IM Flashcards
Healthy immune system functions for: (3)
- Surveillance of the body
- Recognition of foreign material
- Destruction of entities deemed to be
foreign
innate/Natural/Non-Specific Immunity:
Stimulated by structures common to groups of
related microbes; cannot distinguish between
fine differences of foreign substances.
Acquired Immunity:
Very specific response to a distinct macromolecule, also has the ability to “remember” macromolecule and respond more vigorously to the second exposure
The two systems influence
each other:
Innate
stimulates adaptive;
adaptive utilizes innate
mechanisms.
Agranulocytes: (2)
- Monocytes/Macrophages
2. Lymphocytes
Granulocytes (3)
1 Neutrophils
2 Eosinophils
3 Basophils
order of prevalence of leukocytes (5)
neutrophils lymphocytes monocytes eosinophils basophils
Leukocytes or White Blood Cells
All are — and are larger and less
numerous (6000–10,000/μL) than
erythrocytes.
nucleated
Leukocytes or White Blood Cells
The granulocytes are —.
polymorphonuclear
Acute inflammation is protective; it (3)
neutralizes harmful
agents, removes dead tissue and initiates the tissue repair
process.
Damaged cells release inflammatory mediators, which (3)
stimulate the inflammatory process but they can also injure
normal tissue. The mediators can act locally or systemically.
Cardinal Signs of Acute
Inflammation (5)
1. Rubor (Red Discoloration) 2. Calor (Heat) 3. Dolor (Pain) 4. Swelling 5. Loss of Function
Phagocytosis (2)
- Non-self or damaged particles are engulfed by cells.
* Essential part of inflammation and acquired immunity.
Innate Immunity
Accomplished primarily by neutrophils & macrophages.
Macrophages can phagocytize far more & larger material than neutrophils.
Macrophages are already in the tissue.
Innate Immunity
How does a phagocyte recognize its “meal”? (4)
1. Phagocytes contain Toll-Like Receptors (TLRs) that are capable of recognizing generic Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs) 2. Rough surface 3. Native substances should have protein coats that repel phagocytes 4. If a target has an immunoglobulin/antibody attached to it, then it is marked for phagocytosis (opsonization)
Interferons (INF)
• Virally-infected cell secrete —.
INF
Interferons (INF)
Secreted INF cause uninfected
cells to
produce enzymes that
inhibit viral replication, which
prevents spread of the virus to
neighboring cells.
Complement System• Consists of --- distinct components that are in plasma in an inactive form and must be cleaved to become active. Activated by
30
substances on the
surface of microbes.
Complement
System
Cascade of reactions leading to: (3)
(1) enhancement of inflammation,
(2) opsonization of pathogens,
(3) formation of a Membrane-Attack
Complex (MAC) that lyses
pathogens.
Complement
System
Also part of acquired immunity because
antibodies can activate the complement
system (Classical Pathway).
Acquired Immunity
very specific response to a distinct macromolecule (antigen), also has
the ability to “remember” macromolecule and respond more vigorously
to the second exposure. The process requires activation and
lymphocytes (B and T).
Antigens:
Each toxin or type of pathogen
contains one or more specific chemical
compounds in its make up that are different
(antigens). Antigens are molecules capable
of inducing an acquired immune response
by binding to B-cell and T-cell receptors and
the production of antibodies against them.
Antigens are usually surface peptides or
polysaccharides.
Antigen:
Peptides or
polysaccharide that are part
of a molecule on an
organism.
Epitope:
Molecular
group on the antigen
that is recognized by
the immune system.
Antigen Presenting Cells
(APCs) present Antigens on
their surface via
Major
Histocompatability Complex
(MHC) Class II molecules.
APCs bind to and activate
T helper cells (CD4).
T helper (CD4) cells activate
the two branches of Acquired
Immunity:
- Humoral
2. Cell-Mediated
APCs: (3)
- Macrophages
- Lymphocytes
- Dendritic cells
• Macrophages
ingest the pathogen and
induce an inflammatory response, if
appropriate.
• Dendritic cells
ingest the antigen and
migrate to the nearest lymphoid organ
Cell-Mediated Immunity
Activated T cells (Natural Killer and
Cytotoxic T, CD8) result in killing of
infected cells and stimulation of
phagocytosis of bacteria and fungi.
Humoral Immunity
aka Antibody-Mediated
Activated B cells develop into Plasma cells that secrete Immunoglobulins. The antibodies neutralize toxins and viruses and enhancing phagocytosis of bacteria (opsinization)
Activated T & B cells interact with
pathogens & initiate a response in
secondary lymphoid tissues (e.g.
lymph nodes, spleen, nodules
(tonsils, mucosa-associated
lymphoid tissue, etc.)).
After activation, T and B Lymphocytes
replicate a tremendous number of times
(= clones) and are secreted into the
lymphatic circulation. From there they
cycle through the blood, tissue, and back
to the lymph, working as effector cells to
eliminate the antigen for which they are
activated.
