Immunology - Doc Derecho Flashcards
Study of host defense mechanisms
Immunology
Ability of the host to protect itself against foreign organisms
Immunity
_______, _______ and _______ mount the immune response.
Tissues, cells and molecules
Ultimate function of the immune system:
Recognize and Destroy
Foreign substances
Antigens
Antigen + Antibody
Immune response
What is the key to a healthy immune system?
Ability to distinguish between SELF (body’s own cells) and NONSELF (foreign cells)
Mistake self for nonself
Autoimmune disease
Cells carry _______ marker molecules
Self
Cells with foreign markers
Antigen
Body launches an attack
Immune response
Deficient immunity results in increased susceptibility to infections exemplified by _________
AIDS
Defense against infections
Boosts immune defenses and protects against infections
Vaccination
Defense against infections)
Potential for immunotherapy of cancer
Defense against tumors
Deficient immunity can lead to secondary infections after injury and excessive immune responses can lead to FIBROSIS and ORGAN DYSFUNCTION
Clearance of dead cells and tissue repair
Immune responses are the cause of allergic, autoimmune and other inflammatory diseases
The immune system can injure cells and induce pathologic inflammation
Immune responses are barriers to transplantion and gene therapy
The immune system recognizes and responds to TISSUE GRAFTS and newly introduced proteins
Cells arise in ______________ and they interact with antigens in ______________
Primary lymphoid organs
Secondary lymphoid organs
Primary lymphoid organ for T cells development
Thymus
Primary lymphoid organ for B cell development
Bone marrow
Collect antigens from tissues
Lymph nodes
Collects antigens from blood stream mostly B cells
Spleen
Mostly fixed macrophages (KUPFFER CELLS)
Liver
Mostly B cells
Adenoids and tonsils
All immune cells begin as __________ in the bone marrow.
Immature stem cells
*They respond to different cytokines and other signals and they grow into specific immune cell types such as T cells, B cells or phagocytes.
Interesting possibilty for treating some immune system disorders
Stem cells
Can person’s own stem cells be used to regenerate damaged immune responses?
In autoimmune diseases and immune deficiency diseases
Immunity an organism is BORN WITH, genetically determined and effective from birth.
Innate immunity
Present BEFORE EXPOSURE to pathogens
Innate immunity
Nonspecific responses to pathogens
Innate immunity
Same molecules or cells respond to a range of pathogens
Non-antigen-specific
Same response after repeated exposure
No immune memory
Does not generate lasting protective immunity and no racial difference
Innate immunity
First line and relies on mechanisms that exist before infection.
Innate immunity
Rapid response to microbes
Innate immunity
Immediate direct response of innate immunity
0-4 hours
Rapid induced response of innate immunity
4-96 hours
Found in plants, invertebrates and vertebrates
Innate immunity
Immunity that an organism develops during lifetime
Adaptive immunity
*Not genetically determined.
Develops after exposure to antigens (microbes, toxins or other foreign substances)
Adaptive immunity
Very specific response to pathogens
Adaptive immunity
May be acquired naturally or artificially.
Adaptive immunity
Adaptive immunity is mediated by either:
Antibodies (Humoral immunity) Lymphoid cells (Cellular immunity)
Relies on mechanism that adapt after infection.
Adaptive immunity
Adaptive immunity is handled by:
T and B lymphocytes
Adaptive immunity late response:
> 96 hours
Is initiated if innate immune response is not adequate (> 4 days)
Adaptive immunity
Destroy infected cells to eradicate intracellular pathogens
T cells
Secrete antibodies to attack extracellular pathogens
B cells
Each cell responds to a single epitope on an antigen
Antigen-specific immunity
Generates lasting protective immunity
Adaptive immunity
Based upon resistance and acquired during life
Adaptive immunity
Relies on genetic events and cellular growth
Adaptive immunity
Adaptive immunity has ____________, a repeated exposure leads to faster, stronger response.
Anamnestic memory
The two features that best distinguish adaptive and innate immunity are ___________ and ___________.
Specificity and memory
Ensures that distinct antigens elicit specific responses
Specificity
Enables immune system to respond to a large variety of antigens
Diversity
Leads to enhanced respones to repeated exposures to the same antigens.
