Lecture 22. Infection and innate immunity Flashcards
3 processes that provide innate immunity
- Complement
- Myeloid cells and phagocytosis(neutrophils and macrophages)
- Pattern recognition Receptors(PRR)
features of innate immune response
- no memory. 21st and 1st response will be the same
- no ability to learn and change over time
- primordial, oldest type of immunity, ~500 million years ago
- first-line immediate defense
- all living things have the ability to differentiate self and non-self
Viruses
intracellular pathogens
carry the machinery needed to reproduce, but need a host cell to make copies of themselves( eg COVID carries a gene for RNA polymerase)
coat of protein around single RNA or DNA
oldest form of life
defense against viruses relies on adaptive immune system
Mast cell
important
resident in the mucosal tissue region
predominantly responsible for atopic allergy
releases agents that cause local inflammatory response( eg pollen/dust allergy)
give examples of microorganisms that can evade the stomach ph barrier
- chorela
- H-pylori
Anatomical and Physiological barriers
- Intact skin
- ciliary clearance
- low stomach ph
- lysozyme in Tears, Saliva( enzyme degrades the membrane of bacteria)
Dendritic cells
link the innate and adaptive immune response
control the type of immune response
Influenza
-very serious, virulent and infectious
polio
virus that affects neuromuscular junction causes paralysis
- vaccine developed in 1950s
- almost eradicated
- only from human to human
Smallpox
eradicated by vaccine(from cowpox)
pustules formed on the body
HIV
resides in lymphoid tissue, infect T-cells
never eradicated
Bacteria
mostly extracellular pathogens
-defense by innate mechanisms and phagocytosis
staph aureus
produces protease, which cleaves a particular protein which causes skin to slot off
easily develops antibiotic resistance
staph aureus
produces protease, which cleaves a particular protein which causes skin to slot off
easily develops antibiotic resistance
TB
- bacteria
- intracellular
- grows inside macrophages
- difficult to treat, thick coating is relatively impermeable to most drugs
strep pyogenes
bacteria
causes rheumatic fever
yersinia pestis
black plague
bacteria
-2 vectors of transmission:
human fleas
flea picks up from rats
bubonic plague- “buboes” under the armpits in the lymph nodes
-still present cases, but contained
vibrio cholerae
bacteria
- everywhere
- harmless unless prolific in contaminated water
- transmitted through the fecal-oral route
- problem in countries with water contamination
-cholera toxin-gastric leakage
Protozoa and parasites
complex multicellular organisms require direct killing by chemical mediators released by specialist myeloid cells.
- don’t live inside cells, predominantly outside
- basophils, eosinophils, and mast cells release granules filled with cytotoxic chemicals. Degranulation releases these chemicals(eg histamine by mast cells) which kill the parasite
filarial worm
- causes elephantiasis
- buries through the skin
- mid-southern africa
- lymphoedema- lymphatic system is blocked by the worm
2 main types of bacteria
gram +ve stain with gram stain(purple)
gram -ve don’t stain
gram +ve bacteria
-thick peptidoglycan cell wall as a defense
requires phagocytosis and are not killed directly by complement
gram +ve bacteria
-thick peptidoglycan cell wall as a defense
requires phagocytosis and are not killed directly by complement
gram -ve bacteria
thin peptidoglycan layer surrounded by an outer membrane
can often be lysed directly by complement
what is the mechanism of action of beta-lactam antibiotics
block peptidoglycan synthesis
prevent the ability to replicate
what are the steps that neutrophils must go through to find their way to the site of infection
- Activation. Anaphylatoxins or chemokines( tissue damage) are released by the complement and diffuse towards the nearest capillary. Capillaries are lined with endothelial cells(1 cell thick). Endothelial cells recognize the chemical signals and become activated, and start to express selectins on the surface of the inferior wall.
- Tethering. Neutrophil tethers to the inside capillary wall. Mediated by selectins and sialyl lewis X( target for selectins), slowing down the neutrophils.
- Adhesion. strong binding between neutrophil integrins and ICAM-1 on the endothelial cells.
- Diapedesis. Neutrophil squeezes through the space between endothelial cells into the interstitial space outside the capillary
- Chemotaxis. Neutrophils migrates along a chemical gradient(chemokines) to the site of infection
how does the neutrophil cell moves
-the front end of the neutrophil lays down(polymerizes) actin filament, and the end depolymerizes the filaments
What is essential for neutrophil activation
Opsonisation.
Complement binding to the bacteria
what is the importance of complement receptors
CR1 is the most important one, the main neutrophil receptor that recognizes and binds to C3b
Essential for phagocytosis
what is the importance of complement receptors
Myeloid cell receptors that bind activated complement components deposited on bacteria. CR1 is the main neutrophil receptor and binds to C3b. Cross-linking of the surface CRs initiates phagocytosis
2 ways in which innate immune cells can recognize bacteria
- Complement receptors
- FC receptors on the neutrophil
Fcr(antibody) mediated phagocytosis
(Activation through FC receptors)
Antibodies (IgM and IgC) bind to bacterial antigens
It exposes the antibody FC region
Fc receptors on neutrophils bind multivalent Fc sites on the antibody and activate phagocytosis
neutrophil membrane invaginates forming a phagosome
phagosome fuses with the lysosome to form a phagolysosome
phagolysosome acidifies and digests bacteria
the products of digestion are excreted through exocytosis
*innate response but reliant on adaptive immunity-antibodies
Molecular pattern recognition
pattern recognition receptors bind complex molecules that are unique to microbes
-Known as Toll-LIke Receptors(TLR), but there are also others.
TLR are Leucine Rich Repeat(LRR) receptors
-Activation through TLR causes a strong innate immune response through an important inflammation pathway
*also drives adaptive immune response. Amplification switch
regulates the strength, type of the immune response, and how to respond to a particualr organism
-can recognise viruses, bacteria, fungi, protozoa
Pathogen associated molecular patterns(PAMPs)
- many different patterns
- molecules unique to microbes recognized by PRRs
- structurally complex
- evolutionary stable(essential to microbe function)
- stimulate the power “switch” for adaptive response
eg viral DNA, RNA, glycoproteins
TLR4
the TLR for lipopolysaccharide (LPS)
- LPS is a membrane component of all gram -ve bacteria
- tiny ammounts induce a powerful innate response
- LPS is a “pyrogen” -causes fever when injected into the bloodstream
- release of LPS by gram -ve bacterial infections leads to life threatening Septic Shock
septic shock
- overactivation of the immune system in response to LPS
- life threatening
- life support
myeloid cell
A myeloid cell is a type of blood cell that originates in the bone marrow. As a myeloid cell matures into an adult blood cell, it will take on a specific role as a basophil, eosinophil, erythrocyte, macrophage, monocyte, neutrophil, or platelet.
