Download Chapter 21 - Immunity

Chapter 21
Nonspecific Body Defenses and
Immunity
G.R. Pitts, J.R. Schiller, and James F. Thompson, Ph.D.
Defense Systems
1. Innate
(nonspecific)
defenses
– External body
membranes
– Inflammation
• Antimicrobial
proteins,
phagocytes and
other cells
2. Adaptive
(specific)
defenses
– T cells and B cells
Innate Defense System
•
Surface Barriers
– First line of defense: mechanical and chemical protection
1. Skin
2. Mucosal Membranes
•
Internal Nonspecific Defenses
–
1.
2.
3.
4.
5.
Second line of defenses
Phagocytes
Natural Killer cells (NK lymphocytes)
Inflammation
Antimicrobial proteins
Fever
Skin and Mucosal Membranes
Mechanical Protection
• Epidermis
– nose hairs, nails
• Mucous membranes - line certain organ systems
– mucus prevents drying, traps foreign things
– respiratory tract cilia sweep mucus out
• Lacrimal apparatus -- tear glands and ducts
– wash the eye to dilute microbial growth
• Saliva - dilute microbes on the oral cavity
• Urine - flow dilutes, and acid pH helps kill,
microorganisms
• Defecation and vomiting - expel toxins and microbes
Skin and Mucosal Membranes
Chemical Protection: reduce bacterial growth
• Skin
– sebum (unsaturated FA’s) forms oily layer
– perspiration has fatty acids, salts (NaCl), and mildly acid pH
• Lysozyme
– in perspiration, tears, saliva, nasal secretions, other tissue fluids
– enzyme breaks down bacterial cell walls
• Hyaluronic acid
– gel-like matrix in most connective tissues
– slows the spread of many infectious agents
• Gastric juice - stomach nearly sterile due to acid pH, ~2
• Vaginal secretions – mildly acid pH
Innate Defense: Phagocytes
• Macrophages (derived from monocytes) are the
chief tissue phagocytic cells
– Free macrophages wander through tissues in search
of microbes and cellular debris
– Fixed macrophages: Kupffer cells (liver), microglia
(brain), dust cells (lungs)
• Neutrophils become phagocytic when
encountering infectious material
• Eosinophils are weakly phagocytic, deploy
destructive granules against parasitic worms
Mechanism of Phagocytosis
•
•
Chemotaxis
Adherence – recognition
of external carbohydrates
and proteins
– Aided by opsonins
•
•
Ingestion
Killing and digestion
Innate Defense: Natural Killer Cells
– Distinct group of large granular lymphocytes (NK
lymphocytes = Null Killer lymphocytes)
– Nonspecific killers respond to the lack of selfantigens and to the presence of certain surface
oligosaccharides
– Kill virus-infected body cells and some tumor cells
by releasing various defensive molecules – not by
phagocytosis
– Act before the antigen-specific immune system is
activated
– Secrete potent chemical signals that enhance the
inflammatory response
Innate Defense: Inflammation
1. Inflammation
• Signs:
1.
2.
3.
4.
5.
•
Redness
Heat
Swelling
Pain
Loss of Function
Function:
1. Prevent spread of
damage
2. Dispose of pathogens
and debris
3. Set stage for tissue
repair
Inflammation
Stage 1: Vasodilation and
increased vessel permeability
– Macrophages and cells lining the
gastrointestinal and respiratory tracts carry
Toll-Like Receptors (TLRs) that recognize
specific classes of microbes
– TLReceptor activation causes cytokine
release
• promotes inflammation & chemotaxis
– Mast cells secrete histamine
– Other cells secrete various regulatory
factors
• Histamine, kinins, prostaglandins,
leukotrienes, complement
– Cause local vasodilation
– Increase capillary permeability resulting in
edema
http://www.komabiotech.co.kr/technical/review/toll_like_receptor.gif
Inflammation: Stage 1
• Edema – increased plasma filtrate seeps into
tissue spaces bringing some immune proteins
– Helps to dilute harmful substances
– Increases supply of oxygen and nutrients needed
for metabolism, inflammation and repair
– Allows entry of clotting proteins, which reduces the
spread of mibrobes
Inflammation
Stage 2. Phagocyte
moblization
1. Leukocytosis-inducing
factors: increase
neutrophil production
2. Margination
(pavementing)
3. Diapedesis (amoeboid
movement)
4. Chemotaxis of WBCs
• neutrophils – rapid arrival
• monocytes – slower arrival
Inflammation
Stage 3. Tissue
repair
– Tissue regrowth and
repair of damage or
scar formation
– Pus
• dead phagocytes and
other WBCs, damaged
tissue, and perhaps
microbes
• if too numerous for
