N323 - Week 4 (Innate & Adaptive Immunity)

Immunity - Lines of Defense

First

-Second

-Third

Immunity - First Line of Defense

innate immune system

-physical, mechanical, biochemical barrier

-fights off foreign substances

-EX: low pH in stomach kills certain bacteria

Immunity - Second Line of Defense

Inflammation

-characterized by vascular, chemical, & cellular components

-NONspecifc (always happens when injury/infection occurs)

-long term inflammation is bad -> pain, decreased fxn

Immunity - Third Line of Defense

adaptive immunity ("acquired" immunity)

-VERY specific to certain viruses, infections & injuries

-takes time to occur

2 Diagnostic Values Used to Assess Inflammation

CRP & ESR (both nonspecific)

-helps determine whether inflammation is present in the body -> infection or autoimmune disorder (constant inflammation)

CRP

acute phase protein (tells us abt inflammation rn)

-can initiate, amplify, or sustain the inflammatory process

-indicates active inflammation (past 48hr)

ESR

erythrocyte sedimentation rate

-a measure of the rate at which RBCs precipitate out of the plasma

-influenced by fibrinogen levels in the blood

-indicates past inflammation, slower response

Goals of the Body Involving Inflammation (3)

limit & control the inflammatory response

-prevent & limit infection and further damage

-initiate adaptive immune response -> initiate healing

Stages of Acute Inflammation (2)

1. Vascular Stage

2. Cellular Stage

Vascular Stage of Acute Inflammation

vasodilation (risk for low BP)

-increased vascular permeability

Cellular Stage of Acute Inflammation

movement of WBCs from blood vessels into tissue site of inflammation

-phagocytosis begins w/ large influx of neutrophils & macrophages

2 Types of Leukocytes (WBCs)

granulocytes (have granules inside of cells that hold immune properties)

-agranulocytes (have no granules)

Granulocytes (3)

neutrophils

eosinophils

basophils

neutrophils (4)

chief & most common phagocytes of inflammation

-40-60% of WBC differential

-Lifespan of 4 days

-Ingest & destroy pathogens & cellular debris

eosinophils (4)

second most common w/ some phagocytic activity

-2% to 4% of WBC differential

-Unknown life span

-engulf antigen-antibody complexes, defends against parasites

Basophils (3)

0.5% to 1% of WBC differential

-Unknown life span

-Reacts in allergic & inflammatory responses (releases cytokines, not phagocytic)

Agranulocytes (3)

monocytes

-lymphocytes

-natural killer cells

Monocytes (4)

large phagocyte; eventually turn into macrophages

-3% to 8% of WBC differential

-Life span mnths to years

-ingests bacteria, cellular, & tissue debris

Lymphocytes (4)

launch cellular & humoral immune response (have a memory)

-25% to 36% of WBC differential (2nd most in WBC differential)

-life span: days or yrs depending on subtype

-help kill viruses, cancer cells

Types of Lymphocytes (3)

T cells, B cells, Natural Killer Cells (NK cells)

T cells

involved in cellular immunity (recognize & kill viruses through acquired immunity)

B cells

involved in humoral (antibody) immunity

Natural Killer Cells (NK cells)

5-10% in the blood & spleen

-life span unknown

-type of lymphocyte, kill & destroy foreign substances (antigens)

granulocytosis (neutrophilia)

evident in the first stages of infection or inflammation

-increase in WBCs, specifically neutrophils

if the need for neutrophils increases beyond the supply...

then immature neutrophils (banded neutrophils) are released into the blood

shift-to-the-left

term for premature release of immature leukocytes

neutropenia

low # of neutrophils

Why can neutropenia occur? (2)

b/c of prolonged infection (-> neutrophils are used up)

-b/c of of certain drugs or chemotherapy (targets rapidly dividing cells -> pts become very immune suppressed)

Alterations of Leukocyte fxn (4)

leukopenia

-leukocytosis

-hematologic disorders

-nonhematologic disorders

Leukopenia

deficiencies occur in the quality & quantity of leukocytes

(if there's a change in WBCS -> usually infection!)

leukocytosis

# of leukocytes are increased

Many hematologic disorders are..

malignancies (cancer!)

