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THE IMMUNE SYSTEM

Neutrophils

• 60% of WBCs
• ‘Patrol tissues’ as they squeeze out of the
capillaries.
• Large numbers are released during infections
• Short lived – die after digesting bacteria
• Dead neutrophils make up a large proportion
of puss.
Macrophages
• Larger than neutrophils.
• Found in the organs, not the blood.
• Made in bone marrow as monocytes, called
macrophages once they reach organs.
• Long lived
• Initiate immune responses as they display
antigens from the pathogens to the
lymphocytes.
Macrophages
Phagocytosis
Phagocytosis
• If cells are under attack they release histamine.
• Histamine plus chemicals from pathogens mean
neutrophils are attracted to the site of attack.
• Pathogens are attached to antibodies and
neutrophils have antibody receptors.
• Enodcytosis of neutrophil membrane  phagocytic
vacuole.
• Lysosomes attach to phagocytic vacuole  pathogen
digested by proteases
Lymphocytes
• Produce antibodies
• B-cells mature in bone marrow then
concentrate in lymph nodes and spleen
• T-cells mature in thymus
• B and T cells mature then circulate in the
blood and lymph
• Circulation ensures they come into contact
with pathogens and each other
B -Lymphocytes
• There are c.10 million different B-
lymphocytes, each of which make a different
antibody.
• The huge variety is caused by genes coding for
abs changing slightly during development.
• There are a small group of clones of each type
of B-lymphocyte
B -Lymphocytes
• At the clone stage antibodies do not leave the B-
cells.
• The abs are embedded in the plasma membrane of
the cell and are
called antibody receptors.
• When the receptors in the membrane recognise and
antigen on the surface of the pathogen the B-cell
divides rapidly.
• The antigens are presented to the B-cells by
macrophages
B -Lymphocytes
B -Lymphocytes
• Some activated B cells  PLASMA CELLS
these produce lots of antibodies, <
1000/sec
• The antibodies travel to the blood, lymph,
lining of gut and lungs.
• The number of plasma cells goes down after a
few weeks
• Antibodies stay in the blood longer but
eventually their numbers go down too.
B -Lymphocytes
• Some activated B cells  MEMORY CELLS.
• Memory cells divide rapidly as soon as the
antigen is reintroduced.
• There are many more memory cells than there
were clone cells.
• When the pathogen/infection infects again it
is destroyed before any symptoms show.
Antibodies
• Also known as immunoglobulins
• Globular glycoproteins
• The heavy and light chains are polypeptides
• The chains are held together by disulphide
bridges
• Each ab has 2 identical ag binding sites – variable
regions.
• The order of amino acids in the variable region
determines the shape of the binding site
How Abs work
• Some act as labels to identify
antigens for phagocytes
• Some work as antitoxins i.e. they block toxins for
e.g. those causing diphtheria and tetanus
• Some attach to bacterial flagella making them
less active and easier for phagocytes to engulf
• Some cause agglutination (clumping together) of
bacteria making them less likely to spread
Different Immunoglobulins
Type Number of Site of action Functions
ag binding
sites
IgG 2 •Blood •Increase
•Tissue fluid macrophage activity
•CAN CROSS •Antitoxins
PLACENTA •Agglutination

IgM 10 •Blood Agglutination


•Tissue fluid

IgA 2 or 4 •Secretions (saliva, •Stop bacteria


tears, small intestine, adhering to host
vaginal, prostate, cells
nasal, breast milk) •Prevents bacteria
forming colonies on
mucous membranes
IgE 2 Tissues •Activate mast cells
 HISTAMINE
•Worm response
T-Lymphocytes

• Mature T-cells have T cell receptors which


have a very similar structure to antibodies and
are specific to 1 antigen.
• They are activated when the receptor comes
into contact with the Ag with another host cell
(e.g. on a macrophage membrane or an
invaded body cell)
T-Lymphocytes

• After activation the cell divides to form:


• T-helper cells – secrete CYTOKINES
 help B cells divide
 stimulate macrophages
• Cytotoxic T cells (killer T cells)
 Kill body cells displaying antigen
Innate Immunity: Phagocytosis &
Inflammation

• Physical & chemical barriers


• Phagocytosis: macrophages, neutrophils, NK cells
• Engulf and digest recognized "foreign" cells –
molecules
• Inflammatory response
Innate Immunity: Phagocytosis &
Inflammation

Figure 24-6: Phagocytosis


Inflammatory Response: Cytokines Signal
Initiation

• Histamines: from mast cells  swelling, edema, b.


v . dilation
• Interleukins: fever, b.v. gaps  WBC's & proteins
 infection
• Bradykinin: pain & swelling
• Membrane attack complex proteins
Inflammatory Response: Cytokines Signal
Initiation

Figure 24-8: Membrane attack complex


Acquired Immunity: Antigen-Specific
Responses

• Activate T lymphocytes: direct attack


• Activate B lymphocytes to become:
– Memory cells: 20 immune response to that antigen
– Plasma cells: antibodies – attack that antigen
Antigens
u Most are proteins or large polysaccharides from a
foreign organism.
– Microbes: Capsules, cell walls, toxins, viral capsids,
flagella, etc.
– Nonmicrobes: Pollen, egg white , red blood cell surface
molecules, serum proteins, and surface molecules from
transplanted tissue.
u Lipids and nucleic acids are only antigenic when
combined with proteins or polysaccharides.
u Molecular weight of 10,000 or higher.
– Hapten: Small foreign molecule that is not antigenic. Must be
coupled to a carrier molecule to be antigenic. Once antibodies are
formed they will recognize hapten.
Antigens
Epitope:
u Small part of an antigen that interacts with
an antibody.
u Any given antigen may have several
epitopes.
u Each epitope is recognized by a different
antibody.
Epitopes: Antigen Regions that Interact with
Antibodies
Acquired Immunity

Figure 24-13: Functions of antibodies


A. Humoral (Antibody-Mediated) Immunity

– Involves production of antibodies against foreign antigens.