effective removal by
phagocytes, an abscess
may develop
Effects of Inflammation
• Increased blood
flow results in
increased local
temperature and
local cellular
metabolism
• Increased capillary
permeability and
phagocytic
migration to the
injured tissue
Innate Defense: Antimicrobial
Proteins
1. Attack microorganisms directly
2. Interfere with microbial reproduction
•
The most important are:
1. Interferons
2. The Complement System
3. Transferrins which bind Fe2+ in plasma,
inhibiting bacterial growth
Interferons (IFNs)
• Produced by most tissue cells
when infected by a virus
• Diffuses to uninfected cells
and binds to surface receptors
– stimulates macrophages and
natural killer lymphocytes
– stimulates production of
antiviral proteins which block
viral replication
– inhibits growth of virally infected
cells
– suppresses growth of tumor cells
• Alpha IFN is used against:
– hepatitis C virus
– herpes virus (genital warts)
The Complement System
• 20 plasma and cell membrane proteins that
exist as inactive precursors
• When activated, the complement system
functions to “complement” or enhance certain
immune, inflammatory, and allergic responses
• Kills bacteria and certain other microbial cell
types (our cells normally are protected from
complement attack)
• Stimulates chemotaxis in leuckocytes
• Enhances the effectiveness of both nonspecific
and specific defenses
Complement Pathways
Classical Pathway is triggered by the specific
immune system
– Requires binding of antibodies to antigens of
invading organisms
– Complement C1 then binds to the antigen-antibody
complexes (complement fixation)
Alternative Pathway is triggered by nonspecific interaction among factors B, D, and P,
and microbial cell wall polysaccharides
(complement fixation)
Both pathways involve an enzyme cascade
Complement
Pathways
• Both pathways converge
on C3, which cleaves
into C3a and C3b
• C3b initiates formation of
a membrane attack
complex (MAC)
• MAC causes cell lysis by
creating many hundreds
of microscopic holes in
the cell’s plasmalemma
• C3b is also an opsonin
Innate Defense: Fever
• Pyrogens reset the temperature set-point in the
hypothalamus
• Inhibits some microbes from growing
• Increases body’s metabolic rate, which speeds up
immune defenses and tissue repair
• Increases effects of antimicrobial substances
produced by the immune system
• Stimulates liver and spleen to sequester iron and zinc
(needed by microorganisms)
• High fevers are dangerous
Innate Defense System: Review
•
Surface Barriers
1. Skin
2. Mucosal membranes
•
Internal Nonspecific Defenses
1.
2.
3.
4.
5.
Phagocytes
Natural Killer cells (NK lymphocytes)
Inflammation
Antimicrobial proteins
Fever
Adaptive Defense
• The adaptive immune system:
– Acts to immobilize, neutralize, or destroy foreign
substances and cells
– Amplifies the inflammatory response and activates
complement
– Is antigen-specific*, systemic, and has memory
• *Recognizes specific foreign molecules
– Has two interdependent arms
• Humoral, or antibody-mediated immunity (AMI)
• Cellular, or cell-mediated immunity (CMI)
Adaptive Defense
• Definitions:
– Immunity: the ability of the body to defend itself
against specific foreign invaders (molecules or cells)
– Immunogenicity: the ability to stimulate
proliferation of specific lymphocytes and specific
antibody production
– Reactivity: the ability of activated lymphocytes and
their products, antibodies, etc., to interact with
specific antigens
Adaptive Defense
• Definitions:
– Specificity: the antigen triggers focused immune
defenses (from particular lymphocytes lineages)
that respond only to the antigens of this foreign
substance/cell
– Memory: the immune system produces clones of
specific memory lymphocytes (T & B) which react
rapidly when the particular foreign substance/cell is
encountered again
– Specificity and memory differentiate this system
from the nonspecific (innate) defenses
Adaptive Defense
• Antigen – any substance
which provokes specific
immune responses
• Antigenic determinants
– Parts of antigens that trigger
the specific immune
response
– An antigen may be an entire
microorganism or only small
structures or subregions of
large molecules
Most “antigens” are
complex and express
multiple types of
antigenic determinants.
