Week 2 Patho and Immuno Fish review

primary intention healing

Wound healing with opposed, clean edges; rapid healing and minimal scar formation. Has re-epithelialization (surgical and sterile)

secondary intention healing

Wound healing with separated edges and larger defects; slower healing with more scar (no re-epithelialization). Lacks factors in primary healing that helps restore to normal (burns, infections, etc)

purulent (supperative) inflammation

Inflammation with pus, dominated by dead neutrophils and debris; can form abscesses.

Typically caused by staph and strep

abscess

Abscess

capsule of granulation tissue

full of pus, doesn’t heal on it’s own. can rupture or form fistula (ex. Crohns)

fistula

channels formed between 2 preexisting cavities or hollow organs and the surface of the body.

serous inflammation

Mildest inflammation type with clear, watery exudate resembling serum. (burns, blisters, herpes vesicles, autoimmune fluid)

fibrinous inflammation

Inflammation with fibrin-rich exudate that can form fibrous networks on surfaces made of fibrinogen (large plasma protein)

Seen in strep throat, pneumonia, fibrinous pericarditis

ulcerative inflammation

Inflammation involving mucosal surfaces (stomach, intestine, etc) leading to epithelial loss and ulcer formation. peptic ulcers

pseudomembranous inflammation (colitis)

Inflammation with pseudomembrane formation, often due to fibrinopurulent exudate (e.g., C. difficile colitis). AKA antibiotic associated colitis

granulomatous inflammation

A chronic form with granulomas; often cell-mediated; TB and certain fungi are examples.

wound dehiscence

Separation of wound margins due to weak scar or poor healing.

keloid

Hypertrophic scar with excess Type III collagen (immature) from defective remodeling.

“proud flesh”

Labile cells

AKA continously dividing cells, stem cells, bone marrow. Capable of constant regeneration throughout lifespan, helps with repairs. Chemo treatments mess with these. RBCs

Quiescent cells

AKA stable cells.

Cells that do not divide regularly but can re-enter the cell cycle to regenerate if needed (e.g., hepatocytes after partial hepatectomy).

Form parenchymal organs (liver, kidneys, etc)

Nondividing cells

AKA permanent cells.

Cells that do not proliferate ever (e.g., neurons, myocardial cells). Repairs damage with fibrous scarring, gliosis, etc but does not fully repair good as new. Never get the damaged cells back

Wound healing steps

PMNs invade scab and scavenge debris. Replaced 2-4 days later by macrophages (QUARTERBACK) that recruit the 3 main wound healer cells. These + vascularized CT = granulation tissue.

Granulation tissue composure eventually goes from fibronection and type 3 collagen composition → mainly type 1 collagen. Epithelial tissue proliferates and scar is formed

myofibroblasts

Hybrid cells with smooth muscle and fibroblast features; contract wound margins to aid healing. Reduces defect and helps new skin cells (epithelium, collagen, etc) cover the surface injury

angioblasts

Precursors of blood vessels that form new vasculature sprouts in healing tissue. Allow blood with O2 and nutrients into the healing area and support tissue regeneration.

fibroblasts

Cells that produce extracellular matrix, including fibronectin (tensile strength, glue) and collagen (type 3 that matures to type 1).

gliosis

Process of reactive astrocyte proliferation following central nervous system injury, leading to the formation of a glial scar that supports tissue repair but may inhibit regeneration.

cells responsible for gliosis

astrocytes

fibrosis

Formation of excess fibrous connective tissue that can occur in response to injury or inflammation, leading to tissue scarring and impaired function. (heart, etc)

Initiation of classical complement pathway

Binding of C1q to antibodies (IgG or IgM) bound to antigens on a pathogen surface. C1q activates C1r, which in turn activates C1s.

C4 and C2 cleavage

C1s cleaves C4 into C4a and C4b. C4b binds to the pathogen surface and then binds C2. C1s then cleaves C2 into C2a and C2b.

Formation of C3 convertase

C4b2a complex forms the classical pathway C3 convertase, which cleaves C3 into C3a and C3b. C3b binds to the pathogen surface and opsonizes it, facilitating phagocytosis.

Formation of C5 convertase

C4b2a3b complex forms the classical pathway C5 convertase, which cleaves C5 into C5a and C5b. C5b initiates the formation of the membrane attack complex (MAC).

