The Human Immune System: Innate and Adaptive Immunity

Flashcards covering innate immunity mechanisms (WBC ranges, phagocytosis, cytokines, fever, PAMPs/TLRs) and adaptive immunity mechanisms (antibody structure and classes, agglutination, neutralization, T-dependent B-cell activation, immune memory, and types of acquired immunity).

What can a high white blood cell (WBC) count in the blood typically indicate?

It may indicate bacterial infections among other health issues.

According to the normal blood values, what is the normal white blood cell count range and the percentage breakdown of leukocytes for men and non-pregnant women?

The normal WBC count is $5{,}000\text{--}10{,}000\text{ WBCs per cubic millimeter (mm}^3\text{)}$ or $5.0\text{--}10.0 \times 10^9\text{ WBCs per liter}$. The normal percentages are: Neutrophils ($60\text{ to }70\%$), Lymphocytes ($20\text{ to }25\%$), Monocytes ($3\text{ to }8\%$), Eosinophils ($2\text{ to }4\%$), and Basophils ($0.5\text{ to }1\%$).

What are the primary characteristics and relative abundances of neutrophils, monocytes, and dendritic cells?

Neutrophils make up $\sim 65\%$ of WBCs, are phagocytic, and are involved during early stages of infection. Monocytes make up $\sim 5\%$ of WBCs, are phagocytic, and mature into macrophages in tissues. Dendritic cells make up $<1\%$ of WBCs, are phagocytic, and reside in the skin and mucous membranes.

What are the five consecutive phases of phagocytosis illustrated in the diagram?

1. Chemotaxis and adherence (recognition), 2. Ingestion (formation of phagosome), 3. Formation of phagosome / fusion with a lysosome to form a phagolysosome, 4. Digestion of ingested microbes by enzymes and chemicals, and 5. Discharge of waste materials / Exocytosis (residual body).

How do phagocytic cells physically attach to pathogens during the attachment phase of phagocytosis?

Host phagocytic Toll-Like Receptors (TLRs) bind directly to pathogen-associated molecular patterns (PAMPs) on the pathogen surface, which initiates phagocytosis and triggers cytokine release.

What are cytokines and how do they function when released by immune cells?

Cytokines are chemical messenger proteins that mediate communication in the immune system. When released into the bloodstream, they bind to cytokine receptors on target host cells (such as other phagocytes) to trigger gene activation and coordinate immune responses like cell migration.

How does macrophage ingestion of a gram-negative bacterium cause a fever response?

The macrophage ingests the gram-negative bacterium and degrades it in the vacuole/phagosome, releasing endotoxins embedded in the lipopolysaccharide layer. This induces the macrophage to produce more cytokines, which travel via the bloodstream to the hypothalamus and trigger the release of prostaglandins, resetting the thermostat to a higher temperature.

Based on the body temperature graph, what physiological responses cause heat gain and heat loss during a fever?

Heat gain (temperature increase) is driven by vasoconstriction, piloerection, epinephrine secretion, and shivering. Heat loss (temperature decrease following set-point lowering) is driven by vasodilation and sweating.

What is the structural and functional difference between bacterial adhesins and bacterial PAMPs?

Adhesins (ligands) are surface molecules on the glycocalyx, fimbriae, or flagella that bind host cell receptors to allow bacterial entry and tissue adherence. PAMPs are conserved molecular structures shared across groups of bacteria (e.g., flagellin, LPS Lipid A) that bind host Toll-Like Receptors (TLRs) to trigger innate immune defenses.

How do humoral immunity and cellular immunity differ in terms of the pathogens they target?

Humoral immunity (antibody-mediated) combats freely circulating extracellular pathogens in body fluids using B cells, $T_H$ cells, and antibodies. Cellular immunity (cell-mediated) attacks intracellular pathogens that have already entered host cells using T cells, cytotoxic T lymphocytes (CTLs), and macrophages.

What are the structural components and amino acid chain lengths of an antibody molecule shown in this diagram?

An antibody consists of $2$ identical heavy chains ($450\text{--}550$ amino acids) and $2$ identical light chains ($\sim 215$ amino acids), arranged into two antigen-binding Fab arms at the tips and one Fc stem at the base.

