The Immune System: Innate and Adaptive Body Defenses
Immunity: Ability to provide resistance to disease
Innate (nonspecific) system
First line of defense: external body membranes; like skin and mucosae
Second line of defense: antimicrobial proteins, phagocytes and other cells
Adaptive (specific) system
Third line of defense: attacks particular foreign substances
Takes much longer
Innate Defenses: Skin and Mucosae
1. Acidity of skin secretions
2. Stomach acid
3. Saliva and lacrimal fluid contains lysozyme, which destroys bacteria
4. Sticky mucus and ciliated cells of the upper respiratory system
Macrophages – derived from monocytes
Free macrophages – wander through tissue spaces
Dendritic cells (Langerhan’s cells) of epidermis
Fixed macrophages – permanent residents of particular organs
Neutrophils – Become phagocytic when encounter infectious material
Eosinophils – Weakly phagocytic
When they encounter parasitic worms, discharge contents of cytoplasmic
granules all over them.
Mast cells – can bind with, ingest and kill a wide range of bacteria
Mechanism of Phagocytosis
3. Respiratory burst
Internal Defenses: Natural Killer cells
NK cells: can lyse and kill cancer cells and virus infected body cells before adaptive
system is activated.
NK cells are part of large group of granular lymphocytes, unlike lymphocytes of adaptive
system, are nonspecific
Done by recognizing surface markers as “non-self”.
Release cytolytic chemicals called perforins
Also release chemicals that elicit the inflammatory response
Inflammation: Tissue Response to Injury
Inflammatory response: triggered anytime tissues are injured by anything.
1. Prevents spread of damaging agents
2. Disposes of cell debris and pathogens This forces the injured part
3. Sets the stage for repair to rest, which aids healing.
Impairment of function some
Signs of inflammation: consider to be the 5th sign of
redness, heat, swelling and pain. inflammation.
Vasodilation and Increase Vascular Permeability:
1. More blood comes to the area
Inflammatory chemicals are Vasodilation leads 2. fluid leaves the capillaries
released by injured cells to symptoms of and enters the tissues
inflammation 3. macrophages enter the area
in great numbers, to engulf
Sources of inflammatory mediators:
most important: histamine, prostaglandins, complement
1. Stressed tissue cells, Pain, Heat,
2. Phagocytes Impairment
4. Mast cells
5. Blood proteins
Benefits of swelling
1. Helps dilute harmful substances
2. Brings large amounts of oxygen and nutrients
3. Entry of clotting proteins
β-defensin is released in larger quantities from mucosal cells to prevent infection
Area is invaded my more phagocytes
Complement and adaptive immunity is activated if inflammation was caused by pathogens
2. Margination Job: Clean up debris
3. Diapedesis and pathogens
4. Positive Chemotaxis
Interferon – released by some cells infected with viruses
1. Stimulates nearby cells to interfere with viral replication
2. Activates macrophages and
3. mobilizes NK cells
Complement – a group of at least 20 plasma proteins that normally circulate in the blood
in an inactive state.
1. If activated, it unleashes chemical mediators which amplify nearly all
aspects of inflammatory response.
2. Kills bacteria and other cells by lysis
(Our own cells can de- activate complement)
How is it activated? 1. Lead to cell lysis
1. Classic Pathway: Binding of antibodies to foreign invaders. 2. Promote
Complement binds to them (complement fixation) Phagocytosis
2. Alternate pathway: Interact with polysaccharides on 3. Enhance
the surface of certain microorganisms. inflammation
Systemic response to invading microorganisms (Ch 24)
Stimulated by Pyrogens – chemicals secreted by leukocytes and macrophages exposed to
Heat denatures enzymes – high fevers are dangerous!
1. Causes liver and spleen to sequester iron and zinc which bacteria require in
large amounts to multiply
2. Speeds up cellular metabolism to increase regeneration
Must meet (be primed) by the pathogen – takes time.
Meanwhile the nonspecific systems are activated and we feel bad
1. It is specific
2. It is systemic
3 It has memory
Humoral Immunity (antibody mediated immunity) – provided by antibodies in the
Cellular Immunity (cell-mediated immunity) – lymphocytes themselves defend the body
Both respond to the same antigens (substances that provoke an immune response –
recognized as “nonself”)
1. Immunogenicity – ability to stimulate specific lymphocytes and
2. Reactivity – ability to react with the activated lymphocytes
ex: proteins (strongest), nucleic acids, some lipids large
polysaccharides. Also, bacteria, fungi and viruses because of
Incomplete antigens: Haptens
small molecules (peptides, nucleotides, hormones) by themselves do not stimulate
an immune response, but do if they combine with a body protein. (Allergies)
1. Have only reactivity
ex: penicillin, poison ivy, animal dander, detergents, cosmetics …
Places on the antigen where antibodies and lymphocytes may bind
Many different types on one antigen
So one antigen may activate many different types of lymphocytes and antibodies
Self-Antigens: MHC Proteins
Major Histocompatibility Proteins: Surface glycoproteins recognized as “self” by our immune
system, (but not others’)
Class I MHC proteins – found on nearly all body cells
Class II MHC proteins – found on only certain body cells that act in immunity
Cells of the Adaptive Immune System: An Overview
1. B-lymphocytes: produce antibodies - (humoral immunity)
2. T-lympocytes: do not produce antibodies - (cell mediated immunity)
3. Antigen presenting cells – present antigens to other cells
Immature lymphocytes are essentially identical.