Memory
Increases number of antigen-specific lymphocytes to keep pace with microbes
Clonal expansion
Generates responses that are optimal for defense against different types of microbes
Specialization
Allows immune system to respond to newly encountered antigens
Contraction and homeostasis
Prevents injury to the host during responses to foreign antigens
Nonreactivity to self
Innate immunity (immediate: _______)
0-4 hours
Early induced response (early: _________)
4-96 hours
Adaptive immune response (late: _________)
> 96 hours
Provides a barrier to prevent the spread of infection
Innate immunity
Identified and eliminates pathogens by:
- Non-adaptive recognition systems
- Activates molecules that target the microbe and aid in its identification
Innate immunity
Initiates an inflammatory response
Innate immunity
Delivers effector molecules and immune cells to the site of infection
Innate immunity
Provides signals to activate and regulate the type of adaptive immune response generated.
Innate immunity
B7 family:
CD80/86
PD-L
ICOSL
TNFR family
OX40L
Cytokines involve in innate immunity:
IL-12
IL-23
IL-4
Chemokines involve in innate immunity:
CXCR1
CXCR2
CCL20
Clinical, subclinical infection
Natural active immunity
Via breastmilk, placenta
Natural
Vaccination: live, killed, purified antigen vaccine
Artificial active immunity
Immune serum, immune cells
Artificial passive immunity
Antigens enter the body naturally; body produces antibodies and specialized lymphocytes
Naturally acquired - Active
Antibodies pass from mother to fetus via placenta or to infant in the mother’s milk
Naturally acquired - Passive
Antigens are introduced in vaccines: body produces antibodies and specialized lymphocytes
Artificially acquired - Active
Preformed antibodies in immune serum introduced into body by injection
Artifically acquired - Passive
Foreign antigens enter the body
Naturally acquired active
Person CONTRACTS disease which generates specific immune response to the antigen.
Naturally acquired active
Naturally acquired active may be _________ (chickenpox or mumps) or _________ (influenza or intestinal infections)
Lifelong or temporary
Elicits the production of antibodies against antigens.
Humoral immunity
Triggers specialized lymphocytes (T-cells)
Cell-mediated immunity
Examples of naturally acquired PASSIVE:
- Breastmilk
- Colostrum
- IgG
Components of breastmilk
IgA and monocytes
Contains BIFIDUS factors, antibodies that protect the newborn gastrointestinal tract
Colostrum
A type of antibody that is transplacental and protects the infant up to 3 months
IgG
Vaccination
Artifically acquired active
Diphtheria tetanus pertussis (DTP)
Artifically acquired active
Measles mumps rubella
Artifically acquired active
Polio
Artifically acquired active
Haemophilus influenzae type B
Artifically acquired active
Chicken pox
Artifically acquired active
Hepatitis B
Artifically acquired active
Collecting IgG from an infected immune person and transferring this immunity to an unprotected person
Artifically ACQUIRED passive
Snake antivenom injection from horses or rabbits
Artifically ACQUIRED passive
Used in the ttt. of tetanus, diphtheria and mumps
Artifically ACQUIRED passive
Sometimes given to infants who are not producing enough antibodies
Artifically ACQUIRED passive
B-cell immunity
Humoral
Antibody mediated immunity (AMI)
Humoral
Body develops circulating antibodies
Humoral
Globulin molecules in the blood plasma that are capable of attacking the invading agent
Antibodies
Produce the antibodies
B-lymphocytes
T-cell immunity
Cell-mediated
Formation of large numbers of activated T-lymphocytes
Cell-mediated
Specifically crafted in the lymph nodes to destroy the foreign agent
T-lymphocytes
Antibody producing cells that respond to an antigen stimulation
B lymphocytes
B lymphocytes are ______% of circulating lymphocytes
10-15%
B lymphocytes are pre-processed in the ______ during midfetal life and in the ______ during late fetal life and after birth.
Liver
Bone marrow
Migrate to and are preprocessed in the THYMUS GLAND
T lymphocytes
80% of circulating lymphocytes
T-lymphocytes
Mature in bone marrow; develop from stem cells located in the red bone marrow of adults and the liver of a fetus.
B cells
B cells once activated proliferate into two clones of cells:
- Plasma cells - secrete antibodies
2. Memory cells - that may be convered into plasma cells at a later time
Recognize pathogens from previous encounters
Memory cells
Long lived and are ready to mount an attack the next time that specific antigen presents itself.
Memory cells
B cells mature into ________ that produce antibodies
Plasma cells
Key cellular component of immunity
T cells
Precursors to T cells migrate to the ______ then will reach maturity then migrate to various lymph organs where they await contact with antigens.
Thymus
Involved in cellular immunity.
