Micro bio 3

Ilya Metchnikoff

Observed motile amoeba-like cells within larval form of starfish
Reasoned certain cells in animals can ingest and destroy foreign material

Innate immunity

is routine protection present at birth

Adaptive immunity

develops throughout life as body is exposed to microbes or foreign material

Antigens

stimulate production of antibodies that bind and target them for destruction

If invaders breach

sensor systems detect

Sentinel cells

use pattern recognition receptors (PRRs) to identify unique microbial components

Complement system characteristic

found in blood and tissue fluid

Innate effector actions

destroy invaders

Interferons (IFNs)

are signaling proteins (cytokines) produced by host cells in response to pathogens like viruses, bacteria, and cancer cells.

Interferon (IFN) characteristic

secreted with viral infection

Phagocytes

engulf microbes or cell debris by phagocytosis

Fever

interferes with pathogen growth and enhances other immune responses

Physical Barrier

First line of defense all exposed surfaces are lined with epithelium

Epidermis:

many layers of epithelial cells

Mucous Membranes

Digestive, respiratory, genitourinary tracts

Lysozyme characteristic

degrades peptidoglycan

Peroxidases

form antimicrobials; break down hydrogen peroxide

Lactoferrin and transferrin

bind iron

Antimicrobial peptides (AMPs)

Defensins form pores in microbial membranes

Competitive exclusion of pathogens

Cover binding sites, consume available nutrients

Cutibacterium

species degrade lipids, produce fatty acids

E. coli

synthesizes colicins in intestinal tract

Lactobacillus

in vagina produce low pH

Clostridium difficile

a bacterium that causes severe inflammation of the colon (colitis), leading to watery diarrhea, fever, and abdominal pain.

Candida albicans

a fungus naturally found in the vagina in small amounts, but overgrowth causes vaginal yeast infections

hematopoiesis

the continuous, lifelong process of creating new blood cells—red cells, white cells, and platelets—from hematopoietic stem cells

(erythrocytes)

carry O₂

(leukocytes)

the immune system's primary defense, circulating in the blood and tissues to protect the body against pathogens, foreign substances, and diseased cells.

Granulocytes(neutrophils, eosinophils, basophils)

crucial innate immune white blood cells that fight infection and regulate inflammation.

Granulocytes Release granule contents

degranulation

Sentinel cells

(primarily macrophages, dendritic cells, and mast cells) are the body's first-line immune defense, stationed in tissues to detect threats.

Sentinel cells characteristic

identify pathogens or damage via receptors, releasing cytokines and chemokines to initiate inflammation, recruiting other immune cells

Neutrophils(First Responders)

engulf and destroy bacteria; granules contain enzymes, antimicrobials; also called PMNs, increase in number during infection

neutrophil extracellular traps

released DNA that catches microbes, allowing enzymes and peptides from granules to destroy them

Basophils

involved in allergic reactions, inflammation; granules contain histamine

Eosinophils

fight parasitic worms; involved in allergic reactions; granules contain antimicrobials and histaminase

 monocytes

the largest type of white blood cells produced in the bone marrow, serving as a critical, rapid-response unit of the innate immune system.

monocytes characteristic

They circulate in the blood and migrate into tissues to become macrophages or dendritic cells, specializing in phagocytosis (engulfing/killing pathogens), clearing debris, and initiating tissue repair.

Macrophages

specialized immune cells that act as "first responders" to infection and maintain tissue homeostasis by engulfing pathogens, dead cells, and debris through phagocytosis.

Dendritic Cells

Sentinel cells, function as “scouts”

Engulf material in tissues, bring it to cells of adaptive immune system for “inspection”

Lymphocytes

specialized white blood cells essential to the adaptive immune system, primarily functioning to identify and destroy foreign invaders like bacteria and viruses, as well as cancer cells.

Cytokines

small signaling proteins secreted by immune cells (and other cell types) that act as chemical messengers, managing the body’s response to infection, inflammation, and injury.

Chemokines

small signaling proteins that act as chemoattractants to guide the migration of leukocytes (white blood cells) to sites of infection, tissue damage, or inflammation.

Colony-stimulating factors (CSFs):

multiplication and differentiation of leukocytes

Interleukins (ILs)

a large group of cytokine signaling molecules produced mainly by leukocytes to regulate immune responses, inflammation, and hematopoiesis.

Tumor necrosis factor (TNF)

a potent, multifunctional pro-inflammatory cytokine primarily produced by macrophages and lymphocytes to regulate immune responses, cell proliferation, and apoptosis.

A cytokine storm

is a potentially deadly overproduction of cytokines that can occur during an immune response to certain pathogens, including COVID-19

Pattern Recognition Receptors (PRRs)

Allow body to “see” signs of microbial invasion; lead to cytokine secretion

Microbe-associated molecular patterns (MAMPs)

highly conserved molecular structures unique to microbes—such as bacteria, fungi, and oomycetes—that act as elicitors, triggering innate immune responses in plants and animals.

