CHAPTER II – IMMUNITY Flashcards
It is the study of: discriminating self from non-self
IMMUNOLOGY
IMMUNOLOGY PURPOSE:
eliminate non-self components such as infectious agents
Responsible for the surveillance and destruction of substances that are foreign to the body
IMMUNE SYSTEM
Attack microorganism that exists outside the host’s cell or used to attack microorganisms that infect cells
IMMUNE SYSTEM
Defending the body against the development of tumors
IMMUNE SYSTEM
IMMUNE SYSTEM Divided into two main categories based on:
(a) the manner in which the interaction with the foreign substance,
(b) and whether it causes a more efficient response towards a subsequent infection
: silent gene; needs stimulus to develop into cancer
ONCOGENE
: chronic smoking
Oral, mouth, lung cancer
: unhealthy foods, reheating
Colon cancer
(scavenger organ; cleans senescent/old RBCs)
spleen
TYPES OF IMMUNITY
Non-specific immunity
INNATE IMMUNITY
Refers primarily to anatomical, cellular, and humoral defenses that functions in the early stages of host defense
INNATE IMMUNITY
Physical
Barriers; skin, mucus, cilia
Flushing Action: Blinking of eyelids, Peristalsis and Urination
Chemical
Salts: Cerumen and Sebum
Acids: Low pH of Stomach and Vagina
Lipids: Fatty acids in the sebaceous glands and gallbladder
Normal flora
Non pathogenic bacteria in:
oGIT
oVagina
oNasopharynx
Non pathogenic bacteria in:
oGIT –
oVagina –
oNasopharynx –
Citrobacter, Bacteroides, E. coli (passed in stool)
Lactobacillus acidophilus: maintains acidic pH
Streptococcus, Neisseria
Physiologic process
Sneezing
Coughing
Vomiting, Gag reflex
Perspiration
Shivering
Crying
Urinatio
Defacation
Sweat maintains skin pH at
5.6 (acidic)
Acids: Low pH of Stomach and Vagina
oDue to
HCl or Pepsin
Resistant to stomach acid
Causes peptic ulcer
Produces UREASE (alkaline)
Helicobacter pylori
– through ingestion
Vomiting, Gag reflex
Maintenance of normal temperature
Perspiration
– to prevent hypothermia
Shivering
Crying– tears contain
(antibacterial; has IgA)
lysozymes
Others
Body temperature
Oxygen Tension
- < 37oC
Body temperature
– thin air; increased hemoglobin
Oxygen Tension
SECOND LINE OF DEFENSE
CELLULAR FACTORS
NON-CELLULAR/SOLUBLE SUBSTANCES IN BLOOD (HUMORAL FACTORS)
1.Phagocytes
2.Basophil and Mast Cells
3.NK Cells
4.APCs
1.Complement System
2.Cytokines
3.Interferons
4.Inflammatory Reaction
5.Acute reactants
Secretion of factors primarily involve in the second line of defense
CYTOKINES
Promotes inflammatory response
Interleukin-1
Hydrolytic enzymes
Promotes innate immunity
Interleukin-6
Promotes elimination of pathogens through cell lysis
Complement
Kills tumor cells
Tumor Necrosis Factor
Able to interfere with viral replication
INTERFERON
Prevent viruses to reach target cells
INTERFERON
IFN-alpha Other name
Leukocyte IFN
IFN-beta Other name
IFN-gamma Other name
IFN-alpha Primary producers
Null Lymphocytes
IFN-beta Primary producers
Fibroblasts, Epithelial Cells, MACs (macrophages)
IFN-gamma Primary producers
T Helper 1 Cells (CD4), T
Cytotoxic Cells (CD8)
IFN-alpha IFN-beta IFN-gamma Function
Anti - Viral
Sensitive indicators of inflammatory response
ACUTE PHASE REACTANTS
Non-specific test for bacterial infection (comes w/ culture)
ACUTE PHASE REACTANTS
increase rapidly due to infection, injury, or trauma to the tissues
ACUTE PHASE REACTANTS
produced primarily by hepatocytes (liver parenchymal cells) within 12 to 24 hours in response to an increase in certain intercellular signaling polypeptides called cytokines
ACUTE PHASE REACTANTS
– can stimulate APR
IL-1 and hydrolytic enzymes
6-10 (fastest response time)
C-reactive protein
24
Serum amyloid A
Alpha1 - antitrypsin
Haptoglobin
23
Fibrinogen
48-72
Ceruloplasmin
49-72
Complement C3
(carrier protein)
Alpha1 - antitrypsin
Haptoglobin
(coagulation factor I)
Fibrinogen
0.5
C-reactive
protein
3.0
Serum
amyloid A
200-400
Alpha1 -
antitrypsin (carrier protein)
11-400
Fibrinogen (coagulation factor I)
11-400
Fibrinogen (coagulation factor I)
40-200
Haptoglobin (carrier protein)
20-40
Ceruloplasmin
60-140
Complement
C3
0.15.1.0
Mannose-binding protein
1000x
C-reactive
protein
Serum
amyloid A
2-5x
Alpha1 - antitrypsin (carrier protein)
Fibrinogen (coagulation factor I)
2-10x
Haptoglobin (carrier protein)
2x
Ceruloplasmin
Complement C3
