Microbiology Final Material Ch. (13-15 + presentations) see additional Exam 3 materials

characteristic of both adaptive and innate immunity

discrimination of self and non-self

characteristics specific to adaptive immunity

specificity, diversity, timing, and memory

specificity

immunity to each antigen. Does not confer immunity to other antigens

Timing

process of activation, time it takes to educate adaptive immunity to recognize a new antigen

diversity

enormous number of possible cellular receptors and antibodies that recognize trillions of unique foreign substances

immune memory

allows for quick reaction during re-exposure to the same pathogen

humoral immunity

antibody-mediated immunity controlled by B cells (plasma cells)

cellular immunity

cell-mediated immunity controlled by T cells

Types of effector T cells

cytotoxic and helper

antigen

any substance that elicits and immune response

immunogenic

elicits an immune response

determinants of an antigen (immunogenicity)

depends on its size, structural complexity, chemical nature, and degree of foreignness to the host (particularly important for successful transplants)

examples of things that are immunogenic

whole cells, viruses, and some plant molecules

epitopes

antigenic determinant sites that are specific regions of the antigen recognized by antibodies

epitopes per antigen

no limit, there’s often several

immunogenic small molecules

immunogenicity is increased for those structurally repetitive ex. flagella and peptidoglycan

MHC

collection of genes encoding proteins that enable the host to distinguish between self and non-self

Human MHC

HLA: human leukocyte antigen

Class I MHC

found on ALL healthy nucleated cells; they can bind to self antigen, marking the cell as self or to antigens extracted from intracellular pathogens (non-self), signaling an infection

Class II MHC

only found on APCs to present antigens to CD4 (helper) T-cells

Class III MHC

secreted proteins that have immune function but not involved in self/non-self recognition

Antigen presention

function of MHC molecules that is required for T cell activation

antigen presenting cells (APCs)

immune cells that place non-self antigen on MHC-II molecules

T-cell development

maturation of progenitor cells to one of two types of T cells (helper or cytotoxic)

Where T cell development occurs (T step 1: migration)

Common lymphoid progenitor cells migrate from the bone marrow to the THYMUS

Types of T cell receptors (T step 2: sorting)

γδ (migrate to other organs-skin, mucous membranes) and αβ (remain in thymus)

Positive selection (T step 3)

determines which TCR coreceptor the mature T cell will keep, either CD4 or CD8

immature T cells

before positive selection, have both CD4 and CD8

cluster of differentiations

type of molecule that CD4 and CD8 fall under

Negative selection (T step 4)

Screening for TCRs that recognize self and eliminates them (apoptosis). Removes 98% of all CLP entering the thymus.

What happens without negative selection during lymphocyte maturation?

autoimmune diseases

Naive T cells

after negative selection, mature T cells but have not been activated

TCR components

heterodimeric polypeptide receptor (made up of 2 different monomers) and six accessory polypeptides

activation of naive T cells

the shape of an antigen delivered by an APC binds “just right” to the cell’s TCR

immune synapse

complex of an MHC/antigen perfectly bound to the TCR, results in T cell activation through signal transduction

Role of TCR accessory proteins

signal transduction once the proper immune synapse is formed

If MHC complex doesn’t match with the TCR

it moves on and presents the antigen to another T cell until it can complete the immune synapse

CD4 T cells

Helper T cells that bind to MHC II molecules, also assist in CD8 and B cell activation

CD8 T cells

cytotoxic T cells (CTL) that bind to MHC I molecules, may require help from helper T cells to activate

Memory T cells

produced for each type of helper T cell

B cells

sole purpose is to produce antibodies

site of B cell development

BONE marrow where they undergo negative selection to remove self-reactive BCRs

B cell receptor

B cell activation

migrate from bone marrow until they meet a specific antigen recognized by their BCR

result of B cell activation

proliferation and then differentiation into mature B cells

mature B cells

secrete antibodies, AKA plasma cells

Signals required for B cell activation

B cells can bind antigen directly (no APC) but also require cytokines from helper T cells in addition to antigen

precipitation (antibody)

bind to epitope on cell-free molecule in solution to block binding

neutralization (antibody)

bind to viruses to block binding

agglutination (antibody)

cross-link binding to bacterial cell antigens to block binding/attachment

complement fixation (antibody)

binding triggers the complement system and results in cell lysis

opsonization (antibody)

opsonized bacteria/viruses are engulfed more readily

preciptation v. neutralization v. agglutination

all prevent pathogen from moving/acting/activating but the difference is the particle they act upon

antibody diversity

similar concept to T cell receptors, having a diverse range of antibodies increases the likelihood that one will bind to an epitope on a pathogen/antigen

