Unit 1: Nature of the Immune

System

Part 2: Non-specific Immunity

 Organization of the Immune
System
Immune
System

Innate Adaptive
Immunity Immunity

Cellular Humoral Cell-

mediated Humoral
components components Response
Response

Cellular Humoral Cellular Humoral

components components components components
Natural versus Adaptive Immunity
□ Natural immunity – born with the ability to
resist infections by normal bodily functions
□ Adaptive immunity – requires exposure to a
pathogen or microbial agent, upon recovery
lifelong immunity is acquired
 History of Discovering Cellular and
Humoral Components
□ Cellular - Researchers observed that foreign
substances were removed by specialized cells in a
process known as phagocytosis. They
hypothesized that immunity to disease was based
on the action of these scavenger cells

□ Humoral - Other researchers postulated that

noncellular substances in the blood provided
protection from microorganisms
Characteristics of Innate Immunity
□ Present from birth
□ Ready for immediate action (“first
responders”)
□ Nonadaptive/nonspecific
□ No memory
□ Activated the same way each time
□ Found in all individuals
□ Divided into 2 parts: external defense system
and the internal defense system
Innate Immunity:
External Defense System
Composed of physical, chemical, and biological barriers to keep infectious
agents out of the body

□ Anatomical features: skin, mucous membranes, cilia

□ Resident flora
□ Acidic pH
□ Antimicrobial enzymes
Natural Immunity – Intact Skin
□ Difficult for a pathogen to penetrate
■ Sweat creates high salt conditions
■ Oil layer, fatty acids and acid pH present makes
an inhospitable environment for microorganisms
□ Normal flora prevent other microorganisms
from establishing an infection – “competitive
exclusion”
Natural Immunity – Cilia
Natural Immunity – Other Components
□ Stomach acid (HCl)
□ Mucus lining of lungs traps pathogens and
cilia move particles out to throat and it is
swallowed
□ Coughing and sneezing
□ Tears wash away pathogens and have
bactericidal enzymes
□ Flushing action of urine
□ Vaginal pH
□ Wax in ears http://tinyurl.com/27lk4og
Factors Influencing Defense
Mechanisms

□ Age
□ Hormones
□ Drugs and chemicals
□ Malnutrition
□ Fatigue and stress
□ Genetic determinants
Innate Immunity:
Internal Defense System
□ Triggered when the external defense system
has been breached
□ Cells
□ Soluble factors
□ Processes
■ Inflammation
■ Phagocytosis
■ Complement cascade
Inflammation
□ Four cardinal signs/clinical symptoms
□ Steps:
■ Dilation of blood vessels to increase blood flow
to the affected area
■ Chemotaxis - chemicals released which cause
phagocytic white cells to migrate to the area
■ Increased capillary permeability allowing
white cells to go to injured area, a process known
as “diapedesis”
■ Formation of exudate (pus) - same composition
as plasma and it contains antibacterial substances,
phagocytic cells, and drugs and antibiotics, if
present
Inflammation
Inflammation
Phagocytosis
□ Most active phagocytes: neutrophils,
monocytes, macrophages, dendritic cells
□ Prefix phago- or phag- means to eat,
consume, or destroy
□ Enhanced by opsonins
Phagocytosis
Memorize these steps!
1. Adherence physical contact between phagocyte and microbe
2. Engulfment outflowing of the cytoplasm to surround the
microbe
3. Formation of phagosome microbe is completely surrounded
by a part of the cell membrane
4. Granule contact fusion of lysosomal granules with the
phagosome
5. Formation of phagolysosome contents of the lysosome are
emptied into this membrane-bound space
6. Digestion hydrolytic enzymes in vacuole destroy the microbe
7. Exocytosis contents of the phagolysosome are expelled to the
outside
Phagocytosis
Phagocytosis: Recognition
□ Host phagocytes possess pathogen
recognition receptors (PRRs)
■ Encoded by the host’s DNA – they’re already
there, a part of the cell membrane
□ Pathogens possess molecules on their surface
that are absent on our cells – termed
pathogen-associated molecular patterns
(PAMPs)
□ PRRs recognize PAMPs, results in adherence
Phagocytosis: Recognition
□ Besides the PRR + PAMP mechanism, a
phagocyte can know to engulf something if
it’s opsonized
□ 3 major opsonins:
1. CRP
2. Complement components
3. Antibodies
□ Phagocyte has receptors for opsonins
If Pathogen Evades Phagocytosis…
□ If bacteria are not successfully killed locally, may further
invade the host by way of the lymphatics to the regional
lymph nodes
■ within lymph nodes the bacteria meet other phagocytic cells
■ bacteria may overcome these and gain access to the
bloodstream where they meet circulating phagocytes
(neutrophils and monocytes)
■ may pass through the bloodstream and reach organs such as the
liver and spleen where they come into contact with tissue
macrophages
■ although a powerful defense system, this final phagocytic
barrier may be overcome, with seeding of the microorganism to
organs such as bone, brain, and kidney, terminating in fatal
septicemia.
Cells of the Innate Immune System
■ Phagocytic cells
□ Mononuclear phagocytes
□ Polymorphonuclear phagocytes
□ Eosinophils
□ Dendritic cells
■ Mediator cells
□ Basophils and mast cells
□ Platelets
Cells of the Adaptive Immune System