Chemical Nature of Antigens
• “Complete” Ag: complex
macromolecules - usually proteins
(nucleo-, lipo-, glyco-) -sometimes carbohydrates or lipids
– Are immunogenic & reactive
• “Incomplete” Ag: smaller
molecules (haptens)
– react with antibodies but cannot
cause an immune response without
aid (protein carrier)
• e.g., poison ivy, drug allergies
Adaptive Defense
• Antigen receptor diversity
– >1 billion different antigenic
determinants are recognized by the
body
– Genetic recombination shuffles and
reorganizes different Ab genes
• Major histocompatibility complex
antigens (MHC)
– unique to each individual’s cells;
help in identifying what is self
versus foreign
– 2 classes of MHC antigens
(“markers”)
• class I MHC – found on all body
cells except RBC's
• class II MHC - only on antigen
presenting cells (APC’s), thymus
cells, and activated T cells
Antigen-Presenting Cells (APCs)
• APCs phagocytize, process, and present antigens to
lymphocytes
• APCs do not respond to specific antigens
• APCs contribute to coordinating specific immunity
– Macrophages
– Dendritic (Langerhans) cells
– B lymphocytes
The major initiators of adaptive immunity are APCs,
which actively migrate to the lymph nodes and
secondary lymphoid organs and present antigens to T
and B cells
Class I MHC Proteins
• Found on all cells, except RBCs
• Recognized by T lymphocytes and APCs
• Display peptides from endogenous antigens
– Endogenous antigens are:
• Associated with body cells
• Degraded by proteases and enter the endoplasmic
reticulum
• Transported through special membrane channels
• Bound with MHC class I molecules on the ER membrane
• Migrate to the cell membrane as a complex: Ag -- MHC
class I molecule
MHC Class I Proteins
This is a form of Antigen Presentation
Cancer cells often do something quite similar to the virus-infected cells.
(Foreign MHC Class I Ags are the source of tissue transplant rejections.)
MHC Class II Proteins
1. Immune cell identity markers found only on mature B
cells, some T cell classes, and antigen-presenting
cells
2. MHC Class II proteins are synthesized in the ER
3. A phagosome containing a pathogen (with
exogenous antigens) merges with a lysosome
4. MHC Class II proteins migrate into the phagosome
where the antigen macromolecules are degraded and
particular antigen peptides are bound to the MHC
Class II markers
5. Ag-- MHC class II complex then migrates to the cell
membrane and displays antigenic peptide for
recognition by CD4 TH cells
MHC Class II Proteins
This is a key function of our APCs in most Ag-specific defenses.
Lymphocytes Provide Ag Specificity
• B and T lymphocytes develop
in bone marrow
• Lymphocytes mature and
develop immunocompetence
(ability to recognize specific
antigen) in different locations
– B cells mature in the bone
marrow and provide Abmediated immunity
– T cells mature in the thymus
and provide cell-mediated
immunity
Immunocompetent B or T cells
• Naive cells display a unique surface receptor for a
specific antigen once mature
– Receptor expression occurs before a cell encounters
the foreign antigen it may later attack
– It is genes, not antigens, that determine which foreign
substances our immune system will recognize and resist
• Naive cells circulate to secondary lymphoid tissue
where they may encounter antigens later
– B and T cells become fully functional only after binding
with their recognized antigen
Immunocompetent T Cells
• T cells mature in the thymus
under positive and negative
selection pressures
Survive
– Positive selection – outer thymic
cortex
• Selects functional T cells which become
both immunocompetent and potentially
self-tolerant
• Non-selected cells die via apoptosis
Apoptosis
Apoptosis
– Negative selection – inner thymic
cortex
• Kill or regulate off T cells that react with
self-antigens
Immunocompetent B Cells
• B cells become immunocompetent and selftolerant in bone marrow
– Some self-reactive B cells are killed by apoptosis
(clonal deletion)
– Some self-reactive B cells can modify their anti-self
properties (receptor editing)
• Some self-reactive B cells are released from the
bone and are inactivated by negative regulation
(anergy)
Cell-Mediated Immunity
• CMI is involved in most aspects of specific
immune defense
• Three populations of T lymphocytes
regulate specific immunity
– Helper TH cells which carry CD4+ markers
– Suppressor TS cells
– Memory T cells
• cytotoxic TC cells which carry CD8+ markers
destroy tumor cells and virus-infected cells;
they also attack transplanted cells and tissues
Cell -Mediated Immunity
Basic steps
1. Recognition by T lymphocytes of antigen
presented by an antigen-presenting cell with
matching MHC Class II markers
2. Proliferation and differentiation of T cells once