Lymphocyte clonal selection

origin of B and T cells. CLPs become B or T cells and have random rearrangements in the genes for BCR or TCR to vary their specificity. Negative and positive selection result in effective receptors that don’t bind to self and go on to test their receptors on antigens until an immune synapse is formed.

active immunity

body builds it’s own immunity

passive immunity

immunity is given, already in the body but the individual didn’t build it

natural immuntiy

aquired in normal life through normal life experiences

artificial immunity

medicines/vaccines

infection

when a pathogenic microorganism is growing and multiplying within host, may or may not result in disease

pathogenicity

ability of an organism to cause disease, if it can it is a pathogen

virulen

degree of harm (or pathogenicity) inflicted on the host

infectious disease

any change from a state of health, in which the host is incapable of carrying on its normal functions due to the presence of a pathogen or its products

transition of resident microbiota to opportunistic pathogens

if they infect a host away from their typical niche or if the host immune system is compromised

varied/unique microorganism growth and replication requirement

due to host and tissue specificity

extracellular pathogens

remain in tissues and fluids

intracellular pathogens

multiply within host cells

facultative intracellular pathogen

some bacterial species, known to reside within cells in the host but can be grown in pure cultures without host-cell support

obligate intracellular pathogen

all viruses and some bacterial species that are in capable of growth and multiplication outside a host cell (origin of mitochondria)

process of infection

initial exposure, incubation, prodromal stage, illness (plataeu), convalescent period

incubation period

time between pathogen entry and development of signs and symptoms, individuals may be contagious

prodromal stage

pathogen reaches a level at which they cause mild and nonspecific symptoms but aren’t defined enough for a clear diagnosis. Individual is often contagious

illness period

disease is most severe and displays characteristic signs and symptoms. Adaptive immune response is typically triggered by this stage

convalescence

signs and symptoms begin to disappear, recovery stage but may still be contagious

signs

objective, clinically detectable or observable elements of a disease (BP, rash, fever)

symptoms

subjective and patient-described (headache, nausea, fatigue)

syndrome

collection of signs and symptoms

events required for a pthogen to infect a host and subsequently cause disease

1. Transmission and entry

2. outcompete resident microbiota

3. Survive innate host defense mechanisms

4. Cause damage to host cells through their own molecules or immune system activation

Factors that determine transmission/entry of a pathogen

1. virulence of the organism

2. number of invading organisms (infection dose)

3. presence of adhesion and invasion factors

4. immunocompetence of the host

direct transmission

host to host

indirect transmission

host to surface to host

animate source

humans or animals

inanimate source

water or food

Ignaz Philipp Semmelweis

1st person to realize that a pathogen could be transmitted from one person to another

tropism

specificity of pathogen to infect certain cells typically because they have a specific receptor the pathogen can attach to and use for entry

ex. ACE2 for SARS-CoV-2

Importance of tropism

exposure alone is not sufficient for infection, the pathogen must come in contact with appropriate host tissue

contact transmission

host touching, directly or indirectly, a source or reservoir of pathogen

airborne transmission

pathogen is suspended in the air (droplet, droplet nuclei, or dust). Must originate from another source because air is not a medium for growth

Droplets

form from saliva, mucus, and other bodily fluids. Can measure up to 2mm so they require close proximity for transfer between hosts (<1m)

Droplet nuclei

1-5 micrometers and can remain airborne for hours or days and can travel long distances

particles

smaller than 1 micrometer, can become aerosolized and disperse even farther (most contagious diseases)

Dust

can carry endospores or pathogens and is resuspended by any disturbance

overall rule for airborne transmission

the heavier the mode of transmission, the less likely it is to remain suspended

vehicle transmission

indirect transmission by a non-living element, fomite. Can spread the pathogen to multiple hosts and/or spread multiple pathogens it is contaminated with

fomites

non-living element that indirectly transmits pathogens

vector-borne transmission

transmission though vectors, living organisms that can transmit pathogens. The pathogen does not significantly harm the vector but replicates extensively for a more effective transmission

Vertical transmission

unborn child acquires a pathogen from their infected mothers, aka a congenital infection

entry

access to the host through a a portal of entry so the pathogen enters and find cells to infect

portals of entry

skin, respiratory system, gastrointestinal system, urogenital system, and conjunctiva of the eye

after entry pathogens must

attach or adhere for colonization