INNATE IMMUNITY (WEEK 8)

What is the first line of defense in innate immunity?

• intact skin

• mucous membranes + their secretions

• normal flora

• chemical factors

is common to all of us + non specific

What is the second line of defense in innate immunity?

• phagocytes and natural killer cells

• inflammation

• fever

• antimicrobial substances

• common to all of us but comes into play when first line fails

• non specific

What is the third line of defense in adpative immunity?

• specialize lymphocytes t cells and b cells

• antibodies

• specific immunity, initiated if non specific immunity fails

• unique in each individual

What are physical factors?

• barriers to prevent entry of microbes

• processes that remove microbes from the body surface

What does the skin do as a physical factor?

• the skin is a thick barrier of tightly packed epithelial cells

• contains tough keratin

• has dryness and periodic shedding

What do mucous membranes do as a physical factor?

• traps microorganisms

• e.g. mucociliary escalator, lacrimal apparatus

What is an example of endothelial cells as a physical factor?

• blood brain barrier

• keeps brain and spinal cord sterile

What does hair do as a physical factor?

• prevents attachment of microbes to mucous membranes

What do secretions do as a physical factor?

• washes out corresponding area

• e.g. saliva, tears, urine, cerumen, vomit, diarrhea

What are chemical factors?

• substances made by the body to inhibit or kill microbial growth

What do sebaceous glands / sebum do as a chemical factor?

• inhibits microbial growth via low pH

• e.g. fatty acids

What do sweat glands and sweat do as a chemical factor?

• presence of lysozyme breaks down bacterial cell walls

• contains salt and dermicidin

What do gastric juices, vaginal secretions, and urine do as chemical factors?

• has low pH

• e.g. lactic acids

What does saliva do as a chemical factor?

• has low pH, lysozyme, lactoperoxidase, lactoferrin, and IgA antibodies

What do digestive enzymes do as chemical factors?

• contains proteases, lipases, and amylase

What is normal flora?

• wards off growth of pathogens by competitive inhibition

How does normal flora function?

• produce antimicrobial molecules bacteriocins and lactic acid

• uses up space and nutrients to prevent colonization

What are natural killer cells

• type of lymphocyte (agranulocyte)

• recognizes then kills infected body cells / tumour cells

• cells that display foreign antigens stimulate NK cells to release toxic compounds perforin and granzymes

What is perforin?

• proteins that puncture the membrane of abnormal cells

What are granzymes?

• protein digesting enzymes poured into abnormal cells to induce apoptosis / cell suicide

How does the activation of NK cells work?

1. NK cell recognizes MHC 1 on a healthy cell and does not kill it

2. infected cells dont present MHC 1 but presents ligands for the activating receptor

3. NK cell will trigger a response to kill that cell

What is phagocytosis?

• ingestion of microbes or particles by different WBC types

What are the phagocytes?

• neutrophils

• macrophages

What are the steps that occur in phagocytosis?

1. chemotaxis which is the attraction of phagocyte via chemokines

2. adherence which is the attachment of phagocyte TLR to PAMP

3. ingestion which is phagosome formation

4. digestion which occurs in phagolysosome

5. waste removal which occurs in residual body

What is PAMP and what molecule contains it?

• pathogen associated molecular pattern

• microbe has PAMP

What is TLR and what molecule contains it?

• toll like receptors

• phagocyte has TLR

How can microbes evade phagocytosis by inhibiting adherence?

• capsules

• M protein in cell wall

• biofilms

• e.g. S. pneumoniae, H influenzae, S. pyogenes

How can microbes evade phagocytosis by escaping phagosome?

• phospholipases

• e.g. shigella, L. monocytogenes, B. anthracis

Which pathogen evades phagocytosis by preventing phagosome-lyososome fusion?

• HIV

• plasmodium

How can some microbes survive in the phagolysosome?

• mycolic acid

• e.g. mycobacterium tuberculosis

What is inflammation?

• response to tissue injury

• confines and destroy pathogen and repair tissue

• characterized by redness, pain, heat, and swelling

• sometimes causes loss of function

What is the first step to inflammation and what occurs?