Opsonization, Complement activation
C-reactive
protein
(enhancement of phagocytosis; opsonins coat Ag for easy phagocytic recognition
Opsonization
(leads to lysis)
Complement activation
Removal of cholesterol
Serum
amyloid A
Protease inhibitor
Alpha1 -
antitrypsin (carrier protein)
Clot formation
Fibrinogen (coagulation factor I)
Binds hemoglobin
Haptoglobin (carrier protein)
Binds copper and oxidizes iron
Ceruloplasmin
Opsonization, lysis
Complement
C3
Complement activation
Mannose-binding protein
cell-eaters
phagocytes
Cells that engulf and digest foreign materials
phagocytes
Types of phagocytes
1.Neutrophils (Polymorphonuclear neutrophils)
2.Monocytes
3.Macrophages
4.Dendritic Cells
5.Fixed Phagocytes
– best Ag-presenting cell
Dendritic cells
oEngulfs, kills, and process Ag
oPresents fragment to T and B cell
oB cell creates Ab for Ag
oT cell processes and destroys Ag
Dendritic cells
Localized
Fixed phagocytes
Histiocytes
Connective tissue
Alveolar MACs
Lungs
Kupffer Cells
Liver
Littoral Cells
Spleen
Mesangial Cells
Kidneys
Microglia
Nerve cells/brain
Osteoclasts
Bone
Synovial A Cells
Synovial fluid
Hof-Bauer Cells
Placenta
Langerhans Cells
Skin/dermis/epidermis
– from circulating blood to tissues
Diapedesis
– towards Ag due to a chemical messenger called CHEMOTAXIN
Chemotaxis
Indirect interaction:
Direct interaction:
Opsonization
Pattern Recognition Receptors (PRRS)
– enhancement of phagocytosis (C3b, IgG1 and IgG3)
Opsonization
– phagocytes use their PRRS to recognize and adhere to Pathogen Associated Molecular Patterns (PAMPS)
Pattern Recognition Receptors (PRRS)
(Attachment and Recognition)
- Adhesion
(Engulfment)
- Ingestion
Vacuole + Pathogen = (?) (Ag inside the phagocyte)
PHAGOSOME
Occurs in the Phagolysosomes
- Digestion or Killing
Phagosome + Granules = (?) (granules released)
PHAGOLYSOSOME
Modes of killing:
oNitric Oxide
oOxygen Independent Mechanism
oOxygen Dependent Mechanisms
aka respiratory burst – consumption oxygen followed by release of toxic products
oOxygen Dependent Mechanisms
1.Toxic Reactive Oxygen Intermediates
Superoxide anion
Hydrogen peroxide
Hydroxyl Radical
MProduces Hypochlorite (bleach), highly toxic substance
2.Myeloperoxidase
: antibiotic like peptides made by Phagocytes
Defensins
Digestive enzymes:
Lysozymes and Lactoferrin
1.Large granular lymphocytes (LGL)
NATURAL KILLER CELLS
2.Nonspecific immunity
Exist in the body at birth
Not produced by immunologic insult – can act w/o a stimulus
NATURAL KILLER CELLS
3.ADCC (Antibiotic Dependent Cellular Cytotoxicity)
NATURAL KILLER CELLS
4.Non-phagocytic
NK
5.Form rosette in sheep RBC
oSmall flower/small rose
NK cell
- oSurface marker – identity of different cells
oCluster of differentiation
CD 56, CD16
: NK cell exposed to IL-2 and IFN gamma
Lymphokine Activated Cell (LAK)
8.Method of killing
Perforinsm
Apoptosism
Granzymes
9.Target
Tumor cells – immortal cells
Virally infected cells – more effective killing if exposed to IFN-gamma
Transplant tissue (grafted cells and allogenic cells)
NK needs low conc of (?) to act against an Ag
IgG
– identity of different cells
oSurface marker
o– T cell growth factor; strengthen cytotoxic activity of NK cells
IL-2
o – interfere w/ viruses
IFN gamma
(formation of pores causing lysis: ECF enters the cell or Ag → lyse/burst)
Perforins
(programmed cell death)
Apoptosis
(serine proteases that induces cell death)
Granzymes
Overall reaction of the body to injury or invasion by an infectious agent
INFLAMMATION
5 cardinal signs of inflammation:
oRubor – REDNESS
oCalor – HEAT
oTumor – SWELLING
oDolor – PAIN
oFunctio Laesa – LOSS OF FUNCTION
Stages of inflammation:
1.Vascular response
2.Cellular response
From injured cells
1.Vascular response
Mast cells release histamine (recruit WBCs to areas w/ inflammation) and prostaglandin (recruit platelets during bleeding) which promotes vasodilation to promote:
a.Increased blood flow calor and rubor
b.Increased capillary permeability
c.Plasma leakage to tissue causing (tumor and dolor)
2.Cellular response
1st Neutrophils –
2nd Monocytes and MACs –
acute inflammation
chronic inflammation
oAPC
oIL-1
oPromote inflammatory response
ocauses fever
oincrease APR
ostimulate T cells to produce IL-2 for lymphocyte proliferation
Monocytes and MACs
Directly killing infected host cells
1.T Lymphocytes
