Immunology Notes Presentations - Bacteriology

Notes

1. IMMUNOLOGY

TERMINOLOGIES:
1.​Immunology: study of host’s reaction when foreign substances are introduced to the body
2.​Immune System: system by which the body discriminates self from non-self and destroys
nonself
**self: own self or components within us vs non self: external factors or any potentially
harmful substances
3.​Immune Response : involve complex interactions among many different types of body cells
and cellular secretions
a.​Innate/Natural Immunity: non specific immunity; rapidly mobilize when there’s
infection; lacks immunological memory; have the same mechanism of action to
every microorganism
b.​Adaptive/ Acquired Immunity: specific immunity; slower response at first but
when there’s reinfection, it is much faster; recognizes any unique molecule
(antigen) that is present in the microorganism; have immunological memory; have
specific mechanism of action for every microorganism
4.​Resistance: ability to ward off disease thru body defenses
a.​Non-specific resistance: all body defenses that protect the body from any kind of
pathogens
b.​Specific resistance (Immunity): defenses (antibodies) against specific
microorganisms
5.​Susceptibility: vulnerability or lack of resistance

LINES OF BODY DEFENSES:
function:
-​some defenses are designed to keep out some microorganisms
-​other defenses remove the microorganism if they do get in
-​other combats them if they remain inside

Non-Specific Resistance:
1.​first line of body defense: physical & chemical barriers (skin & mucous membranes)
2.​second line of body defense: cellular & molecular components (phagocytic and complement
system)

INNATE IMMUNITY:

A. First Line of Defense
-​nonspecific mechanism; defense against infection that are ready for immediate action; no
prior exposure is required







Physical Barriers/ Mechanical Factors
1.​Skin & Skin Structures
-​divided into layers:
-​epidermis: stratum corneum (outermost): 15-20 layers of stratified keratinized cells
which sloughs off or shed, hence pathogen cannot establish themselves
-​dermis: hair follicles, sweat glands, sebaceous glands = helps in the secretion of
substances such as lactate acid that contributes to the acidity of the skin (pH =
5.6), hence bacteria cannot proliferate as they requires a neutral pH
-​eyes, conjunctival epithelium: have flushing mechanism of tears which has lysozyme that
targets the cell wall of gram positive bacteria
-​skin-associated lymphoid tissue (SALT)
2.​Mucous Membranes
-​mucosal cells: sheds that helps on bacterial removal
-​goblet cells: produces mucus that traps bacteria and contains lysozyme & lactoferrin (binds
& sequester iron)
-​mucosa-associated lymphoid tissue (MALT)
3.​Salivary glands: carries the microorganism away from the cell surfaces; also contains IgA
antibody found in mucus membrane that prevents the attachment of microorganism to
mucosal membrane and secretory membrane; also contains lysozymes
4.​Nasal hairs & cilia: covers the cell of mucus membrane or lower RT; properly inhaled dust
and microorganism, that have become trapped in mucus, upward toward the throat
5.​Epiglottis: covers the larynx during swallowing and prevent microorganisms from entering
the lower RT
6.​Urethra: cleansed by the flow of urine to prevent microbial colonization in urinalysis tract;
flushing mechanism to remove bacteria *slightly acidic
7.​Vaginal secretion: move microorganisms out of the female body

Chemical Barriers
1.​Sebum: composed of fatty acids which inhibit the growth of certain pathogenic bacteria and
fungi
2.​Lysosyme/Muramidase: present in perspiration which helps body temp.; eliminates certain
waste & flush microorganism from the surface of skin
3.​Lactic acid: contributes to the acidity (of skin = 5.6 & vagina = 5)
4.​Lactoperoxidase: enzyme that is intermediate for aerobic phagocytosis *toxic to these
bacteria
5.​IgA: prevents the attachment of microorganism to mucosal membrane
6.​Hydrochloric acid: founds in the stomach that contributes to its acidity (pH = 1) and
degrades any structural protein present in the bacteria

