immunology

function of the immune system is to recognize ____ from __ and to ____ body against nonself

function of the immune system is to recognize ____ from __ and to ____ body against nonself

self, nonself, to defend

an effective immune response requires cooperative interaction between

-specific cells of the immune system

-cellular elements

-cell products

-non-lymphoid elements

desirable consequences of immunity are

-natural resistance

-recovery

-acquired resistance to infectious disease

undesirable consequences of immunity are

-allergy

-transplant rejection

-autoimmunity

example of innate surface epithelial barriers

skin, mucus, tears

innate cells are stored where

free floating in tissue

when monocyte moves to issue it becomes a

macrophage

granulocyte definition

granule containing enzymes and proteins in cytoplasm

two devisions of immune system

innate and adaptive

B lymphocyte location

stay in bone marrow

T lymphocyte location

go to thymus Th or Tc

lymphocytes arise from progenitor cells of the __ and __ in embryo

yolk salk, liver

sole provider for progenitor cells that develop into lymphocytes

bone marrow

continued cellular development and proliferation of lymphoid precursors occur as cells travel to the

primary and secondary lymphoid tissues

primary/central lymphoid organs

bone marrow thymus

secondary lymphoid tissues

-lymphoid

-spleen

-GALT (gut-associated)

-thoracic duct

-BALT (bronchus-associated)

-SALT (skin-associated)

-blood

first line of body defense

-unbroken skin

-mucosal membrane surfaces

-secretions

-physical ability to wash away pathogens

-chemical properties of tears and saliva

microbiota

-regulation of innate immunity functions and homeostasis

-regulation of adaptive immune functions in intestine

-regulation of systemic innate adaptive immune functions

second line of body defense

natural immunity

-innate/ inborn resistance to infection

-nonspecific mechanism

third line of body defense

adaptive immunity

B cells become __ that secretes ____

plasma cells antibodies

specific features of adaptive acquired immunity

-specificity

-memory

innate immune system is an ancient form of host defense that appeared before

adaptive immune system

innate focuses on

few larger groups of microorganisms called pathogen-associated molecular pattern (PAMPS)

-foreign

innate receptors that recognize PAMPS are called

pattern recognition receptors (PRR)

three activation pathways

-classical

-alternate

-mannose-binding lectin

complement protein made in the

liver

compliment is a

glycoprotein- proteins in plasma

over ___ glycoproteins present in active form in serum and all tissue fluids except urine and CSF

25

compliment glycoproteins are heat-liable meaning

disintegrate in heat

complement is activated by a cascade by antigen-antibody, endotoxin, capsules all of which ___ the next step

amplify

three primary functions of compliment

-cell lysis (poke hole, fluid in, cell burst)

-opsonization (flag “look at me”)

-regulation of immune and inflammatory response including immune adherence, anaphylatoxin, and chemotaxis

chemotaxis

tells other cells to move toward infection/inflammation

alterations in compliment proteins

-elevated complement levels

------ increased in many inflammatory conditions, trauma, and acute illness because components such as C3 are acute phase reactants (wound fight off)

-decreased complement levels

------decreased because of excessive activation, currently being consumed (all used up from fighting), or a single complement component is absent because of a genetic defect (sick all the time due to genetics), all can mean liver damage

diagnostic evaluation

indicators for complement testing

-recurrent pyogenic infections, especially meningococcal meningitis, and S. pneumoniae and neisseria species

-angioedema without urticaria

-autoimmune disorders

biological response modifiers: B lymphocytes secrete

specific antibodies

biological response modifiers: T lymphocytes secrete soluble mediators:

-interleukin-2 (IL-2) and other ils

-granulocyte-monocyte colony-stimulating factor (GM-CSF)

-interferon-y (IFN-y)

-tumor necrosis factor- B (TND-B)

biological response modifiers: Natural killer (NK) lymphocytes secrete

interferon-a (IFN-a)

biological response modifiers: Monocytes and macrophages secrete

-interferon a (IFN-a)

-Interleukin-1 (IL-1)

-Tumor necrosis factor-a (TNF-a)

-Granulocyte-monocyte colony-stimulating factor (GM-CSF)

common actions of cytokinesis

-secrete cytokines in rapid bursts, synthesized in response to cell activation

-bind to specific membrane receptors on target cells

-regulate receptor expression in T and B cells, which drives positive amplification or negative feedback

-act on different cell types

-excite same functional effects with multiple cytokines (redundancy)

-act close to the site of synthesis on the same cell or on a nearby cell

-influence the synthesis and actions of other cytokines

Interleukins (type of cytokine)

-molecules made by lymphocytes and act on lymphocytes

-mediate local interactions between leukocytes but do not bind to antigen

-modulate inflammation and immunity by regulating growth, mobility, and differentiation of lymphoid cells

innate major cell source

macrophages NK cells

major cell source of adaptive immunity

t lymphocytes

innate stimuli

virus

adaptive stimuli

protein antigens

innate quantity

possibly high, detectable in serum

innate effects on body

local and systemic

quantity of adaptive

usually low, usually undetectable in serum

adaptive effects on body

local

interferons

-natural defense response to foreign components

-broad actions (enhance the expression of specific genes, inhibit cell production, augment immune effector cells)

-demonstrated to act as (antiviral, immunomodulators (not let get out of control), antineoplastic agents (can destroy non-self cells that are bad or infected ))

tumor necrosis factor

principal mediator of acute inflammatory response to gram-negative bacteria and other infectious microbes

