Immunology

innate immunity

(also known as natural immunity)

immunity a person is born with

includes the first and second lines of defense

non-specific immune response works the same way against all infections

ex. fever and inflammation

acquired immunity

(also known as adaptive/specific immunity)

specific, tailor-made immunity that develops as an individual ages

when exposed to new infections, a person develops acquired immunity for future encounters

make up third line of defense

involvement of B and T cells

broken down into two categories:

humoral immunity

cell-mediated immunity

humoral immunity

(antibody-mediated immunity)

-type of acquired immunity

against extracellular pathogens and is involved with B cell activation, produces antibodies and memory cells

two major functions:

1. tag and destroy infections with antibodies= when infected by bacterial pathogens specific B cells fight this infection through clonal expansion, making more specific B cells, when activated B cells become plasma cells which produce antibodies, short-lived compared to memory cells

2. create memory cells, some B cells are partially activated, becoming memory cells lasting months, years, decades, or lifetimes, do not produce antibodies

B cells are long-lived and do not produce antibodies

plasma cells are short-lived and do produce antibodies

ex. childhood chicken pox usually prevents future infections because of memory cells

type of third line of defense

cell-mediated immunity

-type of acquired immunity

against intracellular pathogens

involved T cells (cytotoxic and helper) and natural killer cells

kill problematic cells

part of third line of defense

kills endogenous invaders= pathogens entering body cells

acts as housekeeping system, monitor humans cells, identifying problems

includes three cell kinds:

1. helper T cell= do not directly kill infected cells, identify infected cells and release cytokines to communicate with other cells and amplify immune responses, activate cytotoxic T cells, CD4 cells

2. cytotoxic T cells= directly kill cells by producing perforin, which inserts into target cell membranes, forming pores that kill cells, also called CD8 cells because recognizing major histocompatibility 1 (MHC-1) proteins on human cells

3. natural killer cells= they kill infected cells by producing perforin, no CD8 MHC 1 communication exist between killer cells and infected cells

high neutrophil levels

extracellular bacterial infection

high eosinophil levels

parasitic worm infection or allergies

high interferon levels

indicate viral infection

primary lymphatic tissues

bone marrow and thymus

secondary lymphatic tissues and organs

lymph nodes= filter lymph nodes and initiate response, B and T cells interact here to process antigens

spleen= filters the blood for infections, white pulp contain lymphocytes that filter blood, red pulp destroys dead red blood cells

tonsils= fight inhaled foreign pathogens

lymphoid tissues:

BALT= near respiratory tract

MALT= near mucous membrane

SALT= under skin throughout body

Peyer’s patch= organized tissue in intestine and lungs, covered in epithelium containing microfold cells that internalize infection

appendix

bone marrow

contains pluripotent stem cells= origin of all blood components

two different lineages:

1. lymphoid stem cells= give rise to natural killer cells and lymphocytes (B and T cells)

2. myeloid stem cells= give rise to red blood cells, platelets, neutrophils, baseophils, eosinophils, mast cells, monoctyes, macrophages, and dendritic cits

lymphocytes

B cells

T cells

Natural killer cells

B cells

originate from lymphoid stem cells and form memory cells

form in bone marrow and active in lymph nodes

circulate blood and present in lymphoid organs

turn into:

1. plasma cells which are the only cells to produce antibodies

2. memory B cells which initiate fast, efficient response upon reinfection

T cells

originate from lymphoid stem cells and form memory cells

produced in bone marrow and mature in thymus

turn into:

1. helper T cells= enhance or suppress immune system actions

2. cytotoxic T cells= attack and kill target cells infected with intracellular pathogens

3. memory T cels= coordinate fast, efficient response upon re-infection

natural killer cells

attack and kill malignant cells and pathogen-infected cells

play roles in both specific and nonspecific defense mechanisms

both innate and acquired immunity

phagocytic cells

monocytes, macrophages, neutrophils, and dendritic cells

recognize, engulf, and destroy foreign cells, immediately stopping infection

monocytes

mononuclear phagocytic leukocytes that circulate for 8 hours before maturing into macrophages

macrophages

phagocytic and antigen-presenting cells

identify, bind to, engulf, and destroy infectious agents

mature monocytes and play a role in antigen presentation

typically localized in specific tissues and names based on location

antigen-presenting cells (APC)= they present antigens to helper T cells, which recognize “non-self” antigens and trigger immune responses