□ Lymphocytes
□ T cells
□ B cells
□ NK cells***see notes below

□ Plasma cells
Hematopoiesis
□ Origin of all these cell types are from pluripotential stem
cells found in the bone marrow
□ These self replicating cells differentiate into two types of
"committed" stem cells: common myeloid precursors and
common lymphoid precursors

1. Myeloid line – produces monocytes, neutrophils,

eosinophils, basophils, erythrocytes, and platelets
2. Lymphoid line – produces lymphocytes (T cells, B cells,
NK cells)
 Phagocytic Cells of Innate Immunity
1. Mononuclear phagocytes – includes both
circulating blood monocytes and tissue
macrophages found in various tissues of the
body
■ Ingest and destroy material such as bacteria, damaged host
cells or tumor cells (non-specific immunity)
■ Not end cells, they may divide
■ Monocytes stay in peripheral blood only briefly – migrate to
tissues, double in size, then called tissue macrophages
■ Phagocytosis takes place to a greater degree in tissues
■ Tissue macrophages named according to tissue location
Phagocytic Cells of Innate Immunity
2. Neutrophils (PMNs)
□ Characterized by a large nucleus with 3-5 lobes,
and neutral staining granules
□ Primary/azurophilic granules (1/3)
□ Secondary/specific granules (2/3)
□ They are end cells
□ Primary function is phagocytosis
□ Marginating pool and circulating pool
□ Able to move into tissues by diapedesis
Neutrophils with Ingested Material
Phagocytic Cells of Innate Immunity
3. Eosinophils
□ Easily distinguished by the
presence of large granules in
their cytoplasm which appear
red/orange when stained
□ Much less phagocytic than
macrophages or neutrophils
□ Function is far from clear,
however the numbers increase
greatly in certain parasitic
diseases and allergic diseases
Phagocytic Cells of Innate Immunity
4. Dendritic cells
□ Not a peripheral blood cell – lives in the
tissues
□ The most potent phagocytic cell in your
body
□ The most effective antigen-presenting cell
in your body

http://en.wikipedia.org/wiki/Dendrite#medi
aviewer/File:Neuron_Hand-tuned.svg
Mediator Cells of Innate Immunity
□ Influence the immune response by releasing various
chemical substances into the circulation
□ Have a variety of biological functions
■ Increase vascular permeability
■ Contract smooth muscle
■ Enhance the inflammatory response
■ Enhance phagocytosis
□ Two types
■ Basophils/mast cells
■ Platelets
Basophils
□ Basophils easily identified due to large numbers of bluish-
black granules in the cytoplasm
□ The granules are a source of mediators such as histamine and
heparin
□ Circulating basophils greatly resemble tissue mast cells and it
is likely that they are closely related in function
□ Caution: basophils don’t differentiate into mast cells (like
monocytes become macrophages). Basophils and mast
cells arise from different lineages
□ Basophils exist only a few hours in bloodstream
□ Both basophils and mast cells play a role in hypersensitivity
(allergic) reactions
□ IgE
Mast cells
□ Resemble basophils
□ Fixed in the tissues: found in the skin, connective
tissue, and mucosal epithelium (respiratory,
genitourinary, and digestive tracts)
□ Long life span, 9-18 months
□ Plays a role in hypersensitivity reactions by binding
IgE
Mast Cell Activation
Platelets
□ Small non-nucleated cells derived from
megakaryocytes of the bone marrow
□ Important in blood clotting
□ Contribute to the immunological tissue injury
occurring in certain types of hypersensitivity
reactions by releasing histamine and related
substances which are contained within
specialized granules in their cytoplasm