1.2 Innate and adaptive immunity

what is innate immunity and its characteristics?

the body's initial defense to prevent infection or eliminate pathogens

• present at all times

• response in min/hours

• not antigen-specific, recognizes groups

• no memory: does not increase with repeated exposure

three main examples of innate immunity:

• mechanical barriers (skin, mucosa; cilia move mucus)

• biologically active substances

• cellular

what are the biologically active substances of innate immunity:

• anti-microbial proteins (skin, mucosa)

• cytokines: IL-1, IL-6, TNF

• acute phase proteins: C-reactive protein (↑ = inflam)

• activation of complement proteins; alternative and lectin pathways

define cytokine:

any of a number of substances, such as interferon, interleukin, and growth factors, which are secreted by certain cells of the immune system and have an effect on other cells

what are the cellular examples of cellular innate immunity?

activation of leukocytes (wbc):

• macrophages (M⏀)

• neutrophils

• NK cells

• mast cells and basophil

• eosinophil

• dendritic cell (DC)

define macrophage (M⏀):

phagocytic cells that are present in most tissues (BIG EATER!)

• derived from blood monocytes; minute amount of wbcs

• phagocytose microbes and dead cells (tuberculosis)

• antigen-pres to T cell

define neutrophils:

phagocytic cells in blood

• aka polymorphonuclear neutrophils (PMN)

• abundant in blood

• enter infected tissue to engulf and kill extracellular pathogens (mainly bacteria like staphylococcus) via phagocytosis and cytotoxic mechanisms

• secrete cytokines

define eosinophil:

cytotoxic cells kill parasites too large for phagocytosis

• comprise minute amount of wbcs

• enter infected tissue through blood

• kill antibody-coated parasites via cytotoxins; substances toxic to helminths

• important in allergy, severe asthma, eczema

what cells are involved in parasite and allergy response?

• mast cell: found in CT throughout body

• basophil: super minute amount of wbcs in blood and similar function to mast cells

both release granules containing histamine, especially import for helminths (parasitic worms)

natural killer cells (NK)

remove tumor cells and infected cells; can kill some via cytotoxic mechanisms

dendritic cells (DC)

found in tissues and function to detect infection and elicit innate and adaptive responses; sentry/soldier of immune response

• secrete cytokines that activate innate responses (IL-1, IL-6, TNF; which recruit neutrophils)

• antigen presentation to T cells

• can go to lymph nodes to activate adaptive response

how does body detect infection?

self vs non-self

• non-self structures that are essential elements of pathogens

receptors of innate immune cells for pathogens are caused…

… pattern recognition receptors (PRR) which recognize pathogen associated molecular patterns (PAMP)

ex: dendritic cels and macrophages are activated when their TLR-4 (PRR) recognize lipopolysaccharide (LPS) from gram-negative bacteria; what prevents bacteria from evading immune system

when are adaptive responses elicited?

when innate are not enough DCs elicit adaptive

• it is energy expensive and you need enough antigen present for one to occur

what cells are phagocytic?

macrophages

what cells are cytotoxic?

eosinophils

NK cells

what cells are phagocytic and cytotoxic?

neutrophils (mainly phagocytic)

what cells release granules? what are in the granules?

mast cells and basinophiils

histamines: allergy and parasite

what are innate immune responses?

• fever

• increased wbcs production in bone marrow

• increase acute phase proteins (C- reactive_

• recruit inflam cells to infection site (by cytokines)

antibody

• B Cells: Immune cells that recognize antigens and produce antibodies.

• Antibodies: Proteins made by B cells to bind and neutralize antigens

  • enable robust phagocytosis

T celll

use cytokines to stimulate innate cells

adaptive (acquired) immunity

defenses mediated by the clonal expansion and differentiation of antigen-specific lymphocytes (B and T cell)

antigen

microbe (foreign substance) recognized by lymphocytes

something B ad T cells react to

• requires sensitization by antigen (Ag); encounter

• develops over days/weeks

• response is antigen-specific (even to strain)

• results in immunological memory: more robust and faster response in future encounters

two classifications of adaptive immune response:

humoral immunity: B cell mediated

cell-mediated immunity: T cell mediated

humoral immunity:

mediated by antigen-specific antibodies produced b activated B lymphocytes (B cells: naive, plasma, memory, regulatory)

each B cell recognize ONE antigen

• BCR = B cell receptor

• antibody (Ag) = immunoglobulin (Ig)

cell-mediated immunity (CMI)

mediated primarily by antigen-specific T lymphocytes (T cells)

• naive T cell: mature but not exposed to antigen

• effector cell: exposure to unique antigen

• recognize small peptide pieces (antigens)

• TCR = T cell receptor for antigen

how can a response to an antigen increase after exposure?

clonal selection central paradigm of immunology

what is clonal selection?

Antigen-specific lymphocytes develop before and independent of exposure to antigen; our bodies theoretically contain lymphocytes that can recognize every bacteria in existence.

Only with exposure an antigen can bind the specific lymphocyte and activate the cells to proliferate to form clones; effectors and memory lymphocytes

eventually clones are deleted

very wasteful, most never used but worth it

what is clonal selection simplified?

proliferation and differentiation to produce effector cells and memory cells (T and B cell)

clones of memroy B cells and clones of plasma cells

have you ever felt clonal selection?

yes! swollen lymph nodes are physical indication of the expansion of B and T cells which show infection or cancer is present

primary lymph node organs

bone marrow; B cell development

thymus; T cell development

secondary lymph node organs

where mature B and T cells hang out

all antigens are sent to the lymph nodes and the lymphocytes can go shopping to find their specific antigen

• adenoid

• tonsil

• lymph nodes

• spleen

• Peyer’s patches; numerous areas of lymphoid tissue in the wall of the small intestine

why does adaptive immunity take longer?

due to cellular division of the clones; need higher numbers for recognition and effector cells to be made

define polyclonal:

collection of antibodies that are produced by different B cell clones in response to a single antigen. These antibodies recognize and bind to multiple epitopes (different parts) of the antigen.

each antigen contains multiple epitopes: Ag-Ab complex the immune complex