Each B cell has ~—
antibodies in its membrane for a
single antigen.
100,000
MHC Class II:
Found on Antigen Presenting Cells (macrophages, dendritic cells, etc.); involved in presenting antigens to T Helper cells for cell mediated immunity
MHC Class I:
code for markers that display unique characteristics of self and foreign antigens when the cell is infected
Antigen Presenting
Cell Membrane
(ex. Macrophage)
Interaction causes (2)
activation of the
T cell and
creation of T cell
clones.
Cell Membrane of
All Nucleated Cells
Interaction causes
destruction of an
infected cell when it
presents a foreign
antigen
T Helper Lymphocytes/Cells (CD4 Cells)
Activated by Antigen Presentation via
MHC Class II (4)
1. Growth and proliferation of Cytotoxic and Suppressor T lymphocytes 2. Growth and proliferation of B lymphocytes 3. Stimulates activation of more T Helper Cells 4. Activation of macrophage system
- Activation of macrophage system (2)
a. Attract & slow/stop macrophage migration away from inflamed regions b. Stimulate more efficient phagocytosis
Cytotoxic T-Lymphocytes/Cells (CD8 Cells)
Activated by Antigen Presentation via MHC Class I. All nucleated
cells can present antigens to Cytotoxic T Cells because
all cells (except RBCs) have MHC I.
- After binding antigens, Cytotoxic T cells: (2)
a. Secrete perforin molecules that punch
holes in the membrane of the target. The
targeted cell will swell and lyse.
b. Release cytotoxic substances (granzymes)
into the target through perforin channels
that stimulate apoptosis
After secreting substances, Cytotoxic
Cells can
unbind and move on to another
cell
Suppressor T Cells (aka Regulatory T cells) (3)
- Capable of suppressing functions of both cytotoxic
and helper T cells - May be a separate type of cell, but they may not
Many T cells may function as suppressors by
secreting inhibitory cytokines - These cells are very important as they limit the
immune system’s ability to attack one’s own tissues
—they add to immune tolerance
B cells and the antibodies they secrete create humoral
immunity. (3)
- B Cells are activated by intact antigens but also by
activated T helper cells. - When B cells are activated, they enlarge and look
like lymphoblasts - Some B cells differentiate into plasmablasts which
later become plasma cells
Some B cells differentiate into plasmablasts which
later become plasma cells (3)
a. One plasmablast will produce 500 plasma cells in 4 days b. A mature plasma cell can produce 2000 immunoglobulins/second c. Immunoglobulins are secreted into the lymph and carried into the blood for circulation.
Fc Region (Constant Portion) determines
(3) The heavy chain also
determines (1)
diffusivity through membranes & tissue,
complement attachment, & other biological
properties.
Ig classification.
Phagocytes have Fc receptors,
so antibody binding to an antigen
can lead to
enhanced phagocytosis (OPSONIZATION).
Most abundant Ig in blood; crosses the placenta
IgG
IgG (7)
– Most abundant Ig in blood; crosses the placenta
– Complement activation
– Opsonizes bacteria
– Neutralizes bacterial toxins and viruses
– Antibody-dependent cell-mediated cytotoxicity mediated
by NK cells & macrophages
– Primary antibody in the secondary response
– Mediates Type II (ex. blood transfusion reaction) and III
(ex. Grave’s Disease, Myasthenia Gravis, Lupus)
Hypersensitivity Reactions
IgE (3)
– Mediates immediate (type I) hypersensitivity reactions
(asthma, hay fever, anaphalysix, food allergies, drug
sensitivity, etc.)
– Defends against parasitic infections
– Activates basophils, mast cells, and eosinophils
IgA (3)
– Secretory Ig; synthesized by plasma cells in exocrine glands (saliva, tears, saliva, etc.)
– Most abundant Ig in the body (mucosal sites)
– Mucosal immunity and neonatal immunity (transfer via breast milk)
IgM (4)
– Most potent activator of complement
– Largest of the immunoglobulins
– The first type produced in response to an antigen
– Membrane bound on B (monomer) but can also be
secreted as a pentamer
Membrane bound on B (monomer) but can also be
secreted as a pentamer
B cells begin to express (2) when they reach
maturity. Expression of (2) antibodies on their
membrane surface allows the B cell to be able to
IgM and IgD
IgM and IgD
respond to
antigens.
IgD (1)
– Membrane bound; Receptor on B lymphocytes
surface and aids in antigen recognition by B
lymphocytes
After activation by antigen, B cells undergo antibody class switching to produce (3) antibodies. This allows daughter cells from the same activated B cell to produce
IgG, IgA or IgE
different types of
antibodies
Mechanisms of
Immunoglobulin
Action (6)
- Neutralization
- Agglutination
- Precipitation
- Complement Fixation
- Opsonization
- Activation of NK Cells
TOLERANCE (immunologic unresponsiveness to self antigens)
is vital for life and develops during preprocessing of T & B
lymphocytes. (2)
- Clonal deletion occurs within the fetal thymus & bone
marrow (central tolerance). - Clonal anergy (peripheral tolerance) is when cells that
are self-antigenic become non-functional.