Whether they become B-cells or T-cells depends on where in the body they become immunocompetent
Immunocometence: ability to recognize foreign antigens by binding to it.
1. T-cells become immunocompetent in the thymus and mature under the direction of thymic
2. Only those with the sharpest MHC survive (only about 2%)
Positive Selection: T-cells able to recognize self MHC (Major Histocompatibility
Complex Proteins) survive, the rest undergo apoptosis.
Negative Selection: Those passing positive selection do this
Those that bind too strongly to MHC are eliminated
Purpose: ensures that T-cells exhibit self tolerance.
Become immunocompetent and self tolerant in the bone marrow.
Little is known about the factors that control B-cell maturation in humans. Self reactive
B-cells are inactivated – anergy, others are killed or undergo apoptosis (clonal deletion)
Primary Lymphoid Organs: thymus and bone marrow
Secondary Lymphoid Organs: all other lymphoid organs
When B or T cells become immunocompetent, the display a unique type of receptor on
their surface enable the cell to recognize and bind to a specific antigen.
Lymphocytes become immunocompetent before meeting antigens – so it is in our genes
not antigens that determine what foreign substances our immune system will be able to
Naïve immunocompetent T & B cells are exported to secondary lymph organs
(lymph nodes, spleen…) where they encounter antigens and thus become fully functional
(antigen activated cells).
Antigen Presenting Cells
Purpose – engulf antigens and present fragments on their surfaces to T- cells for destruction
Types of APCs:
1. Dendritic cells (in CT) Located where they would more likely
2. Langerhans cells (epidermis) encounter antigens
3. Macrophages (lymphoid organs)
4. Activated B-cells
5. Reticular cells
APCs and lymphocytes are found throughout lymphoid tissues, but some tend to be more
numerous in certain areas.
Humoral Immune Response
Antigen Challenge: First encounter with an antigen
B-cell: provokes humoral immune response – produces antibodies
Clonal Selection and Differentiation of B-cells
B-cells is activated (completes differentiation) during antigen challenge: until they meet
their first antigen, they are not yet fully mature.
The antigen “selects” the B cell with the receptors complementary to the antigen.
This B cell makes many clones of itself. Many of these clones differentiate into plasma
cells, which produce antibodies. Other B cells become memory B cells. These remain in
the body in case the antigen invades again.
Immunological Memory – provide memory cells
Primary Immune response – Cellular proliferation and differentiation (to plasma cells which
produce antibodies) on first exposure to antigen
Lag time is 3-6 days Memory cells provide
Peak levels within 10 days – then decline immunological memory
Secondary Immune response – occurs upon re-exposure to same antigen
Memory cells are already there and produce plasma cells within hours.
Peak antibody levels occur within 2-3 days and antibody titers much
higher than in primary response and remains high for weeks or months.
Antibodies bond much tighter to antibodies in secondary response
Antibody titer much higher
Titers remain high for weeks or months Active and Passive Humoral Immunity
Plasma cells keep functioning much longer than the 4-5 days as in primary response
You see the same Active: B-cells produce antibodies
general response 1. Naturally acquired – by getting the disease
in cellular 2. Artificially acquired – vaccines
immunity Active Humoral Immunity: B-cells are actively producing antibodies
Vaccines do not provide the life long immunity that naturally acquired immunity does!
Why? Cellular memory is only poorly established. Why? Explained later.
Passive Humoral Immunity
B-cells not challenged so:
No immunological memory
Borrowed antibodies degrade in 2-3 weeks. Artificial Passive Immunity is
Natural – through the placenta given for diseases that kill before
Artificial – IgG shots or antivenom active immunity can be established
– rabies, tetanus, botulism…
All antibodies have: 2 identical heavy chains (H)
2 identical light chains (L)
A. Make a T or Y shape
B. Have a V (variable) region – antigen binding site
C. Have a C (constant) region – same (or nearly) in all antibodies
1. Forms the stem
2. Determines the class of antibody
3. Common functions of all antibodies in that class
a. Effector regions here dictate
Some can fix complement, 1. what cells and regions it can bind to
some circulate in blood, or are 2. how this class of antibody functions in antigen
found in body secretions or elimination.