identify foreign antigens through receptors for toll-like structures including pili, fimbrae, and LPS, also FC regions

also produce cytokines, specialized proteins for immune system communication

dendritic cells

phagocytic and antigen-presenting cells

antigen-presentation phagocytes found under skin, in mucous membranes, lungs, and intestines

main job is antigen-suppression

called professional antigen presenting cells, digesting foreign invaders and presenting relevant antigens to T cells

eosinophils

primarily deal with parasitic infections, such as microscopic worms, major predominant inflammatory cells in allergic reactions

mast cells

contain granules rich in histamine= inflammatory compound

play a major role in causing allergies

basophils

play a role in allergic reactions, releasing histamine, prostaglandins, serotonin, and leukotrienes

agranular cells

monocytes and lymphocytes

they lack granules

granular cells

mast cells, neutrophils, basophils, and eosinophils

they can lost granules through degredation, when encountering allergens they might release granules containing concentrated chemicals to produce an allergic reaction

leukocytes

contain agranulocytes and granulocytes

granulocytes

basophils

neutrophils

eosinophils

lymphocytes

type of agranulocytes

B cells

T cells

NK cells

monocytes

type of agranulocytes

dendritic cells

macrophages

innate immunity first line of defense

barrier defenses preventing pathogen entry

includes skin and mucous membrane of digestive, respiratory, and urogenital tracts

mucous membrane= most frequently used portal of entry for pathogens

alveolar macrophages= important for first line of defense

innate immunity second line of defense

non-specific defenses attacking pathogens once they enter the body

include phagocytosis, extracellular killing, inflammation, fever, and the complement system

phagocytosis

second line of defense for immune system

process where specialized cells (neutrophils, dendritic cells, monocytes, and macrophased) recognize, ingest, and digest extracellular pathogens

1. recognize and bind to microbe

2. cells engulf microbe to form a phagosome

3. phagosome fuses with lysosome containing harsh digestive chemicals (phagolysosome)

4. microbial debris is released through exocytosis

(lysosome= contains hydrolytic enzymes, toxic reactive oxygen intermediaries, and toxic reactive nitrogen intermediaries)

respiratory burst= phagosomes form, leading to this to occur which produce toxic oxygen metabolites like hydrogen peroxide, superoxide, hypochlorus acid, singlet oxygen, and hydroxyl radicals (increase in oxygen consumption in order to produce oxygen metabolites)

inflammation

cardinal signs of infection: redness, warmth, swelling, pain, and altered function

increases blood flow, expediting tissue repair

part of second line of defense

two categories:

1. acute inflammation= develops quickly, involving chemical mediators, promotes healing, pathogen elimination through capillary dilation, diapedesis, pathogen movement restriction, and phagocyte recruitment

2. chronic inflammatory response= sloer, long lasting, potentially maladaptive, and may cause permanent tissue damage

pyrogens

fever-inducing compounds triggering the hypothalamus to increase core temperature

low-grade fever benefits infection fighting

interleukin 1 (IL-1)= body’s natural pyrogen

complement system

includes complement proteins circulating in blood

bind to and destroy extracellular bacteria

plays important roles in immunity, people with genetic complement system problems are more likely to get certain infections

involved in both second and third line of defenses, both innate and acquired immunity

normally inactive, they become active through complement fixation via three pathways

1. classical pathway= antigen-antibody interactions

2. does not rely on pathogen-binding antibodies

3. lectin complement pathway= activated by mannose-binding lectin binding to pathogen surface mannose residues

killing infection (cytolysis)

way complement proteins neutralize or kill infection

complement protein accumulate on microbe surfaces, drilling in holes that cause lysis

form the membrane attack complex (MAC) puncturing foreign invader membranes

only attack extracellular pathogens

opsonization

way complement proteins neutralize or kill infection

complement proteins act as opsonins which cover the microbe surface and facilitate phagocytosis

opsonins

1. antibodies- can coat microbes and make phagocytosis destruction likely

2. complement proteins= small blood proteins, some bind to infectious microbes and make engulfment more likely

coat with serum components, enhances pathogen visibility and makes phagocytic cell englufment and digestion easier

more opsonins present means higher binding degree between pathogenic microbe and phagocytic cell

C3b protein

chemotaxis

complement proteins act as chemicals attracting immune cells like phagocytes to infection areas