T cells
The 6 cells of Cell Mediated Immunity:
- T helper 2 cells (TH2)
- T helper 1 cell (TH1)
- T supressor cell (TS)
- T cytotoxic cell (TC)
- Natural killer cell (NK)
- Macrophage (MP)
Considered a type of T cell
Natural killer cell
The two main types of T cells each responds to one class of _________.
MHC molecule
Activate phagocytes to kill microbes
CD4+ T cells
Helper T cells have receptors that bind to peptides displayed by the body’s ________ molecules.
Class II MHC
CD8+ T cells
Cytotoxic T-lymphocytes (CTLs)
Destroy infected cells containing microbes or microbial proteins
CD8+ T cells
Cytotoxic T cells (Tc) have antigen receptors that bind to protein fragments displayed by the body’s __________.
Class I MHC molecules
T cells only recognize antigen associated with _______ on cell surfaces.
MHC molecules
In response to antigens found on the APC, the TH2 cells secretes _____________.
Interleukin 2 (IL-2)
Starts cell mediated immunity
Interleukin 2 (IL-2)
_______ signals other T cells specific for antigen to proliferate and become active.
IL-2
Recognize the non-self cell and induce APOPTOSIS (cell self death) in the viral infected or other microbial infected cell.
Cytotoxic T cells (CD8+ CTLS)
Killer T cell
Cytotoxic T cells
Cytotoxic T cells are activated by ________.
TH2 cells
Immunological surveillance that kills abnormal cells that arise by mutations.
Cytotoxic T cells (CD8+ CTLS)
Produce cytokines and direct immune response
Helper T cells (Th cells)
Effector mechanism that involves T- lymphocytes
Cell-mediated immune response (CMIR)
Eliminate intracellular microbes that survive within phagocytes or other infected cells.
Cell-mediate immune response
Effector mechanism that involve B-lymphocytes
Humoral immune response
Mediated by antibodies and eliminate extracellular microbes and their toxins.
Humoral immune response (HIR)
Formed as a result of antibodies produce by B plasma cells attract phagocytes which destroys pathogen
Antigen-antibody complexes
Cells taking part in immune response under humoral or antibody-mediated immunity:
- APC (Macrophage or dendritic cell)
- T cell
- B cell
T cells activated by binding to certain antigens
T-independent antigens
No memory cells generated
T-independent antigens
Weaker response than T-dependent Ag
T-independent antigens
Most antigens require co-stimulation to evoke a B-cell response.
T-dependent antigens
Antibody production stimulated with help from ______.
TH
Most antigents are ____________.
T-dependent
T-dependent antigens trigger humoral response by B cells only with the participation of _______________.
Helper T cells
1 from many B cell (Each lymphocyte bears a specific receptor to the antigen)
Selection of B cells
Activation of B cells:
- Selection of B cells
- Recognition of antigens
- Processing of Ag by macrophages
- Ag presentation by macrophages to B cells
- Triggering of the B cell by the Ab or TH cells
- Clonal proliferation
- Production of Plasma cells and memory cells
- Secretion of Ig into the serum
Mature lymphocytes with an ANTIGEN RECEPTOR but have not encountered the antigen.
Naive lymphocytes
Function is antigen recognition
Naive lymphocytes
The preferential migration of naive lymphocytes is to _________________, the sites where antigens are concentrated and immune responses start.
Peripheral lymphoid organs (lymph nodes)
Have received confirmation of the danger of the antigen and are able to PROLIFERATE MORE LYMPHOCYTES SPECIFIC FOR THAN ANTIGEN.
Activated lymphocytes
Descendants of activated lymphocytes
Effector lymphocytes
Capable of performing the functions required to eliminate microbes (“effector molecules”)
Effector lymphocytes
Responsible for cytokine secretion (helper cells) and killing of infected cells (CTLs)
Effector lymphocytes
Long-lived descendants of activated lymphocytes
Memory lymphocytes
Functionally SILENT CELLS
Memory lymphocytes
Can revert back to activated lymphocytes with stimulation from the same antigen.
Memory lymphocytes
Mount rapid responses to antigen challenge (secondary responses)
Memory lymphocytes
Most CLONE CELLS become _____________.
Antibody-secreting plasma cells (effector cell-short-lived cells)
___________ secrete specific antibody at a higher rate than B cells.
Plasma cells
Production of specific clones of effector T cells and memory clones
Primary response
Develops in several days and DOES NOT limit the infection
Primary response
More pronounced, faster and more effective at limiting the infection.
