UNDERSTANDING IMMUNITY

Learning Objectives:
Upon completing the lecture the students should be able to:
a) Understand the physiology of the immune system.
b) Describe and differentiate various types of immunity.
c) Explain the phases of immune response and its pathogenesis.
d) Discuss the common clinical symptoms as well as prophylaxis and
therapy involved with each type of reaction.
e) Appreciate the significance of the immune system in combating
diseases.
Introduction
- Constellation of responses to attacks from outside the body; some of
the processes involved are:
- Antigen substance that elicits an immune response

- Immune system has a series of dual natures, the most important of

which is self/non-self recognition. The others are: general/specific,
natural/adaptive, innate/acquired, cell-mediated/humoral,
active/passive, primary/secondary.
- Parts of the immune system are antigen-specific, systemic (not
confined to the initial site, but work throughout the body), and have
memory (recognize and mount an even stronger attack to the same
antigen the next time)
- Sometimes the process breaks down and the immune system attacks

self-cells – in the case of autoimmune diseases

- There are cases where the immune response to innocuous substance
is inappropriate – in the case of allergies – and the simple substance
that elicits the response is called an allergen.
 All blood cells are manufactured by stem cells, which live mainly
in the bone marrow – process hematopoiesis. The stem cells
produce hemocytoblasts that differentiate into the precursors for all
the different types of blood cells. Hemocytoblasts mature into three
types of blood cells: erythrocytes (RBC), leukocytes (WBC), and
thrombocytes (platelets).
Leukocytes are subdivided into:
1. Granulocytes (containing large granules in the cytoplasm); consist
of:
a) neutrophils (55-70%)
b) eosinophils (1-3%)
c) basophils (0.5-1.0%)
2. Agranulocytes (without granules) – circulate in the blood and lymph
systems, and make their home in the lymphoid organs
a) lymphocytes
b) monocytes
The Lymph System
- Lymph is an alkaline (ph > 7.0) fluid that is clear, transparent and
colorless;
- It flows in the lymphatic vessels and bathes tissues and organs in its
protective covering
- No RBCs in lymph and it has lower protein content than blood, it is
slightly heavier than water.
- Lymph flows from the interstitial fluid through lymphatic vessels up
to either the thoracic duct or right lymph duct, which terminate in
the subclavian veins, where lymph is mixed into the blood.
- Lymph carries lipids and lipid-soluble vitamins absorbed from the GI
tract. Since there is no active pump in the lymph system, there is no
back-pressure produced. The lymphatic vessels, like veins, have one-
way valves that prevent backflow. Along these vessels, there are
small bean-shaped lymph nodes that serves as filters of the
lymphatic fluid. It is in the lymph nodes where antigen is usually
presented to the immune system.
The human lymphoid system has the following:
1. Primary organs: bone marrow (in the hollow center of the bones)
and the thymus gland (located behind the breastbone above the
heart), and
2. Secondary organs at or near possible portals of entry for pathogens:
adenoids, tonsils, spleen (located at the upper left of the abdomen),
lymph nodes (along the lymphatic vessels with concentrations in the
neck, armpits, abdomen, and groin), Peyer’s patches (within the
intestine), and the appendix
TYPES OF IMMUNITY
1. Adaptive Immunity
a) Natural
a.1 Passive (maternal)
a.2 Active (Infection)
b) Artificial
b.1 Passive (antibody transfer)
b.2 Active (Immunization
2. Innate Immunity
TYPE 1: INNATE IMMUNITY
- Is what we are born with; nonspecific; all antigens are attacked pretty
much equally; genetically based and we pass it on to our offspring

