Overview of the Innate Immune System

Immunity

Ability to ward off disease

Susceptibility

Vulnerability to a disease

Innate Immunity

Generalized defenses against all pathogens

Adaptive Immunity

Specialized defenses against a specific pathogen

Antigen

A compound that induces an immune response

Antibody

Immuno-protein that binds an antigen

Cytokine

Small proteins involved with short ranged cell signaling

Chemokine

A cytokine that directs cell movement

First line of defense

Intact skin, mucous membranes and their secretions, normal microbiota (barriers)

Second line of defense (first responders)

Phagocytes, such as neutrophils, eosinophils, dendritic cells, and macrophages, inflammation, fever, antimicrobial substances

Third line of defense

Specialized lymphocytes: T cells and B cells, antibodies (adaptive immunity)

Physical Factors

Skin, mucosal membranes and washing action

Chemical Factors

Sebum, wax, low pH, enzymes and gastric juice

Normal Microbiota

Presence of normal microbiota inhibits pathogens by competing for nutrients, producing bacteriocins, altering the environment

Skin

Largest organ of the body; outer most layer composed of dead keratinized cells, high salt concentration, A pH3-5

Mucosal Membranes

Found in respiratory, gastrointestinal and genitourinary tracts

Goblet cells

Specialized cells that secrete mucus (glycoprotein)

Ciliary Escalator

Ciliated cells transport mucus

Lacrimal Apparatus

Continually washes away microbes and debris; ex) urination, defecation, vomiting

Lysozyme

Breaks down peptidoglycan of cell wall, found in mucosal layers, saliva, tears, perspiration

Amylase

Enzyme in saliva that breaks down starches

IgA

inhibits bacterial attachment

Lowering pH of skin or mucosal membranes

May lead to opportunistic infections

blood

consists plasma and formed elements (cells and cells fragments including erthyrocytes, platelets, and leukocytes)

Leukocytes

White blood cells

Granulocytes Include

Neutrophils, Basophils and Eosinophils

Eosinophils

Produce toxic proteins which are good at taking them out, 3%, dark pink to orange granules, 3x bigger than red blood cells, bi lobe nucleus

Neutrophils

Phagocytosis, most common white cell 70%, has 4-5 multi cat poop lobe nucleus, dark blue granules, 2x size of blood cells

Basophils

Release histamine, least common< 1%, dark purple granules, bi(2) lobe nucleus, small (about the size of red blood cell),

Sometimes lobes are not visible due to the granules

Granulocytes

contain visible granules when theyre stained

Agranulocytes Include

Monocytes (Macrophages, Dendritic cells) & Lymphocytes (T-cells, B-cells & Natural killer cells)

Natural killer cells

kills cancer cells and virus infected cells

B-cells

recognizes antigens and produces antibodies

T-cells

play a central role in cell-mediated immunity, mature in the thymus and help the immune system identify and destroy infected or abnormal cells.

T cells consist of

memory t cells, regulatory t cells, helper T cells, cytotoxic T cells

Lymphocytes

natural killer cells , second most common, 20%, have large nucleus,

Contain B&T natural killer cells

Cytolysis

the breaking or bursting (lysis) of a cell

Dendritic cells

Foster communication system between innate and adaptive system

Monocytes

phagocytosis, kidney bean shape, 3-5%

Agranulocytes

do not contain visible cytoplasmic granules (but are present)

Lymphatic System

Defense against infection and disease

lymphatic system steps

1. Collects fluid from tissues (called lymph) that leaks out of blood vessels.

2. Lymph enters tiny tubes called lymphatic capillaries.

3. Lymph flows through bigger lymph vessels.

4. Passes through lymph nodes, where germs and bad stuff are filtered out.

5. Lymph drains into large lymphatic ducts.

6. Finally, lymph joins the bloodstream near the heart through veins.

Phagocytosis

Ingestion and destruction of foreign material by cells such as Neutrophils, Eosinophils, Dendritic cells and especially Macrophages

lymph nodes

Bean-shaped filters that cluster along the lymphatic vessels of the body. They function as a cleanser of lymph as wells as a site of T and B cell activation

lymph node pathway

•Enters via afferent lymphatic vessels

-Encounters nodules, Immune cells (like B and T cells) check the lymph for germs or harmful stuff.

•Exits via efferent lymphatic vessels

PAMPs

Pathogen Associated Molecular Patterns -special markers found on germs immune system sees as red flags to start fighting infection.

PRRs

Pattern Recognition Receptors -like security sensors in immune cells. They detect danger signs (PAMPs) on germs and alert the immune system to fight back.

Chemotaxis

Movement of phagocytes towards the site of infection

Adherence

Binding of phagocyte to microbe

Phagosome

Phagocytic vesicle formed during phagocytosis

Phagolysosome

Fusion of phagosome with a lysosome

Digestive enzymes

Include lysozyme, lipases, proteases, nucleases, and reactive oxygen species generated by oxidative burst

Oxidative Burst

Process where NADPH oxidase produces superoxide to kill bacteria

Superoxide dismutase

Converts superoxide to hydrogen peroxide (H2O2)

NADPH oxidase

Uses electron from NADPH to produce superoxide (O2•)

Residual body

Contains indigestible material after digestion in phagolysosome

Discharge of waste materials

Final step in phagocytosis where waste is expelled from the cell

Streptococcus pyogenes

Bacterium known for evasion of phagocytosis

Capsules & M proteins

Inhibit adherence of pathogens. (streptococcus progenes, S. pneumoniae)

Leukocidins

Kill phagocytes.