What are the distinct functions of the variable (V) regions and constant (C) regions of an antibody?

Variable (V) regions contain unique amino acid sequences that together form the antigen-binding sites and dictate specificity for a particular antigen. Constant (C) regions support antibody structure on the light chain and determine antibody class and effector interactions on the heavy chain.

What is the primary function of the stem (Fc region) of an antibody?

Formed by the constant regions of the two heavy chains, the stem determines antibody class, acts as a target for phagocytes (like macrophages) to bind and engulf the antigen-antibody complex, and can anchor the antibody to B-cell membranes as a B-cell receptor.

Which structural forms correspond to monomer, dimer, and pentamer antibody classes?

IgD, IgE, and IgG exist as monomers; IgA exists as a dimer; and IgM exists as a pentamer featuring $10$ antigen-binding sites.

What are the key properties, abundance, and primary role of IgM antibodies?

IgM is the first antibody class to appear after initial antigen exposure, makes up $6\%$ of serum antibodies, remains largely in blood vessels, and is the largest antibody class (pentamer), making it highly effective at agglutinating bacteria.

What are the abundance, distribution, and functions of IgG antibodies?

IgG makes up $80\%$ of serum antibodies, is found in blood, lymph, and intestine, is the second class to respond, crosses the placenta to provide passive immunity to the fetus, and enhances phagocytosis.

What are the characteristics and physiological locations of IgA antibodies?

IgA makes up $13\%$ of serum antibodies, is common in mucous membranes and body secretions (saliva, tears, and breast milk), prevents microbial attachment to mucous surfaces, and protects nursing infants from gastrointestinal infections.

What is the relationship between an antigen and an epitope?

An antigen is a foreign substance or molecular structure recognized by the immune system, whereas an epitope is the specific, localized region on that antigen to which an antibody's binding site directly attaches.

How does agglutination protect the host against pathogens?

Antibodies bind to epitopes on multiple pathogens simultaneously, cross-linking them into clumps; this reduces the number of distinct infectious units and makes them easier targets for phagocytes.

How does neutralization by antibodies prevent infection?

Antibodies bind directly to surface epitopes on bacteria or viruses, blocking their ability to adhere to host mucosal cells or tissues and promoting their subsequent phagocytosis.

What sequence of events leads to B-cell activation and antibody production against T-dependent antigens?

1. B-cell receptors bind an antigen's epitope. 2. The antigen is internalized and digested. 3. Antigenic fragments complex with MHC class II and are displayed on the B-cell surface. 4. A matching T helper ($T_H$) cell binds the MHC II-antigen complex. 5. The $T_H$ cell secretes cytokines that activate the B cell. 6. The B cell undergoes clonal expansion, differentiating into plasma cells (which secrete antibodies) and memory cells.

What is the function of the Major Histocompatibility Complex class II (MHC II) on B cells?

MHC II is a membrane glycoprotein complex on antigen-presenting cells that binds processed antigenic fragments internally and displays them on the B-cell surface to attract and engage matching T helper ($T_H$) cells.

How do antibody kinetics differ between a primary immune response and a secondary immune response?

In a primary response, antibody production peaks at $\sim 2\text{ weeks}$ and is initially dominated by IgM. In a secondary response, memory B cells produce a quicker response (peaking in $2\text{--}7\text{ days}$) that is dominated by IgG, yielding significantly higher antibody concentrations that persist longer.

Why is long-term immunity not always maintained against every pathogen?

Some pathogens mutate constantly into new structural forms that existing antibodies can no longer recognize, necessitating annual vaccinations, repeated exposures, or booster shots.

What are the four branches of adaptive immunity shown in the classification chart, and how do their sources differ?

1. Naturally acquired active: antigens enter naturally and the body induces antibodies/lymphocytes. 2. Naturally acquired passive: antibodies pass from mother to fetus via placenta or to infant via milk. 3. Artificially acquired active: antigens enter via vaccines and the body produces antibodies/lymphocytes. 4. Artificially acquired passive: preformed antibodies in immune serum are introduced by injection.