Surface Barriers or Mucosal Immunity

1. Skin – cannot be penetrated by most organisms unless it has an
opening
2. Pathogens are expelled from the lungs by ciliary action as the tiny
hairs move in an upward motion; coughing and sneezing abruptly
eject both living and nonliving things from the respiratory system;
flushing action of tears, saliva and urine also force out pathogens, as
does the sloughing off of skin.
3. Sticky mucus in respiratory and gastrointestinal tracts traps many
microorganisms.
4. Acid ph (< 7.0) of skin secretions inhibits bacterial growth. Hair
follicles secrete sebum that contains lactic acid and fatty acids both
of which inhibit the growth of some pathogenic bacteria and fungi.
5. Saliva, tears, nasal secretions, and perspiration contain lysozyme, an
enzyme that destroys gram positive bacterial cell walls causing cell
lysis. Vaginal secretions are also slightly acidic (after the onset of
menses). Spermine and zinc in semen destroy some pathogens.
Lactoperoxidase is a powerful enzyme found in mother’s milk.
6. The mucosa in the stomach secretes hydrochloric acid and protein-
digesting enzymes that kill may pathogens.
Normal florae produce bacteriocidins, defensins, cationic proteins, and
lactoferrin which work to destroy other bacteria that compete for
their niche in the body

- Each of the cells in the innate immune system binds to antigen using
pattern-recognition receptors. These hundred of receptors are
encoded in the germ line of each person. This immunity is passed
from generation to generation. They recognize patterns of bacterial
lipopolysaccharide, peptidoglycan, bacterial DNA, dsRNA, and other
substances. They are set to target both gram (+) and gram (-) bacteria.
TYPE 2: ADAPTIVE OR ACQUIRED IMMUNITY
Parts of the immune system are changeable and can adapt to
better attack the invading antigen.

a) Cell-mediated immunity – produces immune responses in which

antibodies are not involved in the elimination of antigens

Macrophages engulf antigens, process them internally then

display parts of them on their surface together with some of their
own proteins. This sensitizes the T cells to recognize these antigens. T
cells are primed in the thymus, where they undergo two selection
processes. The first positive selection process weeds out only those T
cells with the correct set of receptors that can recognize the MHC
molecules responsible for self-recognition. Then a negative selection
process begins whereby T cells that can recognize MHC molecules
complexed with foreign peptides are allowed to pass out of the
thymus.
b) Humoral Immunity
Involves the primary and memory responses that produce
antibodies. Antibodies, also called Immunoglobulins or Igs,
constitute, the gamma globulin part of the blood proteins. They are
soluble proteins secreted by the plasma offspring (clones) of primed
B cells. The antibodies inactivate antigens by:

b1) complement fixation proteins attach to antigen surface and

cause holes to form, i.e., cell lysis
b2) neutralization – binding to specific sites to prevent attachment –
this is the same as taking their parking space
b3) agglutination – clumping
b4) precipitation – forcing insolubility and setting out of solution
C. PHASES OF IMMUNE RESPONSE
PRIMARY IMMUNE RESPONSE
The response that occurs after a harmful antigen has been
encountered for the first time is a primary immune response. When
an antigen enters the body the body has no antibodies that can be
specific enough to fight the antigen. Usually this kind of lag phase
occurs for a minimum of 10 days to 4 weeks. IgM is produced first,
followed by IgG, Memory and TH cells are also produced. Memory B
cells can also be activated to produce the other classes of antibody in
subsequent immune responses.
Immunology – study that deals with physiological responses, in which
the body (host) recognizes itself from nonself (foreign substances)
Antigen – chemical substances that bind to and react with the antibody
Antibodies – proteins and immunoglobulins secreted in the
bloodstream by B-cells/lymphocytes; neutralize bacterial toxin
Plasma cells – produce antibodies
Agglutination – cross-linkage of antigens by antibodies
SECONDARY IMMUNE RESPONSE (MEMORY IMMUNE RESPONSE)

- second or subsequent encounter with the same antigen produces

responses by memory B cells and memory TH2 cells
D. CELLS AND TISSUES OF THE IMMUNE SYSTEM

