Immunology final

types of immunity

passive natural acquired, passive artificial acquired, active natural acquired, active artificial acquired

passive natural acquired immunity

immunity acquired from antibodies passed in breast milk or placenta

passive artificial acquired immunity

immunity gained through antibodies harvested from another person or animal

active natural acquired immunity

immunity gained through illness and recovery

active artificial acquired immunity

immunity acquired through a vaccine

variolation

process where people who had not had smallpox were exposed to material from smallpox sores of others through scratch in arm or inhalation, the first type of vaccination

vaccination purpose

attempting to stimulate adaptive immune system to create memory- helper T cell, killer T cells, B cells

memory B cells

antigen coming to secondary lymph organ via lymph or blood

memory helper T cells

Antigen presenting cell must present the antigen on MHC II

memory killer T cells

infected cell must present the antigen on MHC I

types of vaccines

non-infectious, attenuated, carrier

non-infectious vaccines

killed, subunit, conjugated, carrier(vector), DNA, mRNA; cause the body to make memory B and helper T cells but do not cause production of memory killer T cells, not able to infect or replicate (unless improperly made)

killed vaccines

dead organisms, treated with physical or chemical agent (heat, chemicals, radiation) to inactivate/kill them, ex- polio, typhoid,

Cutter incident

improper manufacturing at cutter laboratories resulted in release of insufficiently inactivated polio vaccines that paralyzed almost 200 vaccine recipients and close contacts

subunit vaccines

materials isolated from disrupted or lysed organisms (acellular pertussis), virus-like particles (in capsid that doesn’t contain viral genetic info) display antigens from agent, toxoids- inactivated/weakened toxins (diphtheria, tetanus), recombinant- terminology to describe genetic modification (Hep B, Hib)

conjugated vaccines

combine different antigens to improve response

carrier/vector vaccines

genetically modified live virus so it’s non-infectious, replicating and non-replicating types

DNA vaccines

naked DNA extracted from pathogen → host cells takes up DNA and makes proteins of pathogen, ex- zika, ZyCoV-D, west nile

mRNA vaccines

modified mRNA packaged and delivered in lipid nanoparticles → mRNA code translated and displayed as foreign to body, ex-covid-19

live attenuated vaccines

weakened versions of pathogens but can still infect host, mimic kind of protective immunity found in people that have survived a live infection, infects host’s Antigen presenting cells, results in memory B cells, memory helper T cells, memory killer T cells, ex- sabin polio, MMR

sabin polio vaccine

polio virus reproduced in monkey kidney cells that resulted in virus still infectious but very weak

carrier (viral vector) vaccines

introduces a single gene from a pathogenic microbe into a virus that doesn’t cause live disease, replicating or non-replicating carrier infects host’s APCs → APCs produce pathogenic microbe proteins → protein fragments presented on MHC I molecules → results in memory B cell, Th cells, Tk cells (J&J covid vaccine)

herd/community immunity

a situation in which a sufficient proportion of a population is immune to an infectious disease to make its spread from person to person unlikely, even unvaccinated individuals have some protection because the disease has little opportunity to spread

efficacy of non-infectious vaccines

can’t contract actual illness, easy to manufacture, don’t elicit same response as live pathogen, often need adjuvant to get active reaction

efficacy of live vaccines

much more closely mimic real pathogen, difficult to manufacture, illness can be contracted and recipient can get sick

adjuvant

means helper, help stimulate immune system to increase the immune response to non-infectious vaccines, not immunogenic, causes mild inflammation, attracts phagocytes and accelerates phagocyte activation and presentation to T cells

types of adjuvants

aluminum (causes inflammation for longer lasting immunity and possible Th1 response), oil-emulsion (same as aluminum), TLR antagonists (activate TLR pathways via inflammatory cytokines), combinations

vaccine preservatives

needed in multi-dosage vials to protect vaccine from anything outside vial, ex- thimerosal (ethyl mercury), residual materials from manufacturing process (egg protein, tissue culture ingredients, formaldehyde)

hypersensitivity reactions

4 types that all require prior exposure to antigen- Type I (immediate, IgE), Type II (antibody, IgM, IgG), Type III (immune complex, IgM, IgG), Type IV (cell mediated, T cells)

type I hypersensitivity

rapid- occurs within minutes of exposure, allergen enters body → APCs present it on MHC II to T cells → differentiation to Th-2 subtype via IL-4 causes B cells to make IgE → allergen-specific IgE antibodies bind to mast cells via Fc receptor → 2nd exposure to antigen → cross-linking induces degranulation/activation of mast cells → release of histamine causes local/systemic anaphylaxis, hay fever, food/drug allergies

type II hypersensitivity

IgG and/or IgM antibodies bind to cellular antigen → lead to complement activation and cell lysis → IgG can mediate ADCC with cytotoxic T cells, NK cells, macrophages, and neutrophils; includes rbc destruction after transfusion with mismatched blood types or during hemolytic disease of newborn

antibody-dependent cell-mediated cytotoxicity (ADCC)

