Immunology & vaccination

IMMUNOLOGY

PROF. FATIMA MayTESORO,RPH,MSPHARMDefenses of the Host

Nonspecific Defenses of the Host

• Susceptibility Lack of resistance to a disease • Resistance Ability to ward off disease• Nonspecific resistance Defenses against any pathogen• Specific resistance Immunity, resistance to a

specific pathogen• Virulence Degree of pathogenecity• Attenuation Reduction of virulence• ANTIGEN Component of foreign material w./c interacts with immune

system• Epitope antigenic determinant

2 IMMUNE SYSTEM RESPONSE

• INNATE – non- specific; no time lag,not intrinsically affected by contact to infectious agent.

• ADAPTIVE – time lags; requires highly specific recognition of antigen and immunological memory ( DIPTHERIA)– Humoral– Cell mediated

• HUMORAL – effector cells are B lymphocytes & antigen recognition occur through interaction with antibody

• CELL MEDIATED – effector cells is T lymphocytes and antigen recognition occur through interaction with a peptide antigen w/ T receptors

CELL OF THE IMMUNE SYSTEM

Host Defenses

Figure 16.1

• Skin• Epidermis consists of tightly packed cells with• Keratin, a protective protein

Mechanical Factors

• Mucous membranes• Ciliary escalator: Microbes trapped in mucus are

transported away from the lungs• Lacrimal apparatus: Washes eye• Saliva: Washes microbes off• Urine: Flows out• Vaginal secretions: Flow out

Mechanical Factors

• Fungistatic fatty acid in sebum• Low pH (3-5) of skin• Lysozyme in perspiration, tears, saliva, and tissue

fluids• Low pH (1.2-3.0) of gastric juice• Transferrins in blood find iron• NO inhibits ATP production

Chemical Factors

• Microbial antagonism/competitive exclusion: Normal microbiota compete with pathogens.

Normal Microbiota

Formed Elements In Blood

Table 16.1

• Percentage of each type of white cell in a sample of 100 white blood cells

Differential White Cell Count

Neutrophils 60-70%

Basophils 0.5-1%

Eosinophils 2-4%

Monocytes 3-8%

Lymphocytes 20-25%

• Neutrophils: Phagocytic• Basophils: Produce histamine• Eosinophils: Toxic to parasites, some phagocytosis• Monocytes: Phagocytic as mature macrophages• Fixed macrophages in lungs, liver, bronchi• Wandering macrophages roam tissues• Lymphocytes: Involved in specific immunity

White Blood Cells

• Phago: eat• Cyte: cell• Ingestion of microbes or particles by a cell,

performed by phagocytes

Phagocytosis

Phagocytosis

Figure 16.8a

Microbial Evasion of Phagocytosis

• Inhibit adherence: M protein, capsules

Streptococcus pyogenes, S. pneumoniae

• Kill phagocytes: Leukocidins Staphylococcus aureus

• Lyse phagocytes: Membrane attack complex

Listeriamonocytogenes

• Escape phagosome Shigella

• Prevent phagosome-lysosome fusion

HIV

• Survive in phagolysosome Coxiella burnetti

• Redness• Pain• Heat• Swelling (edema)• Acute-phase proteins activated (complement,

cytokine, kinins)• Vasodilation (histamine, kinins, prostaglandins,

leukotrienes)• Margination and emigration of WBCs• Tissue repair

Inflammation

Chemicals Released by Damaged Cells

• Histamine Vasodilation, increased permeability of blood vessels

• Kinins Vasodilation, increased permeability of blood vessels

• Prostaglandins Intensity histamine and kinin effect

• Leukotrienes Increased permeability of blood vessels, phagocytic attachment

Inflammation

Figure 16.9a, b

Inflammation

Figure 16.9c, d

• Hypothalamus normally set at 37°C• Gram-negative endotoxin cause phagocytes to

release interleukin 1• Hypothalamus releases prostaglandins that reset

the hypothalamus to a high temperature• Body increases rate of metabolism and shivering to

raise temperature• When IL-1 is eliminated, body temperature falls.

(Crisis)

Fever: Abnormally High Body Temperature

• Serum proteins activated in a cascade.