PAMPs/Pathogen -associated molecular patterns

not exclusive to pathogens

PRR’S Found at

Cell surface, endosome/phagosome, Free in cytoplasm

Dendritic cells Characteristic

have both TLRs and CLRs (C-type lectin receptors)

RIG-like receptors (RLRs)

in cytoplasm detect viral RNA

NOD-like receptors (NLRs)

in cytoplasm detect microbial components or cell damage

NLRs in macrophages or dendritic cells

combine with other proteins to form inflammasome

The Interferon Response 1

Pattern Recognition Receptors (PRRs) detect viral RNA by sensing pathogen-associated molecular patterns (PAMPs) and produces interferon (IFN)

The Interferon Response 2

Interferon causes neighboring cells to express inactive antiviral proteins (iAVPs)

The Interferon Response

iAVPs activated by viral dsRNA and Degrade mRNA, stop protein synthesis, infected cells undergo apoptosis

The Complement System

a crucial part of the innate immune system, consisting of over 30-50 blood and tissue proteins that act as a proteolytic cascade to identify and eliminate pathogens.

Alternative pathway

triggered when C3b binds to foreign cell surfaces (C3 unstable, so some C3b always present)

Lectin pathway:

pattern recognition molecules (mannose-binding lectins, or MBLs) bind to mannose of microbial cells, interact with complement system components

Classical pathway:

activated by antibodies bound to antigen, which interact with complement system

Opsonization:

C3b binds to bacterial cells and foreign particles, promotes engulfment by phagocytes that attach to opsonins (like C3b)

Inflammatory Response:

C5a attracts phagocytes to area; C3a and C5a increase permeability of blood vessels, induce mast cells to release cytokines

membrane attack complexes (MACs)

formed by proteins C5b, C6, C7, C8, and C9 molecules assembling in cell membranes of Gram-negatives

Molecules in host cell membranes

bind regulatory proteins that inactivate C3b, preventing opsonization or triggering of alternative pathway(Regulation)

Phagocytosis 1

Chemotaxis , direct (receptors bind mannose) and indirect (binding to opsonins) ,and engulfment

Phagocytosis 2

Phagosome maturation and phagolysosome formation

Phagocytosis 3

Destruction , digestion, and exocytosis

giant cells

macrophage fusion

Macrophages characteristic

Live weeks or months; regenerate lysosomes

exudate

a protein-rich fluid that contains transferrin, complement system proteins, antibodies, and other substances to counteract invading microbes. Leaks into tissue with inflammation.

diapedesis

the passage of blood cells—primarily white blood cells (leukocytes)—through intact capillary walls into surrounding tissues.

pus

Dead neutrophils accumulate; along with tissue debris

abscess

A localized collection of pus within a tissue

Acute inflammation

mainly neutrophils; macrophages clean up damage by ingesting dead cells and debris

chronic inflammation

macrophages, giant cells accumulate, and granulomas form

Necrosis:

traumatic cell death due to damage/self-destruction of host cells

Apoptosis

programmed cell death; does not trigger inflammatory response

Pyroptosis and necroptosis characteristic

triggers an inflammatory response that sacrifices infected cells

pyrogens

fever-inducing cytokines

Frederick Loeffler

found club-shaped bacteria

Emil von Behring

injected diphtheria toxin into guinea pigs that had recovered from diphtheria; they did not get ill

Berlin, 1891:

antitoxin first given to a child, who recovered

T Cell characteristic

mature in the thymus

Cytotoxic T cell

induce apoptosis in self cells infected with viruses or are otherwise “corrupt,” “corrupt” host cells

Helper T cell

directs/assists the various immune responses by activating attacking cells

Humoral Immunity

Eliminates microbial invaders and toxins in the blood or tissue fluids

B cells

Programmed to produce Y-shaped proteins called antibodies

B cell characteristics

develop in bone marrow

antibodies(immunoglobulins)

bind to specific antigens, marking them as an invader to be eliminated

T-cell receptors (TCRs)

only bind an antigen “presented” by one of the body’s own cell

have a CD8 marker/MHC 1

Cytotoxic T cells

have a CD4 marker/MHC 2

Helper T cells

B-cell receptors (BCRs)

are membrane-anchored antibodies

 two arms of the BCR

two identical antigen-binding sites

Immune tolerance,

prevents inappropriate adaptive immune responses from damaging the body’s own tissues

Central tolerance -

as lymphocytes mature (T cells in the thymus and B cells in the bone marrow), immature T and B cells that recognize “self” molecules are eliminated

Peripheral tolerance

prevents mature T and B cells that were not eliminated during central tolerance from reacting against self or other harmless molecules

Naïve lymphocyte

never encountered antigen; cannot react until it receives confirming signals​