If SELF tolerance fails =
autoimmune disease
–% of
autoimmune
diseases occur in
women
90
skipped
Theories for why immune tolerance
fails… (5)
1. Failure of regulation of self-reactive lymphocytes 2. Exposure of T lymphocytes to antigens previously sequestered from the immune system 3. Molecular mimicry by invading pathogens. 4. Modification of self antigens 5. Inappropriate expression of Class II MHC Molecules (antigen-presenting molecules)
skipped
- Molecular mimicry by invading
pathogens. (2)
a. Invading antigens have a similarity to self-antigens b. Occurs in Rheumatic Fever: Streptococcal M protein resembles a portion of cardiac myosin
skipped
Examples of Autoimmune Diseases (8)
• Rheumatic Fever • Myasthenia Gravis • Systemic Lupus Erythematosus • Rheumatoid Arthritis • Sjogren’s Syndrome • Multiple Sclerosis • Type I Diabetes • Graves’ Disease
Treatment includes (2)
immunosuppression and/or plasmapheresis.
mediator: Antibody (IgE)
type:
reaction:
I (immediate, anaphylactic)
IgE antibody is induced by allergen, binds to mast cells
and basophils. On succeeding exposures, the allergen
cross-links bound IgE and induces degranulation of mast
cells & basophils. Ex. Allergic and Anaphylactic reactions,
Asthma
mediator: Antibody (IgG)
type:
reaction:
II (cytotoxic)
Antigens on a cell surface combine with antibody; this
leads to complement-mediated lysis.
Ex. Blood transfusion reactions, Hemolytic disease of the
newborn
mediator: Antibody (IgG)
type:
reaction:
III (immune complex)
Antigen-antibody immune complexes are deposited in
tissues, complement is activated, and polymorphonuclear
cells are attracted to the site. They release lysosomal
enzymes, causing tissue damage. Ex. Systemic Lupus
Erythematous, Grave’s Disease, Myasthenia Gravis
mediator: cell
type:
reaction:
IV (delayed)
Helper T lymphocytes sensitized by an antigen release
lymphokines upon second contact with the same antigen.
The lymphokines induce inflammation and activate
macrophages, which, in turn, release various mediators.
Ex. Contact dermatitis
Immediate Hypersensitivity Reactions, Type I (5)
a. One of the most powerful immune reactions
b. Occurs when IgE stimulates mast cells and
basophils
c. Release of secretory products from mast cell
granules (ex. Histamine) causes:
d. Immediate Hypersensitivity begins within minutes of
antigen introduction
e. There is also a late phase reaction
b. Occurs when IgE stimulates mast cells and
basophils (2)
• There is an extremely strong attraction between the two
(one mast cell/basophil can bind 500,000 IgEs)
• Mast cells & basophils are most concentrated in the lung,
skin, and GI tract
c. Release of secretory products from mast cell
granules (ex. Histamine) causes: (2)
• Increases vascular permeability, vasodilation, bronchial and
visceral smooth muscle contraction, salivary and bronchial
secretions, and inflammation
• INCREASES respiratory resistance, DECREASES BP
Can be life threatening if severe due to
bronchoconstriction and vasodilation -
ANAPHALYXIS
d. Immediate Hypersensitivity begins within minutes of
antigen introduction
IgE-primed mast cells can remain in the tissues for years. A person retains the capacity to react immediately upon re-exposure. Next time allergen molecules contact the mast cells, they bind across adjacent receptors and stimulate degranulation
e. There is also a late phase reaction (2)
• Inflammatory infiltration of eosinophils, basophils,
neutrophils, and lymphocytes 2-4 hours after degranulation
of mast cells & basophils
• This stage is capable of damaging tissue
Treatment and Prevention of Type I Allergic Response (3)
- Avoid the allergen
- Take drugs that block
the action of
lymphocytes, mast
cells, or chemical
mediators - Undergo
desensitization
therapy
- Undergo
desensitization
therapy (3)
– Controlled injections of the antigen – Works by producing IgG antibodies rather than IgE – IgG considered to be “blocking antibodies”
If you are “allergic”, you produce —
antibodies in response to environmental
allergens
IgE
If you are “allergic”, you produce IgE
antibodies in response to environmental
allergens (6)
• Hay Fever • Asthma • Drug hypersensitivity (penicillin) • Food allergies (most common: peanuts, fish, cow milk, eggs, shellfish, soybeans) • Urticaria (hives) • Anaphylaxis
Delayed –Type Hypersensitivity Reactions. Type IV
Hypersensitivity. Mediated by T cells (3)
a. The pathogen does not cause much damage to the tissue b. Instead, helper and cytotoxic T Cells are activated (increasingly so on repeat exposures) c. Produce a cell-mediated immune reaction, stimulating macrophage recruitment and inflammation d. Damage is delayed 1-2 days • Normally restricted to tissue area exposed to pathogen