Biological Barriers:
1.​Normal flora/ Microbiota

2. Microbial Sensors:
-​if a pathogen enters the skin, it will be confronted by macrophages & other phagocytic cells
which possesses these microbial sensors
1.​Toll-like Receptors: function as Pattern Recognition Receptor (PRR) which recognizes
Pathogen Associated Molecular Pattern (PAMPs); when PRR detected PAMPs they will
bind w/ PAMPs and trigger receptors

Substance Recognized Target Microorganism
TLR found on Cell Surfaces
TLR1 lipopeptides Mycobacteria
TLR2 peptidoglycan, lipoproteins, zymosan Gram-pos bacteria, Mycobacteria, Yeast
TLR4 lipopolysaccharide, fusion proteins, mannan Gram-neg bacteria, RSY fungi
TLR5 flagella Bacteria w/
TLR6 lipopeptides, lipoteichoic acid, zymosan Gram-pos bacteria, Mycobacteria, Yeast
TLR found on Endosomal Compartments
TLR3 double-stranded RNA RNA viruses
TLR7 single-stranded RNA RNA viruses
TLR8 single-stranded RNA RNA viruses
TLR9 double-stranded DNA DNA viruses, bacterial DNA
TLR10 unknown unknown

2.​NOD-like Receptors
3.​RIG-1nlike Helicase & MDA-5

B. Second Line of Defense

Reticuloendothelial System
-​involves mononuclear phagocytic cells
-​flushing action of lymph fluid

Phagocytosis
-​ingestion of microorganism or may particulate matter by cell phagocyte
-​phagocytes (PMN WBC & macrophages) engulf and dispose of microorganism
and cell debris
-​Ellie Metchnikoff: discovered phagocytosis; introduced foreign substance in a starfish larvae
and observed motile cells where they targeted & eliminated the foreign substances
-​aided by the process of endocytosis: uptake of substance from external environment going
inside the cell **vs. exocytosis: release of substance to external environment
-​major events of phagocytosis
1.​initiation: result of tissue damage
1.​chemotaxis: movement of cell in a certain direction towards foreign substances
-​aided by stimulation of chemotoxin: substances that directs the movement of the
cell (e.g. antibodies, complement)
2.​engulfment: ingest foreign substances thru membrane invagination
3.​digestion: killing of foreign substances
-​specific steps of phagocytosis:
1.​adherence: physical contact between phagocytic cell & microorganism
-​mediated by opsonins: plasma proteins that helps the attachment of
microorganism to cell surface; they coats the microorganism = opsonization
2.​engulfment: cytoplasm of cell will surround the microorganism
3.​formation of phagosome: microorganism is completely surrrounded by cell wall
which is now the phagosome: vesicle that is formed around microorganism
-​phagosome can act as bacteriostatic (inhibition) or bactericidal (killing)
4.​granule contact: lysosomal granule will fuse w/ phagosome forming
phagolysosome
-​aside from lysosomal granule, it can also aided by hydrolytic enzymes that
produces toxic oxygen derived products (e.g. radicals, hydrogen peroxide)
5.​formation of phagolysosome: combination of phagosome & lysosome; the
contents of lysosome will empty now into phagosome
6.​digestion: killing of microorganism
7.​excretion: the contents now will be expelled outside = Exocytosis
-​phagocytes/ phagocytic cells:
1.​Granulocytes
a.​Neutrophil/ Polymorphonuclear cells (50-70%): highly phagocytic &
motile; active in initial stage of infection
-​primary/ azurophilic granules: myeloperoxidase, acid hydrolase,
defensins, elastase, proteinase-3, cathepsin G
-​secondary/ specific granules: collagenase, lysozymes, lactoferrin,
gelatinase, respiratory burst component
-​tertiary: phosphatase
*** 50% is found in marginating pool: adheres to blood vessel; movement
to blood vessel wall = diapedesis & 50% is found in circulating pool:
circulates freely
a.​Eosinophil (1-5%): produce toxic proteins against certain parasites
(esp. helminths)
-​less efficient phagocytosis as they lack of digestive enzymes
-​neutralized basophil and mast cell *since if there’s allergic rxn, basophil
increases
*** Charcot-Leyden Crystal: formed after prolonged eosinophilic rxn
b.​Basophils (<1%): inducing & maintaining allergic rxns
-​release substances: histamine (contracts the smooth muscle during
inflammation & allergic responses), heparin (natural anticoagulant),
chemotactic, factor A