Membrane attack complex

Lyses phagocytes.

Shigella & Rickettsia

Escapes phagosome.

HIV & Mycobacterium tuberculosis

Prevents phagosome-lysosome fusion.

Coxiella burnettii

Survives in phagolysosome.

Inflammation

Nonspecific response to tissue injury caused by pathogen/physical trauma.

Cardinal signs of inflammation

Redness (rubor), Warmth (calor), Pain (dolor), Swelling (tumor), Altered function (functio laesa).

Cytokines in inflammation

Regulate and initiate inflammation

results of inflammation being initiated

increases capillary dilation, blood flow, expression of adhesion molecules, and development of fibrin clot to restrict pathogen movement

Histamine

Causes vasodilation and increased permeability of blood vessels.

Kinins

Cause vasodilation and increased permeability of blood vessels.

Prostaglandins

Intensify histamine and kinin effect.

Leukotrienes

Increase permeability of blood vessels and phagocytic attachment.

pathway of inflammation being initiated

injury or infection → chemicals released → blood vessels widen and leak → immune cells arrive → white blood cells cleanup to help heal tissue → inflammation signs appear

diapedesis

the passage of blood cells through the intact walls of the capillaries, typically accompanying inflammation.

Fever

Abnormally high body temperature as a systemic response to infection.

hypothalamus

regulates body temperature at 37'C, may release prostaglandins to raise temp

Interleukin-1 (IL-1)

Released by phagocytes in response to gram-negative endotoxins. causes fever

increased body temperature

increases production of t cells and transferrins, Intensifies effects of antiviral interferons, May inhibit bacterial enzymes (metabolism), Aid in tissue repair

Transferrins

Decrease availability of free iron in the body.

Complement System

30+ serum proteins that defend against bacterial infection and enhance antibody responses. (bridge between innate&adap) -dispose of wastes

mechanisms of action for complement system

opsonization, inflammation, cytolysis

Opsonization

Coating of microbe with serum components to enhance recognition and phagocytosis. (works in conjunction with antibodies)

Cytolysis

Puncture cell membranes causing cell lysis. (membrane attack complex)

C3

Inactivated C3 splits into activated C3a and C3b.

C5a

calls phagocytes to the infection site, helping the body clear out pathogens efficiently.

complement system steps

1. activation of complement proteins

2. C3 splits into C3a (calls immune cells -inflammation) and C3b (sticks to germs -opsonization).

3. C3b helps cut C5 into C5a (another inflammation booster and immune cell attractant) and C5b (starts the formation of a special complex)

4. C5b & other complement proteins help build a hole-making complex (MAC) that bursts the germ and kill it

5. C3a and C5a cause blood vessels to become leaky and attract immune cells like neutrophils and macrophages. (chemotaxis) and clean up everything

Classical Complement Pathway steps

1. Antibodies bind to a pathogen (bacteria, virus).

2. C1 complex binds to the antibodies on the pathogen.

3. C1 activates the inactives C2 and C4, which both split and join C2a & C4b to form C3 convertase.

4. C3 convertase splits C3 into C3a (causes inflammation) & C3b (sticks to the pathogen, tagging it).

5. C3b helps form C5 convertase, which splits C5 into: C5a (attracts immune cells, causes inflammation) & C5b (starts forming the Membrane Attack Complex).

6. C5b binds to C6, forming the C5b6 complex (stabilizing it)

7. C5b, C6, C7, and C8 bind together sequentially and

insert into the microbial plasma membrane, where they function as a receptor to attract a C9 fragment;

8. C9 fragments are added to form a channel. Together, C5b through C8 and the multiple C9 fragments form the

membrane attack complex, resulting in cytolysis. (MAC)

9. Membrane Attack Complex (MAC) forms and creates holes in the pathogen, killing it.

Mast cell

A type of immune cell that releases histamine during allergic reactions.

C3a

A fragment that promotes inflammation and attracts immune cells.

Membrane attack complex (MAC)

A structure formed by C5b, C6, C7, C8, and multiple C9 fragments that disrupts microbial membranes.

Classical Pathway

A complement activation pathway (innate) initiated by antigen-antibody complexes. (adaptive)

Alternative Pathway

A complement activation pathway that does not require antibodies.

Lipid-carbohydrate complex

A structure on the surface of microbes that can activate the alternative pathway.

Lectin Pathway

A complement activation pathway initiated by lectin binding to carbohydrates on microbes.

Interferons

Cytokines produced by macrophages and lymphocytes that are effective against viral infections.

Antiviral Proteins (AVPs)

Proteins that degrade viral mRNA and inhibit protein synthesis to combat viral infections.

Iron-Binding Proteins

Proteins that sequester free iron to limit its availability to pathogens.

Antimicrobial Peptides (AMPs)

Short polypeptides that have a broad spectrum of activity against various pathogens.

mode of action for Antimicrobial Peptides (AMPs)

inhibition of cell wall synthesis, damage to cytoplasmic membrane, attacking a pathogens DNA/RNA