, but dendritic cells are not
connected to the nervous system. Dendritic cells
are very important in the process of antigen
presentation, and serve as a link between the
innate and adaptive immune systems.
12. Macrophages
ď Macrophages and newly recruited
monocytes, function in phagocytosis and
intracellular killing of microorganisms.
ďIn addition, macrophages are capable of
extracellular killing of infected or altered self
target cells.
ďFurthermore, macrophages contribute to
tissue repair and act as antigen-presenting
cells, which are required for the induction of
specific immune responses
13.
14. Other immune cells
⢠Basophils and mast cells mediate
inflammatory response by secreting
histamine, leucotriens and platelet activating
factor.
⢠Eosinophils: their main function is anti
parasitic, though they also participate in
allergic reactions.
â They produce Major Basic Proteins (MBP) and
Eosinophil Cationic Protein (ECP) that cause
disruption and defragmentation of parasite
membranes respectively (Kumar & Clark, 2002)
15. Nk & Lymphokine Activated Killer cells
ďNK and LAK cells can nonspecifically kill virus
infected and tumor cells and produce macrophage
activating factor INF-Îł.
ďAbility of the NK cells to protect against infections
is enhanced by cytokine secreted by macrophages
that have encountered microbes.
ďNk cells also express receptors for the portion of
some IgG Abs and used these receptors to bind to
cells coated with Antibodies..
16. Amtimicrobial substances
⢠Interferon (IF- ι ,β ,γ) are produced by viral-
infected cells and other wbcs. They diffuse to
neighboring cells and induce them to produce
antiviral proteins to prevent replication of viruses
⢠Complement are a group of 20 proteins in serum.
ďź Some complement initiate the Membrane Attack Complex
(MAC) that causes cytolysis.
ďź some complement cause the release of histamine
ďź Others act as opsonins
17. inflammation
⢠Tissue injury especially that following the establishment
and multiplication of microbes elicit an inflammatory
response.
⢠This is done by dilation of blood vessels by cytokines
and IL-1.
⢠Adhesion molecules such as selectins cause leukocyte
to attach to vascular endothelial cells and migrate to the
site of injury
⢠Leukocyte engulf the microbe and intracellular
digestion occurs leading to an increased pH thus
causing protease to lyse the leukocytes.
⢠Macrophages arrive at the site and engulf leukocytic
debris as well as the microbes.
18. fever
⢠Due to the presence of foreign substances or their products,
⢠IL-1(interleukin 1) is secreted by macrophages which induces
the production of prostaglandin E.
⢠Prostagladin-E (PG-E) resets the thermostat of the
hypothalamus to a higher temperature ( above 370 C)
⢠Metabolic rate increases, and there is muscles spasms. Body
temperature increases.
⢠When the stress is removed, the temperature is reset to 370 C,
sweating and temperature loss mechanism sets in.
19. Adaptive immunity
⢠Adaptive immunity occurs in response to
antigen exposure. It is specific, and it shows
memory.
⢠Passive immunity is transmitted by antibodies
or lymphocytes preformed in another host.
⢠Active immunity is induced after contact with
foreign antigens e.g immunization with live or
killed infectious agents or their antigens .
20. ⢠Adaptive response can be antibody-mediated
(humoral) or cell-mediated or both.
⢠After interaction of a pathogen with the innate
immunity its major antigen are taken up by
Antigen Processing Cells (APC) e.g macrophages
and dentritic cells.
⢠These antigens appear on the surface of
macrophages complexed with proteins encoded
by the major histocompatibility complex (MHC)
and represented to clones of T cells.
21. What is the MHC
⢠The Major Histocompatibility Complex OR Human Leucocyte
Antigen (MHC, or HLA) is a type of protein expressed on the surface
of host cells that interacts with T-cell receptors (TCRs ie CD8 and
CD4 cells) of T cells.
⢠Virtually all the body's cells, including APCs, express class I (MHC-I)
on their surface. Only APCs express class II (MHC-II) i.e have both
MHC-I and MHC-II.
⢠When antigen enters a body cell and is broken down, the products of
this breakdown are sent to the surface of the cell coupled with MHC-I.
This forms the MHC-I/Ag complex, and usually occurs when a virus
or bacterium enter a cell and are broken down by intracellular
defenses.
22. Contâ
⢠This can also occur in APCs, but APCs
additionally process the antigen that they
phagocytose, presenting it as an MHC-II/Ag
complex on the surface of their cells.
⢠After this presentation the two arms of
immune response : cell-mediated and antibody
âmediated develop concurrently.
23. Cell-mediated immunity
⢠T cells can be subdivided into two broad types: T
helper cells and T cytotoxic cells.
⢠T helper cells express a T-Cell Receptor that will
interact with APC surfaces. Specifically, they
interact with the MHC-II/Ag complex on the surface
of APCs, and the TCR is stabilized in its binding by
a CD4 receptor.
⢠Upon binding, T helper cells release cytokines,
which act as chemotactic agents to call for more T
helper cells, T cytotoxic cells, APCs, and B cells.
24. ⢠T cytotoxic cells contain CD8 receptors encounter
body cells that have been invaded and are presenting
MHC-I/Ag on their surface
⢠Upon binding, the CD8+ cells differentiate, much
like naive B cells, into memory T cells and cytotoxic
T lymphocytes (CTLs), effector cells that cause the
MHC-I/Ag-presenting cell (the "altered self cell") to
die (apoptosis)
⢠CTLs trigger apoptosis by secreting a perforin that
allows the entry of a serine protease (Granzyme B)
which activates intracellular executioner caspases
25. ⢠*T cells can interact with antigen only after it has been
processed, either by a normal body cell (MHC-I) or by
an APC (MHC-II).
ďDifference between the two types of T cells:
⢠T helper cells react to exogenous antigen, phagocytosed
by APCs, presented on MHC-II, via binding with TCR
and CD4.
⢠T cytotoxic cells react to endogenous antigen (such as
viral or cancer proteins), broken down by lysosomes in
many types of body cells, presented on MHC-I, via
binding with TCR and CD8.
27. ⢠The major pathway of the adaptive immune response
28. a) Antibody-mediated arm
⢠B cells can bind both to antigen when it is free and
unprocessed or can be stimulated by cytokines
produced by CD4+ T cells when they recognise
antigens complexed with class II MHC proteins.
⢠B cells made in the bone marrow with their specific
membrane bound Immunoglobulin (Ig) (antibody)
already specified. The Ig itself is made up of two
medial heavy chains (both identical) with two lateral
light chains (also identical) attached to the "top" of
the heavy chains, which form a Y shape.
29.
30. ⢠Before they encounter antigen, B cells are
known as "naive." Once they encounter
antigen, the naive B cells will undergo clonal
expansion; an activated B cell will form some
daughter memory B cells and some plasma
cells.
⢠The memory cells will lie in wait for a second
encounter with the antigen, while the plasma
cells will begin a massive secretion of antibody
⢠**B cells can bind to antigen when it is free
and unprocessed in the body, much like APCs
can.
31. Contâ
⢠Also the helper CD4+ T cells recognise pathogen
antibodies complexed with class II MHC proteins on
the surface of APC and produce cytokines that activate
B cells expressing antibodies
⢠Major host defence functions of antibodies include
neutralisation of toxins and viruses and opsonization of
pathogen which aids in uptake by phagocytic cells.
⢠Antibody mediated defence is important against
pathogens that produce toxins(e.g Clostridium tetani) or
polysacharrides capsules that interfer with
phagocytosis(e.g the pneumococci)
⢠It applies mainly to extracellular pathogens