Lymphatics & Immunity

Lymphoid Tissue

• Organs and tissues are referred to as ‘lymphoid’

because they deal with lymphocytes.

• It is in the lymphoid tissue that many of the

regulatory processes of the immune system take
place.

• Lymphoid tissue is found at key points within the

body where it is best able to encounter invaders,
and so initiates the immune response.
 Lymphoid Organs

• Spleen
 The largest lymphoid organ
 Is a site for lymphocyte proliferation
 Cleanses the blood by removing antigens, aged and
defective erythrocytes and platelets
 Stores platelets
 Salvages iron from aged or damaged RBC for later
re-use
 Produces erythrocytes in the foetus
 Lymphoid Organs
• Thymus
 Secretes hormones (thymopoietin and thymosin) to mature
T cells
 Does not fight antigens
 Starts shrinking at puberty and becomes practically non-existent in old
age
• Tonsils
 Gather and remove antigens that enter the pharynx from food or
inhaled air.
• Peyer’s patches
 On the wall of the small intestine, in the appendix, and some in the
large intestine
• Others
 MALT (mucosa-associated lymphatic tissue) in genitourinary and
respiratory organs which protects passages open to the exterior world.
 The
lymphatic
system
The lymph nodes
are also of
particular
importance.
They filter the
lymph to remove
antigens with
macrophages or
lymphocytes.
A lymph node
 Cell Revision Stem cells
simplified
Erythrocytes
Leukocytes Platelets

Other
Lymphocytes
leukocytes

T cells B cells Granulocytes Monocytes

T helper cells Plasma cells Neutrophils

Macrophages

Immunoglobulins
T cytotoxic cells Eosinophils
(Igs)

Basophils
 Principles of Immunity

• The immune system defends the body against

invasion by foreign substances often referred to
as antigens or pathogens.
• There are 2 types of immune responses
 Non-specific immunity
• Non-specific defenses respond immediately to protect the
body from all foreign substances, whatever they are.
 Specific immunity
• Specific defenses need to first ‘meet’ or be primed by an
initial exposure to a foreign substance (antigen) before it
can protect the body against it.
 Non-specific immunity

• Has two lines of defense a.k.a.

“innate defenses”
 1st line of defense
• The skin and the mucous membranes
 2nd line of defense
• Phagocytes
 A cell that “eats” an invading foreign substance
by engulfing it and destroying it with enzymes
 E.g. Macrophages, Kupffer cells in liver,
Microglia in brain, Neutrophils, Eosinophils
 Non-specific immunity

 2nd line of defense (cont’d)

• Natural killer cells
 A group of lymphocytes that are non-specific.
 Destroy cancer and virus infected cells directly
or by “ordering” the cell itself to undergo
apoptosis (cell suicide).
• Inflammation
 Is an immune response that removes the injurious
effects of harmful substances. It also promotes the
healing process of tissues.
 Non-specific immunity

 2nd line of defense (cont’d)

• Antimicrobial proteins
 Interferons
• A protein secreted by a virus-infected cell
to protect non-infected cells.
 Complement
• A.k.a. complement system.
• A group of proteins floating in blood that
enhances immunity (non-specific and
specific).
 Non-specific immunity

 2nd line of defense (cont’d)

• Fever
 A high temperature that is set off by pyrogens
(chemicals released by leukocytes when they
encounter foreign substances).
 Destroys micro-organisms that replicate better
at 35ºC.
 Specific immunity

 Can be considered as the 3rd line of defense

a.k.a. “Adaptive defenses”.
 Takes longer to start than non-specific
immunity.
 Needs to be “primed” (stimulated by another
cell or a foreign substance).
 Has the following characteristics
• Specificity
• Systemic
• Memory
 Specific immunity

 Specificity
• Aims its action at precise pathogens.
 Systemic
• Occurs over the whole body, not just the
site of infection.
 Memory
• Can remember the pathogens it has
encountered to mount a faster attack on
subsequent invasions.
 Specific immunity

 Divided into
• Humoral immunity
 Humoral: as in humors (body fluids)
 Immune response from antibodies. They tag bacteria,
bacterial toxins, free viruses so other leukocytes can
destroy them (e.g. phagocytes or complements).
• Cell-mediated immunity
 Immune response from lymphocytes (i.e. cells)
 They destroy cells infected with bacteria, virus,
parasites, cancer, or from a graft (i.e. non-self cells).
• The destruction is direct or indirect (tagging of the
invaded cells so that other leukocytes can destroy
them)
 Antigens