cross the placenta barrier…
Named for C regions on heavy chains
IgD Always bound to B-cell surface so acts as B-cell receptor
IgG Most abundant in plasma
Only class that can cross the placenta
Can fix complement
IgE Almost never found in blood
Involved in allergies “trouble makers”
IgA Occurs in both diner and monomer forms
Dimer – secretory IgA: mucus and secretions to body surface
Prevents pathogens from gaining entry
IgM Occurs in both monomer and pentameter forms
First released to blood from plasma cells
Can fix complement
Antibodies do NOT destroy antigens
They form antigen-antibody complexes and
inactivate them and tag them for destruction
Defensive mechanisms used by antibodies
Neutralization PLAN: Precipitation
Agglutination Most important Lysis (Complement)
Complement fixation Neutralization
Works against cellular antigens like bacteria, mismatched blood…
1. Antibodies bind to cells
2. This causes change in shape exposing complement binding sites
3. This triggers complement fixation to antigenic cell surface
4. This causes lysis of the cell
Remember chemicals released during complement activation greatly enhance inflammatory
response and promote phagocytosis and opsonization – a positive feedback mechanism
Antibody blocks specific sites on viruses or bacterial exotoxins
The toxic effect is lost if the antigen cannot bind to tissue cell receptors
Antibody complex later pahgocytized.
Because antibodies have more than one antigen binding site, they can bind to the same
determinant on more than one antigen at a time. So antigen antibody complexes can form lattices
– when they do this it is called agglutination.
Soluble molecules are cross-linked to large complexes that settle out (more easily engulfed now).
Students read the section about commercially
prepared Monoclonal Antibodies
Cell Mediated Immune Response
(T-cells are much more diverse than B-cells)
Antibodies provide only partial immunity.
Useless against things like tuberculosis bacillus (it is inside body cells to multiply)
T-cells: Two major types – CD 4 and CD 8
T4 cells (T helper) TH cells
T8 cells cytotoxic TC cells destroy body cells that harbor anything foreign
Other types that exist are suppressor T cells and memory T cells
Antibodies work in the extra-cellular environment (in humors). Secretions, blood, ECF… and
do not enter tissues unless a lesion is present and then it is a race: antibodies are specialized to
attach to intact bacteria and soluble molecules. Antibodies do not destroy antigens! They just
tag them and make it easier for other cells (phagocytes) to destroy them.
What happens to T cells after Pathogens are destroyed?
Proliferation peaks within a week after exposure to antigen trigger.
Period of apoptosis 7-30 days (activated T cells die off – dangerous to keep them around
since they produce huge amounts of inflammatory cytokines).
Some 1000s of T clones become memory T cells that persist for life (for same antigen).
Specific T cell Roles
Helper T cells – central role in adaptive immunity
Once activated (by an antigen) function to stimulate proliferation of T and B cells that
have already bound to an antigen.
Without T Helper
cells, there is no
Cytotoxic T cells immune response!
See Table: Cells
of the Adaptive
immune system TC cells are the only ones that can attack and kill other cells.
Search through blood, lymph and lymphoid tissues
For cells infected with anything& transplants
As long as antigen and co-stimulatory signal is present.
See picture: how does it work? Different TC cells
use different chemicals, but the result is the same in the end:
Lysis. So, also called cytolytic T cells.
Organ Transplants and Prevention of Rejection
1. Autografts: tissue grafts transplanted from one body site to another in the same person
2. Isografts: grafts donated to a patient by a genetically identical individual, an identical twin.
3. Allografts: grafts transplanted from individuals that are not genetically identical but belong to the
4. Xenografts: grafts taken from another species, such as transplanting a baboon heart into a human.
Autografts and isografts are always successful and xenografts work only temporarily. Allografts are
most commonly used, but finding a perfect match is virtually impossible. At least a 6-antigen match is
required. Patient is then treated with immunosuppressant drug, which often have severe side effects.
Homeostatic Imbalances of Immunity
Immunodeficiency Hypersensitivity – allergies
1. SCID 1. Acute or Type I hypersensitivites
2. AIDS a. Anyphylaxis
b. Anyphylactic shock
Autoimmune diseases c. Atopy
1. Multiple Sclerosis 2. Subacute Hypersensitivities
2. Myasthenia gravis a. Cytotoxic (type II) reactions
3. Grave’s disease 3. Immume complex (type III hyrpersensitivity
4. Type I diabetes mellitus a. Farmer’s lung
5. Systematic lupus erythematosus 4. Delayed hypersensitivities (Type IV) reactions
6. Glomerulonephritis a. Transfusions of mismatched blood
7. Rheumatoid arthritis b. Allergic dermatitis
c. Mantoux and tine tests for tuberculosis
d. Cell-mediated hypersensitivity