Lecture 22. Infection and innate immunity

Question 1

3 processes that provide innate immunity

Answer 1

• Complement
• Myeloid cells and phagocytosis(neutrophils and macrophages)
• Pattern recognition Receptors(PRR)

Question 2

features of innate immune response

Answer 2

• 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

Question 3

Viruses

Answer 3

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

Question 4

Mast cell

Answer 4

important
resident in the mucosal tissue region
predominantly responsible for atopic allergy
releases agents that cause local inflammatory response( eg pollen/dust allergy)

Question 5

give examples of microorganisms that can evade the stomach ph barrier

Answer 5

• chorela
• H-pylori

Question 6

Anatomical and Physiological barriers

Answer 6

• Intact skin
• ciliary clearance
• low stomach ph
• lysozyme in Tears, Saliva( enzyme degrades the membrane of bacteria)

Question 7

Dendritic cells

Answer 7

link the innate and adaptive immune response
control the type of immune response

Question 8

Influenza

Answer 8

-very serious, virulent and infectious

Question 9

polio

Answer 9

virus that affects neuromuscular junction causes paralysis

• vaccine developed in 1950s
• almost eradicated
• only from human to human

Question 10

Smallpox

Answer 10

eradicated by vaccine(from cowpox)
pustules formed on the body

Question 11

HIV

Answer 11

resides in lymphoid tissue, infect T-cells
never eradicated

Question 12

Bacteria

Answer 12

mostly extracellular pathogens
-defense by innate mechanisms and phagocytosis

Question 13

staph aureus

Answer 13

produces protease, which cleaves a particular protein which causes skin to slot off
easily develops antibiotic resistance

Question 14

staph aureus

Answer 14

produces protease, which cleaves a particular protein which causes skin to slot off
easily develops antibiotic resistance

Question 15

TB

Answer 15

• bacteria
• intracellular
• grows inside macrophages
• difficult to treat, thick coating is relatively impermeable to most drugs

Question 16

strep pyogenes

Answer 16

bacteria
causes rheumatic fever

Question 17

yersinia pestis

Answer 17

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

Question 18

vibrio cholerae

Answer 18

bacteria

• everywhere
• harmless unless prolific in contaminated water
• transmitted through the fecal-oral route
• problem in countries with water contamination

-cholera toxin-gastric leakage

Question 19

Protozoa and parasites

Answer 19

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

Question 20

filarial worm

Answer 20

• causes elephantiasis
• buries through the skin
• mid-southern africa
• lymphoedema- lymphatic system is blocked by the worm

Question 21

2 main types of bacteria

Answer 21

gram +ve stain with gram stain(purple)
gram -ve don’t stain

Question 22

gram +ve bacteria

Answer 22

-thick peptidoglycan cell wall as a defense
requires phagocytosis and are not killed directly by complement

Question 23

gram +ve bacteria

Answer 23

-thick peptidoglycan cell wall as a defense
requires phagocytosis and are not killed directly by complement

Question 24

gram -ve bacteria

Answer 24

thin peptidoglycan layer surrounded by an outer membrane
can often be lysed directly by complement

Question 25

what is the mechanism of action of beta-lactam antibiotics

Answer 25

block peptidoglycan synthesis prevent the ability to replicate

Question 26

what are the steps that neutrophils must go through to find their way to the site of infection

Answer 26

1. 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. 2. Tethering. Neutrophil tethers to the inside capillary wall. Mediated by selectins and sialyl lewis X( target for selectins), slowing down the neutrophils. 3. Adhesion. strong binding between neutrophil integrins and ICAM-1 on the endothelial cells. 4. Diapedesis. Neutrophil squeezes through the space between endothelial cells into the interstitial space outside the capillary 5. Chemotaxis. Neutrophils migrates along a chemical gradient(chemokines) to the site of infection

Question 27

how does the neutrophil cell moves

Answer 27

-the front end of the neutrophil lays down(polymerizes) actin filament, and the end depolymerizes the filaments

Question 28

What is essential for neutrophil activation

Answer 28

Opsonisation. Complement binding to the bacteria

Question 29

what is the importance of complement receptors

Answer 29

CR1 is the most important one, the main neutrophil receptor that recognizes and binds to C3b Essential for phagocytosis

Question 30

what is the importance of complement receptors

Answer 30

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

Question 31

2 ways in which **_innate_** immune cells can recognize bacteria

Answer 31

- Complement receptors - FC receptors on the neutrophil

Question 32

Fcr(antibody) mediated phagocytosis (Activation through FC receptors)

Answer 32

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

Question 33

Molecular pattern recognition

Answer 33

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

Question 34

Pathogen associated molecular patterns(PAMPs)

Answer 34

- 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

Question 35

TLR4

Answer 35

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

Question 36

septic shock

Answer 36

- overactivation of the immune system in response to LPS - life threatening - life support

Question 37

myeloid cell

Answer 37

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.