Immunology Normal and Abnormal

define immunity

Ability of host to resist damage by a foreign agent (antigen); Includes homeostasis (health) and disease response in host

define immunology

study of immune responses of cellular and molecular events after the host interacts with foreign macromolecules

define immunotherapy

is a medical term defined as the “treatment of disease by inducing, enhancing, or suppressing an immune response”.

define antigen (AG)

foreign substance that immune system responds by series of cellular interactions

what characteristics must an antigen possess?

foreign, molecular size, chemical composition and complexity, route and dose of antigen, adjuvant to enhance immunologic recognition of AG, haptene and carrier adduct to mount an immune response to smaller molecules

define phagocytosis

engulf and digest AG; neutralize

define antigen presenting cells (APC)

macrophage, dendritic cell, or B lymphocytes recognize AG and present to effector cells

define antigen processing

AG links to appropriate Major Histocompatibility Complex (MHC) and lymphocyte receptor

define haptene

small molecule that is somewhat antigenic but alone can not elicit an immune response

examples of haptenes:

Hydralazine & SLE, Penicillin & Hemolytic anemia, Urushiol from poison ivy (quinone)

define carrier

large immunogenic molecule that when couple with haptene will elicit an immune response; forms haptene-carrier adduct to create the immunologic response

define microbiota

the ecological community of commensal, symbiotic and pathogenic microorganisms that literally share our body space

what are the classes of antigens?

exogenous, endogenous, autologous, and allogenic

examples of exogenous antigens

microorganisms, drugs, pollen, etc.

What are endogenous antigens?

xenoantigen - tissue antigen that can cross react with an exogenous antigen, something that can occur within the host

What are autologous antigens?

autoantigen - self antigens, organ specific antigen

examples of allogenic antigens (alloantigen)?

blood groups, HLA

clinical significance of exogenous antigens

patient susceptible to infection, patient may present with allergies or asthma

clinical significance of endogenous antigens

post-strep glomerulonephritis, rheumatic fever, pathogenesis of immune disease

clinical significance of autologous antigens

autoimmune diseases (SLE, RA, diabetes)

clinical significance of allogenic antigens

transfusion reactions, transplant rejection

define epitopes

antigenic determinants on an antigen

where are antigens located on/in bacteria?

the cell wall

what is the paratope

antigen binding site - the matching portion of antibody or lymphocyte receptor that binds to the epitope

what can occur once the paratope binds to the epitope

the bacterial cell will be able to initiate an immunologic response

examples of innate leukocytes

neutrophils, eosinophils, monocytes, dendritic cells

what are toll-like receptors (TLR)?

family of pattern recognition receptors (PRR) on surface of innate antigen-presenting cells (APC)

what are the steps in innate immunity?

Pathogen-associated molecular patterns (PAMPs) - molecules associated with pathogen groups (AGs) and bind to their corresponding pattern-recognition receptors (PRRS) on APC with release of IL-12. Then IL-12 binds to IL-12 receptors on iNK cells. Neutrophils then migrate by chemotaxis to pathogen to engulf and destroy.

how do pattern recognition receptors (PRRs) recognize a broad range of antigens?

thru PAMPS

what are iNKT?

invariant natural killer cells that bridge response to AG between innate and adaptive immunity

which type of immunity is immediate and non-specific

innate

how can the innate immune system activate the adaptive immune system?

PRRs (TLRs) get activated and have phagocytic uptakes occur either by a macrophage or neutrophils; through this there can be co-activation of B cells, antigen presentation by macrophage, complementary proteins, and pro-inflammatory cytokines will release. Depending on the kind of antigen, there may be release of cell-mediated adaptive immunity (TCR, effector T cells) or these cells will become activated and become plasma cells and release antibodies

which immunity provides the first defense against antigen invasion (e.g. infections) and occurs within hours?

innate

examples of innate immunity defense mechanisms:

epithelial barriers to prevent antigens from entering the host and other processes such as: phagocytosis, NK cells, and the complement system to eliminate antigens (uses pre-existing cells/mediators and/or receptors)

T/F: innate and adaptive immunity are present at birth

false

what is opsonin-dependent phagocytosis?

In opsonin-dependent phagocytosis, the process is facilitated by opsonin; molecules that bind to the surface of pathogens and enhance their recognition by phagocytes. Opsonins are usually antibodies (like IgG) or complement proteins (like C3b) that attach to pathogen surfaces, making them more recognizable to phagocytic cells.

what is opsonin-independent phagocytosis?

recognition of pathogens by phagocytes does not require opsonins. Instead, phagocytes directly recognize pathogen-associated molecular patterns (PAMPs) on the surface of microbes through pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs).

which cells are innate leukocytes?

neutrophils, eosinophils, antigen presenting cells (APC), monocytes, and dendritic cells

binding of AG ligan with TLR enables what?

recognition by phagocyte to engulf pathogen

Toll-like receptors and Pathogen-associated molecular patterns on cell surface od neutrophils, monocytes, dendritic cells, and T and B cells can recognie what:

bacteria, fungi, and viruses

what are the components of biochemical barriers on epithelial surfaces that provide protection?

antimicrobial peptides, cathelicidins, and densins

what are antimicrobial peptides?

positively charged polypeptides found in leukocytes

what do cathelicidins do

disrupt cell membrane of bacteria

what do defensins do

kill bacteria

examples of our body’s physical defense and mediators:

epithelial barriers, normal bacterial flora, destruction by acid secretion and digestive enzymes, resistance of skin to invasion by microorganism, mucus of respiratory tract, normal urine flow and pH

soluble factors of the innate immune barriers?

