Innate and Adaptive Immunity in the Skin

At a glance:
 Innate immune responses
o Are used by the host to immediately defends itself
o determine the quality and quantity of many adaptive immune responses;
o are short lived; have no memory;
o include physical barriers (skin and mucosal epithelia);
o include soluble factors such as complement, antimicrobial peptides, chemokines, and
cytokines;
o include cells such as monocytes/ macrophages, dendritic cells, natural killer cells, and
polymorphonuclear leukocytes.
 Adaptive immune responses
o have memory;
o have specificity;
o are long lasting;
o in skin, are initiated by dendritic antigen- presenting cells in the epidermis (Langerhans cells)
and by dermal dendritic cells;
o are executed by T lymphocytes and antibodies produced by B lymphocytes/plasma cells.

Innate immune (always present)

 Immune mechanisms that are used by the host to immediately defend itself are referred to as innate
immunity.
 These include physical barriers such as the skin and mucosal epithelium; soluble factors such as
complement, antimicrobial peptides, chemokines, and cytokines; and cells, including
monocytes/macro- phages, DCs, natural killer cells (NK cells), and poly-morphonuclear leukocytes
(PMNs)
 Direct functions of cells of the innate immune system:
o (1) rapid detection of microbes,
o (2) phagocytosis, and
o (3) antimicrobial activity.
 Indirect role
o Instructing and determining the type of adaptive T and B cell responses.
o By inducing inflammation, the innate immune response can also induce tissue injury.
1. Antimicrobial peptides
Antimicrobial peptides identified in resident skin cells, including:
 Human b-defensins
o HBD-1 (against Gram-negative bacteria and appears to play a role in keratinocyte
differentiation)
o HBD-2 (first found in Psoriasis lesion, effective against Gram-negative bacteria (ex,
Escherichia coli, P. aeruginosa) and weak against Gram-positive bacteria)
o HBD-3 (also first found in Psoriasis lesion, effective against Gram-positive bacteria.)
 Cathelicidin (LL-37)
o Are cationic peptides with a structurally variable antimicrobial domain at the C-
terminus
 Psoriasin,
o Elicits its antimicrobial effect by permeabilization of bacterial membranes.
o Secreted predominantly by keratinocytes and plays a major role in killing the common
gut bacterium E. coli
 RNase 7
o Broad-spectrum antimicrobial activity against S. aureus, P. acnes, P. aeruginosa, E.
 coli, and C. albicans
 Dermcidin
o antimicrobial peptide that is expressed by human sweat glands.
o have broad antimicrobial activity against S. aureus, E. coli, E. faecalis, and C.
albicans

2. Inflammatory response
PMNs:
 Neutrophils
 Most abundant
 Neutral staining granulocytes
 Early response
 Eosinophils
 Large coarse granules
 Parasites and allergic response
 Basophils
 Proteolytic enzymes
 Parasites and allergies
Dendritic cells:
 Rare cells found in respiratory and GI tract complex maturation process
 Main function is to process antigen material and present it on the cell surface to the T cells of
the immune system.
 They act as messengers between the innate and adaptive immune systems

Natural killer cells:

 Large granulocytes
 Kill and lyse tumors without previous exposure

Pathogen/pattern recognition:
 The WBCs recognize pathogens and their pattern of activity on their surfaces.
 PAMPS-pattern recognition molecular patterns that look for pattern recognition receptors which
trigger the response, bind to leukocytes and chemical response, leads to response.

Toll like receptors (TLR):

 Found in bone marrow
  Essential components of innate immune response and are one of the key factors involved in
recognizing and defending against invading pathogens.
 Marks the key molecular events that ultimately lead to innate immune responses and the
development of antigen specific acquired immunity.

Cytokines:
 Chemical mediators that are released into surrounding tissue
 Their release has an effect on the behavior of cells around them such as interleukins and interferons
(interfere with virus infections and recognition of virus cells)

Complement proteins:
A part of the innate immune system, the three pathways are:
 classical pathway
o recognizes antigen/antibody of the adaptive immune system bound to the surfaces of
microbes
 lectin pathway
o mannose-containing bacterial carbohydrates, mannose binding lectin is recognized
lead to cell lysis
 alternative pathway
o recognizes microbial molecules without antibodies.

Adaptive Immune (acquired immunity)

 A system that is able to recognize and react to large numbers of microbes and non-microbes, able to
distinguish between related microbes, creates immunological memory after an initial response to a
specific pathogen, two types are humoral and cellular immunity, this process is the basis of
vaccinations.
 Initiated by dendritic APCs in the epidermis (LCs) and dermis (dermal DCs or DDCs) and executed
by T lymphocytes and antibodies.

b cells
 will secret antibodies that detect diverse microbes
t cells
 recognize only peptides on the antigen presenting cells
MCH complexes
 important to t cells and their ability to function in the immune response. they are important for
rejection of transplanted organs. MCH is used to test to see if you could be a donor
Humoral immunity (antibody mediated response)
 involves b cells that recognize antigens or pathogens that are circulating in the lymph or blood
(humor is a medieval term for body fluid)
Immunoglobins
 major components of the humoral immune response system, they are synthesized by plasma cells and
lymphocytes found in the serum and other body fluids and tissues including the urine, spinal fluid,
lymph nodes and spleen. they are specialized antibodies that is used by the immune system to
neutralize pathogens such as pathogenic bacteria and viruses
immunoglobin subtypes:
IgA
found in mucus, saliva, tears and breast milk. protects against pathogens
IgD
part of the b cell receptor, activates basophils and mast cells
IgE
protects against parasitic worms, responsible for allergic reactions
IgG
secreted by plasma cells in the blood, able to cross the placenta into the fetus (gone had disease)
IgM
may be attached to the surface of a b cell or secreted into the blood, responsible for early stages of immunity
(miserable, have disease)

cellular immunity (cell mediated response)

 involves mostly t cells and responds to any cell that displays aberrant MHC markers including cells
invaded by pathogens, tumor cells or transplanted cells including bacteria, parasites and all viruses
that cannot be destroyed by antibodies. detected primarily at microbes that survive in phagocytes and
microbes that infect non-phagocytic cells
passive immunity
 transferred from another source, transferred from mother to fetus ex.IgA (most common) and IgG.
can also be given via the transfer of antibodies produced by other people, specifically for diseases
gamma goblins which boosts cellular response meaning the immune systems