The Complement System

Figure 16.10

Effects of Complement Activation

• Opsonization or immune adherence: enhanced phagocytosis

• Membrane attack complex: cytolysis

• Attract phagocytes

Figure 16.11

Effects of Complement Activation

Figure 16.12

Classical Pathway

Figure 16.13

Alternative Pathway

Figure 16.14

Lectin Pathway

Figure 16.15

Some bacteria evade complement

• Capsules prevent C activation• Surface lipid-carbohydrates prevent MAC formation• Enzymatic digestion of C5a

• Alpha IFN & Beta IFN: Cause cells to produce antiviral proteins that inhibit viral replication

• Gamma IFN: Causes neutrophils and macrophages to phagocytize bacteria

Interferons (IFNs)

Interferons (IFNs)

Figure 16.16

1

2

3

4

5

Viral RNA from an infecting virus enters the cell.

The infecting virus replicates into new viruses.

The infecting virus also induces the host cell to produce interferon on RNA (IFN-mRNA), which is translated into alpha and beta interferons.

Interferons released by the virus-infected host cell bind to plasma membrane or nuclear membrane receptors on uninfected neighboring host cells, inducing them to synthesize antiviral proteins (AVPs). These include oligoadenylate synthetase, and protein kinase.

New viruses released by the virus-infected host cell infect neighboring host cells. 6 AVPs degrade viral

m-RNA and inhibit protein synthesis and thus interfere with viral replication.

• Innate (nonspecific) Defenses against any pathogen• Immunity Specific antibody and

lymphocyte response to an antigen• Antigen (Ag) A substances that causes the

body to produce specific antibodies or sensitized T cells

• Antibody (Ab) Proteins made in response to an antigen

Terminology

• Serology Study of reactions between antibodies and antigens

• Antiserum Generic term for serum because it contains Ab

• Globulins Serum proteins• Gamma () globulin Serum fraction containing Ab

Serum Proteins

Figure 17.2

The Immune Response

• Acquired immunity Developed during an individual's lifetime

• Humoral immunity Involves Ab produced by B cells

• Cell-mediated immunity Involves T cells

Acquired Immunity

• Naturally acquired active immunity– Resulting from infection

• Naturally acquired passive immunity– Transplacental or via colostrum

• Artificially acquired active immunity– Injection of Ag (vaccination)

• Artificially acquired passive immunity– Injection of Ab

Antigenic Determinants• Antibodies recognize and react with antigenic determinants or epitopes.

Figure 17.3

Haptens

Figure 17.4

Antibody Structure

Figure 17.5a-c

• Monomer• 80% of serum antibodies• Fix complement• In blood, lymph, intestine• Cross placenta• Enhance phagocytosis;

neutralize toxins & viruses; protects fetus & newborn

• Half-life = 23 days

IgG antibodies

• Pentamer• 5-10% of serum

antibodies• Fix complement• In blood, lymph, on B cells• Agglutinates microbes;

first Ab produced in response to infection

• Half-life = 5 days

IgM antibodies

• Dimer• 10-15% of serum

antibodies• In secretions• Mucosal protection• Half-life = 6 days

IgA antibodies

• Monomer• 0.2% of serum antibodies• In blood, lymph, on B cells• On B cells, initiate immune

response• Half-life = 3 days

IgD antibodies

• Monomer• 0.002% of serum

antibodies• On mast cells and

basophils, in blood• Allergic reactions; lysis

of parasitic worms• Half-life = 2 days

IgE antibodies

• Bone marrow gives rise to B cells.• Mature B cells migrate to lymphoid organs.• A mature B cells recognizes epitopes.

Clonal Selection

Clonal Selection

Figure 17.8

Self-tolerance

• Body doesn't make Ab against self• Clonal deletion

– The process of destroying B and T cells that react to self antigens

The Results of Ag-Ab Binding

Figure 17.9

Antibody titer:• Is the amount of Ab in serum

Figure 17.10

Monoclonal Antibodies• Hybridomas are produced by fusing a cancer cell

with an Ab-secreting plasma cells• The hybridoma cell culture is immortal and

produces monoclonal Abs (Mabs)• Immunotoxins: Mabs conjugated with a toxin to

target cancer cells• Chimeric Mabs: Genetically modified mice that

produce Ab with a human constant region• Humanized Mabs: Mabs that are mostly human,

except for mouse antigen-binding

Monoclonal Antibodies

Figure 17.11

• Interleukin-1 Stimulates TH cells• Interleukin-2 Activates TH, B, TC, and NK cells• Interleukin-12 Differentiation of CD4 cells• -Interferon Increase activity of macrophages• Chemokines Cause leukocytes to move to an

infection

Immune system cells communicate via cytokines

• Specialized lymphocytes, mostly T cells, respond to intracellular Ags

• After differentiating in the thymus, T cells migrate to lymphoid tissue

• T cells differentiate into effector T cells when stimulated by an Ag

• Some effector T cells become memory cells

Cell-Mediated Immunity

• M (microfold) cells in• Peyer's patches which contains• Dendritic cells which are antigen-presenting cells

and• T cells

Pathogens entering the gastrointestinal or respiratory tracts pass through:

Dendritic cells present antigens

Figure 17.12

• Helper T Cells (CD4, TH)– TH1 Activate cells related to cell-mediated immunity

– TH2 Activate B cells to produce eosinophils, IgM, and IgE

• Cytotoxic T Cells (CD8, TC)– Destroy target cells with perforin

T Cells

• Delayed Hypersensitivity T Cells (TD)– Associated with allergic reaction, transplant rejection,

and tuberculin skin test

• Suppressor T cells (TS)– Turn off immune response when Ag no longer present

T Cells

Helper T Cells

Figure 17.13

Cell-mediated Cytotoxicity

Figure 17.14

Nonspecific Cells

• Activated macrophages: Macrophages stimulated by ingesting Ag or by cytokines

• Natural killer cells: Lymphocytes that destroy virus-infected cells, tumor

Figure 17.15

T-independent Antigens

Figure 17.17

B cell

T-independent Antigens

Figure 17.16

Antibody-Dependent Cell-Mediated Cytotoxicity

Figure 17.18

Vaccine History

• Variolation: Inoculation of smallpox into skin (18th century)

• Vaccination: Inoculation of cowpox into skin• Herd immunity results when most of a

population is immune to a disease.

• DtaP– Diphtheria: Purified diphtheria toxoid– Pertussis: Acellular fragments of B. pertussis– Tetanus: Purified tetanus toxoid

• Meningococcal meningitis: Purified polysaccharide from N. meningitidis

• Haemophilus influenzae type b meningitis: Polysaccharides conjugated with protein

• Pneumococcal conjugate vaccine: S. pneumoniae antigens conjugated with protein

Principal Vaccines

• Smallpox: Live vaccinia virus• Poliomyelitis: Inactivated virus• Rabies: Inactivated virus• Hepatitis A: Inactivated virus• Influenza: Inactivated or attenuated virus• Measles: Attenuated virus• Mumps: Attenuated virus• Rubella: Attenuated virus• Chickenpox: Attenuated virus• Hepatitis B: Antigenic fragments (recombinant

vaccine)

Principal Vaccines Used in the United States to Prevent Viral Diseases in Humans

Precipitation Reactions

• Involve soluble antigens with antibodies

Figure 18.3

Agglutination Reactions

• Involve particulate antigens and antibodies

• Antigens may be:• On a cell (direct

agglutination) • Attached to latex

spheres (indirect or passive agglutination)

Figure 18.4

Antibody Titer

• Is the concentration of antibodies against a particular antigen

Figure 18.5

Hemagglutination• Hemagglutination involves agglutination of RBCs.• Viral hemagglutination inhibition tests for antibodies by the

antibodies' ability to prevent viruses from agglutinating RBCs.

Figure 18.7

Neutralization Reactions

• Eliminate the harmful effect of a virus or exotoxin

Figure 18.8b

Complement Fixation

Figure 18.9.1

Complement Fixation

Figure 18.9.2

Fluorescent Antibody Techniques (Direct)

Figure 18.10a

Fluorescent Antibody Techniques (Indirect)

Figure 18.10b

Enzyme-Linked Immunosorbent Assay(Direct ELISA)

Figure 18.12a

Enzyme-Linked Immunosorbent Assay (Indirect ELISA)

Figure 18.12b

Serological Tests

Figure 18.13

Serological Tests

• Direct tests detect antigens (from patient sample)• Indirect tests detect antibodies (in patient's serum)

Serological Tests

• Agglutination: Particulate antigens• Hemagglutination: Agglutination of RBCs• Precipitation: Soluble antigens• Fluorescent-antibody technique: Antibodies linked to

fluorescent dye• Complement fixation: RBCs are indicator• Neutralization: Inactivates toxin or virus• ELISA: Peroxidase enzyme is the indicator