Secondary response
Cytotoxic reactions against intracellular parasites
Secondary response
Delayed hypersensitivity (e.g Tuberculin test)
Secondary response
Allograft rejection
Secondary response
Under primary response, _________ to antigen produces NO ANTIBODIES in serum for several days.
Initial exposure
Primary response has a gradual INCREASE in titer. First of IgM and then of IgG observed after ________ days.
3 to 6
Most B cells become plasma cells. Some B cells become long living memory cells.
Primary response
Peak levels of plasma antibody after a primary response are achieved in _________ and gradual DECLINE of antibodies follows.
10 days
Subsequent exposure to the same antigen displays a FASTER and MORE INTENSE Ab response within an hour.
Secondary response
It is due to the existence of __________ which rapidly produce plasma cells upon antigen stimulation.
Memory cells
In secondary response, antibody levels peak in ____________.
2 to 3 days
Antibody levels in the blood can remain HIGH FOR WEEKS TO MONTHS.
Secondary response
Memory cells initiate a faster, more efficient response upon reinfection.
Immunity
The antibody marks the antigen for destruction.
Antigen-antibody interlock
Antigen is derived from two words:
ANTIbody GENerator
Most antigens are __________ or ____________.
Proteins or large polysaccharides
When an antigen elicits an immune response it is often referred to as a ___________.
Immunogen
Reactive portion of the antigen
Epitope
Reacts chemically with an antibody to form the antigen-antibody complex or immune complex.
Epitope
Two essential properties of antigens include:
- Immunogenicity
2. Ability to stimulate immune system
Belong to a family of large molecules known as IMMUNOGLOBULINS
Antibodies
Antibodies belong to the gamma-globulin fraction of serum proteins called _______________.
Immunoglobulins (Igs)
Has two identical antigen-binding sites
Immunoglobulins
Specific for the epitope that provides it production
Immunoglobulins
Y shaped or T shaped polypeptides
Antibodies
Antibodies consist of ____ POLYPEPTIDES
4
Antibodies are covalently linked by ___ disulfide bonds.
4
This is the part of the antibody that binds to the antigen.
Fab region
The stem of the antibody that functions as a “red flag” and notifies the rest of the immune system: “here I am come and help”
Fc region
2 constant regions
Fc fragment and crystallizable
2 variables regions
Fab fragment and antigen binding
Contain hypervariable amino acid sequences
Variable regions
Bind antigen (specific immunity)
Hypervariable regions
Most common form
IgG
First response to antigen
IgM
Secreted from mucus membranes
IgA
B cell activation
IgD
Histamine reactions and allergies
IgE
Cannot cross placenta
IgD
Prevents attachment of bacteria to epithelial surface
IgA
Effective in agglutination
IgM
Crosses blood vessels
IgG
Cannot cross placenta
IgM
Crosses placenta (passive immunity to fetus)
IgG
Monomeric and 70-75% of total immunoglobulin
IgG
Pentameric and cannot cross the placenta
IgM
Monomeric in SERUM
IgA
Secreted in high quantities in SECONDARY EXPOSURES
IgG
Secreted first during exposure
IgM
5-10% of serum antibody
IgA
IgG 4-fold rise or fall means:
Active infection
Activates the complement
IgM
DIMERIC with secretory component in the lumen of the GI tract and in respiratory tract
IgA
Opsonize antigens for phagocytosis
IgG
Used as a marker of RECENT INFECTION
IgM
Neutralizes microbes and toxins
IgA
Neutralizes toxins and viruses and can activate the complement
IgG
Presence of IgM in newborns means __________.
Infection
Sero-diagnosis of tuberculosis
IgA
Protects the fetus and newborn (passive immunity)
IgG
*only Ig transferred across the placenta
Single positive of IgM in serum or CSF indicates:
Recent or active infection
Synthicial respiratory virus tests
IgA
Circulates in the blood but can easily exit to the tissues
IgG
Detect early phase of infection
IgM
Provides localized protection on mucosal surfaces
IgA
MOST ABUNDANT circulating antibody
IgG
Especially effective against microorganisms and clumping antigens
IgM
Most common form
IgG
First antibodies produced in response to a MILD INFECTION
IgM
Are circulating antibodies found in the circulatory system with IgG
IgM
IgG or IgM reacts with epitopes on the host cell membrane and activates the ______________
Classical component pathway
Causes lysis of the cell
Membrane attack complex
Produced as a first response to many antigens
IgM
Levels remain HIGH TRANSIENTLY
IgM
Produced after IgM
IgG
Higher levels persist in small amounts throughout life
IgG
Produced in large amounts during secondary response
IgG
Persistence of antigen sensitive “memory cells” after primary response
IgG
Found in mucus, tears, saliva, sweat, blood and human milk
IgA
Protects surface tissues and prevents adherence of microorganisms
IgA
*This is important in respiratory, gastrointestinal and genitourinary tract infections
True or False:
IgD is monomeric.