3. -​regulate T helper cell response; stimulate IgE production

2.​Agranulocytes:
a.​Monocytes (4-10%): not actively phagocytic in blood, but when they
enter the body tissues & mature, they become macrophage *precursor
cell of macrophage
-​w/ peroxidase but no alkaline phosphatase
3.​Macrophages (25-80um): part of monocyte-macrophage system that initiates and
regulates immune response
-​fxn: microbial killing, anti-tumor activity, intracellular parasite eradication,
phagocytosis, cell mediators secretion
-​w/o peroxidase

Adipose tissue Adipose tissue
macrophage
Peritoneal cavity Peritoneal macrophages
Bone Osteoclasts Peyer’s patch LysoMac
Bone marrow/
Blood
Monocytes Placenta Hofbauer cells
CNS Microglia Pulmonary alveoli Alveolar macrophages
Granuloma Epitheloid cells Red pulp of spleen Red pulp macrophages
Liver Kupffer cells Skin & Mucosa Langerhans cells
Lymph nodes Sinus histiocytes Kidney Intraglomerular mesangial cells
CT Tissue macrophages leading to giant cells

4.​Dendritic cells: covered w/ long membranous extension *resembles nerve cells
-​most effective antigen-presenting cell (APC) and most potent phagocytic
cells
-​fxn: phagocytosis & presentation of antigen
-​classification:
-​langerhans cells: not only a macrophage, but also a dendritic cell
-​interstitial dendritic cells: found in major organs
-​interdigitating dendritic cells
5.​Mast cells: resembles basophils but different lineage **basophil is from BM; mast
cell is from tissue; larger than basophils w/ small round nucleus and more granules
-​granules: ACP, ALP, Protease
-​lifespan: 9-28 months
-​fxn: allergic response; antigen-presenting cell; enhance and suppress adaptive
immune response
6.​Natural Killer Cell/ Null Lymphocyte (10%): do not express markers of T & B
cells; kill target cells w/o prior exposure ***T&B cells fxn are on adaptive immunity;
NK cells bridge the rxn between innate & adaptive immunity
-​essential mediators of virus immunity & even tumor cells by recognition of Major
Histocompatibility Complex (MHC) = they bring the antigen to the surface of the
cell for lymphocyte to recognize them
-​no surface markers but w/ antigens:
-​CD16: receptor for nonspecific end antibodies; lyse antibody-coated cells
-​CD56
Inflammation
-​defense response against microbial infection, physical/and or chemical agents; reinforcement
mechanism against microbial survival and proliferation in tissues & organs
-​fxn:
-​destroy infectious agents and remove its by-products from the body
-​limits the effect of injurious agent and its by-products by confining or walling it off
-​5 signs of inflammation:
1.​Rubor: redness (due to increased blood flow in the site of inflammation)
2.​Calor: heat/ fever (due to increased blood flow in the site of inflammation)
3.​Dolor: pain (release of histamine & ranitidine which stimulates the nerve endings)
4.​Tumor: swelling/ edema (accumulation of fluid)
5.​Functio laesa: loss of fxn (chronic inflammation)
-​major events:
a.​vasodilation: increased diameter of blood vessel to facilitate the increased blood
flow in infected site
b.​increase in capillary permeability: there’s a tight junction in between of epithelial
cells that will contract = widening the gap of junction, hence facilitating the
migration of wbc & macrophages in site of inflammation = influx of fluid & cells into
tissue
c.​influx of phagocytes: when the phagocytic cells are already in the inflammation
site, they will elicit their mechanism
d.​resolution & repair: initiated by fibroblasts
-​mediators of inflammation:
-​histamine: principal mediator of inflammation which binds to the receptors of
capillaries & venules causing vasodilation and increased capillary permeability
-​kinnins: same fxn w/ histamine
-​acute phase proteins: sensitive inhibitors; and increases when there’s
inflammation by 25% due to injury; produced by hepatocytes (liver cells)
-​c-reactive protein: opsonization, complement activation; ↑by 1000x
-​serum amyloid A: removal of cholesterol; ↑by 1000x
-​alpha1-antitrypsin: protease inhibitor; ↑by 2-5x
-​fibrinogen: clot formation; ↑by 2-5x
-​haptoglobin: binds hemoglobin; ↑by 2-10x
-​ceruloplasmin: binds copper and oxidizes iron; ↑by 2x
-​complement C3: opsonization, lysis; ↑by 2x
-​MBP: complement activation
-​defensins: produces pores in bacterial membrane = leakage of cellular contents
-​alpha-defensins: found in gastrointestinal tract
-​beta-defensins: found in respiratory tract