WBCs with Fc receptors (monocytes, neutrophils, eosinophils, NK cells), bind to cells with IgG or IgM antibodies

hemolytic disease of the newborn

type II hypersensitivity rxn, antibody-antigen complexes accumulate and deposit in tissues which causes inflammation, Rh+ father and Rh- mother → Rh- mother carrying first Rh+ fetus is exposed to Rh antigens from fetus and produces anti-Rh (IgG) antibodies → no rxn occurs with 1st child → 2nd Rh+ fetus receives anti-Rh antibodies from placenta and its RBCs are damaged

type III hypersensitivity

IgG and/or IgM antibodies, antigen-antibody complexes deposited in tissues → complement activation provides inflammatory mediators (phagocytes) and recruits neutrophils, enzymes released from neutrophils damage tissue; includes post-streptococcal glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus

type IV hypersensitivity

inappropriate/excessive immune response from T cells, 2 types- delayed type (DTH) and T-cell mediated cytotoxicity, no antibody involvement, can be directed against self or exogenous antigens, T cells secrete cytokines which activate macrophages and cytotoxic T cells, longest hypersensitivity rxn; includes contact dermatitis, type I diabetes mellitus, poison ivy, multiple sclerosis

humoral immunity involves

B cells and antibodies

hapten

a substance that on its own does not invoke an immune response but when combined with protein can become highly antigenic

oil-emulsion adjuvants

MF59 and AS03, used in influenza H5N1 and H1N1 vaccines, induce strong response including local cell death and production of danger signals (DAMPs), causes inflammation which results in longer lasting immunity, reactogenic

TLR agonist adjuvants

transmembrane receptors predominantly expressed by innate immune cells, deliver downstream signal transduction and initiates inflammatory response, provides ‘danger’ signal to induce effective immune response that leads to long-lasting protection, promising in vaccines against cancer, AIDS, and malaria

sepsis

systemic immune response caused by infection from pathogen throughout body, cells respond and produce large quantities of cytokines (TNF) through positive feedback loop to point of cytokine storm, increased blood vessel permeability causes organ damage, drop in BP results in septic shock

allergies

type I hypersensitivity, overproduction of IgE in response to harmless allergens, atopic individuals push Th2 response of producing more IgE

autoimmunity

memory response to normal tissue, loss of tolerance, caused by failure of tolerance processes, 3 conditions needed- MHC presents self peptide, T and B cells recognize self antigen, and failure of self-tolerance; can be organ-specific or systemic, may involve antibodies, T cells, or immune complexes

induction of autoimmunity

infections and molecular mimicry, chronic inflammation, trauma exposes sequestered antigen and alters gut microbiota

hypersensitivity

response to innocuous antigens causing harm

autoimmune vs hypersinsitivity

all autoimmune conditions are hypersensitive reactions but not all hypersensitive reactions are autoimmune conditions

Th1 bias

CTL, NK cells, macrophages; used against intracellular viruses and bacteria in tissues, if things go wrong autoimmunity occurs

Th2 bias

mast cells, B cells, eosinophils; used against parasites, helminths, and bacteria in gut/GIT, if things go wrong allergies occur

Hashimoto’s thyroiditis

organ-specific autoimmunity of thyroid, autoantibodies and sensitized Th1/CTLs specific for thyroid antigen produced, antibodies interfere with iodine uptake, induces DTH, type II hypersensitivity rxn produces anti-TSH receptor antibodies

type 1 diabetes mellitus

organ-specific autoimmunity of pancreas, attack against insulin-producing beta cells in pancreas, CTLs infiltrate pancreas and activate macrophages → cytokines released, autoantibodies produced, DTH response

myasthenia gravis

organ-specific autoimmunity of muscles, autoantibodies bind nicotinic acetylcholine receptors on motor end plates of muscles → block normal binding of Ach and induce complement-mediated lysis of cells → progressive weakening of skeletal muscles → cytotoxic/type II hypersensitivity

systemic lupus erythematosus (SLE)

system-specific autoimmunity against DNA and self structures, deposition of immune antigen-antibody complexes activates complement, type III hypersensitivity

multiple sclerosis

systemic autoimmune condition, MC cause of neurologic disability in western countries of northern hemisphere, auto-reactive T cells form inflammatory lesions along myelin sheaths around nerve fibers in brain and spinal cord, type IV hypersensitivity, more frequent in women

rheumatoid arthritis

systemic autoimmune condition, antigen-antibody complexes produced (IgM binds IgG), type III hypersensitivity, chronic inflammation in joints, more frequent in women

congenital (primary) immunodeficiency

inherited single gene mutation affects formation and function of thymus so no T cell maturation occurs, mild to severe, can be innate (phagocytic- macrophages, neutrophils, AP dendritic cells) or adaptive (B cells, T cells), DiGeorge syndrome, SCID

