Ch. 16, 17, 18 - Immunity

Pluripotent step cells differentiate into

Myeloid & Lymphoid stem cells

What are the myeloid stem cells?

• Mast cells

• Eosinophils

• Basophils

• Neutrophils

What are the lymphoid stem cells?

• Macrophages

• Dendritic cells

• T cells

• B cells

• NK cells

Innate immunity involves

1st & 2nd line of defense

• Fast & nonspecific

• External, internal, chemical barriers

1st line: Physical factors

• Skin (+keratin)

• Mucous membranes

• Ciliary escalator

• Washing actions (tears, urine, saliva)

1st line: Chemical factors

• Secretions (skin ph = 3-5)

• Lysozyme

• Sebum

• Lactic acid in vagina

• Stomach acid

• Normal microflora

2nd line of defense

• Phagocytic cells

• Inflammation

• Fever

• Antimicrobial substances

What are the phagocytic cells?

• Macrophages

• Neutrophils

• Dendritic cells

Describe the function of phagocytic cells

• Engulfs & destroys pathogens

• Acts as antigen presenting cells (APCs)

Aspects of phagocytosis

• Chemotaxis & adherence to phagocyte

• Phagolysosome

• Residual body (indigestible material)

• Antigen presenting

How do pathogens evade phagocytosis?

• M protein or capsule prevents adherence

• Leukocidins kill macrophages

• Lysis of phagolysosome

• Escape

• Prevents fusion

• Survive inside phagolysosome

How does Streptococcus pyogenes & S. pneumoniae evade phagocytosis?

Preventing adherence to macrophage

How does Staphylococcus aureus evade phagocytosis?

Leukocidins kills the macrophage

How does Listeria monocytogenes evade phagocytosis?

Lysis of phagolysosome

How does Shigella escape phagocytosis?

Breaks out of phagosome

How does HIV & M. tuberculosis evade phagocytosis?

Prevents fusion of phagosome & lysosome

How does Coxiella bunetii evade phagocytosis?

Survives in the acidic environment of the phagolysosome

Mast cells during inflammation

Release histamine

Margination

Phagocytes stick to the blood vessel walls

Emigration

Blood vessel walls become leakier and will release some macrophages

Antimicrobial substances include

• Complement systems

• Interferons

• Defensins

What are the complement systems?

Proteins that attack & lyse microbes

What are interferons?

Proteins secreted by virus infected cells to inhibit viral multiplication

What are defensins?

Proteins secreted by activated macrophages to destroy pathogens

How do complement proteins attack & lyse microbes?

• Opsonization

• Cytolysis

• Activation of inflammation

Opsonization

Protein tagging for macrophages to easily identify & recognize pathogen

Agglutination

Clumps together microbes to allow more to be ingested by phagocytosis

How do complement proteins stimulate inflammation?

Releases histamine

Innate immunity is

• Present in all animals before exposure to any pathogen

• Fast & nonspecific

Adaptive immunity is

• Acquired & Specific

• Develops after exposure to pathogen

• Slower

• Humoral & cell-mediated responses

Functions of specific immunity

• Recognize the pathogen

• Destroy the pathogen

• Remember the pathogen

• Discriminate between self & non-self cells

Antigen

Substance stimulating the body to produce specific antibodies

Antibody

Protein made in response to antigens

Complement

Serum that binds antigens & antibodies to form a reaction

Serology

Study of reactions between antigens & antibodies

Antiserum

Serum containing antibodies

Leukocytes

• White blood cells

  • Neutrophils

  • Macrophages

  • Lymphocytes

Lympchocytes

B-cells & T-cells

B-cells produce

Antibodies & can differentiate into plasma cells

T-cells provide

Cell-mediated defense, sensing which one is infected

Where are lymphocytes produced

In the bone marrow

• B-cells mature in bone marrow

• T-cells mature in thymus

How do lymphocytes recognize an antigen

Binds to an epitope (small portion of the antigen)

• B-cells & T-cells have 100,000 identical antigen receptors

Describe the B-cell antigen receptor

• Y-shaped with 2 identical heavy chains & 2 light chains

Regions of the B-cell receptor

• Constant

• Variable

• Transmembrane

Variable region of the B-cell receptor

• At the very end of the receptor

• Provides antigen specificity

What happens when a B-cell binds to an antigen

1. Proliferates identical clones of cells

2. Differentiates to plasma & memory cells

Plasma cells

Produce free antibodies that will circulate and bind to antigens

Memory cells

Long-living B-cells that will remember a certain antigen

Describe clonal selection

The proliferation of populations that will respond to one specific antigen

How many antigens can B-cells recognize?