Activating other immune cells, producing cytokines and regulating the immunes response
1.T Lymphocytes
With surface receptors (like NK cells) – used to attach to Ags/immunogen
1.T Lymphocytes
Participate in T cell activation
2.B Lymphocytes
Bind to Ab via Ag-presentation
2.B Lymphocytes
Needs Ag-presenting cell and T cell in order to be stimulated
2.B Lymphocytes
Co-stimulation and cytokine production
2.B Lymphocytes
Affects anti-microbial defenses and tissue inflammation
2.B Lymphocytes
Serves as regulator cells that will modulate both cellular and humoral response
2.B Lymphocytes
Major cells involed in humoral-mediated immunity
2.B Lymphocytes
Capable of producing an Ab
3.Plasma cells
Ab-producing B cell – has encountered an Ag that further matured to produce an Ab
3.Plasma cells
Major humoral component
1.Antibodies
THIRD LINE OF DEFENSE
CELLULAR COMPONENTS
HUMORAL COMPONENTS
T cell
B cell
Plasma cell
Abs
Cytokines
Antibody mediated (noncellular)
Humoral-Mediated Immunity
Cell mediated
Cell-Mediated Immunity
B lymphocyte (able to interact w/ Ag and further matures into a plasma cell to produce Ab)
Humoral-Mediated Immunity
T lymphocyte
Cell-Mediated Immunity
Antibodies in serum
Humoral-Mediated Immunity
Direct cell-to-cell contact or soluble products secreted (has corresponding receptors to bind to an antigen → stimulates reaction for B cells to go to the area → secretion of soluble products like Ab and cytokines)
Cell-Mediated Immunity
Primary defense against bacterial infection
Humoral-Mediated Immunity
Defense against viral and fungal infections, intracellular organisms, tumor antigens, and graft rejections (transplanted tissues or cells)
Cell-Mediated Immunity
Extracellular microbes (acting on bacteria: can exist w/o a host cell)
Humoral-Mediated Immunity
B lymphocyte (able to bind to EM)
Humoral-Mediated Immunity
Secreted antibody
Humoral-Mediated Immunity
Block infections and eliminate extracellular microbes
Humoral-Mediated Immunity
Phagocytosed microbes in macrophage (will get a fragment from the phagocytosed Ag → present to B and T cell)
Cell-Mediated Immunity
Intracellular microbes (e.g. viruses: requires host cell) replicating within infected cell
Cell-Mediated Immunity
Helper T lymphocyte (has particular receptors to bind w/ PM in the macrophage)
Cell-Mediated Immunity
Cytotoxic T lymphocyte
Cell-Mediated Immunity
Activates macrophages to kill phagocytosed microbes
Cell-Mediated Immunity
Kill infected cells and eliminate reservoirs of infection
Cell-Mediated Immunity
Host: responsible for producing
Active Immunity
Nonself: immunity is derived from the immune response another source’s Abs and are passively transferred to the host
Passive Immunity
Ag (production of own Ab)
Active Immunity
Ig, anti-sera
Passive Immunity
Longer/Lifelong (Ex. Past exposure to chicken pox creates immunity)
Active Immunity
Transient/Temporary (Ex. Booster dose)
Passive Immunity
Less effective for Newborns (IS is not yet developed; rely on Abs from the mother; 0-3 mos old – fever can induce death)
Active Immunity
More effective for newborns
Passive Immunity
Effective in adults
Active Immunity
Less effective in adults
Passive Immunity
More prophylactic (prevention and protection)
Active Immunity
More therapeutic or prophylactic (treatment)
Passive Immunity
: experience infection (Ex. Past exposure to chicken pox creates immunity)
Natural Active
: serum sickness (created from the lab; Ex. Serum sickness – type of allergic reaction leading to urticaria)
Artificial passive
Long term immunity
Active Immunity
Immediate reaction and protection
Passive Immunity
Slow because Ag is detected then Ab is produced
Active Immunity
Short term immunity
Passive Immunity
Macromolecules that is capable triggering an adoptive immune response by inducing formation of antibodies or sensitized T cells of an immunocompetent host
Immunogen
Substances that reacts with antibody or sensitized T cells but may not evoke an immune response
Antigen
Is a foreign substance usually protein and polysaccharide
Antigen
Triggers a specific immune response and induces the formation of a specific antibody or T cells response or both
Antigen
Combines with an antibody
Antigen
Active regions of an immunogen (that binds to antigen-specific receptors on lymphocytes or to secreted antibodies.
