Immunity

Patho Exam 2

types of immunity

innate, adaptive

innate immunity

natural barriers

lines of defense

first - natural barriers

second - inflammation

third - adaptive/acquired immunity

first line of defense

physical and chemical barriers, skin, low pH and temp, GI GU and resp tract linings, antibacterial peptides in mucus sweat saliva tears earwax

antimicrobial peptides

cathelicidins, defensins

second line of defense

nonspecific, cellular and chemical components, rapidly initiated, no memory cells

causes of inflammation

infection, mechanical damage, ischemia, nutrient deprivation, extreme temp, radiation

cardinal signs of inflammation

redness, heat, swelling, pain, loss of function

vascular response to inflammation

BV dilation, increased vasc permeability and leakage, WBC adherance to inner walls of vessels, migration through vessels - diapedesis

local manifestations of inflammation

dilute toxins, carry plasma proteins and leukocytes to injury site, carry bacterial toxins and debris away from site

exudate

fluid and cells such as protein and debris; includes serous, fibrinous, purulent, hemorrhagic

serous exudate

watery, indicates early inflammation

fibrinous exudate

thick clotted, indicates more advanced inflammation

purulent exudate

aka suppurative, indicates bacterial infection

hemorrhagic exudate

indicates bleeding

systemic manifestations of inflammation

fever, leukocytosis (left shift), increased plasma protein synthesis

fever

caused by exogenous and endogenous IL-1 pyrogens, acts directly on hypothalamus

chronic inflammation

>2 wks, often related to unsuccessful acute inflammatory response

wound healing overview

regeneration - most favorable outcome

resolution - return injured tissue to original structure and function

repair - replace destroyed w/ scar tissue

scar tissue

primarily composed collagen to restore tensile strength

primary intention

heal under conditions of minimal tissue loss, original structure and function restored

secondary intention

require significantly more tissue replacement (open wound), scar formation

phases of wound healing

1. Hemostasis

2. Inflammation

3. Proliferation

4. Remodeling/Maturation

phase 1: hemostasis

coagulation and infiltration (platelets, neutrophils, macrophages) , fibrin mesh of clot acts as scaffold , platelets release growth factors

phase 2: inflammation

debridement, neutrophils and macrophages clean wound

phase 3: proliferation

wound begins to heal, BV and lymph drain debris, vasc dilation and permeability reverse, fibroblast proliferation/new tissue formation, collagen synthesis, epithelialization, wound contract (myofibroblasts), cellular differentiation occurs, begins 3-4days post injury continues 2 wks

phase 4: remodeling/maturation

begins several weeks post injury may last 2 years, cellular differentiation continues, scar tissue forms, scar remodeling

dysfunctional wound healing - inflammatory phase

ischemia, hemorrhage, hypovolemia, fibrous adhesions, excess scar formation, infection, wound sepsis, hypoproteinemia, mx

wound dysfunction- reconstructive phase

impaired collagen matrix assembly (malnutrition) - keloid , hypertrophic scar

impaired epithelialization - anti inflamm steroids, hypoxemia, nutritional deficiencies, cleaning w/ H202

impaired contraction - contractures result from excessive myofibroblast tension

dehiscense

wound disruption, wound pulls apart at suture line, 5-12 days post suture, caused by excessive strain sepsis obesity, serous drainage increased, too much tension to weakened skin

aging immunity

impaired/delayed inflamm likely result of chronic illness (DM, cardio d/o), mx may interfere w/, infections more common elderly, diminished immune function

adaptive immunity

acquired, works together w/ inflammation ,recognizes foreign (non self) substances - antigens , long term protection, slower than innate but more specific , has memory

end products of adaptive immunity

lymphocytes (T, B) , antibodies (immunoglobulin - Ig)

clonal diversity

each T/B cells specifically recognize only one particular antigen, occurs in primary lymphoid organs migrates to secondary,

primary lymphoid organs

T cells - thymus

B cells - bone marrow

clonal selection

antigen processed and presented to immune cells by APCs (antigen presenting cells), cell interaction T helper (Th) and APCs, results differentiation B cells into active antibody producing plasma cells and T cells into effector cells

humoral immunity

B cells and circulating antibodies in primary cells , direct inactivation of microorganism or action of inflamm mediators , primarily protect against bacteria and viruses

cellular immunity

differentiates t cells , primarily protects against viruses and cancer

humoral and cellular immunity relationship

work together to provide immunity and memory, respond more rapidly and efficiently on subsequent exposure to same antigen

antigen

molecule that can react w/ antibodies or receptors on B/T cells , mostly proteins

immunogenic antigen

antigen that can trigger immune response, results in production of antibodies or functional T cells ; dependent on foreignness, size, chemical complexity, and amount

haptens

small molecular weight antigens, cannot trigger immune response themselves but can when bound to carrier protein

antibody

immunoglobulin (Ig), produced by plasma cells, G A M E D

IgG

most abundant (80-85%), transpprted across placenta, accounts for most protective activity against infections, four classes - IgG1 2 3 4