C3a and C5a proteins

antigen

foreign molecule that can elicit immune response and react with that responses products

typically large, complex molecules, any bacterium part and fungi, viruses, food particles, and dust

enter body through drinking, swallowing, or inhaling, insect bites, or needles, skin breaks, skin grafts

hapten= small organic molecule only eliciting immune response when attached to a larger carrier, like a protein, most drugs are haptens ex. penicillin

epitopes

also known as antigenic determinants, region of antigen that binds directly to antibody

proteins are most antigenic

where B cell, T cell, and antibodies recognize and bind to these epitopes

recognized by only one type of antibody type

cytokines

soluble proteins and glycoproteins acting as intercellular mediators or signaling molecules, facilitating intercellular communication

three groups based on location:

1. autocrine function= acting on the same cell that secreted them

2. paracrine function= acting on nearby cells

3. endocrine function= when having systemic effect, distant cells

classes:

interleukins= released by leukocytes which impact other leukocytes

colony-stimulating factors= stimulate immature leukocyte differentiation in bone marrow, allowing quick infection response with appropriate cell types

tumor necrosis factors= stimulate cell destruction to inhibit tumorigensis

interferons= primary response to viral infection

monokines= released form mononuclear phagocytes like monocytes

lymphokines= released from T lymphocytes

third line of defense (acquired or adaptive immunity)

conveying specific immunity

main players are B cells, T cells, and natural killer cells

specific immunity characteristics:

1. tolerance and recognition of self vs non-self: need to know what is foreign or not, negative selection inactivates and destroys developing B and T cells which would react against body tissues via apoptosis, leading to anergy= unresponsiveness preventing immune system from destroying “self” cells

2. specificity

3. heterogeneity

4. memory

antibodies

Y-shaped molecules of four polypeptide chains

two identical heavy chains and two identical light chains, held together by disulfide bonds

fab region= region where antigen binds to it,

fc fragment= mediates binding to host tissue, immune cells, and complement proteins, when fab fragments bind to bacterial membrane antigens, fc fragments stick out for complement proteins, macrophages, and neutrophils to bind and begin bacterium destruction

FAB has more diversity than FC

bivalent= able to bind to two identical antigens simultaneously via two identical antigen binding sites in fab fragments

five major antibody classes

IgA= major antibody in secretions, salvia, tears, vaginal fluids, and milk

IgD= co-expressed with IgM, plays a role in B cells and basophil activation

IgE= plays role in allergic reactions

IgG= majoring circulating antibody, allows placental crossing and entering fetus

IgM= first antibody produced during immune response

Major Histocompatibility Complexes (MHC’s)

membrane glycoproteins playing major role in acquired immunity

coded by the human leukocyte antigen (HLA) complex

MHC1= directly involved in cell-mediated immunity, found on almost all nucleated cell surfaces

bind to cytoplasm-originating peptides, present antigen, T cell recognize foreign antigens and kill infected cells

MHC2= found on antigen-presenting cells, macrophages, dendritic cells, and B cells

they bind to fragments outside of cells, when macrophages digest foreign bacteria, they present portions of digested bacteria on surfaces via MHC2 molecules, helper t cells then recognize antigens and initiate immune response via clonal selection

Two antigen classes based on processing

1. t dependent antigens= targets with T cell help, tend to be small with inaccessible antigenic determinants, antigen-presenting cells process antigens and present them to helper T cells, making antigenic determinants more accessible, b cells than become active, proliferate, and produce antibodies

2. T-independent antigens= typically large with readily accessible antigenic determinants, binding directly to B cells without helper T cell assistance

primary infection

IgM

secondary infection

IgG

anamnestic response

Antibody-Antigen binding (immune complex formation) has important consequences

1. neutralization= bind to surface of viruses or toxins and preventing target binding, ex. tetanus from Clostridium tetani and toxins from Diphtheria

2. complement fixation= complement proteins become active and destroy target cells by poking holes, classical pathway is antigen-antibody

3. agglutination= occurs when antibodies bind to insoluble bacterial cell antigens, causing bacteria to cross-link and clump up, immobilizing bacteria

4. precipitation= occurs when antibodies bid to soluble antigens, forming heavy molecule networks that precipitate in solution. inflammation results when immune complex in body, involves soluble agents

5. opsonixation= occurs when foreign invaders are coated with opsonin, makes them more visible to immune system and more likely to be destroyed via phagocytosis