 A foreign substance that causes

an immune response.
 Examples of antigens
 Proteins, bacteria, fungi, pollen grains,
etc.
 Drugs (e.g. penicillin), chemicals
(poison ivy, animal dander, detergents,
cosmetics, metals, etc.).
 Self and non-self

How does the body recognise what an antigen is and

what self is?
 All cells in the body have MHC (major
histocompatibility complex) proteins located on their
surface.
 These proteins are highly specific for each individual
(i.e. foreign substances and other people have
different proteins).
 The proteins act like tags to indicate they are “self”
(belonging to the body).
 When the immune cells come in contact with
proteins they do not recognise, they mount an
immune attack against that foreign substance.
 This implies that all cells are constantly checked to
work out which is self and which is not.
Cells of the adaptive system

 Lymphocytes
• B cells
• T cells

 Antigen-presenting cells
 Lymphocytes

 Originate in bone marrow.

 Mature i.e. become immunocompetent
in:
• Bone marrow for B cells
• Thymus for T cells
 They mature as Helper T-cells, Cytotoxic T-
cells, or other types (Regulator T-cells,
Gamma
 Only immunocompetent lymphocytes
are able to bind foreign substances.
 Antigen-presenting cells

 A.k.a. APCs
 Engulf antigens and present part of it to
T-cells who will start mounting a cell-
mediated response or stimulate a
humoral response (by triggering the B-
cells)
 The APCs mostly are:
• Dendritic cells (a.k.a. Langerhan’s) in
connective tissue and skin
• Macrophages
• B-cells
 Humoral Immune Response
 The production of antibodies in response to an
encounter between an antigen and an
immunocompetent B-cell
• Remember: this response is efficient for “free” antigens
 Steps involved:
1. B-cell becomes activated when it binds an antigen or when a
Helper T-cell activates it (this is more common and more
efficient)
2. Synthesis of clones of the B-cell
3. Clones become:
• Memory cells
• Or plasma cells (most clones become plasma cells)
4. Plasma cells secrete antibodies specific to the antigen
5. Antibodies roam around the body and attach themselves to the
antigen marking them for destruction.
6. Other leukocytes destroy the antigen-antibody complexes.
 Note: antibodies DO NOT destroy antigens; they only mark them
for destruction (see further notes on antibodies).
 Humoral Immune Response

 On first exposure, it takes 3-6 days to

release the first antibodies and up to 10 days
for levels to peak.
• This explains why people feel sick for so many
days if they have never come across that antigen
before.

 On subsequent exposures, people may have

little or no symptoms because they have
memory cells. When these cells come in
contact with the same antigen, the synthesis
of antibodies is much faster. The response
will differ from one individual to another.
Active and Passive immunity

 Active
• When a person synthesises her/his own
antibodies because she/he has been
exposed to an antigen.
 This can be “naturally” i.e. by getting a cold,
flu, a disease, playing with dirt, etc.
 It can also be via immunisation (vaccines).
When you get a vaccine, you are given an
antigen (in a different form than the original
type). This stimulate your immune system to
form antibodies.
• The antibodies you make yourself may
last a lifetime.
Active and Passive immunity

 Passive
• When a person receives antibodies from
another person. Here the person does not
make her/his own antibodies.
 E.g. Foetuses and breastfed babies obtain
antibodies from their mothers.
 E.g. People who receive immunoglobulin
(antibody) injections. Very useful for people
who are immunodeficient or for antigens that
are very fast at destroying tissue (e.g. snake
venom)
 Passive immunity only lasts 2-3 weeks. It
does, however, provide a time frame that
allows a person to produce their own
antibodies.
 Antibodies

 A.k.a. immunoglobulins or Igs

 Are proteins
 Are classified in 5 different
categories:
• IgM, IgG, IgA, IgD, IgE
• They have different functions and
may be found in different locations.
 E.g. IgE is involved in allergies
 Antibodies

 What happens when antibodies bind

antigens?
• They become antibody-antigen complexes
and one of the following events occur
 P - Precipitate the antigens (make them less
soluble) and phagocytes can destroy them
more easily
 L - Lysis. Attract complements that lyse (break
down) the complexes
 A - Agglutinate. Form clumps so that
phagocytes can get to them more easily.
 N - Neutralise the dangerous sites on antigens
that often release toxins to the body until
phagocytes get to them.
Cell-mediated immune response