Membrane attack complex (MAC) process

C5b recruits C6, C7, C8, and multiple C9 molecules to form the MAC. The MAC creates pores in the pathogen's membrane, leading to lysis.

Regulation of classical complement pathway

C1 inhibitor (C1-INH) inhibits C1r and C1s, preventing excessive complement activation. Deficiency can lead to hereditary angioedema.

Classical pathway overall

First complex in classical complement activation (C1q, C1r, C1s) that binds IgG/IgM Fc regions.

Trimolecular complex that recognizes antibodies on antigen.

Recognition: C1q recognizes and fixes to Fc combining site on IgG (need 2) or IgM. It activates C1r from proenzyme to active molecule, which then activates C1s.

Activation: C1s cleaves C4 and C2 into C4-C2 complex (aka c3 convertase). Binding site on C4 is now able to attach to cell surface. Only substrate to C4-C2 is C3. It splits C3 into C3a and bigger C3b.

C3a leaves and acts as anaphylactoxin (C5a same). It can cause degranulation and histamine release from mast cells, smooth muscle contraction, and hydrolytic enzyme release from neuts.

C3b associates with C3 convertase to make C4-C2-C3b trimolecular complex (aka C5 convertase).

C3b generates intrinsic sites for IAP. C4-C2 attaches C3b to cell surfaces with with sites on them.

C5 gets cleaved like C3 by C5 convertase into C5a and C5b. C5b is focal point for Membrane Attack Unit (MAC).

MAC uses C5b, C6,7,8 and that attaches to target membrane and also recruits C9 to create poly C9. This opens transmembrane channel to cell interior (burrows), causing K+ to leave and water enter. Cell swells, macromolecules escape and cell is lysed.

Empty cell is phagcytosed

C3 convertase

Enzyme complex (C4b2a) that cleaves C3 to C3a and C3b in the classical pathway.

C5 convertase

Enzyme complex that cleaves C5 to C5a and C5b; formed after deposition of C3b

Membrane Attack Complex (MAC)

Pore-forming complex (C5b-6-7-8-9) that lyses target cell membranes.

Anaphylatoxins

C3a and C5a; small fragments that promote inflammation and mast cell degranulation.

Immune adherence phenomenon

Process by which C3b-coated targets bind phagocytes to enhance phagocytosis. Occurs when opsonization facilitates the recognition and destruction of pathogens by immune cells.

Classical pathway - concise

Complement activation triggered by antibody-antigen complexes; sequential activation to C3 and beyond. 3 steps: Recognition, Activation, Membrane Attack

How many IgG for complement?

2

How many IgM for complement?

1

Complement end result?

lysis

How many antibody isotypes?

5 heavy chains, 2 light chains

IgG

Major circulating Ig (80%); crosses placenta and protects fetus w passive immunity; activates complement cascade; opsonizes pathogens (make tasty). Secreted in milk.

IgA

Secretory antibody found in tears, saliva, gut lumen, and secretions; also in milk for neonates; secretory form with J chain and secretory component. 10-15% of Ig.

IgM

First antibody produced in a primary response; pentameric with up to five binding sites; activates complement. 5-10% of Ig.

IgE

Less than 1%. Antibody of allergy and parasite defense; binds to basophils/mast cells; mediates degranulation and hypersensitivity.

IgD

B cell surface receptor; helps recognize antigens and activates B cells to plasma cells. Less than 1% Ig.

Which antibodies in breastmilk?

IgG and mostly IgA

Which antibodies activate complement?

IgM and IgG

Which antibody crosses the placenta?

IgG

what are the 2 anaphylactoxins?

C3a and C5a promote inflammation and mast cell degranulation

secretory antibody

isotype IgA that plays a crucial role in mucosal immunity/protection by neutralizing pathogens and preventing their adherence to mucosal surfaces.

reaginic antibody

IgE that mediates allergic reactions by binding to allergens and triggering mast cell degranulation.

Reasons for fever besides infection

cancers, autoimmune disease, exercise, hot weather, vascular occlusions, drugs

What to do with fever of unknown origin

Look into respiratory, urogenital, skin/soft tissue. Hypothalamus regulates temp.

Macrophage jobs

Macrophages call fibroblasts in wound healing and also produce cytokines in infection- especially in gram negative sepsis by toll-like receptors

Toll-like receptors

proteins that play a key role in the immune system by recognizing pathogens and activating immune responses.