• vasodilation and increased permeability of blood vessels

• mast cells and resident macrophages recognize pathogens

• these release chemicals like histamine and chemokines

What is the second step to inflammation and what occurs?

• phagocyte migration and phagocytosis

• phagocytes appear within an hour to start walling off + destroying pathogens

• phagocytes may die when they engulf large numbers of microbes and damaged tissues

  • leads to pus formation

What is the third step to inflammation and what occurs?

• tissue repair which occurs once all harmful substances have been removed and neutralized

• WBCs contribute to repair by stimulating fibroblasts

• chronic inflammation occurs when pathogens remain in underlying tissues

  • forms granulomas

What occurs in the process of a fever?

• hypothalamus sets body temperature to around 37 C

• prostaglandin release is triggered by pathogens and cytokines

• body temp increases via shivering, increasing metabolic rate, and vasoconstriction

What does a prostaglandin do in a fever?

• resets the hypothalamus to an abnormally high body temperature

What is the purpose of a fever?

• inhibit bacterial growth

• speeds up body reactions for faster repair

  • e.g. more T cell production, intensifying interferon effect

What are the complications of fevers?

• tachycardia

• dehydration

• acidosis

• seizures in young children

• death

What is the complement system?

• consists of > 30 plasma proteins where C3 is the central player

• acts in a cascade where one reaction triggers another for amplification

• initiated by factors including microbial surface molecules and antibodies

What occurs in cytolysis as an outcome of complement activation?

1. C3 splits into C3a and C3b

2. C3b splits into C5

3. C5 splits into C5a and C5b

4. C5 combines with C6, C7, C8, and C9 to form membrane attack complex for cytolysis

What occurs in opsonization as an outcome of complement activation?

1. C3 splits into C3a and C3b

2. C3b coats the microbe to enhance phagocytosis

What occurs in inflammation as an outcome of complement activation?

1. C3 splits into C3a and C3b

2. C3b splits into C5

3. C5 splits into C5a and C5b

4. C5a and C3a combine with the mast cell

How do bacteria prevent the formation of the membrane attack complex?

• gram positive cells are less susceptible to cytolysis bc of their thick peptidoglycan cell walls

• bacterial capsules contain compounds that prevent MAC insertion

• some gram negative bacteria alter the structure of their outer membranes (LPS)

How do bacteria break down C5a?

• some gram positive / negatiove cocci release an enzyme that can break down C5a

What is an interferon?

• a class of cytokine produced by cells during pathogen infection

What is a gamma interferon?

• induces neutrophils and macrophages to kill bacteria

• produced by lymphocytes

• (IFN-y)

What are alpha and beta interferons?

• diffuse to uninfected neighbouring cells

  • these cells are induced to produce antiviral proteins to disrupt viral multiplication

• used as anti viral drugs with limits

• produced by virus infected host cells

What does iron do in the human body?

• important for functioning of both human cells and prokaryotes

  • e.g. electron transport chain, enzyme function, O2 transport

What are iron binding proteins?

• proteins in the human body that bind to, store, and transport free iron to deprive prokaryotes and inhibit their growth

• fevers increase the release of these proteins

• pathogens fight back with siderophores

What are the types of iron binding proteins?

• lactoferrin in tears

• transferrin in blood and tissue fluids

• ferritin in liver, spleen, and bone marrow

• hemoglobin in RBCs

What are antimicrobial peptides?

• short peptides at around 12-50 amino acids

• produced by many cells and are triggered by microbial antigens

What do antimicrobial peptides do?

• kill bacteria, viruses, fungi, and eukaryotic parasites

What are the modes of action for antimicrobial peptides?

• form pores in plasma membrane

• inhibit cell wall synthesis

• destroy DNA / RNA

What are defensins?

• neutrophils which damage bacteria and fungi cell membranes

What are dermicidins?

• present in sweat

What are bacteriocins?

• E.coli in microbiome which kill pathogenic bacteria in the colon