Immunology

The study of the physiological mechanisms that humans use to defend their bodies from invasion by other organisms

Immunology
Based on observations that survivors of a disease were untouched (immune) when challenged with the agent again Immune response (IR) -critical to survival based on effects of immune deficiency diseases -complex, interconnected, redundant - over-activity may cause problems.. Hypersensitivity, autoimmune disease

Intro. to Immunology Figure 1.11

Studies found there were two branches of IR: innate and adaptive immunity Note imp. of having both aspects of IR If you could choose to have only one branch which one would you choose?

Branches of the Immune System

Innate = Nonspecific resistance = defenses that protect us from ANY pathogen Adaptive = Specific resistance = defenses that protect us from A particular pathogen

Figure 1.9
Innate Rapid (minutes/hours) Fixed Limited specificities Constant during response Adaptive Slow (days/weeks) Variable Numerous highly selective Improves during response

Nonspecific Immune System Non-adaptive Innate immunity

First and second line of defense - 1st->barriers & chemicals of skin and MM - 2nd-> phagocytosis, inflammation etc. Provides rapid response to invaders Generalized response using a limited number of recognition specificity Response does not improve during response or if re-exposed

Figure 8-5 (Old Book)

Note the chronology of innate and adaptive IRs

Specific Response Adaptive Acquired

Third line of defense Humoral & cell mediated response Involves B&T lymphocytes, macrophages, Antibodies Slow but efficient response ( days ->wks) Variable but highly selective specificity Improves during response, with re-exposure

Figure 8-5 (old book)

Innate IR First Line of Defense

Skin both physical and chemical barriers Mucus Membranes both physical and chemical barriers - resp. - gi - gu - conjunctiva

Figure 1.5

Physical barriers. Strong ones in blue. More vulnerable ones in red.

Figure 1.6

Skin
Layers of cells -continuous -closely packed -antimicrobial secretions - Sebum (fatty acids..) - Keratin - Lysozyme (damages gm.pos.cell walls) - Beta defensins -cathelicidins (e.g. dermacidin which damages membranes of microbes) Continually shed skindecreases #s of microbes

Oily skin secretions

Oils secreted from oil & sweat glands are antimicrobial (.. acidic) Some of these unsaturated FA are degraded by staphylococcal bact. oleic acid ( acts on gm neg and some fungi) When these unsaturated FA are degraded by staphylococcal bacteria volatile gases = BO (Q:Why is washing imp.? A: to microbial #s Sebum ( triglycerides) degraded by P. acnes FA which can be irritating to dermis inflammation

Keratin
Produced by keratinocytes (outer layer) Scleroproteins Major component of hair, skin, nails Most org. cannot enzymatically attack it ( exception dermatophytes)

Lysozyme (muraminadase)
Antimicrobial enzyme Present on skin, in tears, mucus and inside of phagocytes Acts primarily on gm pos. bacteria Disrupts Beta (14) glycoside bond between NAM and NAG in PG of cell wall

Beta Defensins
Antimicrobial peptides Present in epidermis, resp. tract, gi tract etc Kill bacteria, viruses, fungi Act on membrane Released in a harmless form which becomes active in lower ionic strength soln. of sweat, tears, gut.

Skin is hyperosmotic
High conc of NaCl is antimicrobial

Intact healthy skin

Most effective barrier against microbes More effective defense than any Mucus Membrane Few organisms can invade it. (The few that can invade it produce keratinase e.g. fungi that cause ringworm (i.e. athletes foot), hookworms & schistosomes

Conjunctiva
Mucous membrane (MM) that acts as a physical barrier Note physical protection offered by eyebrow, eyelashes, eyelid & tears Physical release of tears flushing org. from site Mucus sticky & slimy substance that binds org. to PX their entry Chemically, mucus contains glycoproteins called mucins , proteoglycans & enzymes that help repair and protect mucosal surfaces. Lysozyme & Beta defensins are also on MM

Upper Resp. tract

MM lines entire upper resp. tract acting as a physical barrier Nasal tract -nasal hairs help filter particles > 10um -air flow helpful in thrusting microbes onto mucosal lining - humidification enlarges org. making them more easily phag. - sneezing elimination - sticky mucus binds org. & px entry - cilia move mucus blanket full of org. toward pharynx to be expelled

Lower Resp. tract

Epiglottis blocks org. entry Coughing or sneezing expel microbes Mucus blanket traps org. (<10um) Mucociliary escalator of lower airway expels mucus blanket @ rate of 1-3 cm/hr. .Moves upward.

Chem protection: MM contain Beta defensins, lysozyme, etc

Genitourinary tract
Physical barrier - length of urethra correlates to frequency of bladder inf. ( Urethra of males av. 20 cm while in females av. 5 cm. Females have 14x more bladder inf. than males.) - periodic flushing out of org. by release of urine, secretions & mucus

Genitourinary tract
Chemical barriers - urine has a pH of 6 - antimicrobials in urine ( urea, uric acid, hippuric acid, fatty acids, mucin) -acidic vaginal secretions due to conversion of glycogen to lactic acid by Lactobacilli (pH 3-5) - Prostatic antibacterial factor in males

Gastrointestinal tract
Physical - saliva washes org. from mouth - shedding of columnar epithelial cells of gut shedding of bact. - peristalsis-> expulsion of some org.

Gastrointestinal tract
Chemical barriers - Saliva has lysozyme, Beta defensins, mucus - Stomach secretes acids (pH 2) , antimicrobial enzymes - small int. contains pancreatic enzymes, bile & enzymes which have antimicrobial activity -Paneth cells of int. tract secrete lysozyme & cryptins - large int. is protected by actions of normal flora

Importance of Normal Flora

Colonize sites & protect humans from pathogens by - using up nutrients - occupying attachment sites - releasing antimicrobials (e.g.bacteriocins) Estimated that we would live only 1 month without our Normal flora

Figure 1.2 illustrates the importance of normal flora

Second Line of Defense Phagocytosis & Inflammation:

Phagocytosis involves pathogen recognition & destruction (Fig. 1-7).

Inflammation is a part of second line of defense of the innate IR (Figure 1-8)

After Innate IR, the adaptive IR follows (Figure 1-10)

This Specific IR results in proliferation of lymphocytes specific for the invading pathogen.

In a perfect world
Because the innate is able to recognize self from non-self in a general fashion, it is rapid. It often effective in halting the pathogen enough to allow the specific IR to develop so as to rid this specific pathogen from the body.

Figure 1-11
More is known about the adaptive IR but we do know that having BOTH of these IRs intact is the best option.