activated
3. Production of clones of identical effector T cells
capable of recognizing a specific antigen
4. Appropriate action (help, attack, memory,
suppression) from T cell subclones
T Cell
ActivationStep 1:
Antigen
Binding
and Antigen
Presentation
T Cell Activation- Step 2: Co-Stimulation
• T cells must bind to
MHC Class II surface
receptors on an APC
• After co-stimulation
with cytokines, T cells
enlarge, proliferate,
and form clones
• Activated T cells
differentiate and
perform functions
according to their T
cell class
T Lymphocyte Activity
• Primary T cell response usually peaks within a
week
• T cells then undergo apoptosis within a month
• Reduced activity parallels elimination of antigen
• This is a negative feedback control
• A few Memory T cells remain to respond to any
future exposure to the same antigen
Helper TH Lymphocytes
• Regulatory cells that play a
central management role in
the immune response
• Once primed by APC antigen
presentation, TH cells:
– Stimulate proliferation of other
T cell classes
– Stimulate B cells that have
already become bound to
antigen
• There is NO coordinated
immune response without TH
cell function
Helper TH Lymphocytes
• TH cells interact directly with B cells that have antigen
fragments on their surfaces bound to MHC Class II
receptors
• TH cells express CD4+ cell identity markers
• TH cells stimulate B cells to divide more rapidly and
begin antibody formation
• B cells may be activated without TH cell help by
binding to T cell–independent antigens (certain
microbial polysaccharides)
• Most antigens, however, require TH co-stimulation to
activate B cells
• Cytokines released by TH amplify nonspecific defenses
Cytotoxic Tc Lymphocytes
• TC cells express CD8+ cell identity markers
• TC cells, or killer T cells, are the only T cells that can
directly attack and kill other cells
• They circulate throughout the body in search of body
cells that display the antigen to which they have been
sensitized
• Their targets include:
–
–
–
–
Virus-infected cells
Cells with intracellular bacteria or parasites
Cancer cells
Foreign cells from blood transfusions (WBCs and platelets)
or tissue and organ transplants
Cytotoxic Tc Lymphocytes
• Bind to self/anti-self complexes on any body
cell
• Infected or abnormal cells can be destroyed as
long as appropriate antigen and co-stimulatory
regulators (e.g., IL-2) are present
• [In contrast, Natural Killer cells activate their
killing machinery when they bind to a different
MHC-related cell surface marker on cancer
cells, virus-infected cells, and transplanted
cells]
Cytotoxic Tc Lymphocyte Actions
• Secrete perforins which cause cell lysis by creating
transmembrane pores
• Secrete lymphotoxin which fragments the target cell’s DNA
• Secrete gamma interferon which stimulates macrophage attack
Suppressor Ts Lymphocytes
• TS cells – immune regulatory cells which release
cytokines that suppress the activity of both T cells
and B cells
• Generated when other specific T cell clones are
generated
• Negative feedback control to bring the body back to
normal after the “battle” has been won
Antibody-Mediated Immunity
• Antigen challenge – the first encounter
between an antigen and a naive B lymphocyte
• Antigen presentation usually occurs in the
spleen or a lymph node, but can occur in any
lymphoid tissue
• Antigen presentation usually made by a
macrophage, but some B cells can react
directly against certain bacterial antigens
• Binding of the antigen to the B cell’s specific Ag
receptor activates the B cell
Primary Response
Activated B cells grow and divide, forming clones bearing the
same antigen-specific receptors and secreting the same antigenspecific Ab
• Most clone cells become
plasma cells that secrete
specific antibodies
• Clones that do not
become plasma cells
become B memory cells
that can respond to
subsequent exposures to
the same antigen
Primary Response
• Initial B cell differentiation, proliferation, and
Ab synthesis requires time after the first Ag
exposure
• Lag period: 3 to 6 days after antigen challenge
• Peak plasma levels of antibody are achieved in
~10 days
• Antibody molecules also reach the interstitial
fluids, especially where inflammation exists
• Antibody levels then decline gradually if there is
no additional Ag exposure
Secondary Response
• Any subsequent exposure to the
same antigen
• Sensitized memory cells (B and
T) respond within hours
• Antibody levels peak in 2 to 3
days at higher plasma levels
than in the primary response
• Activated B subclones generate
antibodies that bind with
greater affinity
• Plasma antibody levels can
remain high for weeks to
months
Primary and Secondary Antibody Responses
Immunological Memory