IgA

2 subclassess:

IgA1 - predominantly in blood

IgA2 - predominantly in normal body secretions

IgM

largest Ig, first antibody produced during response to antigen (typical primary immune response), syntehsized during fetal life

IgE

least concentrated Ig in circulation, act as mediator many allergic rxns, defends against parasites

IgD

low concentration in blood, primarily located surface of developing B cells, functions as one type of B cell receptor

primary immune response

initial exposure, during latent period B cells differentiate, after 5-7 days IgM antibody for specific antigen detected, IgG response = to or slightly less than IgM response, immune system “primed”

secondary immune response

more rapid than primary, larger amounts of antibody produced, IgM produced similar quantities to primary response but IgG produced much greater amount

active immunity

antibodies/T cells produced after natural exposure or immunization, long lived

passive immunity

preformed antibodies/ T cells transferred from donor to recipient, natural (across placenta) or artificial, temporary/short lived

allergy

exaggerated response against environmental pathogen

autoimmunity

misdirected response against host’s own cells, breakdown of self tolerance during which body begins to recognize self antigens as foreign

alloimmunity

directed against beneficial foreign tissues (transplants, transfusions)

sequestered antigen

some self antigens may be sequestered/hidden from immune system, immunologically privileged sites separated from circulation by barriers, not seen by immune system, if area damaged antigen released causing injury

contributing factors to autoimmunity

sequestered antigens, molecular mimicry, neoantigens, survivial of forbidden clone, defective peripheral tolerance, genetic factors

molecular mimicry

antigens resemble/mimic particular self antigen, ex acute rheumatic fever

neoantigen

new antigen, can cause allergic rxn that leads to autoimmunity, bind to self protein, immune reaction against neoantigen leads to immune reaction to self

forbidden clone

some T/B cells have receptors that react to self antigens, supposed to be destroyed and undergo apoptosis, autoimmunity can result from survival of this forbidden clone

defective peripheral tolerance

tolerance to self antigens in secondary lymphoid structures, Treg cells normally suppress response against self, may result in expansion of clones and development of autoimmune disease, SLE

myasthenia gravis

autoimmune disease of neuromuscular junction, antibodies against nicotinic acetylcholine receptor on post synaptic membrane in neuromusc junction, loss of aCH at motor endplate causes weakness

SLE patho

chronic multisystem inflammatory disease, deposition of circulating immune complexes containing antibody against host DNA, autoantibodies against - nucleic acids, erythrocytes, coagulation proteins, phospholipids, lymphocytes, platelets

SLE clinical manifestations

arthralgias (arthritis), vasculitis, rash, renal disease, hematologic changes (esp anemia), cardiovasc disease

SLE dx

eleven findings are common, presence of at least 4 indicates disease - malar rash, discoid rash, photosensitivity, oral/nasopharyngeal ulcers, nonerosive arthritis, serositis, renal d/o, neurologic d/o, hematologic d/o, immunologic d/o, ANA presence

transient neonatal alloimmunity

fetus expressing antigens not found in mother

ABO system

A and B codominant

individuals have antibodies to A and B antigens they lack

O universal donor

AB universal recipient

ABO incompatibility

alloimmunity rxn

A - incompatible w/ B and AB

B - incompatible w/ A and AB

AB - compatible w/ all

O - incompatible w/ A B and AB

Rh system

primarily expressed on erythrocytes

Rh positive : expresses D antigen on RhD protein (DD, Dd)

Rh negative : not express D antigen (dd) , may make anti D antibodies if exposed to Rh + erythrocytes

Hemolytic disease of newborn

Rh negative mother gives birth Rh positive infant

graft rejection

alloimmune rxn, main focus for acceptance is matching human leukocyte antigens (HLA) - DR locus

transplant rejection

hyperacute - immediate, rare, preexisting antibody to graft antigens

acute - cell mediated response against unmatched HLA antigens

chronic - months or yrs, due to weak cell mediated rxn against minor HLA antigens

deficiencies in immunity

impaired function T cells, B cells, phagocytes, and/or complement

primary - congenital, genetic, most often result of single gene defect

secondary - acquired, caused by other illnesses (more common) / factors (including trauma, stress)

immunodeficiency

hallmark - recurrent severe infections often w/ opportunistic organisms

severe combined immunodeficiency (SCID)

most severe immunodeficiency

reticular dysgenesis - most severe form

ADA (adenosine deaminase) deficiency - results in excess purine

X linked - due to defect in IL receptor

JAK3 (janus kinase 3) deficiency - cannot respond to cytokines

Wiskott Alrich Syndrome (WAS)

IgA and IgG levels usually normal but IgM levels severely depressed

DiGeorge Syndrome

partial or complete absence of T cell immunity from a partial thymus

combined deficiencies without nonimmunologic abnormalities

SCID, WAS, Digeorge syndrome

defects in innate immunity

chronic mucocutaneous candidiasis - primary defect of T cells in response to specific infectious agent , yeast Candida Albicans