4. The Complement System










-​defensive system of serum proteins that participate in lysis of foreign cells, inflammation, &
phagocytosis; pro-inflammatory (induce inflammatory response)
-​contains more than 30 soluble particles
-​3 pathways of activation:
1.​Classical Pathway: activated by antigen-antibody complex (specifically IgM & IgG)
-​have 9 components: C1 - C9 (C1 > C4 > C2 > C3 > C5 > C6 > C7 > C8 > C9)
-​membrane attack complex (C5b, C6, C7, C8, C9) = induces cell lysis
-​C8 = initiate pore formation
-​C9 = polymerize MAC
-​C3b = key intermediate in all pathways; w/o this, a person is susceptible
to severe recurrent infections
-​deficient to C5 to C8 = susceptible to Neisseriae infections
2.​Alternative Pathway: activated thru direct interaction w/ bacterium (activating
surfaces that is foreign specifically gram +/- cell wall)
3.​Lectin Pathway/ Mannose Binding Lectin Pathway: activated by pathogen
surfaces (e.g. lipopolysaccharide = recognizes carbohydrates spec. mannose)
-​recognizes Salmonella, Neisseriae, Listeria, Streptococcus
-​3 bases of complement system (regardless of pathways):
-​initiation: recognition event that initiates complement cascade
-​classical = antigen-antibody complex; alternative = activating surfaces;
lectin = pathogen surfaces
-​activation/ amplification: activation of early components
-​classical = C1 to C3; alternative = factor B & factor D to C3b; lectin =
MASPs to C4
-​membrane attack complex: initiated by C5b
-​fxn/ biological effects:
-​Cytolysis: MAC will insert themselves to the cell membrane of the bacteria which
will lead to a loss of osmotic integrity causing a cell lysis; due to the destruction of
plasma membrane causing the cellular contents to break out
-​Chemotaxis: movement of phagocytic cell thru a receptor (chemotaxin) specifically
the complement factor 5a
-​Opsonization: coating of antigen to facilitate phagocytosis
-​Anaphylatoxins: promotes vasodilation and increase vascular permeability (C3a &
C5a = potent promoters of vasodilation)


Interferons
-​classes of similar antiviral proteins produced by certain animal cells after viral stimulation
-​produced by virus infected cells; interferes w/ viral multiplication

Origin Biological Activity
Type 1: does not require any stimulation
INF-Alpha Null lymphocyte
aka Leukocyte interferon
antiviral, increases MHC Class I expression
INF-Beta Fibroblasts, Epithelial cells
aka Fibroepithelial interferon
antiviral, increase MHC Class I expression
Type 2
INF-Gamm
a
Immunologicaly stimulated lymphocytes major macrophage activator, induces MHC Class II;
synergize w/ TNF; augments NK cell activity; antagonist
to IL-4

ADAPTIVE IMMUNITY:

-​highly specific
-​w/ immunologic memory
-​exposure required
-​classification: humoral or cell-mediated immunity