Severe combined Immunodeficiency syndrome (SCIDS)

defect in protein needed to make BCRs and TCRs caused by defective cytokine signaling, VDJ segment rearrangement results in no functioning B cells or T cells, treated with bone marrow transplants, David Vetter the ‘bubble kid’

bare lymphocyte syndrome type I

MHC class I deficiency, both innate and adaptive immune systems compromised from absent MHC I on CD8 T cells and NK cells, MC from loss of TAP1 or TAP2 proteins

hyper IgM syndrome

x-linked, nonfucntional CD40/CD40L coupling of B cells to Th cells, results in B cells unable to class-switch so they only secrete IgM, T cells don’t activate APCs and B cells- no memory

x-linked agammaglobulinemia (XLA)

inherited immune disorder caused by inability to produce B cells or antibodies, mutated gene from protein Bruton tyrosine kinase (BTK)

leukocyte adhesion deficiency (LAD)

defect in integrin adhesion molecules means WBC recruitment is inhibited- no integrin to stop rolling of leukocyte so they have no way to get into cells or tissues, results in common bacterial and fungal infections

classical pathway deficiency

C2 deficiency, most common, includes lectin pathway, causes recurrent infections of upper respiratory tract, ear infections and colds,

lectin complement pathway deficiency

mannose binding lectin deficiency, not primary but common in 5-30%, increases susceptibility to bacterial infections

alternative complement pathway deficiency

rare, 2 cases of factor D, 1 case factor B, properdin deficiency is x-linked, causes susceptibility to Neisseria meningitis

acquired (secondary) immunodeficiency

from- infection, drug treatment or immunosuppression, malnutrition, disease, age; AIDS and HIV-1; treated by blocking agents and highly active anti-retroviral treatment (HAART)

HIV-1/AIDS

major cause is human immunodeficiency virus 1, major cause of acquired immunodeficiency, targets CD4+ Th cells, mortality typically due to opportunistic infections, viral entry into cells by infecting Th cells in area → hijacks cellular machinery to reproduce → CTLs stimulated trying to destroy infected cells

why HIV-1 so oftenly defeats immune system

uses enzyme reverse transcriptase to make DNA from its RNA and insert it into host DNA where it can stay in latent state undetected for years, high mutation rate also allows virus to evade immune system

3 phases of HIV infection

acute → asymptomatic → AIDS

AIDS criteria

evidence of infection with HIV, CD4 T cell count below 200, occurrence of opportunistic infections

#1 and 2 causes of death

1- heart disease, 2- cancer

non blood cell cancers

solid tumors, carcinomas- most common, epithelial origins, sarcomas- least common, found in bone, fat, and cartilage

blood cell cancers

leukemias- arise from early lymphoid or myeloid cells, lymphomas- spread to lymphatic system, swollen nodes, myeloma- arises from B cells

spontaneous cancers

most common, result from exposure over time, environmental link- chemicals, radiation (UV, ionizing), diet, metabolism, tumor cells produce proteins that activate CTLA-4 and PD-1 on itself, conflict between self-tolerance and surveillance

virus-associated cancers

CTLs effectiveness is limited due to hiding viruses, HPV, Hep B (liver), Epstein-Barr (Brukitt’s lymphoma), herpes virus (kaposi’s sarcoma), HTLV leukemia

cancer characteristics

a result of an accumulation of multiple events, generally not inherited, changes in DNA of one cell over lifetime, invade (proliferate and produce malignant tumors that invade healthy tissue), metastasize (spread to other areas of body and establish secondary tumors), rare at cellular level, loss of balance between division, differentiation, and cell death

proto-oncogenes

encode proteins that have various functions in cell’s normal activities, a good guy

oncogenes

mutated version of proto-oncogene, encodes proteins that promote loss of growth control and conversion of a cell to a malignant state, act dominantly, Ras, a bad guy