 Target infected cells or antigens that are

presented by APCs
• Remember: when antigens are attached to cells or
hiding in cells, the humoral response does not
work. Likewise, the cell-mediated immune
response does not recognise “free” antigens.
 Steps involved:
1. APCs or infected cells present the antigen
(or part of it) on their cell surface

2. The immunocompetent T-cell (can be a

helper T-cell or a cytotoxic T-cell) binds to
the antigen.
Cell-mediated immune response

 Steps involved (cont’d):

3. Release of cytokines (chemicals) from the
APC or infected cell as well as the T-cell
itself
This promotes the proliferation (cloning) of
the T-cell
• A helper T-cell will clone into many other helper
T-cells as well as memory helper T-cells
• A cytotoxic T-cell will clone into many other
cytotoxic T-cells as well as memory cytotoxic T-
cells.
Cell-mediated immune response

 Steps involved (cont’d):

4. The cytokines released by the T-cells also
attract other cells that will help destroy the
antigens.
• The cytokines from Helper T-cells
• Attract immune cells, e.g. macrophages,
cytotoxic T-cells, eosinophils, etc. which
destroy the infected-cells
• Activate B-cells to make antibodies against
that particular antigen
• The cytotoxic T-cells directly destroy the infected
cells
• The cytokines from the cytotoxic T-cells also
enhance the destruction process by attracting
other immune cells
Cell-mediated immune response

 Note: the role of Helper T-cells is very

important to the immune response.

 Without Helper T-cells, there is NO adaptive

response. This is because they are either
directly involved or promote the activation of
other cells.

 The disease AIDS is the destruction of the

helper T-cells.
 Other T-cells

 There are other types of T-cells. These

are:

• Regulatory T-cells (a.k.a. suppressor T-

cells)
 Their function is to suppress the immune
response (useful to prevent rejection of
transplanted organs)

• Gamma delta T cells

 Mostly found in the intestine and destroy
stressed or damaged cells there. I.e. act like
natural killer cells.
 SUMMARY

What actually occurs when we encounter

pathogens?
• 1st line of defense
 Initially, pathogens are attacked by non-
specific mechanisms at body surfaces

• 2nd line of defense

 Phagocytes, NK cells, inflammation,
interferons, complements, and fever
 SUMMARY (cont’d)
• 3rd line of defense
 Specific immunity
• T cells are presented with the foreign substance.
 This increases the production of Helper T-cells and Cytotoxic T-cells,
as well as memory cells
 Helper T-cells enhance the effect of many cells, such as cytotoxic T-
cells and B-cells
 Cytotoxic T-cells kill the infected cells directly
 B-cells clone and produce Igs and memory cells
• Antibodies roam the blood and mark the antigens for destruction
• B-cells can bind “free” antigens and release antibodies (Igs) which
mark the antigens for destruction
• The antigens/foreign substances are destroyed by
immune cells
• All of this is under the control of many chemicals called
cytokines which are released by cells and foreign
substances. Every cytokine has a different role.
 Immune system malfunction

• Because of the complexity of the

immune system, many things can go
wrong.
• The body’s defenses may be
exaggerated, misdirected, or either
absent or depressed, resulting in a
hypersensitivity disorder, autoimmune
disorder, or an immune deficiency
disorder.
 Hypersensitivity disorders

An exaggerated or
inappropriate immune
response, which may lead to
various hypersensitivity
disorders e.g. allergies,
anaphylactic shock,
transfusions reactions,
and contact dermatitis.
Allergies
 Auto-immune disorders

• Autoimmune disorders are

characterised by an abnormal
response to the body’s own tissue, i.e.
attacking “self”.
 The body loses its ability to distinguish self
from non-self.
 Examples are rheumatoid arthritis,
systemic lupus erythematosus (SLE or
lupus), psoriasis, and type I diabetes.
Rheumatoid Arthritis (RA)
 Immunodeficiencies

• Immunodeficiencies include both congenital

and acquired conditions in which the
production or function of immune cells or
chemicals is abnormally inadequate for the
task.
 The most well known of the acquired
immunodeficiences is AIDS (Acquired
Immunodeficiency Syndrome) which cripples the
immune system by interfering with the activity of
helper T cells.
 The most severe congenital condition is SCID
(Severe Combined Immunodefiency Disease) in
which there is a severe lack of both B cells and T
cells.
 Key Study Points

• Discuss the 3 phases of immune response

• Outline the differences between innate and
adaptive defenses
• Describe the processes of humoral and cell-
mediated immunity
• Explain the role of each immune cells (I.e.
macrophages, interferons, complement, B-
cells, T-cells, etc.)
• Define cytokines