Many nonhematologic malignancies do wut?

metastasize to the bone marrow, affecting leukocyte production

Phagocytes

neutrophils

-eosinophils

-basophils

-monocytes & macrophages

Neutrophils as phagocytes

predominate in early inflammatory response (1st there)

-ingest bacteria, dead cells & cellular debris

-cells are short lived & become a component of the purulent exudate (dead WBCs)

Eosinophils as phagocytes

mildly phagocytic

-defense against parasites & regulation of vascular mediators (digest bigger complexes)

Basophils as phagocytes

least prevalent granulocytes (small %)

Monocytes & Macrophages as phagocytes

monocytes are produced in the bone marrow -> enter the circulation -> migrate to the inflammatory site (where they develop into macrophages)

-macrophages typically arrive at the inflammatory site 23 hrs or later after neutrophils

Initial Cellular Response to Inflammation

neutrophils come then monocytes come (bcome macrophages)

Cellular Components of Immunity (3)

erythrocytes

-platelets

-leukocytes (granulocytes, monocytes, lymphocytes)

Cytokines

responsible for activating other cells and regulating inflammatory response

-(some WBCs release these to signal that we need help, macrophages release these)

Types of Cytokines (2)

Chemokines

-Interleukins (IL)

Chemokines are synthesized by...

synthesized by many cells (macrophages, fibroblasts, endothelial cells) in response to proinflammatory cytokines

Role of Chemokines

help control movement of cells & bacteria in the body -> help facilitate WBC movement from blood vessels to site of injury

Interleukins (IL) are produced by...

Produced primarily by macrophages and lymphocytes in response to a pathogen or stimulation by other products of inflammation

Role of Interleukins (3)

help w/ cell communication

-have inflammatory & anti-inflammatory response

-continue to help stimulate immune response & communicate where injury is

Tumor necrosis factor-alpha secreted by..

secreted by macrophages & toll-like receptor recognition

Tumor necrosis factor-alpha

signaling protein, part of the immune system

-involved in any injury

-help w/ movement of cells, helps WBCs adhere & brings more adaptive immune cells to the site

mast cells (2)

cellular bags of granules located in the loose connective tissues close to blood vessels

-found in skin, digestive lining, & respiratory tract

What do mast cells contain?

histamine (another signaling molecule), cytokines & chemotaxis factors (factors that help w/ cell movement)

What are mast cells induced by?

induced by inflammation & injury -> triggers release of granules so they can go to site of injury

Chemical Release of Mast Cells occurs in 2 ways:

Degranulation

Synthesis

Degranulation

the release of the contents of mast cell granules

Synthesis

mast cells make more beyond wut is present in granules

EX: make prostaglandins (involved in inflammation)

Basophils

found in blood & probably fxn in same way as mast cells

-no phagocytosis, but bring more cells to site

natural killer cells (NK cells)

-recognize & ...

-uses...

-produces...

-part of...

recognize & eliminate cells infected w/ viruses

-uses inhibitory & activating receptors to allow differentiation btwn normal & abnormal cells (good at differentiation!)

-produces cytokines & toxic molecules (kills cells!)

-part of innate & adaptive immune response (not antigen specific); similar to t cells & b cells

Receptors of Histamine (2)

H1 Receptor

H2 Receptor

H1 receptor (3)

proinflammatory

-present in smooth muscle cells of the bronchi

-can cause temporary airway constriction (bronchoconstriction) & vasodilation (lowers BP) if we have extreme activation of H1 receptors

H2 receptor (3)

anti-inflammatory

-present on parietal cells of the stomach mucosa

-induces the secretion of gastric acid

Adaptive immunity

When our body remembers certain pathogens, viruses, antigens...

-takes time!

