Immunology I

autoimmune diseases

• issues in adaptive immunity

• ex: type I diabetes, rheumatoid arthritis, systemic lupus erythematosus (SLE)

autoinflammatory diseases

• issues in innate immunity

• ex: periodic fever syndrome

pathogens

• “disease-causing agents”

• common types:

  • bacterium

  • virus

  • fungus (ex: yeast)

  • parasite (ex: malaria)

infection

pathogenic organism enters body and multiplies, may not cause disease

disease

• host cells damaged because of infection

• evidence of illness

• disease may be caused by the pathogen itself, toxins it releases, and/or immune response to pathogen (ex: cytokine storm)

pathogenic bacteria

• can harm host by…

  • direct tissue destruction

  • high numbers of bacteria blocking normal function

  • release of toxins (exotoxins from live bacteria, endotoxins from dead bacteria)

• bacteria can be killed by antibiotics

• symptoms: varied, depends on “tropism”

• bacteria have lipopolysaccharide (LPS) in outer membrane and peptidoglycan in cell walls → pathogen associated molecular patterns (PAMPs), recognized by pathogen recognition receptor (PRR) on immune cells of non-specific immunity

tropism

ability of a specific pathogen to target or infect a specific organ/tissue

virus

• requires a host cell for energy and to reproduce

• can harm host by…

  • interfering with host cell function or energy supply

  • destroying host cell

  • inducing host cell apoptosis

  • transforming host cell (make it cancerous)

• disease/symptoms depend on…

  • type of cells virus enters (tropism)

  • rate of replication

  • ability to avoid host defenses

  • damage caused to host cell

• unaffected by antibiotics

• viral nucleic acids are PAMPs

parasite

unaffected by antibiotics

non-specific (innate) immunity

• first line of defense

• inherited/innate

• reacts immediately, but not as powerful as specific immunity

• ex: physical barriers, cell-mediated PAMP-PRR, humoral

specific (adaptive) immunity

• all defenses that develop specifically in response to a specific pathogen

• acquired based on individual’s pathogen exposure

• first exposure to a new pathogen → responds in ~14 days

• subsequent exposures → responds within one day

• ex: T lymphocytes, B lymphocytes

humoral immune response

• antibodies and other circulating molecules

• pathogens free in blood and tissues → extracellular threats

• most bacteria, parasites, fungi, viruses (when out of host cells)

• toxins released by pathogens

cell-mediated immune response

• immune cells directly interact/touch pathogen

• pathogens that have gained access into cells → intracellular threats

• viruses (when inside host cells), some bacteria, protozoa, self cells that have gone bad (cancer prevention)

leukocytes (WBCs)

• ameboid-like movements (crawl by changing shape)

• extravasate (force way through vessel into tissue → diapedesis)

• granulocytes → granules contain enzymes, histamine, etc., short life (< 3 days)

• agranuloctytes → longer life (> 100 days)

leukopoiesis

• all leukocytes are born in bone marrow

• some mature in other lymphoid organs

• stimulated by various cytokines

granulocytes

• neutrophils

• eosinophils

• basophils

• mast cells

agranulocytes

• lymphocytes (B cells, T cells)

• natural killer cells

• dendritic cells

• monocytes

neutrophils

• most common WBC

• phagocytic

eosinophils

• detoxify foreign substances

• secrete enzymes that dissolve clots

• fight parasitic infections

basophils

release anticoagulant heparin

mast cells

release histamine (allergic response)

monocytes

• phagocytic

• can mature into macrophages

lymphocytes

provide specific immune response (including antibodies)

dendritic cells

• phagocytic

• present antigens to activate specific immunity

natural killer (NK) cells

• cytotoxic

• kill abnormal host cells (virus-infected, tumor cells)

• cell death by apoptosis

macrophages

• tissue macrophages (histiocytes) → all tissues

• Kupffer cells → liver

• alveolar macrophages → lungs

• microglia → CNS

B lymphocytes (B cells)

• produced in bone marrow

• make and secrete antibodies into the blood

• mature in response to a pathogen → turn into plasma B cells and memory B cells

• antibody-mediated (humoral) immune response

T lymphocytes (T cells)

• born in bone marrow and mature and differentiate in thymus into subtypes

• subtypes → helper, killer/cytotoxic, regulatory

• cell-mediated immune response

primary lymphoid organs

• bone marrow, thymus

• where lymphocytes are born and mature

secondary lymphoid organs

• lymph nodes, spleen, tonsils, Peyer’s patches

• where lymphocytes monitor and come into contact with antigen-presenting cells and pathogens and get activated

spleen

filters pathogens from blood

lymph nodes

filter/capture pathogens from lymph (immune surveillance)

cytokines

• general name for small proteins released by immune cells, usually in response to a pathogen stimulus

• regulate immune response by affecting the behavior of other cells

• actions may be autocrine (act on self), paracrine (act on nearby cells), or endocrine (circulate and act on distant cells)

• there are many different types of cytokines

  • largest class is interleukins (IL) → common therapeutic target

pro-inflammatory cytokines

cause tissue inflammation

chemokines

released at site of infection and disperse → direct immune cell migration

pyrogens

• stimulate fever

• increase temperature setting in thermoregulatory control center of hypothalamus

• mild/moderate fever helps recover from bacterial infection

interferons

• non-specific, short-acting, against viruses

• reduce viral replication and assembly, plus many other actions

epidermis

• outer layer of skin

• physical barrier to protect against invasion of pathogens

• sweat, shedding epidermis

• keratinocytes → PRRs, release antimicrobial peptides and cytokines, activate immune response within dermis

dermis

• connective tissue

• resident neutrophils, macrophages, and dendritic cells

  • PRRs detect pathogen PAMPs

  • engulf pathogens by phagocytosis

  • release chemokines and other cytokines to activate immune response

epithelial membranes

• mucus layer → physical barrier to trap and protect against pathogens

• intestinal crypts → secrete antimicrobial peptides

peristalsis

helps clear out pathogens (failure may cause bacteria overgrowth)

stomach acidity

gastric juice (pH ~2) kills many microbes

conducting zone

• mucus layer and cilia on epithelial cells → physical barrier to trap and transport pathogens out of the respiratory tract → “mucociliary escalator”

• antimicrobial peptides

alveoli

resident alveolar macrophages trap/remove particles and pathogens

ureter/bladder

acidity of urine

genital tracts

• cervical mucus

• vaginal lactic acid

phagocytosis of pathogens

• digestive enzymes from lysosome break down engulfed bacteria

• first phagocytes to act → local resident macrophages and other residents at infection site

• first to migrate in → neutrophils (“first responder”)

• later → monocytes from blood that mature into macrophages, dendritic cells

chemotaxis

• migrate from circulation into tissue with infection

• follow increasing concentration of chemokines

• mechanism:

  1. rolling

  2. capture

  3. adhesion and activation

  4. spreading

  5. diapedesis (extravasation)

  6. migration into tissue along chemokine gradient

  7. phagocytosis of bacteria

  8. pathogen vacuole fuses with lysosome → digestion

MHC-I

• fragments of pathogen inside host cell are processed

• presented on host cell surface by special complex MHC class I

• marks cell for cell-mediated destruction by killer T cells

• all nucleated host cells express MHC I