-simulates recruitment of neutrophils and monocytes to sites of infections

-activates neutrophils and monocytes to eradicate microbes

hemopoietic stimulators

-stem cell factors (c-kit ligand)

-colony-stimulating factor (CSFs)

-transforming growth factor B (TGF-B)

-chemokines

acute phase proteins

group of glycoproteins associated with the acute phase response with

-inflammation

-infection

-malignant neoplasia

-carious diseases or disorders

-trauma

-surgical procedures

-drug response

acute response can measure

response to therapy or inflammatory diseases

Acute Phase reactants

synthesized rapidly in response to tissue injury

varying degrees of increase, some decrease

examples:

-C-reactive protein (CRP)

-procalcitonin (PCT)

-a1-antitrypsin

-ceruloplasmin

C reactive protein (CRP)

-1000 fold increase when tissue damage (rapid)

-opsonin (flag)

-activates complement

-indicator of acute inflammation

CPR diagnostic use

low- no inflammation

high- inflammation

-evaluation and detecting inflammatory disease

-screening for inflammatory and malignant disease

-monitoring therapy or inflammatory disease

-fastest responder and most sensitive indicator of acute inflammation

-CPR v ESR

CRP use in diagnostics

-rises abruptly with trauma including surgery

-return to basal slate within 7-10 days

-if evaluation continues, sepsis or infection may be occuring. Maybe unreliable in some disorders

-CRP maybe a better predictor than LDL as a benchmark for cardiovascular risk (LDL can form plaque, CRP released in response)

Alpha1-antitrypsin

increased production in inflammation

inside granule is neutrophil elastics if not in check

alpha1-antitrypsin will stop it

inflammation symptoms

redness, fever, swelling, and pain

immunogen characteristics

a macromolecule capable of triggering an adaptive immune response and then reacting with the antibodies produced

antigen characteristics (self)

any substance that may be specifically bound by an antibody molecule or t-lymphocyte receptor (trigger)

hapeten (non-self transplant cells) characteristics

a lower molecular weight molecule that can be bind to an antibody but must be attached to a macromolecule as a carrier to stimulate immune response

epitope

specific part of antigen that reacts specifically with antibody/t-lymphocyte

histocompatibility antigens

major histocompatibility complex (MHC)

-referred to as human leukocyte antigens (HLAs)

-surface of nucleated cells and tissues (HAS TO HAVE NUCLEUS)

-recognize as self

histocompatibility antigens important in

-transplantation

-paternity testing

-forensic medicine

-disease associations

two classes od MHC molecules

1 and 2

autoantigens

“self antigens”

-failure to recognize self produces autoantibodies

blood group antigens

certain antigens, especially those of the Rh system, are integral structural components of the erythrocyte RBC membrane

chemical nature of antigens

-antigen (immunogen)

-protein, large polysaccharide, or combination of carbohydrate and protein (glycoprotein) 1,2,3

-rarely composed of lipids

physical nature of antigens

-foreignness (route of entry and degree)

-degradability

-molecular weight

-structural stability (more=better)

-complexity (more=better)

general characteristics of antibodies

-isolated in the gamma globulin fraction of protein by electrophoretic separation

-primary function to combine with corresponding antigen

immunoglobulin classes

IgM-2

igG- most important

IgA-3

igD

igE

Antigen structure- ig M

-5 binding sites

-1st released in response

-can’t cross placenta

antigen structure- igG

-high in plasma/serum

-2nd response

-can cross placenta

antigen structure- ig A

-mucus membrane

-highest number antibody

Antigen structure- secretory ig A

-highest in molecular weight

-the secretory component is how it can move through mucus

antibody structure- ig E

-allergic reaction

-parasympathetic infection

-mask cell w histamine

immunoglobulin variants

-isotype

allotype

-idiotype

isotypic

all animals of species

allotypic

variations between species

idiotypic

variation within one person

antibody synthesis

-primary antibody response

-secondary (anamnestic) antibody response

functions of antibodies

principal functions- to bind antigen

may also exhibit secondary effector functions and behave as antigens

affinity

-initial force

-how well one antigen is able to join one antibody

-Greatest igG

avidity

how many binding sites there are

-greatest Ig M

molecular basis of antigen-antibody reactions

-types of bonding

-goodness of fit (better fit better reaction)

-detection of antigen-antibody reactions

-influence of antibody types of agglutination (visualize reaction)

origin and development of blood cells: 2-8 weeks of life (dont memorize)

erythroblasts formed in islets of yolk sac

origin and development of blood cells: 2-5 months of gestation (dont memorize)

liver and spleen are major sites of hematopoiesis

-granular leukocytes also appear

origin and development of blood cells: fourth month of gestation (dont memorize)

bone marrow begins to produce blood cells

origin and development of blood cells: fifth month of gestation (dont memorize)

bone marrow assumes ultimate role as primary site of hematopoiesis

granulocytic cells: neutrophils

-defense against bacterial infection (most common)

-essential component of innate immune response

-roles in phagocytosis

-2 pools (circulating and marginating)

2 pools in neutrophils

circulating (blood)

marginating (tissue)

neutrophil cell

-lots of granules that destroy foreign

-inside granule is enzyme that kills bacteria

-dark purple nucleus (multiple)

-pink

microbicidal primary neutrophil

myeloperoxidase

eosinophils

eosinophils are homeostatic regulators of inflammation

-low # in body

eosinophil cell

-bilobed dark purple

-increases during parasitic reaction

-allergy reaction

-large

basophil

hypersensitivity reaction (tissue form of basophil = mast cell)

basophil cell

-huge granulocytes

-very dark purple

-rare to see in blood smear

-high level uncommon