• Immunization is
possible because
memory B cells and
memory T cells
persist after the
initial Ag exposure
• with any subsequent exposure, the immune system
responds more quickly, forcefully
• secondary response - antibodies produced during
subsequent exposures are produced in greater
quantities and have a greater attraction for antigen
Antibodies
• Are unique soluble proteins secreted by
activated B cells and plasma cells in response
to an antigen
• Are capable of binding specifically with that
antigen
• Constitute much of the gamma globulin fraction
of plasma proteins
• Also called immunoglobulins
Basic Antibody Structure
• Four polypeptide chains
linked together with disulfide
bonds
• The four chains bound
together form an antibody
monomer
• Each chain has a variable (V)
region at one end and a
constant (C) region at the
other
• Variable regions of the heavy
and light chains combine to
form the antigen-binding
site
Ag
Antibody Structure
• Antibodies responding to different antigens
have different V regions but the C region is the
same for all antibodies in a given antibody class
• C regions form the stem of the Y-shaped
antibody monomer and determine:
– the class of the antibody
– the cells and chemicals to which the antibody can
bind
– how an antibody class functions in eliminating
antigens
Classes of Antibodies
• IgD: monomer attached to the surface of B cells,
important in B cell activation
• IgM: pentamer released by plasma cells during the
primary immune response
• IgG: monomer that is the most abundant and diverse
antibody in primary and secondary responses; crosses
the placenta and confers passive immunity
• IgA: dimer that helps prevent attachment of
pathogens to mucosal surfaces
• IgE: monomer that binds to mast cells and basophils,
causing histamine release when activated
Antibody Functions
• All antibodies form an antigen-antibody (immune)
complex
• Antibodies do not directly destroy antigen, though
they may immobilize or inactivate Ag
• Antibodies act as opsonins and tag Ag for immune
attack and destruction
• Defensive mechanisms triggered by antibodies include
neutralization, agglutination, precipitation,
opsonization, and complement fixation
Antibody Mechanisms of Action
1. Neutralization: Antibodies bind to and block
specific sites on viruses or exotoxins, thus
preventing these antigens from binding to receptors
on tissue cells
Antibodies bind to the same determinant on more than
one antigen forming antigen-antibody complexes
that are cross-linked into large lattices
2. Agglutination: Cellular antigens are cross-linked,
causing cell clumping
3. Precipitation: Soluble molecules are cross-linked
into large insoluble complexes
Antibody Mechanisms of Action
4. Opsonization: Bound Abs facilitate
phagocyte adherence
5. Complement Fixation: IgM and IgG
antibodies bound to cellular Ags bind
complement via the Classical Pathway
•
•
The complement cascade causes chemotaxis,
opsonization, phagocytosis and cell lysis
Complement activation enhances the inflammatory
response
Summary of Antibody Actions
Figure 21.13
Monoclonal Antibodies
• Monoclonal antibodies are purified tissue
culture preparations of a specific antibody for a
single antigenic determinant which are
produced from descendents of a single B cell
• Commercially prepared monoclonal antibodies
are used:
– To provide passive immunity
– In research applications
– In clinical laboratory testing
– In the treatment of certain cancers
Adaptive Immunity: Summary
• A defensive system with two interdependent
arms (CMI & AMI) that uses lymphocytes,
APCs, and specific molecules to recognize and
destroy foreign substances
• Adaptive immune responses depend on the
ability of its cells to:
– Distinguish foreign from self molecules
– React with foreign substances (antigens) by binding
to them
– Communicate with one another to effect a
coordinated protective response specific to those
antigens
Adaptive Immunity: Summary
• To start an immune response, APCs, B and T
lymphocytes must recognize foreign antigen
• Antigen-Presenting Cells and some B cells
recognize and immediately bind to certain
antigens in the blood, the extracellular fluid
(ECF), or other tissue spaces
• More often, B and T cells only recognize
antigen (protein fragments) when Ag is
presented by the macrophages in combination
with MHC Class II surface markers and
stimulation is provided by Th lymphocytes
Summary of
the Immune
Response
Clinical Classification of Immunity
• Active Immunity: the body’s own B and T lymphocytes
encounter antigens and produce specific responses against
them; immunological memory does occur
– Naturally Acquired – response to a microbial or parasitic infection