Components of Adaptive Immunity

humoral response

-cellular response

(both produce memory cells!!)

humoral response

B lymphocytes produce antibodies (immunoglobins)

-bind to antigens on bacteria & viruses

cellular response

effector T cells

-kill target directly

-stimulate other leukocytes

Cluster of Differentiation (CD)

T cells that differentiate from one another

EX.. CD4 and CD8

CD4

are T helper cells

-HIV targets CD4 cells

CD8

are T cytotoxic cells (good at killing foreign substances that they recognize)

active immunity

immunity u develop after being exposed to infection (antigen) or from getting a vaccine (immunization)

-body creates antibodies

Natural vs Artificial Active Immunity

Natural: antibodies made after exposure to an infection

-Artificial: antibodies made after getting a vaccination

passive immunity

immunity u acquire from someone or something else

(preformed antibodies or T cells are administered)

Natural vs Artificial Passive Immunity

Natural: antibodies transmitted from mother to baby (e.g via mother's milk)

-Artificial: Antibodies acquired from an immune serum medicine

**Antigens def

Any substance that causes ur body to make antibodies (have an immune response)

Antigens bind w/...

-Antigens are not necessarily...

-Sometimes, we have...

antibodies, receptors on T & B cells

-not necessarily immunogens

-sometimes, we have self antigens (we can tell btwn self & foreign antigens) -> if we cant differentiate (autoimmune disorder)

Types of Antigens (2)

immunogens

-haptens

Immunogens

induce production of antibodies, T and B cells

-all immunogens are antigens but not all antigens are immunogens

Haptens

too small to be immunogens by themselves but become immunogenic after combining w/ larger molecules that act as carriers for the haptens

-(the larger the molecule the bigger the response)

Immunogens are characterized by...

differences in structure & fxn

Classes of Immunoglobins (Antibodies) (5)

IgG

IgM

IgA

IgD

IgE

**in order of importance

IgG

most common (85% of antibodies)

-give us our most protective immunity (most important)

-can be given as passive immunity in pregnancy

IgM

largest of our antibodies

-usually the first antibody produced in response to antigen

-synthesized early in infancy (babies make it themselves)

-can also be see in utero (if baby was exposed to infection in utero)

IgA

seen in bodily secretions (blood)

-helps trap things in our mucous & mucous membranes

-1st line of adaptive immune response

IgD

part of B cell response (tends to sit on early B cells)

-helps initiate a response

IgE

usually at low concentrations ideally

-associated w/ allergic responses

-helps defend against parasites along w/ our eosinophils

Antibody Fxns

Direct (neutralization, agglutination, precipitation)

-Indirect (inflammation, phagocytosis, complement)

Direct Functions of Antibodies (3)

neutralization

agglutination

precipitation

Neutralization

inactivates antigens by blocking binding of antigens to receptors (neutralizes antigens)

Agglutination

clumps molecules together so they cannot bind

Precipitation

make an antigen into an insoluble precipitate (liquid type form)

Indirect Fxn of Antibodies (3)

Inflammation

Phagocytosis

Complement

inflammations

kills antigens by bringing more WBCs to the site

Phagocytosis

kills antigens by engulfing them

complement

antibodies activate proteins

-system of proteins that protein our body (part of immune system)

Immune System in Pediatric Patients (4)

sufficient IgM

-deficient IgG & IgA responses

-maternal antibodies provide protection

-immunologically immature (high risk for infections especially in first 2 yrs of life)

Immune system in Geriatric Patients (4)

decreased T cell activity

-decreased thymic size

-decreased thymic hormone production

-decreased antibody response to antigens

Thymus

small gland located in chest cavity, part of our immune system

Hypersensitivity Reactions

when the immune system causes harm to the body

-when things go wrong...

Altered Immune Responses (3)

allergies

-autoimmunity

-alloimmunity

allergy

exaggerated response against an environmental antigen

autoimmunity

misdirected response against the host's own cells

Alloimmunity

directed against beneficial foreign tissues (e.g. transfusions, transplant)

3 Variables of Hypersensitivity

1. Original "insult"

2. Individual's genetic makeup

3. Immunologic processes