antimicrobial peptides (defensins, cathelicidins), bacterial toxins, innate cytokines

what is our second line of defense?

innate immunity inflammatory response

functional cells of the innate inflammatory response:

granulocytes (neutrophils, eosinophils, basophils), mast cells, macrophages/monocytes, NK cells, dendritic cells, platelets

functional cells of the innate immune barriers:

epithelial cells

soluble factors of innate inflammatory response:

lysozymes, kinins, complement, C-reactive protein, interferons, and chemokines.

what are lysozymes

complement factors (3a, 5a), acute phase proteins (e.g.C-reactive protein), and interferon

what are chemokines/chemotactic cytokines?

directs circulating leukocytes to areas of inflammation - chemokines link innate and adaptive immune responses using chemokines and receptors

what are interleukins

interleukin-1 (IL-1) is a pro-inflammatory mediator produced by macrophages and activates phagocytes and lymphocytes

which factor is active in both innate and acquired immunity?

interleukin-1

IL-1 is an endogenous pyrogen and reacts with what to cause fever

hypothalamus

what are interferons

protect against viruses and modulate inflammatory process

things that reduce gastric pH:

achlorhydria, H2 blockers, PPIs

things that cause breaks in skin barriers

burns, surgical incisions, penetrating trauma, vascular access devices

things that cause impaired mucociliary function in lungs

smoking, flu (secondary respiratory infections)

things that cause impaired esophageal or epiglottal function

endotracheal intubation, stroke, recumbent positiont

things that cause altered urine flow

renal stones, bladder catheter, anatomic deformity obstructing urine outflow

things that disrupt GI and vaginal flora

antibiotics

things that cause anatomical alterations of the heart

endocarditis

which type of immunity develops later such as days after antigen invasion and is mediated by lymphocytes and mediators

adaptive

what are the two types of adaptive immunity?

humoral and cell-mediated

what cells play a role in humoral immunity

B lymphocytes which mature into antibodies

what cells play a role in cell mediated immunity

T lymphocytes which develop effector T cells

soluble factors for adaptive immunity:

antibodies, cytokines, complement

organs involved in the immune system:

tonsils, adenoids, lymph nodes, lymphatic vessels, thymus, spleen, appendix, Peyer’s patches, bone marrow

what do lymph nodes do

filter lymphatic fluid which contains antigens, immune cells, and cell debris - during this process, antigens are presented to lymphocytes in LN with immune response elicited with cell proliferation, LN enlarge

normal range of leukoccytes (WBC)

4000 - 10,000 cell/mm3

what are lymphocytes

mononuclear cells - B or T cells

when B cells mature they release:

specific antibody to an antigen

when T cells mature they release:

cytokines

what makes up 25-35% of WBCs?

lymphocytes

what are monocytes?

mononuclear phagocytes

what are specific mononuclear phagocytes called

macrophage - can act as an antigen presenting cell

which cells are polymorphonuclear

neutrophils, eosinophils, and basophils

what makes of 50-60% of WBCs?

neutrophils

which cells are phagcocytes?

neutrophils and eosinophils

which cells are auxiliary cells

basophils, mast cells, and platelets

where do WBCs come from?

Haemopoietic stem cells will produce mononuclear cells (B or T) and are released to the blood circulation. These cells can also produce natural killer cells, macrophages, granulocytes, and mast cells. The thymus causes maturation of the T lymphocytes

what are B lymphocytes?

recognize soluble or cell surface AG and differentiate into antibody (AB) forming plasma cells - neutralize microbe, phagocytosis, and complement activation

what are T helper lymphocytes (CD4+ cells)

recognize AG on surface of antigen presenting cells (APC) and secrete specific cytokines that stimulate other immune cell responses and inflammation - Activation of macrophages, inflammation, and activation (proliferation and differentiation) of T and B lymphocytes

what are cytotoxic lymphocytes (CTL) or CD8+ cells?

recognize AG in invaded cells through MHC molecules and APC and destroy these cells; killing of infected cells - can release cytokines to kill cell

what are regulatory T lymphocytes (TREGS)

Limit or down regulate activation of other lymphocytes and prevent autoimmunity (response to self) - suppression of immune response; Keep in check the immune system so the cytotoxic cells don’t kill everything and are downregulated to some degree by these TREGS

what are natural killer cells

recognize changes on cells invaded by an antigen and destroy these cells. NK cells are part of Innate Immunity - killing of infected cells

what is the overview process of going from stem cell to mature cell?

pluripotent stem cell —→ oligopotent stem cell —→ monopotent progenitor -—> maturation ——> mature cell

which cytokine/growth factors come from erythrocytic progenitor

EPO and IL-3

which cytokine/growth factors come from megakaryocytic progenitor

TPO and IL-11

which cytokine/growth factors come from neutrophilic progenitor

G-CSF

which cytokine/growth factors come from monocytic progenitor

M-CSF

which cytokine/growth factors come from eosinophilic progenitor

IL-5 and GM-CSF

which cytokine/growth factors come from basophilic progenitor

IL-3 and GM-CSF

what do EPO and IL-3 mature into?

erythocytewhat do TPO and IL-11 mature in to

what do TPO and IL-11 mature into

platelets

what does G-CSF mature into

segmented neurotphil

what does M-CSF mature into

monocyte

what do IL-5 and GM-CSF mature into

eosinophils

what do IL-3 and GM-CSF mature into

basophils