L21- the innate immune response

describe cytokine secretion

a brief, self-limited event

• local and systemic

what does it mean when cytokine secretion is pleiotropic

there are multiple biological actions

what does it mean when cytokine secretion is redundant

there are shared biological actions

how do cytokines initiate their actions

by binding to specific membrane receptors on target cells

what do external signals of cytokines regulate

the expression of cytokine receptors and the responsiveness of cells to cytokines

what produces the mediators and regulators of innate immunity

produced mainly by macrophages in response to infectious agents

what produces the mediators and regulators of adaptive immunity

produced mainly by T lymphocytes in response to specific recognition of foreign antigens

what produces the stimulators of haematopoeisis

produced by bone marrow stromal cells and leukocytes

what do stimulators of hematopoiesis do

stimulate the growth and differentiation of immature leukocytes

list some of the important cytokines

• IL2

• IL1

• TNF a

what are the 2 main groups of chemokines

• CXC

• CC

how many types of chemokines are there

>50

what is the full name of chemokines

chemotractive cytokines

list the effects of cytokines secreted by macrophages

• inflammation

• chemotactic

• fever

• acute phase response

what do cytokines secreted by macrophages act on

• vascular endothelium

• lymphocytes

describe antimicrobial peptides

• ampipathic

• innate

• small

what does ampipathic mean and why is it useful

contains both polar and non-polar properties

• can destabilise the lipid bilayer

what effects do antimicrobial peptides have on host cells

immunomodulatory (regulates immune system)

what are antimicrobial peptides produced by

innate cells and epithelial cells

what does inflammation increase

• vascular permeability

• expression of adhesion molecules (cell transport)

• blood supply

what are the signs of inflammation

• erythema (red)

• oedema (swelling)

• loss of function

• heat

• pain

what does inflammation aim to do

restore homeostasis and limit damage, helping the body to recover

what are the triggers of inflammation

• inappropriate immune response

• pathogens

• tissue damage

summarise the steps of inflammation

• bacteria trigger macrophages to release chemokines and cytokines

• vasodilation increases vascular permeability

• inflammatory cells migrate into the tissue, releasing inflammatory mediators that cause pain

what are the mediators of inflammation

• complement products

• macrophage/ T-cell-derived cytokines

• mast cells

• prostaglandins, leukotrienes, thromboxane, NO

how do complement products mediate inflammation

(C5a > C3a)

• endothelial cells

• increase blood flow/permeability/binding of phagocytes to endothelial cells

• activate mast cells

how does the local inflammation mechanism work, using Gram-ve bacteria from cut on the hand as an example

• PRR on macrophage is stimulated

• release of TNFalpha but controlled

• positive outcome

what is endotoxic shock

excessive cytokine release in gram-ve bacterial infection

what are the widespread effects of cytokines on vascular endothelium from endotoxic shock

• circulatory shock

• disseminated intravascular coagulation (DIC)

describe the mechanism of systemic inflammation using gram-ve bacteria infection of the blood as an example

• PRR on macrophage is stimulated

• uncontolled release of TNFalpha

• negative outcome

what is another term to describe systemic inflammation

toxic shock

what is a cytokine storm

elevated levels of circulating cytokines and immune cell hyper-activation

what cytokines are involved in a cytokine storm

pro-inflammatory cytokines

what infections cause cytokine storms

• SARS-CoV-2

• yersinia pestis

• cancers

• autoimmune diseases

what do cytokine storms cause

• organ failure

• disseminate intravascular coagulation

• can be lethal

how many more immune cells does the GI tract have than on the skin

200X

what is the GI tract constantly exposed to

• commensals (bacteria)

• food

• pathogens

what separates the luminal contents of the GI tract from the host

a single layer of cells

what do paneth cells secrete

AMPs (NOD2 role- Crohn’s disease)

what are the GI host-immune interactions

• saliva, pH, bile, peristalsis

• microbiome

• IgA secretion

• complement

• tight junctions

• paneth cells

how does the microbiome suppress proliferation/colonisation of pathogens

IL1 beta activation, AMP production, TH17 cell differentiation

What is Crohn’s disease

IBD

• autoimmune

who does Crohn’s disease affect

• 1 in 500 people

• aged 15-35

what are the symptoms of Crohn’s disease

• fatigue

• fever

• abdominal pain

• diarrhea

• weight loss

• skin lesions

what causes Crohn’s disease

autoreactive T cells against intestinal floral antigens

• TH1 cell infiltration

• macrophages

what is the treatment for Crohn’s disease

• immunomodulation

• surgery

• diet

what are the humoral components of Crohn’s disease

• cytokines

• complement

• altered AMP levels

• antibodies