True
Present on the surface of B lymphocytes functions in the initiation of an immune response
IgD
0.2% of serum antibody
IgD
Functions as MEMBRANE RECEPTOR
IgD
Has a role in antigen stimulated lymphocyte differentiation
IgD
*Role unclear
Effects of complement system:
- Enhances inflammatory response (Attracts phagocytes)
- Increases phagocytosis through opsonization or immune adherence
- Creates membrane attack complexes (cytolysis)
Series of 30 plasma (serum) proteins activated in a cascade
Complement system
Work together to “complement” the action of antibodies in destroying bacteria
Complement system
Plays a role in the initiation of the inflammatory response
IgE
Found in the BLOOD SERUM
IgE
Also rid the body of antibody-coated antigens (antigen-antibody complexes)
Complement system
Plays a role in immunity to helminthic parasites
IgE
Possibly involved in the lysis of parasitic worms
IgE
IgE are antibodies responsible for ____________.
Allergic reaction
Principal actors in the complement system are 11 proteins:
C1 through C9
B and D
0.002% of serum antibody
IgE
Mediates type I hypersensitivity
IgE
Associated with ANAPHYLAXIS
IgE
Serodiagnosis of infectious and noninfectious allergies (allergic bronchopulmomary aspergillosis, parasitic diseases)
IgE
Does not require a specific antibody to get started.
Alternative pathway
Can be triggered by infectious agents in absence of antibody
Alternative complement pathway
*It has the same terminal sequence of events as the classical pathway
Alternative complement pathway does not require _____, _____ or ______.
C1, C2 or C4
Combines with factors B, D and P on the surface of a microbe
C3
No antibody involved, once C3a and C3b are formed they participate in cytolysis, inflammation and opsonization
Alternative complement pathway
Does nor require a specific antibody to get started.
Lecithin pathway
Effects of complement activation:
- Opsonization or immune adherence: enhanced phagocytosis
- Membrane attack complex: Cytolysis
- Attract phagocytes
Coat bacteria and promote attachment of micoorganism to phagocyte
Opsonin (complement proteins or antibodies) / Opsonization
Prevent complement activation
Capsules
Prevent MAC
Surface lipid-carbohydrates of some gram-negatives
Enzymatic digestion of _______ by gram positives
C5a
A drug given to transplant patients in order to block immunological rejection
Cyclosporin
Cyclosporin blocks synthesis of ________.
IL-2
Makes sure markers of self on the donor’s tissue are as similar as possible to those of the recipient.
Tissue typing
Each cell has a double set of ____ major tissue antigens and each of the antigens exists.
6
In bone marrow transplants, a _________ is extremely important.
Close match
Type I hypersensitivity occurs within _______ after exposure to allergen.
30 minutes
The _____ of IgE binds to mast cells or basophils.
Fc
When IgE binds to allergens, ___________ are released.
Fluid phase mediators
Uses patient’s serum to measure specific IgE.
RAST (radioimmunoassay test)
Takes 5-12 hours
Type II hypersensitivity
Involves TC cell or antibody plus complement lysis
Type II hypersensitivity
Incompatible blood transfusion
Type II HPS
Erythroblastosis fetalis
Type II HPS
Thrombocytopenic purpura
Type II HPS
Occurs in 3-8 hours
Type III HPS
Requires Ab+ slight excess of solubilized antigen
Type III HPS
Activation of complement
Type III HPS
Precipitation of immune complex in sensitive tissues
Type III HPS
Occurs in 24-48 hours
Type IV HPS
Allergic contact dermatitis to gold and other metal and poison ivy
Type IV HPS
Indurated hard bump consisting of macrophages signaled by thee TH1 cell to migrates to the site of specific antigen
Type IV HPS
Glomerulonephritis
Type III
IDDM (juvenile onset diabetes)
Type IV HPS
Systemic lupus erythematosus
Type IV
Rheumatoid arthritis
Type III
From loss of self tolerance
Autoimmune disease