EPITOPE (antigenic determinant)
Binds either on T-cell receptor and Antibodies
EPITOPE (antigenic determinant)
Determinant site which are recognized by T cells or B cells
EPITOPE (antigenic determinant)
The ability of antigen to react specifically with a free Ab or membrane coupled antibody (B Cell Receptor)
Antigenicity
oSurface markers of B cells are Abs instead of CDs
Antigenicity
The ability to induce a humoral or cell mediated immune response
Immunogenicity
A specific protein that is produced in response to an immunogen and reacts with an antigen
Antibody (Ab)
A substance that is non-immunogenic
oImmunogenic if a complete Ag
oAntigenetic but no immunogenic
HAPTEN
But it can react with the products of a specific immune response with no Antibodies formation.
HAPTEN
Non Protein and Low Molecular Weight (Less than 10,000) that could never induce an immune response when administered by themselves unless it coupled to a carrier molecule.
HAPTEN
Has the property of antigenicity but not immunogenicity
HAPTEN
FACTORS INFLUENCING IMMUNOGENECITY
Foreignness
Size
Chemical Composition and Complexity
Route dosage and timing
Adjuvants
the more different the composition, the greater the response
Foreignness
: derived from the same individual
: derived from the same species
: derived from different species (gives increased response)
: ag found in unrelated plants and animals, crossreact with Ab of another
Autoantigen
Alloantigen
Heteroantigen
Heterophile antigens
oDonor:
alloantigen
oPig heart:
heteroantigen
The larger the (?), the more the immune response
MW
Potent Ag :
> 10,000 Daltons
Good immunogen
oAlbumin: 40, 000 D
Excellent immunogen
oHemocyanin: 1M Daltons
Chemical Composition and Complexity
Most immunogenic=
2nd:
Non immunogenic:
protein
Polysaccharide
lipids and nucleic acids
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.
are the most effective
Intravenous and intraperitoneal
are stronger stimulus than subcutaneous or intramascular
Intradermal
Smaller the (?), the less response
dose
Substance added to vaccine and less immunogenic molecules (Hapten) to increase the immune response
Adjuvants
Adjuvants Function:
oStimulate T cells : enhance cell mediated immunity
oStimulate B cells: enhance humoral response
oStimulate phagocytosis
Adjuvants Examples:
oCFA: Complete Freund’s Adjuvant
oLPS: Lipopolysaccharide
oAlum adjuvant
oSqualene
Water in oil emulsion of Mycobacterium/ Bordetella pertussis/MTB
Toxic to humans
Used for animal trial (mouse, guinea pigs)
CFA: Complete Freund’s Adjuvant
Stimulate B cells
LPS: Lipopolysaccharide
Stimulate phagocytosis
Used in human vaccines
Alum adjuvant
From shark oil, for HIV vaccine
Squalene
are antigens which can directly stimulate the B cells to produce antibody without the requirement for T cell help.
T-independent antigens
In general, polysaccharides are
T-independent antigens
T-independent antigens Examples
oPneumococcal polysaccharide, lipopolysaccharide
oFlagella
are those that do not directly stimulate the production of antibody without the help of T cells.
T-dependent antigens
Proteins are
T-dependent antigens
T-dependent antigens Examples
oMicrobial proteins
Typically polysaccharides with the ability to induce B-cell proliferation and antibody secretion in the absence of T cells
T-independent antigen
An immunogen that requires T cell cooperation with B cells to synthesize specific antibodies
T-dependent antigen
Do not require the help of T cells for the activation of B cells
T-independent antigen
Require the help of T cells for the activation of B cells
T-dependent antigen
Examples: Polymeric molecules with repeated antigenic determinants such as polysaccharides
T-independent antigen
Examples: Protein antigens
T-dependent antigen
Multivalent (higher chance to bind w/ B cell w/o T cell)
T-independent antigen
Monovalent (only 1 epitope)
T-dependent antigen
Slower and take several days to initiate a response
T-independent antigen
Fast and require 1-2 days
T-dependent antigen
React with all Ig isotypes
T-independent antigen
React predominantly with IgM
T-dependent antigen
Do not produce long-lasting antibody titers
T-independent antigen
Produce long lasting serum antibody titer
T-dependent antigen