Lymphocytes:

T/ Thymic cells B/ Bone marrow cells
population 60-80% 20%
site thymus bone marrow
lifespan longer shorter
lymph node location paracortical cortical
identification rosette formation in surface of RBC surface immunoglobulin
end product cytokines antibodies

5. antigen CD2, CD3, CD4, CD8 CD19, CD20, CD21, CD40, MHC II

Antigens: substance that can provoke the production of antibody
-​foreigness
-​size
-​chemical & structural complexity
-​degradability
-​dosage, route, and timing of antigen administration
A. Humoral-Mediated Immunity
-​major component: antibodies
-​mechanism: antibody mediated
-​cell type: B lymphocytes
-​mode of action: antibodies in serum
-​purpose: primary defense against bacterial infection

Antibody: substances produced in response to antigenic stimulation that is capable of specific
interaction w/ provoking immunogen
-​fxn:
-​neutralize toxic substances
-​facilitate phagocytosis & kill microbes
-​combine w/ antigens on cellular surfaces and thereby cause destruction of these
cells either extravascular or thru action of complement

Classes of Immunoglobulin
A.​IgG (70-75%) *most abundant in serum
-​monomer
-​can cross the placenta
-​strong precipitin but moderate agglutinin
-​fxn:
-​immunity to newborn
-​fixing complement
-​opsonization
-​neutralization of toxins
Subclass Frequency Disulfide bond Remarks
IgG 1 67% 2 most efficient IgG
IgG 3 7% 15 best in complement fxn; largest hinge region
IgG 2 22% 4 cannot cross the placenta
IgG 4 4% 2

B.​IgM (5-10%)
-​pentamer (star shaped)
-​2 forms:
-​monomeric: membrane bound
-​pentameric: joining chain
-​macroglobulin (sedimentation rate: 19 S)
-​first to appear after antigenic stimulation
-​no memory cells
-​more efficient than IgG
-​fxn:
-​complement fixation
-​agglutination
-​opsonization
-​toxin neutralization
-​remember:
-​most efficient at triggering the classical complement pathway
-​more efficient at agglutination rxn
-​surface receptor for antigen
C.​IgA (10-15%)
-​predominant in secretions; effector function at mucous membranes
-​2 forms:
-​monomer (IgA1): found in serum
-​polymeric (IgA2): held together by J-chain; secretory IgA
-​fxn:
-​IgA1 (anti-inflammatory agent): down regulate IgG-mediated phagocytosis,
chemotaxis, bactericidal activity, & cytokine release
-​IgA2: keep antigens from penetrating farther into the body
D.​IgG (0.001%)
-​monomer
-​found on surfaces of V cells as antigen receptor
-​activation of B cells
-​immune regulation; formerly believed as anti-idiopathic Ab
-​more susceptible to proteolysis
-​in the serum: no protective function
E.​IgE (<0.0005%)
-​monomer
-​most heat-labile
-​located on mast cells & basophils
-​involved in allergic & hypersensitivity rxns
-​provides protection against parasitic worms
-​no typical immunoglobulin reactions

6. Antibody Immune Response
1.​Lag phase
2.​Log phase
3.​Plateau phase
4.​Decline phase

Primary Antibody Response Secondary Antibody Response
- predominant antibody produces: IgM
- longer lag phase
- decrease/ low antibody titer
- predominant antibody produced: IgG
- shorter lag phase; longer stationary phase; more
gradual decline phase
- increased antibody titter
- faster & stronger response

Comparison of Types of Acquired Immunity












B. Cellular-Mediated Immunity
-​mechanism: cell mediated
-​cell type: T-lymphocytes
-​mode of action: direct cell to cell contact or soluble products secreted by cells
-​purpose: defense against viral & fungal infections, intracellular organism, tumor antigens and
graft rejection
-​cytokines
-​interleukins: mediators that act between leukocytes

APPLICATION OF IMMUNOLOGY
1.​Antisera
2.​Vaccine