tumor suppressor genes

encode proteins that restrain cell growth, act recessively, p53, a good guy

internal safeguards against cancer

proto-oncogenes, tumor suppressor gene p53, proteins that help prevent mutations and can fix damaged DNA, can induce apoptosis if genetic damage is severe

immunosurveillance

the immune system actively monitoring, identifying, and eliminating cancerous cells, eliminating pathogens and reducing chronic inflammation that is pro-tumor

hyperactive macrophages

secrete TNF which can kill certain types of cancer, bacille calmette guerin is potent immune stimulator and TB vaccine, effective because macrophages are everywhere and quick-acting and innate

both macrophages and NK cells

need cytokines to become activated, chronic inflammation suppresses macrophages and NK cells reducing their ability to fight cancer

the antibody that is anti-tumor

IgM, naturally produced, recognizes new antigens and modified ‘normal’ antigens, can activate complement, being used in cancer treatments to mark cells for macrophages via monoclonal antibodies

CAUTION against cancer

Change in bowel or bladder habits, A sore throat that doesn’t heal, Unusual bleeding or discharge, Thickening or lump in breast, Indigestion or difficulty swallowing, Obvious change in growth or mole, Nagging cough or hoarseness

vaccines tied to cancers

Hep B- liver cancer, HPV- cervical cancer, therapeutic cancer vaccines

traditional cancer treatments

radiation, chemotherapy, surgery

cancer detection

cell morphology (pap smear), clinical manifestations, biochemical tests (PSA test), imaging (mammogram), microarray gene expression (screen global gene expression)

monoclonal antibodies

immortal antibodies produced from hybridoma cell containing good properties of plasma B cell and cancerous B cell- plasma B cell gives high affinity for specific antigen, produce antibodies quickly, and directly destroy target but are short-lived while cancerous B cells are immortal, large quantities made in lab targeting specific antigen, injected into patient

monoclonal antibodies and RA

#1 treatment for RA, RA caused by inflammation from macrophages releasing TNF, TNF can be blocked by monoclonal antibodies, drawback is patient becomes immunocompromised

monoclonal antibodies and non-hodgkin hymphoma

NHL is blood cell cancer that arises when B cells have mutations that block maturation, CD20 protein on surface of immature B cells and in high concentrations of NHL patients, monoclonal antibodies bind to CD20 and tag them for destruction but spare blood stem cells and long-lived plasma B cells

monoclonal antibodies and breast cancer

25% breast cancer patients have tumors that express large amounts of the HER2 growth factor receptor which can cause cancer cells to proliferate and metastasize when its ligates, monoclonal antibodies can bind to HER2 receptors and block grow signals

monoclonal antibodies and psoriasis

thick and scaly skin plaques characteristic of psoriasis have strong causation with with IL-17, IL-17 causes keratinocytes to proliferate when they shouldn’t, monoclonal antibodies can block interaction between IL-17 and its receptor on keratinocytes, drawback is IL-17 is cytokine that protects against fungal infections

T cell treatments

can be used to treat diseases, assist ‘natural’ T cells that need help to get job done, T cell immunotherapy uses T cells that have been modified by genetic engineering to make them ‘better, faster, and stronger’, T cells often found in removed tumors (tried to fight cancer off but there weren’t enough of them)

adoptive T cell transfer

TIL cells (tumor infiltrating lymphocytes that tried to fight off a tumor) removed from tumor and grown in lab then tested for tumor recognition and increased proliferation → injected back into patient to treat cancer and had promising results (especially in melanomas)

chimeric antigen receptor (CAR) T cell therapy

targets B cell cancers (lymphomas and multiple myeloma), concept is to use genetic engineering to modify a patient’s T cells so they produce an artificial T cell receptor with 3 parts (recognition domain, signal protein, and co-stimulatory signal) that allow cell to skip normal activation requirements of T cells and scan and read more than just MHC, customized to each patient, won’t matter what cancer cells are displaying on MHC because it can read and recognize the cancer cells themselves; in clinical trial 60% kids treated were alive 5 years later

Hib vaccine

covers Haemophilus influenza B, bacterial, non-infectious polysaccharide/toxoid conjugate

Prevnar 13 and Pneumovax 23 vaccines

covers pneumonia, bacterial, non-infectious polysaccharide conjugate

meningococcal vaccine

covers meningitis, bacterial, non-infectious recombinant

DTaP vaccine

covers diphtheria, tetanus, and pertussis, bacterial, non-infectious (diphtheria and tetanus-toxoid, pertussis- subunit)

Hep B vaccine

viral, non-infectious recombinant

rotavirus vaccine

viral, live attenuated

IPV polio vaccine

viral, non-infectious whole inactivated