- Phagocyte – cell that attracts (by chemotaxis), adheres to, engulfs,

and ingests foreign bodies
- Promonocytes made in the bone marrow, when released into the
blood called circulating monocytes, matures into macrophages (“big
eaters”)
- Once macrophage phagocytizes a cell, it places some of its proteins
(epitopes), on its surface - these surface markers serve as an alarm
to other immune cells that then infer the form of the invader – all
cells that do this are called antigen presenting cells (APCs)
- Non-fixed or wandering macrophages roam the blood vessels and can
even leave them to go to the infection site where they destroy dead
tissue and pathogens
-
- Natural killer cells move in the blood and lymph to lyse cancer cells
and virus-infected body cells
- Polymorphonuclear neutrophils, (called polys) – phagocytes with no
mitochondria and get their energy from stored glycogen; nondividing,
short-lived (half-life of 6-8 hours, 1-4 day lifespan); segmented
nucleus

Major types of Lymphocytes:

- Peripheral blood contains 20—50% of circulating lymphocytes. The
rest move in the lymph system.
1. B cells – produced in the stem cells of the bone marrow; they
produce antibody and oversee humoral immunity
2. T cells nonantibody-producing lymphocytes produced in the bone
marrow but sensitized in the thymus and constitute the basis of cell-
mediated immunity.
a) Cytotoxic or killer T cells (CD8+) – do their work by releasing
lymphotoxins, which cause cell lysis
b) Helper T cells (CD4+) – serve as managers, directing the immune
response. They secrete chemicals called lymphokines that stimulate
cytotoxic T cells and B cells to grow and divide, attract neutrophils,
and enhance the ability of macrophages to engulf and destroy
microbes
c) Suppressor T cells inhibit the production of cytotoxic T cells once
they are unneeded, lest they cause more damage than necessary
d) Memory T cells are programmed to recognize and respond to a
pathogen once it has invaded and been repelled
Neutrophils, macrophages, eosinophils, basophils, platelets and mast
cells – assist in eliminating antigens from the body. Their functions
may be phagocytic, proinflammatory, cytotoxic, regulatory or a
combination of these
FIVE CLASSES OF IMMUNOGLOBULINS

1. IgM – pentamer; biggest Ig (macroglobulin); 1 st in

response to initial exposure to an antigen; predominant Ab
involves in ABO blood group; effective in agglutinating
microorganism
2. IgA – dimer; secretary Ab; most common form in mucous
membranes (body secretions); found in tears, saliva, mucus, milk,
small intestine, sweat
3. IgD – monomer; unknown function; found in blood, lymph and on
the surface of B cells
4. IgG – monomer; most predominant; only immunoglobulin can cross
placenta; protect newborn; enhances phagocytosis (removes
unwanted substances); neutralizes toxin
5. IgE – monomer; allergic antibodies; present during hypersensitivity
reactions; binds to mast cells and basophils

Monoclonal antibodies – an antibody with unique amino acid

sequences derived from a single cell or cell line; overcome unwanted
effects of the immune system
Immunity – ability of the immune system to recognize and defend the
host against harmful substances and microbes
Herd Immunity – is the presence of immunity to a disease in most of
the population; principle states that a sufficient number of persons
immune to a disease reduces circulation of the organism

TYPES OF ACQUIRED IMMUNITY

1. Naturally Acquired Immunity
a) Naturally Acquired Active Immunity – obtained when person is
exposed to antigens in the course of daily life, e.g. measles &
chickenpox (Acquired from previous infection)
b) Naturally Acquired Passive Immunity – transfer of antibodies from
a mother to her unborn child, a mechanism known as “transplacental
transfer” (Mother to child)
2. Artificially Acquired Immunity
a) Artificially Acquired Active Immunity – results from vaccination,
or also called as immunization (Acquired from Toxin, Toxoids,
Administration of Antigen)
b) Artificially Acquired Passive Immunity – involves the introduction
of antibodies (rather than antigen) into the body (Acquired from
gamma globulin, immune serum, antitoxins)