CHAPTER II – IMMUNITY Flashcards by Arriane Cyrel (MTI)

It is the study of: discriminating self from non-self

IMMUNOLOGY

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IMMUNOLOGY PURPOSE:

eliminate non-self components such as infectious agents

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Responsible for the surveillance and destruction of substances that are foreign to the body

IMMUNE SYSTEM

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Attack microorganism that exists outside the host’s cell or used to attack microorganisms that infect cells

IMMUNE SYSTEM

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Defending the body against the development of tumors

IMMUNE SYSTEM

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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

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: silent gene; needs stimulus to develop into cancer

ONCOGENE

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: chronic smoking

Oral, mouth, lung cancer

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: unhealthy foods, reheating

Colon cancer

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(scavenger organ; cleans senescent/old RBCs)

spleen

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TYPES OF IMMUNITY

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Non-specific immunity

INNATE IMMUNITY

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Refers primarily to anatomical, cellular, and humoral defenses that functions in the early stages of host defense

INNATE IMMUNITY

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Physical

Barriers; skin, mucus, cilia
Flushing Action: Blinking of eyelids, Peristalsis and Urination

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Chemical

Salts: Cerumen and Sebum
Acids: Low pH of Stomach and Vagina
Lipids: Fatty acids in the sebaceous glands and gallbladder

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Normal flora

Non pathogenic bacteria in:
oGIT
oVagina
oNasopharynx

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Non pathogenic bacteria in:
oGIT –
oVagina –
oNasopharynx –

Citrobacter, Bacteroides, E. coli (passed in stool)

Lactobacillus acidophilus: maintains acidic pH

Streptococcus, Neisseria

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Physiologic process

Sneezing
Coughing
Vomiting, Gag reflex
Perspiration
Shivering
Crying
Urinatio
 Defacation

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Sweat maintains skin pH at

5.6 (acidic)

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Acids: Low pH of Stomach and Vagina
oDue to

HCl or Pepsin

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Resistant to stomach acid
Causes peptic ulcer
Produces UREASE (alkaline)

Helicobacter pylori

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– through ingestion

Vomiting, Gag reflex

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Maintenance of normal temperature

Perspiration

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– to prevent hypothermia

Shivering

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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

Serum amyloid A Alpha1 - antitrypsin Haptoglobin

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)

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)

1. Adhesion

(Engulfment)

2. Ingestion

Vacuole + Pathogen = (?) (Ag inside the phagocyte)

PHAGOSOME

Occurs in the Phagolysosomes

3. 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

5.Form rosette in sheep RBC oSmall flower/small rose

NK cell

6. 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

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