– Antibodies are produced by a subset of lymphocytes called B
cells.
– B cells that are stimulated will actively secrete antibodies and
are called plasma cells.
– Antibodies are found in extracellular fluids (blood plasma,
lymph, mucus, etc.) and the surface of B cells.
– Defense against bacteria, bacterial toxins, and viruses that
circulate freely in body fluids, before they enter cells.
Antibodies are Proteins that Recognize Specific Antigens
Consequences of Antibody Binding
Consequences of Antibody Binding
Immunological Memory
Antibody Titer: The amount of antibody in the
serum.

Pattern of Antibody Levels During Infection


1. Primary Response:
– After initial exposure to antigen, no antibodies are
found in serum for several days.
– A gradual increase in titer, first of IgM and then of
IgG is observed.
– Most B cells become plasma cells, but some B cells
become long living memory cells.
– Gradual decline of antibodies follows.
2. Secondary Response:
– Subsequent exposure to the same antigen displays
a faster and more intense antibody response.
– Increased antibody response is due to the
existence of memory cells, which rapidly produce
plasma cells upon antigen stimulation.
Antibody Response After Exposure to Antigen
T Lymphocytes: Cell Mediated Immunity

• T cell receptors: cell activated to antigen


• Major histocompatability complex (MHC)
• Helper T cells:
– Cytotoxic T cells: perforins, granzymes, (apoptosis) &
Fas
T Lymphocytes: Cell Mediated Immunity

Figure 24-16: T lymphocytes and NK cells


– Antigens that stimulate this response are mainly
intracellular
– Requires constant presence of antigen to remain
effective.
– Unlike humoral immunity, cell mediated immunity
is not transferred to the fetus.
– Cytokines: Chemical messengers of immune cells.
– Over 100 have been identified.
– Stimulate and/or regulate immune responses.
• Interleukins: Communication between WBCs.
• Interferons: Protect against viral infections.
• Chemokines: Attract WBCs to infected areas.
– T cells are key cellular component of immunity.
– T cells have an antigen receptor that recognizes
and reacts to a specific antigen (T cell receptor).

– T cell receptor only recognize antigens combined


with major histocompatability (MHC) proteins on
the surface of cells.
• MHC Class I: Found on all cells.
• MHC Class II: Found on phagocytes.
T Cells Only Recognize Antigen Associated
with MHC Molecules on Cell Surfaces
Types of T cells
1. T Helper (TH) Cells: Central role in immune
response.
• Most are CD4+
• Recognize antigen on the surface of antigen presenting
cells (e.g.: macrophage).
• Activate macrophages
• Induce formation of cytotoxic T cells
• Stimulate B cells to produce antibodies.
Central Role of Helper T Cells
2. Cytotoxic T (Tc) Cells: Destroy target cells.
• Most are CD4 negative (CD4 -).
• Recognize antigens on the surface of all cells:
– Kill host cells that are infected with viruses or
bacteria.
– Recognize and kill cancer cells.
– Recognize and destroy transplanted tissue.
• Release protein called perforin which forms a
pore in target cell, causing lysis of infected cells.
Cytotoxic T Cells Lyse Infected Cells
Allergic Response:
Inflammation Reaction to Non-pathogen
• First exposure: sensitization
– Activation
– Clone B cells
– Form antibodies
– Memory cells
• Re-exposure
Many antibodies
Activated Ts
– Intensified
• Inflammation
Allergic Response:
Inflammation Reaction to Non-pathogen

Figure 24-19: Allergic responses


Allergies

• When the immune system responds to harmless


substances
• Allergens – antigenic substances which do no real
harm
• Allergens include house dust, animal skin, pollen,
house dust mite and its faeces
Allergies

• Histamine causes blood vessels to widen and


become leaky.
• Fluid and white blood cells leave capillaries.
• The area of leakage becomes hot, red and inflamed
Defenses against Bacteria: Complement P
Activates:

• Make membrane attack complex  kill


bacteria
– Inflammation: + recruit phagocytes, B & T
lymphocytes
– (Acquired response  antibodies, cytotoxic Ts … if
needed)
Defenses against Bacteria: Complement P
Activates

Figure 24-17: Immune responses to bacteria


Viral Defense:
Summary of Innate & Acquired
Responses

• Circulating antibodies inactivate or target virus


(opsins)
• Macrophage  inflammation, interferon, cell
activation
– Helper, cytotoxic T, NK & B cells 
plasma c. antibodies
Viral Defense:
Summary of Innate & Acquired
Responses

Figure 24-18: Immune responses to viruses