– Artificially Acquired – response to a vaccine of dead or attenuated
(weakened) pathogens
• Passive Immunity: An outside source of immune cells or
molecules is provided to a recipient; immunological memory
does not occur; protection ends when the donated materials
are naturally eliminated from the body
– Naturally Acquired – the mother to her baby via the placenta (IgG) or
via lactation (colostrum/milk) (IgM & IgA)
– Artificially Acquired – the injection of serum, gamma globulin, or
leukocyte transfusion
Clinical Classification of Immunity
Organ and Tissue Transplants
• The four major types of grafts are:
– Autograft – graft transplanted from one site on the body to
another in the same person
– Isograft – graft between identical twins (or clones);
individuals with the same genotype
– Allograft – graft between individuals that are not identical
twins, but belong to same species
– Xenograft – grafts taken from another animal species
Prevention of Graft Rejection
• Donors are selected to minimize differences in MHC
Class I antigens = HLA (human leukocyte antigens)
– Unnecessary for routine blood transfusions since RBCs lack
HLAs
• Prevention of rejection is accomplished by using
various immunosuppressive drugs
– Survival and longevity of grafts have varying success
• Immunosuppressive drugs depress the patient’s
immune system so it is less effective in defending
against pathogens and cancer
Pathologies: Immunodeficiencies
• Human Immunodeficiency Virus
– HIV enters certain cell types by receptor
mediated endocytosis
• infects primarily helper T cells
• attaches to the CD4 protein on cell surface
– A retrovirus
• carries its genetic material as RNA
• inserts its genetic material into host cell DNA
with the enzyme reverse transcriptase
• cell makes copies of the virus, releases them for
further infection
– May be carried silently in cells for years, being
passed on during ordinary mitosis
– Activation of HIV life cycle destroys THelper cells
– Weakened immune response to all foreign
invaders, benign or aggressive
Pathologies: Autoimmune Diseases
• Multiple Sclerosis (MS) – myelin sheath
(white matter) attacked and destroyed
• Myasthenia Gravis – ACh receptors at neuromuscular junction of skeletal muscle attacked
and destroyed
• Grave’s Disease – thyroid cells’ TSH receptor
attacked and stimulated causing excess thyroid
hormone (T3 & T4) production
• Type I Diabetes - destruction of pancreatic
islet cells eliminates insulin secrection
Pathologies: Autoimmune Diseases
• Systemic Lupus Erythematosus (SLE) –
generalized attack on connective tissues and
nuclear antigens
• Glomerulonephritis - destruction of the
glomerular capillaries causes impaired renal
function
• Rheumatoid Arthritis - destruction of the
synovial membranes in joints
Pathologies: Cancer
• The immune system probably evolved first to
respond to cancer cells
– when a new cancer cell develops, new surface
marker proteins (tumor antigens) often appear
– if the immune system recognizes these new surface
markers as non-self, it will destroy the cell
expressing them
– this immune surveillance is most effective in
eliminating virus-induced tumor cells because they
tend to express viral antigens which are not “self”
• Leukemias and Lymphomas – cancers of
leukocytes
Pathologies: Hypersensitivities
• Immediate hypersensitivities (allergies)
– First exposure merely sensitizes one to an allergen
(penicillin, venoms, dust, mold, pollen, etc.)
• APCs digest and inappropriately present the allergen
• Subclones of B cells secreting IgE predominate in
response
• Anti-allergen IgE attaches to mast cells and basophils
– Later exposures produce dramatic responses
• Antigen binds to IgE on mast cells and basophils
• Ag-IgE binding triggers these cells to release much
histamine and other inflammatory molecules
• Local reactions – swelling, rashes, erythema, itching
• Systemic reactions – asthma, anaphylactic shock, death
Pathologies: Subacute
Hypersensitivities
• Caused by IgG and IgM
• Occurs 1-3 hr after exposure and lasts 10-15 hr
• Cytotoxic reactions
– Ab bind to Ag on specific cells causing phagocytosis and
complement-activated lysis
– May occur after transfusion of mismatched blood
• Immune-complex hypersensitivities
– Ag’s are widely distributed or insoluble Ag-Ab complexes
can’t be removed
– Intense inflammation
– Severe damage to local tissue
– Also involved in autoimmune diseases
Pathologies: Delayed Hypersensitivities
• Occurs 1-3 days after exposure
• Cell-mediated immune response
• Causes mild swelling to serious cytotoxic tissue
damage (contact dermatitis, e.g., TB skin test,
poison ivy, latex gloves, etc.)
• [Note: Sometimes allergies may be temporarily
transferred by blood or plasma transfusions.]
End Chapter 21