Unit 8: Innate immunity

Innate immunity

initial defences to prevent infection

Innate immunity specificity

non-specific; defences act in response to all pathogens

Innate immunity formation

built-in mechanisms; structures/chemicals are present at birth

Innate immunity memory

none; same response regardless of prior exposure

Adaptive immunity definition

response to pathogens

Adaptive immunity specificity

specific; defences act in response to one type of bacterial strain or virus

Adaptive immunity formation

builds up over time; requires exposure to antigens

Adaptive immunity memory

strong response with a second exposure to the same antigen

Innate immunity lines of defence

first, second

First line of defence

initial barriers to pathogens to prevent entry and colonization

Second line of defence

a response to infection once the first line has been bypassed

First line of defence physical factors

barriers that prevent entry OR processes that remove microbes from the body surface

Barriers

skin, mucus membranes, endothelia

Skin

tightly packed epithelial cells that contain keratin

Mucus membranes

contain epithelial cells bound by tight junctions; mouth, lungs, urinary + digestive tracts
- mucus produced to cover, protect, trap

Endothelia

tightly packed cells
- ex. blood-brain barrier

Blood-brain barrier

endothelial physical factor; contains very tight cell junctions preventing pathogens from entering the central nervous system

Mechanical action

used to flush mucus-trapped microbes out of the body
- ciliary escalator
- shedding skin cells
- flushing action of urine, tears, etc

Ciliary escalator

in the lungs, use cilia to propel mucus out of lungs which is then swallowed or coughed/sneezed out

Normal flora competitive inhibition

prevents the growth of other microbes by out-competing pathogens for nutrients and by taking up all spaces that can be colonized

Chemical factors

substances or enzymes continuously produced by body cells
- sebum
- acids
- lysozyme
- IgA
- enzymes

Sebum

produced by sebaceous glands in the dermis to seal off pores of hair follicles

Acids

produced by normal flora to create a mildly acidic environment on the skin to inhibit pathogen colonization

Lysozyme

in saliva, sweat, tears; can break down bacterial cell walls

IgA

antibodies that protect the respiratory tract

Digestive enzymes

in saliva - salivary amylase
lower digestive tract - pancreatic amylase

Second line of defence chemical defences

1. AMPS
2. acute phase proteins
3. complement proteins

Antimicrobial peptides (AMPS)

group of chemicals with broad-spectrum antimicrobial activity

Production of AMPS

- some continuously, some in response to infection
- some by body cells, some by normal flora

Defensins

antimicrobial peptides produced by body cells

Bacteriocins

antimicrobial peptides produced by normal flora

Acute phase proteins

produced in the liver and secreted into the blood in response to inflammatory molecules
- ferritin, fibrinogen, mannose-binding lectin

Complement proteins

- group of proteins that circulate in inactive forms in the blood
- activated in a cascade = rapid response

Complement activation methods

1. classical
2. mannose-binding lectin (MBL)
3. alternative

Classical complement activation (method 1)

- antibody binds to bacterium
- C1 protein recruited + activated
- C3 protein recruited + activated

Mannose-binding lectin (MBL) complement activation (method 2)

- mannose-binding lectin binds to carb on microbial surface
- C3 protein recruited + activated

Alternative complement activation (method 3)

C3 protein directly recruited + activated

C3 protein

splits into C3a + C3b upon activation

Outcomes of complement activation

1. opsonization
2. cytolysis
3. enhanced inflammation

Opsonization (outcome 1)

enhanced phagocytosis; C3b coats microbe, more easily identified by macrophages

Cytolysis (outcome 2)

- C3b recruits + activates C5
- C5 splits into C5a + C5 b
- C5b combines with C6, C7, C8, C9 = membrane attack complex

Membrane attack complex (MAC)

C5b, C6, C7, C8, C9; inserts into the cell membrane
> ECF rushes in > microbial lysis

Enhanced inflammation (outcome 3)

C3 a + C5a combine and bind to mast cells
> increased histamine

How microbes avoid the complement system

- capsule
- gram-neg outer membrane
- gram-pos enzyme

Capsule + avoiding complement system

inhibits opsonization and prevents insertion of the MAC

Gram-neg cells + avoiding complement system

can alter the structure of the outer membrane to prevent MAC insertion

Gram-pos cocci + avoiding complement system

can release an enzyme that breaks down C5 protein

Cytokines

soluble proteins that act as communication signals between cells
- interleukins, chemokines, interferons

Interleukins

cytokines that modulate many parts of the immune system

Chemokines

cytokines that recruit WBC to sites of infection, tissue damage, and inflammation

Interferons

cytokines important for defence against viral replication

Inflammation-eliciting mediators

contribute to inflammation response
- histamine, leukotrienes, prostaglandins, bradykinin

Leukotrienes

inflammation-eliciting mediators with longer-lasting effects than histamine

Prostaglandins

inflammation-eliciting mediators that also play a role in fever

Bradykinin

inflammation-eliciting mediator that increases vascular permeability > edema

Second line of defence cellular defences

- granulocytes
- agranulocytes

Granulocytes

WBC with lobed nuclei and granules in the cytoplasm
- mast cell, basophil, neutrophil, eosinophil

Mast cells

reside in tissues to produce histamine

Basophils

produced histamine in response to allergic reactions

Neutrophils

eliminate bacteria through phagocytosis or the production of extracellular traps (NET's, webs of DNA)

Eosinophils

protect against protozoan and helminthic infections by releasing degradative enzymes

Agranulocytes

WBC with no granules in the cytoplasm
- natural killer cells, monocytes

Natural killer cells

use nonspecific mechanisms to recognize abnormal body cells > induce apoptosis in them

Monocytes

after movement into body tissue, differentiate into dendritic cells and macrophages

Process of phagocytosis

1. extravasation of leukocytes to infected site
2. pathogen recognition
3.pathogen degradation

Extravasasion

entry of phagocytes into infected tissue
- positive chemotaxis

Pathogen recognition

PAMP on pathogen attached to by PRR on phagocyte

Pathogen degradation

1. pseudopods form around microbe and a phagosome is made
2. lysosome inside macrophage contains hydrogen peroxide + enzymes
3. lysosome fuses with phagosome > phagolysosome
4. microbe digested
5. indigestible material excreted by exocytosis

How microbes avoid phagocytes

- capsule
- molecules that lead to phagocyte death
- phagocytosis as mechanism for entry
- biofilms

Acute inflammation

immediate response to injury is vasoconstriction to minimize blood loss
> histamine > vasodilation + vascular permeability > symptoms of inflammation

Chronic inflammation

occurs when immune system unable to clear pathogen
- pathogens remain in the deeper tissues, form granulomas
- tissue scarring

Granulomas

pockets of infected tissue surrounded by WBC

Fever

prostaglandins released during infection > hypothalamus elevates body temp thru negative feedback loops

During fever

- vasoconstriction > pale skin
- shivering
- increased metabolism

Enhancement of immune system by fever

- inhibits the growth of many pathogens
- isolates iron storages away from microbes