10^15

Describe IgM

• Largest immunoglobulin (pentamer)

• First antibodies produced for initial infection

• In blood & lymph

Describe IgG

• Monomer

• Enhances phagocytosis, neutralizes toxins & viruses, protects fetus

• In blood, lymph, intestine

Describe IgA

• Dimer

• Protection in mucosal surfaces

• In secretions; tears, saliva, milk, intestine

Describe IgE

• Monomer

• Allergic reactions (releases histamine)

• Mast cells & basophils

What immunoglobulins secondary response is affected by memory cells?

IgG will have a stronger secondary response due to memory cells

What immunoglobulins secondary response is NOT affected by memory cells?

IgM will have no memory of previous infection

How do antibodies protect us?

1. Agglutination

2. Opsonization

3. Neutralization

4. Activation of complement

5. Cell-mediated cytotoxicity

Describe T-cell receptors

• 2 different chains

• Same regions as B-cell (variable, constant, transmembrane)

• Destroy infected or affected host cells

Clonal deletion

• Process of each cell being tested for the antigen

• T-cells will recognize infected body cells and attack it before it attacks your own cells

Class I MHC proteins

• Found on all nucleated cells

• Identifies “self”

• Displays antigens to cytotoxic T-cells

Class II MHC proteins

• Antigen-presenting cells

• Dendritic cells, macrophages, B-cells

• Displays to helper T-cells & Cytotoxic T-cells

Helper T-cells

Interacts with MHC II & activates B/T-cells

• Stimulates B-cells to differentiate into plasma cells

Cytotoxic T-cells

Interacts with MHC I & activates cell apoptosis

• Secretes perforins

Double recognition

• T-cells recognize the antigen & the affected or infected host cells

• Differentiate between MHC I or MHC II

Immunization

Results from vaccine stimulating immunity

Vaccines

Induces antibody production & cell-mediated immunity to protect host from future infection

Booster doses

Allows the body to build up defense (memory cells)

What immunizations require boosters?

• Tetanus

• Diphtheria

• Whooping cough

• Polio

Whole cell vaccines

Live attenuated (avirulent) or inactivated-kills antigen

Acellular or subunit vaccine

Piece of bacteria & can combine different component of the pathogen with others

Conjugated vaccine

Capsule + protein

Nucleic acid vaccine

DNA or RNA

Describe attenuated vaccines

• Longer term protection w/o booster

• Closely mimics actual infection

Attenuated viral vaccines

Measles, rubella, polio (Sabin), chicken pox

Attenuated bacterial vaccines

TB (BCG), typhoid

Disadvantages of attenuated vaccines

• More serious side effects

• Can revert back to virulency

Describe inactivated/kills vaccines

Killed by heat

Inactivated viral vaccines

Rabies, polio (Salk), influenza

Inactivated bacterial vaccines

Whooping cough, cholera, pneumonia

Describe acellular/subunit vaccines

• Fragments of a pathogen stimulating immune response

  • Capsule, toxin, proteins

• Subunit are produced by genetic modification

Example of a subunit vaccine

Hepatitis B virus

Part of acellular vaccines are capsular polysaccharides, why does it have a poor immune response?

B/c it does not involved T-cells

Describe conjugated vaccines

Attaches antigen to carrier protein that will activate T-cells

Describe nucleic acid vaccines

DNA or RNA fragment introduced

Advantages of nucleic acid vaccines

• Artificially produced, purity assured

• Good immunological memory

• Can be mixed & injected as one vaccine

• Cheap

Example of a nucleic acid vaccine

Covid

Why do vaccine-preventable diseases persist?

• Not eliminated in the environment

• Requires extra boosters

• Unvaccinated

• Poverty & lack of health infrastructure

Phase 1 of clinical trials

Is the drug/treatment safe?

Phase 2 of clinical trials

Does the drug/treatment work?

• Does not pick up all the risks

Phase 3 of clinical trials

Is the drug/treatment better than what we have?

• Does not pick up all the risks

• Double blind studies are used

• Submitted to FDA for approval

Phase 4 of clinical trials

What else can we learn about the drug/treatment?

• More side effects will show

• Large population

Multivalent vaccines

Individual vaccines combined

• DaPT-polio-Hib

  • Diphtheria, acellular Pertussis, Tetanus, polio (salk), H. influenzae

Adjuvants

Non-toxic materials added to vaccines to enhance immunogenicity

• Multivalent uses aluminum salts

Difference between the Salk & Sabin polio vaccines

• Salk is using an inactivated virus

• Sabin is using an attenuated virus

Why are annual vaccinations for influenza required?

The virus gets new strains from antigenic variation